A. Skolarikos (Chair), H. Jung, A. Neisius,
A. Petřík, B. Somani, T. Tailly
G. Gambaro (Consultant nephrologist)
Guidelines Associates: N.F. Davis, R. Geraghty,
R. Lombardo, L. Tzelves
Guidelines Office: C. Bezuidenhout
© European Association of Urology 2024
Urolithiasis
EAU Guidelines on

UROLITHIASIS - LIMITED UPDATE APRIL 2024 2
TABLE OF CONTENTS PAGE
1. INTRODUCTION 6
1.1 Aims and scope 6
1.2 Panel composition 6
1.3 Available publications 6
1.4 Publication history and summary of changes 6
1.4.1 Publication history 6
1.4.2 Summary of changes 6
2. METHODS 6
2.1 Data identification 6
2.2 Review 7
3. GUIDELINES 7
3.1 Prevalence, aetiology, risk of recurrence 7
3.1.1 Introduction 7
3.1.2 Stone composition 7
3.1.3 Risk groups for stone formation 8
3.2 Classification of stones 10
3.2.1 Stone size 10
3.2.2 Stone location 10
3.2.3 X-ray characteristics 11
3.3 Diagnostic evaluation 11
3.3.1 Diagnostic imaging 11
3.3.1.1 Evaluation of patients with acute flank pain/suspected ureteral

stones 11
3.3.2 Diagnostics - metabolism-related 12
3.3.2.1 Basic laboratory analysis - non-emergency urolithiasis patients 12
3.3.2.2 Analysis of stone composition 12
3.3.2.3 Recommendations for laboratory examinations and stone analysis 12
3.3.3 Diagnosis in special groups and conditions 13
3.3.3.1 Diagnostic imaging during pregnancy 13
3.3.3.2 Diagnostic imaging in children 13
3.3.3.2.1  Summary of evidence and recommendations for

diagnostic imaging in children 14
3.4 Disease Management 14
3.4.1 Renal colic 14
3.4.1.1 Summary of evidence and recommendations for the management

of renal colic 15
3.4.2 Management of sepsis and/or anuria in obstructed kidney 15
3.4.2.1 Summary of evidence and recommendations for the management

of sepsis and anuria 16
3.4.3 Medical expulsive therapy 16
3.4.3.1 Summary of evidence and recommendations for MET 16
3.4.4 Chemolysis 17
3.4.4.1 Summary of evidence and recommendations for chemolysis 17
3.4.5 Extracorporeal shock wave lithotripsy (SWL) 17
3.4.5.1 Summary of evidence and recommendations for SWL 19
3.4.6 Ureteroscopy (retrograde and antegrade) 19
3.4.6.1 Summary of evidence and recommendations for retrograde URS,

RIRS and antegrade ureteroscopy 21
3.4.7 Percutaneous nephrolithotomy 22
3.4.7.1 Summary of evidence and recommendations for endourology

techniques for renal stone removal 24
3.4.8 General recommendations and precautions for stone removal 24
3.4.8.1 Antibiotic therapy 24

3UROLITHIASIS - LIMITED UPDATE APRIL 2024
3.4.8.2 Antithrombotic therapy and stone treatment 25
3.4.8.2.1  Summary of evidence and recommendations for
antithrombotic therapy and stone treatment 26
3.4.8.3 Obesity 26
3.4.8.4 Stone composition 26
3.4.8.5 Contraindications of procedures 27
3.4.9 Specific stone management of ureteral stones 27
3.4.9.1 Conservative treatment/observation 27
3.4.9.2 Pharmacological treatment, medical expulsive therapy 27
3.4.9.3 Indications for treatment of ureteral stones 27
3.4.9.4 Selection of procedure for removal of ureteral stones 28
3.4.9.4.1  Summary of evidence and recommendations for

selection of procedure for active removal of ureteral
stones 28
3.4.10 Specific stone management of renal stones 29
3.4.10.1 Conservative treatment (observation) 29
3.4.10.2 Pharmacological treatment of renal stones 30
3.4.10.3 Indications for stone removal of renal stones 30
3.4.10.4 Selection of procedure for active removal of renal stones 30
3.4.10.4.1 Stones in the renal pelvis or upper/middle calyces 30
3.4.10.4.2 Stones in the lower renal pole 30
3.4.10.5  Summary of evidence and recommendations for the management

of renal stones 31
3.4.11 Laparoscopy and open surgery 32
3.4.11.1 Recommendation for laparoscopy and open surgery 32
3.4.12 Steinstrasse 32
3.4.12.1 Summary of evidence and recommendations for steinstrasse 32
3.4.13 Management of patients with residual stones 33
3.4.13.1 Recommendation for management of patients with residual stones 33
3.4.14 Management of specific patient groups 33
3.4.14.1 Management of urinary stones and related problems during pregnancy 33
3.4.14.1.1  Summary of evidence and recommendation for the
management of urinary stones and related problems

during pregnancy 34
3.4.14.2 Management of stones in patients with urinary diversion 34
3.4.14.2.1  Summary of evidence and recommendation for the
management of stones in patients with urinary diversion 34
3.4.14.3 Management of stones in patients with neurogenic bladder 35
3.4.14.3.1  Summary of evidence and recommendation for the
management of stones in patients with neurogenic

bladder 35
3.4.14.4 Management of stones in patients with transplanted kidneys 35
3.4.14.4.1  Summary of evidence and recommendation for the
management of stones in patients with transplanted

kidneys 36
3.4.14.5 Special problems in stone removal 36
3.4.15 Management of stones in children 36
3.4.15.1 Clinical presentation 36
3.4.15.2 Conservative management 37
3.4.15.3 Medical expulsive therapy in children 37
3.4.15.4 Extracorporeal shock wave lithotripsy 37
3.4.15.5 Endourological procedures 37
3.4.15.6 Open and laparoscopic/robot-assisted stone surgery 38
3.4.15.7 Special considerations on recurrence prevention 38
3.4.15.8  Summary of evidence and recommendations for the management

of stones in children 38
3.5 Radiation exposure and protection during endourology 39

UROLITHIASIS - LIMITED UPDATE APRIL 2024 4
4. METABOLIC EVALUATION AND RECURRENCE PREVENTION 40
4.1 General metabolic considerations for patient work-up 40
4.1.1 Evaluation of patient risk 40
4.1.2 Urine sampling 41
4.1.3 Timing of specific metabolic work-up 41
4.1.4 Reference ranges of laboratory values 41
4.1.5 Risk indices and additional diagnostic tools 41
4.2 General considerations for recurrence prevention 43
4.2.1 Fluid intake 43
4.2.2 Diet 44
4.2.3 Lifestyle 44
4.2.4 Summary of evidence and recommendation for recurrence prevention 44
4.3 Stone-specific metabolic evaluation and pharmacological recurrence prevention 45
4.3.1 Introduction 45
4.4 Calcium oxalate stones 46
4.4.1 Diagnosis 46
4.4.2 Interpretation of results and aetiology 48
4.4.3 Specific treatment 50
4.4.4  Summary of evidence and recommendations for pharmacological

treatments for patients with specific abnormalities in urine composition
(based on 24-hour urine samples) 50
4.5 Calcium phosphate stones 50
4.5.1 Diagnosis 51
4.5.2 Interpretation of results and aetiology 51
4.5.3 Pharmacological therapy 51
4.5.4  Summary of evidence and recommendation for the management of calcium
phosphate Stones 52
4.6 Disorders and diseases related to calcium stones 52
4.6.1 Hyperparathyroidism 52
4.6.2 Granulomatous Diseases 52
4.6.3 Primary Hyperoxaluria 52
4.6.3.1 Summary of evidence and recommendation for the management of
primary hyperoxaluria 53
4.6.4 Enteric hyperoxaluria 53
4.6.5 Renal tubular acidosis 53
4.6.5.1 Summary of evidence and recommendations for the management

of tubular acidosis 55
4.6.6 Nephrocalcinosis 55
4.6.6.1 Diagnosis 55
4.7 Uric acid and ammonium urate stones 55
4.7.1 Diagnosis 56
4.7.2 Interpretation of results 56
4.7.3 Specific treatment 56
4.7.4  Summary of evidence and recommendations for the management of uric

acid- and ammonium urate stones 57
4.8 Struvite and infection stones 57
4.8.1 Diagnosis 58
4.8.2 Interpretation 58
4.8.3 Specific treatment 58
4.9 Cystine stones 59
4.9.1 Diagnosis 59
4.9.2 Specific treatment 60
4.9.2.1 Pharmacological treatment of cystine stones 60
4.9.3  Summary of evidence and recommendations for the management of cystine

stones 61
4.10 2,8-Dihydroxyandenine stones and xanthine stones 61
4.10.1 2,8-Dihydroxyadenine stones 61
4.10.2 Xanthine stones 61
4.10.3 Fluid intake and diet 61

5UROLITHIASIS - LIMITED UPDATE APRIL 2024
4.11 Drug-induced stones 61
4.12 Matrix Stones 62
4.13 Unknown stone composition 62
4.13.1  Recommendations for investigations for the assessment of patients with

stones of unknown composition 62
5. FOLLOW-UP OF URINARY STONES 63
6. BLADDER STONES 66
6.1 Prevalence, aetiology, and risk factors of bladder stones 66
6.2 Presentation 67
6.3 Diagnostic evaluation 67
6.3.1 Diagnostic investigations for bladder stones 67
6.3.2 Diagnosing the cause of bladder stones 67
6.4 Disease Management 68
6.4.1 Conservative treatment and Indications for active stone removal 68
6.4.2 Medical management of bladder stones 68
6.4.3 Bladder stone interventions 68
6.4.3.1 Suprapubic cystolithotomy 68
6.4.3.2 Transurethral cystolithotripsy 68
6.4.3.2.1 Transurethral cystolithotripsy in adults 68
6.4.3.2.1.1  Lithotripsy modalities used during
transurethral cystolithotripsy in adults 69
6.4.3.2.1.2 Transurethral cystolithotripsy in children 69
6.4.3.3 Percutaneous cystolithotripsy 69
6.4.3.3.1 Percutaneous cystolithotripsy in adults: 69
6.4.3.3.2 Percutaneous cystolithotripsy in children: 69
6.4.3.4 Extracorporeal shock wave lithotripsy 69
6.4.3.4.1 Shock wave lithotripsy in adults 69
6.4.3.4.2 Shock wave lithotripsy in children 70
6.4.3.5 Laparoscopic cystolithotomy 70
6.4.4  Treatment for bladder stones secondary to bladder outlet obstruction in

adult men 70
6.4.5 Special situations 70
6.4.5.1 Neurogenic bladder and stone formation 70
6.4.5.2 Bladder Augmentation 71
6.4.5.3 Urinary diversion 71
6.4.5.4 Treatment of stones in patients with bladder augmentation or

urinary diversion 71
6.5 Bladder stones follow-up 72
6.6 Summary of evidence and recommendations for the treatment of bladder stones 73
7. REFERENCES 75
8. CONFLICT OF INTEREST 117
9. CITATION INFORMATION 117

UROLITHIASIS - LIMITED UPDATE APRIL 2024 6
1. INTRODUCTION
1.1 Aims and scope
The European Association of Urology (EAU) Urolithiasis Guidelines Panel has prepared these guidelines to
help urologists assess evidence-based management of stones/calculi in the urinary tract and incorporate
recommendations into clinical practice. This document covers most aspects of the disease, which is still
a cause of significant morbidity despite technological and scientific advances. The Panel is aware of the
geographical variations in healthcare provision. In addition, information on the management of bladder stones is
now also included in these guidelines.
It must be emphasised that clinical guidelines present the best evidence available to the experts
but following guideline recommendations will not necessarily result in the best outcome. Guidelines can never
replace clinical expertise when making treatment decisions for individual patients but rather help to focus
decisions - also taking personal values and preferences/individual circumstances of patients into account.
Guidelines are not mandates and do not purport to be a legal standard of care.
1.2 Panel composition
The EAU Urolithiasis Guidelines Panel consists of an international group of clinicians with expertise in this area.
All experts involved in the production of this document have submitted potential conflict of interest which can
be viewed on the EAU website Uroweb: http://uroweb.org/guideline/urolithiasis/.
1.3 Available publications
A quick reference document (Pocket guidelines) is available. This is an abridged version, which may require
consultation together with the full-text versions. Several scientific publications are available [1-3]. All documents
are accessible through the EAU website Uroweb: http://uroweb.org/guideline/urolithiasis/.
1.4 Publication history and summary of changes
1.4.1 Publication history
The EAU Guidelines on Urolithiasis were first published in 2000. Standard procedure for EAU Guidelines includes
an annual assessment of newly published literature in the field to guide future updates. This 2024 Urolithiasis
Guidelines present a limited update of the 2023 publication.
1.4.2 Summary of changes
The 2024 Urolithiasis Guidelines have undergone a major revision and restructuring of text, as well as a review of all
recommendations.
2. METHODS
2.1 Data identification
Recommendation within the Guidelines are developed by the panels to prioritise clinically important
care decisions. The strength of each recommendation is determined by the balance between desirable and
undesirable consequences of alternative management strategies, the quality of the evidence (including certainty
of estimates), and the nature and variability of patient values and preferences. This decision process, which can
be reviewed in the strength rating forms which accompany each guideline statement, addresses a number of
key elements:
1.  the overall quality of the evidence which exists for the recommendation [4];
2.  the magnitude of the effect (individual or combined effects);
3.  the certainty of the results (precision, consistency, heterogeneity and other statistical or study
related factors);
4.  the balance between desirable and undesirable outcomes;
5.  the impact and certainty of patient values and preferences on the intervention
Strong recommendations typically indicate a high degree of evidence quality and / or a favourable
balance of benefit to harm and patient preference. Weak recommendations typically indicate availability of lower
quality evidence, and/or equivocal balance between benefit and harm, and uncertainty or variability of patient
preference [5].

7UROLITHIASIS - LIMITED UPDATE APRIL 2024
Additional information can be found in the general Methodology section of this print, and online at the EAU
website: https://uroweb.org/guidelines/urolithiasis/ publications-appendices. A list of associations endorsing
the EAU Guidelines can also be viewed online at the above address.
2.2 Review
The 2015 Urolithiasis Guidelines were subjected to peer review prior to publication. Chapter 6, detailing the
treatment and follow-up of bladder stones was peer-reviewed in 2019.
3. GUIDELINES
3.1 Prevalence, aetiology, risk of recurrence
3.1.1 Introduction
Stone incidence depends on geographical, climatic, ethnic, dietary, and genetic factors. The recurrence risk is
basically determined by the disease or disorder causing the stone formation. Accordingly, the prevalence rates
for urinary stones vary from 1% to 20% [6]. In countries with a high standard of life such as Sweden, Canada or
the USA, renal stone prevalence is notably high (> 10%). For some areas, an increase of more than 37% over the
last 20 years has been reported [7-9]. There is emerging evidence linking nephrolithiasis to the risk of chronic
kidney disease (CKD) [10] .
Stones can be stratified into those caused by: infections, non-infectious causes, genetic defects [11, 12]; or
adverse drug effects (drug stones) (Table 3.1). See also section 3.2.
Table 3.1: Stones classified by aetiology
Non-infection stones
• Calcium oxalate • Calcium phosphate • Uric acid
• Ammonium urate*
Infection stones
• Magnesium ammonium phosphate • Highly carbonated apatite • Ammonium urate
Genetic causes
• Cystine • Xanthine • 2,8-Dihydroxyadenine
Drug stones
*In children in developing countries; in patients with anorexia or laxative-abuse.
3.1.2 Stone composition
Stone composition is the basis for further diagnostic and management decisions. Stones are often formed from
a mixture of substances. Table 3.2 lists the most clinically relevant substances and their mineral components.
Table 3.2: Stone composition
Chemical name Mineral name [13] Chemical formula
Calcium oxalate monohydrate Whewellite CaC
2O
4.H
2O
Calcium oxalate dihydrate Weddelite CaC
2O
4.2H
2O
Basic calcium phosphate Apatite Ca
10(PO
4)
6.(OH)
2
Calcium hydroxyl phosphate Carbonate apatite Ca
5(PO
4)
3(OH)
b-tricalcium phosphate Whitlockite Ca
3(PO
4)
2
Carbonate apatite phosphate Dahllite Ca
5(PO
4)
3OH
Calcium hydrogen phosphate dihydrate Brushite CaHPO
4.2H
2O
Calcium carbonate Aragonite CaCO
3
Octacalcium phosphate - Ca
8H
2(PO
4)
6.5H
2O
Uric acid Uricite C
5H4N
4O
3

UROLITHIASIS - LIMITED UPDATE APRIL 2024 8
Uric acid dihydrate Uricite C
5H
4O
3.2H
20
Ammonium urate - NH
4C
5H
3N
4O
3
Sodium acid urate monohydrate - NaC
5H
3N
4O
3.H
2O
Magnesium ammonium phosphate hexahydrate Struvite MgNH
4PO
4.6H
2O
Magnesium acid phosphate trihydrate Newberyite
Magnesium ammonium phosphate monohydrate Dittmarite
Cystine -
Xanthine - -
2,8-Dihydroxyadenine - -
Proteins - -
Cholesterol - -
Calcite - -
Potassium urate - -
Trimagnesium phosphate - -
Melamine - -
Matrix - -
Drug stones Active compounds
crystallising in urine
-
Foreign body calculi - -
3.1.3 Risk groups for stone formation
Determination of the risk for stone formation is imperative for pharmacological treatment. Previous stone
history (recurrence, regrowth, stone surgeries) is a fundamental element in determining risk for stone formation.
About 50% of recurrent stone formers have just one-lifetime recurrence [9, 14]. A review of first-time stone
formers calculated a recurrence rate of 26% in five years’ time [15]. Highly recurrent disease is observed in
slightly more than 10% of patients. Stone type and disease severity determine low- or high-risk stone formers
(Table 3.3) [16-32].
However, the risk status of stone formers should be determined in a holistic way taking into consideration not
only the probability of stone recurrence or regrowth, but also the risk of chronic kidney disease (CKD), end-
stage kidney disease (ESKD), and metabolic bone disorder (MBD) [33, 34]. A comprehensive evaluation of stone
risk in patients should also include the risk of developing CKD, ESKD, and MBD (Tables 3.4, 3.5, and 3.6) [33].
Urolithiasis can compromise renal function because of the renal stone (obstruction, infection), renal tissue
damage due to the primary condition causing stone formation (some genetic diseases, nephrocalcinosis, enteric
hyperoxaluria, etc.), or urological treatments for the condition [33]. Certain risk factors have been shown to be
associated with such a risk in stone formers, as shown below.
Table 3.3: High-risk stone formers [16-32]
General factors
Early onset of urolithiasis (especially children and teenagers)
Familial stone formation
Recurrent stone formers
Short time since last stone episode
Brushite-containing stones (CaHPO
4.2H
2O)
Uric acid and urate-containing stones
Infection stones
Solitary kidney (the kidney itself does not particularly increase the risk of stone formation, but prevention of
stone recurrence is of crucial importance to avoid acute renal failure)
Chronic Kidney Disease (CKD)

9UROLITHIASIS - LIMITED UPDATE APRIL 2024
Diseases associated with stone formation
Hyperparathyroidism
Metabolic syndrome
Mineral Bone Disorder (MBD)
Nephrocalcinosis
Polycystic kidney disease (PKD)
Gastrointestinal diseases (i.e., enteric hyperoxaluria due to jejuno-ileal bypass, intestinal resection, Crohn’s
disease, malabsorptive conditions, urinary diversion, exocrine pancreatic insufficiency, and bariatric surgery).
Increased levels of vitamin D
Sarcoidosis
Spinal cord injury, neurogenic bladder
Genetically determined stone formation
Cystinuria (type A, B and AB)
Primary hyperoxaluria (PH)
Renal tubular acidosis (RTA) type I
2,8-Dihydroxyadeninuria
Xanthinuria
Lesch-Nyhan syndrome
Cystic fibrosis
Drug-induced stone formation (see Table 4.11)
Anatomical abnormalities associated with stone formation
Medullary sponge kidney (tubular ectasia)
Ureteropelvic junction (UPJ) obstruction
Calyceal diverticulum, calyceal cyst
Ureteral stricture
Vesico-uretero-renal reflux
Horseshoe kidney
Ureterocele
Environmental and professional factors
High ambient temperatures
Chronic lead and cadmium exposure
Table 3.4 Risk factors for CKD and ESKD in stone formerss
Risk factors for CKD/ESKD in stone formers
Female gender
Overweight
Frequent UTI
Struvite stones
Acquired single kidney
Neurogenic bladder
Previous obstructive nephropathy
Ileal conduit
Furthermore, some specific kinds of urolithiasis also carry a particular risk of developing CKD/ESKD as shown
below.

UROLITHIASIS - LIMITED UPDATE APRIL 2024 10
Table 3.5 Risk factors for CKD and renal stones
Risk of chronic kidney disease and renal stones
• Possible risk of CKD
„Xanthine stones
„Indinavir stones
„Distal renal tubular acidosis (incomplete)
„Primary hyperparathyroidism
„Eating disorders and laxative abuse
„Medullary sponge kidney
• Moderate risk of CKD
„Brushite stones
„2,8-Dihydroxyadenine stones
„Sarcoidosis
„Pyelo-ureteral or ureteral strictures
• High risk of CKD
„Cystine stones
„Struvite stones
„Stones in a single kidney
„Distal renal tubular acidosis (complete)
„Secondary hyperoxaluria (bariatric surgery, inflammatory bowel disease, bowel resection and
malabsorptive syndromes)
„Other forms of nephrocalcinosis (often associated with genetic conditions with hypercalciuria)
„Anatomical abnormalities of the kidney and urinary tract (for example, horseshoe kidney, ureterocele
and vesicoureteral reflux)
„Neurological bladder
• Very high risk of CKD
„Primary hyperoxaluria
„Autosomal dominant polycystic kidney
Table 3.6 Risk factors for metabolic bone disease and calcium renal stones
Risk of metabolic bone disease and calcium renal stones
• Distal renal tubular acidosis (complete or incomplete)
• Medullary sponge kidney
• Primary hyperparathyroidism
• Malabsorptive syndromes
• Fasting hypercalciuria
• Genetic disorders
3.2 Classification of stones
Urinary stones can be classified according to size, location, X-ray characteristics, aetiology of formation,
composition, and risk of recurrence [2, 9, 32] .
3.2.1 Stone size
Stone size can be reported in a single, two or three dimensions. Currently, the guidelines still use the linear
measurement of cumulative stone diameter to stratify stones in < 5 mm, 5-10 mm, 10-20 mm, and > 20 mm for
use in the treatment algorithm.
3.2.2 Stone location
Stones can be classified according to anatomical position: upper, middle, or lower calyx; renal pelvis; upper,
middle, or distal ureter; and urinary bladder.

11UROLITHIASIS - LIMITED UPDATE APRIL 2024
3.2.3 X-ray characteristics
Stones can be classified according to plain X-ray appearance [kidney-ureter-bladder (KUB) radiography] (Table
3.7), which varies according to mineral composition [35]. Non-contrast-enhanced computed tomography (NCCT)
can be used to classify stones according to density, inner structure, and composition, which can affect
treatment decisions (Section 3.3) [35, 36] .
Table 3.7: X-ray characteristics
Radiopaque Poor radiopacity Radiolucent
Calcium oxalate dihydrate Magnesium ammonium phosphate Uric acid
Calcium oxalate monohydrate Cystine Ammonium urate
Calcium phosphate Xanthine
2,8-Dihydroxyadenine
Drug-stones (Section 4.11)
3.3 Diagnostic evaluation
3.3.1 Diagnostic imaging
The most appropriate imaging modality will be determined by the clinical situation, which will differ depending
on if a ureteral or a renal stone is suspected.
Standard evaluation includes a detailed medical history and physical examination. Patients with
ureteral stones usually present with loin pain, vomiting, and sometimes fever, but may also be asymptomatic
[37]. Immediate evaluation is indicated in patients with solitary kidney, fever or when there is doubt regarding a
diagnosis of renal colic. Ultrasound (US) should be used as the primary diagnostic imaging tool, although pain
relief, or any other emergency measures, should not be delayed by imaging assessments. Ultrasound is safe
(no risk of radiation), reproducible and inexpensive. It can identify stones located in the calyces, pelvis, and
pyeloureteric and vesico-ureteral junctions (US with filled bladder), as well as in patients with upper urinary tract
(UUT) dilatation. Ultrasound has a sensitivity of 45% and specificity of 94% for ureteral stones and a sensitivity
of 45% and specificity of 88% for renal stones [38, 39] .
The sensitivity and specificity of KUB is 44-77% [40]. Kidney-ureter-bladder radiography [41] is helpful
in differentiating between radiolucent and radiopaque stones and could be used for comparison during follow-
up.
3.3.1.1 Evaluation of patients with acute flank pain/suspected ureteral stones
Non-contrast-enhanced computed tomography has become the standard for diagnosing acute flank pain and
has replaced intravenous urography (IVU). Non-contrast-enhanced CT can determine stone location, burden, and
density. When stones are absent, the cause of abdominal pain should be identified. In evaluating patients with
suspected acute urolithiasis, NCCT is significantly more accurate than IVU or US [42, 43] .
Non-contrast-enhanced CT can detect uric acid and xanthine stones, which are radiolucent on plain films, but
not indinavir stones [44] . Non-contrast-enhanced CT can determine stone density, the inner structure of the
stone, skin-to-stone distance, and surrounding anatomy; all of which affect the selection of treatment modality
[45]. The advantage of non-contrast imaging must be balanced against the loss of information on renal function
and urinary collecting system anatomy, as well as higher radiation dose [46-49].
Radiation risk can be reduced by low-dose CT, which may, however, be difficult to introduce in
standard clinical practice [50-53]. In patients with a body mass index (BMI) < 30, low-dose CT has been shown to
have a sensitivity of 86% for detecting ureteral stones < 3 mm and 100% for calculi > 3 mm [54]. A meta-analysis
(MA) of prospective studies [55] has shown that low-dose CT diagnosed urolithiasis with a pooled sensitivity of
93.1% (95% CI: 91.5-94.4), and a specificity of 96.6% (95% CI: 95.1-97.7%). Dual-energy CT can differentiate uric
acid containing stones from calcium-containing stones [36].
Summary of evidence LE
Non-contrast-enhanced CT is used to confirm stone diagnosis in patients with acute flank pain, as it is
superior to IVU.
1a
Computed tomography imaging enables 3D reconstruction of the collecting system, as well as
measurement of stone density and skin-to-stone distance.
2a
Consider a contrast study if stone removal is planned and the anatomy of the renal collecting system
needs to be assessed.
3

UROLITHIASIS - LIMITED UPDATE APRIL 2024 12
Recommendations Strength rating
Immediate imaging is indicated with fever or solitary kidney, and when diagnosis is doubtful.Strong
Use non-contrast-enhanced computed tomography to confirm stone diagnosis in patients
with acute flank pain following initial ultrasound assessment.
Strong
3.3.2 Diagnostics - metabolism-related
Besides imaging, each emergency patient with urolithiasis needs a succinct biochemical work-up of urine and
blood test. At this point, no distinction is made between high- and low-risk patients for stone formation.
3.3.2.1 Basic laboratory analysis - non-emergency urolithiasis patients
Biochemical work-up is similar for all stone patients (see 3.3.2.3). However, if no intervention is planned,
examination of sodium, potassium, C-reactive protein (CRP), and blood coagulation time can be omitted. Only
patients at high risk for stone recurrence should undergo a more specific analytical programme [17]. Stone-
specific metabolic evaluation is described in Chapter 4.
The easiest method for diagnosing stones is by analysis of a passed stone using a validated method
as listed in section 3.3.2.3. Once the mineral composition is known, a potential metabolic disorder can be
identified.
3.3.2.2 Analysis of stone composition
Stone analysis should be performed on all first-time stone formers.
In clinical practice, repeat stone analysis is needed in the case of:
• recurrence under pharmacological prevention;
• early recurrence after interventional therapy with complete stone clearance;
• late recurrence after a prolonged stone-free period [56, 57].
Patients should be instructed to filter their urine to retrieve a concrement for analysis. Stone passage and
restoration of baseline renal function should be confirmed.
The preferred analytical procedures are infrared spectroscopy (IRS) or X-ray diffraction (XRD) [58,
59]. Equivalent results can be obtained by polarisation microscopy. Chemical analysis (wet chemistry) is
generally deemed to be obsolete [58, 60].
3.3.2.3 Recommendations for laboratory examinations and stone analysis [17, 23, 61-63]
Recommendations Strength rating
Urine
Dipstick test of spot urine sample:
• red cells;
• white cells;
• nitrites;
• approximate urine pH;
• urine microscopy and/or culture.
Weak
Blood
Serum blood sample:
• creatinine;
• uric acid;
• (ionised) calcium;
• sodium;
• potassium;
• blood cell count;
• C-reactive protein.
Strong
Perform a coagulation test (partial thromboplastin time and international normalised ratio) if
intervention is likely or planned.
Strong
Perform stone analysis in first-time formers using a valid procedure (X-ray diffraction or
infrared spectroscopy).
Strong

13UROLITHIASIS - LIMITED UPDATE APRIL 2024
Repeat stone analysis in patients presenting with:
• recurrent stones despite drug therapy;
• early recurrence after complete stone clearance;
• late recurrence after a long stone-free period because stone composition may change.
Strong
3.3.3 Diagnosis in special groups and conditions
3.3.3.1 Diagnostic imaging during pregnancy
In pregnant women, radiation exposure may cause non-stochastic (teratogenesis) or stochastic (carcinogenesis,
mutagenesis) effects. Teratogenic effects are cumulative with increasing doses and require a threshold dose

(< 50 mGy are considered as safe) and depend on the gestation age (minimum risk prior to the 8th week and
after the 23rd week). Carcinogenesis (dose even < 10 mGy present a risk) and mutagenesis (500-1000 mGy
doses are required, far in excess of the doses in common radiographic studies) get worse with increasing dose
but they do not require a dose threshold and are not dependent on the gestational age [64].
There is no imaging modality that should be routinely repeated in pregnant women. Scientific societies and
organizations agree on the safety of the diagnostic evaluation when the US [65], X-ray imaging [66, 67], and MRI
[68] are used as and when indicated [69-76]. A radiographic procedure should not be withheld from a pregnant
woman if the procedure is clearly indicated and doing so will affect her medical care.
It is generally recommended that an investigation resulting in an absorbed dose to the foetus of
greater than 0.5 mGy requires justification.
Ultrasound (when necessary, using changes in the renal resistive index and transvaginal/transabdominal US with a
full bladder) has become the primary radiological diagnostic tool when evaluating pregnant patients suspected of
renal colic. However, normal physiological changes in pregnancy can mimic ureteral obstruction [72-74].
Magnetic resonance imaging can be used, as a second-line option [70], to define the level of
urinary tract obstruction, and to visualise stones as a filling defect [77]. The use of gadolinium is not routinely
recommended in pregnancy to avoid toxic effects on the embryo [72].
For the detection of urolithiasis during pregnancy, low-dose CT is associated with a higher positive
predictive value (95.8%), compared to MRI (80%) and US (77%). As per White et al., low-dose CT offers improved
diagnostic accuracy that can avoid negative interventions such as ureteroscopy [78]. Although low-dose CT
protocols reduce radiation exposure, judicious use is currently recommended in pregnant women as a last-line
option [72].
Summary of evidence LE
Only low-level data exist for imaging in pregnant women supporting US and MRI. 3
Recommendations Strength rating
Use ultrasound as the preferred method of imaging in pregnant women. Strong
Use magnetic resonance imaging as a second-line imaging modality in pregnant women.Strong
Use low-dose computed tomography as a last-line option in pregnant women. Strong
3.3.3.2 Diagnostic imaging in children
Children with urinary stones have a high risk of recurrence; therefore, standard diagnostic procedures for
high-risk patients apply, including a valid stone analysis (Section 3.1.3 and Chapter 4). The most common
nonmetabolic disorders facilitating stone formation are vesicoureteral reflux (VUR), UPJ obstruction, neurogenic
bladder, and other voiding difficulties [79] .
When selecting diagnostic procedures to identify urolithiasis in children, it should be remembered
that these patients might be uncooperative, require anaesthesia, and may be sensitive to ionising radiation.
Again, the principle of ALARA (As Low As Reasonably Achievable) should be observed [80-84].
Ultrasound
Ultrasound is the primary imaging technique [85] in children. Its advantages are the absence of radiation and no
need for anaesthesia. Imaging should include both the fluid-filled bladder with adjoining portion of the ureters, as
well as the upper ureter [80]. Colour Doppler US shows differences in the ureteral jet [86] and resistive index of the
arciform arteries of both kidneys, which are indicative of the grade of obstruction [87]. Nevertheless, the US may
fail to identify ureteral stones and provides limited information on renal function [88].

UROLITHIASIS - LIMITED UPDATE APRIL 2024 14
Plain films (KUB radiography)
Kidney-ureter-bladder radiography can help to identify stones and their radiopacity and facilitate follow-up.
Intravenous urography
The radiation dose for IVU is comparable to that for voiding cystourethrography (0.33 mSV) [89]. However, the
need for contrast medium injection is a major drawback.
Non-contrast-enhanced computed tomography
Low-dose CT protocols have been shown to significantly reduce radiation exposure [90-92]. Sedation or
anaesthesia is rarely needed with modern high-speed CT equipment.
Magnetic resonance urography
Magnetic resonance urography (MRU) cannot be used to detect urinary stones. However, it might provide
detailed anatomical information about the urinary collecting system, the location of an obstruction or stenosis in
the ureter, and renal parenchymal morphology [93].
3.3.3.2.1 Summary of evidence and recommendations for diagnostic imaging in children
Summary of evidence LE
Ultrasound is the first-line imaging modality in children when a stone is suspected; it should include the
kidney, fluid-filled bladder, and the ureter next to the kidney and the (filled) bladder.
2b
A kidney-ureter-bladder radiography (or low-dose NCCT) is an alternative investigation if US will not
provide the required information.
2b
Recommendations Strength rating
Complete a metabolic evaluation based on stone analysis in all children. Strong
Collect stone material for analysis to classify the stone type. Strong
Perform ultrasound as first-line imaging modality in children when a stone is suspected; it
should include the kidney, fluid-filled bladder, and the ureter.
Strong
Perform a kidney-ureter-bladder radiography (or low-dose non-contrast-enhanced computed
tomography) if ultrasound will not provide the required information.
Strong
3.4 Disease Management
The treatment of urolithiasis is based on many parameters and is individualised for each patient. Parameters
such as the size, number, location, and constitution of the stones are the cornerstones for deciding the
treatment. In addition, the morphology, shape, volume, mobility, and hardness of the stone should be
considered. Finally, the anatomy and compliance of the entire pelvic-calyceal system should be assessed for
each patient. The design of therapeutic algorithms including all the above parameters is difficult mainly due to
the great diversity of lithiasis disease per patient. Furthermore, there is a significant lack of comparative clinical
studies to support development of algorithms using parameters other than stone size and composition.
3.4.1 Renal colic
Pain relief
Non-steroidal anti-inflammatory drugs (NSAIDs) (including metamizole dipyrone), and paracetamol are effective
in patients with acute stone colic [94] and have better analgesic efficacy than opioids [95]. Ibuprofen compared
to ketorolac is a more rapid-acting drug in controlling pain caused by renal colic with a similar side effect profile
[96].
Pain relief from intramuscular (i.m.) diclofenac compared favourably with those from intravenous (i.v.) ibuprofen
and i.v. ketorolac; however, no recommendation can be given due to the way in which the results have been
reported [97]. The addition of antispasmodics to NSAIDs does not result in better pain control. Patients receiving
NSAIDs are less likely to require further analgesia in the short term. It should be taken into consideration that
the use of diclofenac and ibuprofen increased major coronary events [94, 95]. Oral diclofenac in the long-term
increases the risk of cardiovascular events and upper GI bleeding [98]. Patients with significant risk factors for
cardiovascular events should be treated with diclofenac only after careful consideration. As risks increase with
dose and duration, the lowest effective dose should be used for the shortest duration [99]. Non-steroidal anti-
inflammatory drugs may affect renal function in those patients with pre-existing decreased GFR.

15UROLITHIASIS - LIMITED UPDATE APRIL 2024
In an RCT including 150 patients, Intradermal sterile water injection (ISWI) and diclofenac (i.m.) were shown
equally effective for pain relief in acute renal colic. Intradermal sterile water injection may be an alternative to
NSAIDs in pregnant patients or others where NSAIDs are contra-indicated [100].
Opioids, particularly pethidine, are associated with a high rate of vomiting compared to NSAIDs and
carry a greater likelihood of further analgesia being needed [94, 101]. If an opioid is used, it is recommended
that it is not pethidine. Combination of opioids and NSAIDs increase analgetic effect compared to opioids alone
[102]. Acupuncture seems to be effective in renal colic alone or in combination with analgetic drugs, but there is
limited data [103, 104].
Prevention of recurrent renal colic
Facilitation of passage of ureteral stones is discussed in Section 3.4.9. For patients with ureteral stones that are
expected to pass spontaneously, NSAID tablets or suppositories (e.g., diclofenac sodium, 100-150 mg/day, 3-10
days) may help reduce inflammation and the risk of recurrent pain [105, 106]. Although NSAID can affect renal
function in patients with already reduced function, it has no functional effect in patients with normal renal function
[107].
The systematic review and MA by Hollingsworth et al., [108] addressed pain reduction as a secondary
outcome and concluded that medical expulsive therapy (MET) seems efficacious in reducing pain episodes of
patients with ureteral stones.
If analgesia cannot be achieved medically, drainage, using stenting, percutaneous nephrostomy, or
stone removal, is indicated [109].
3.4.1.1 Summary of evidence and recommendations for the management of renal colic
Summary of evidence LE
Non-steroidal anti-inflammatory drugs are very effective in treating renal colic and are superior to opioids.1b
For symptomatic ureteral stones, stone removal as first-line treatment is a feasible option in selected
patients.
1b
Recommendations Strength rating
Offer a non-steroidal anti-inflammatory as the first drug of choice; depending on
cardiovascular risk factors and side effects.
Strong
Offer opiates (hydromorphine, pentazocine or tramadol) as a second choice. Weak
Offer renal decompression or ureteroscopic stone removal in case of analgesic refractory
colic pain.
Strong
3.4.2 Management of sepsis and/or anuria in obstructed kidney
The obstructed kidney with all signs of urinary tract infection (UTI) and/or anuria is a urological emergency.
Urgent decompression is often necessary to prevent further complications in infected hydronephrosis
secondary to stone-induced, unilateral, or bilateral, renal obstruction.
Decompression
There are two options for urgent decompression of obstructed collecting systems [110]:
• placement of an indwelling ureteral stent
• percutaneous placement of a nephrostomy tube.
Several systematic reviews on the subject have been published, all of which emphasize that the available
literature comparing different drainage modalities for obstructing stones with or without infection is scarce,
based on small cohorts and of medium to very low quality [110]. There appears to be no difference in success
rate or complication rate of both procedures and there is not a difference in time to defervescence in the
population presenting with fever. Both meta-analyses identified patients receiving a nephrostomy tube to have a
longer stay in the hospital. Based on the available data, a DJ stent has a more negative impact on the patients’
quality of life in comparison with a nephrostomy tube, which can be explained mainly by the stent-related
symptoms that these patients experience [111, 112].
Definitive stone removal should be delayed until the infection is cleared following a complete course of
antimicrobial therapy. A small RCT showed the feasibility of immediate ureteroscopic stone removal combined

UROLITHIASIS - LIMITED UPDATE APRIL 2024 16
with an appropriate antibiotic regimen; however, at the cost of longer hospital stay and higher analgesic
requirements [113] .
Further measures
Along with urgent decompression of the obstructed and infected urinary collecting system, both urine- and
blood samples should be sent for culture-antibiogram sensitivity testing and antibiotics should be initiated
immediately [114, 115]. The regimen should be re-evaluated in the light of the culture-antibiogram results.
Although clinically well accepted, the impact of a second antibiogram test on treatment outcome has not yet
been evaluated [116]. Intensive care might become necessary.
3.4.2.1 Summary of evidence and recommendations for the management of sepsis and anuria
Summary of evidence LE
For decompression of the renal collecting system, ureteral stents and percutaneous nephrostomy
catheters are equally effective.
1b
Recommendations Strength rating
Urgently decompress the collecting system in case of sepsis with obstructing stones, using
percutaneous drainage or ureteral stenting.
Strong
Delay definitive treatment of the stone until sepsis is resolved. Strong
Collect (again) urine for antibiogram test following decompression. Strong
Start antibiotics immediately (+ intensive care, if necessary). Strong
Re-evaluate antibiotic regimen following antibiogram findings. Strong
3.4.3 Medical expulsive therapy
Several drug classes including α-blockers, calcium channel inhibitors, and phosphodiesterase type 5 inhibitors
(PDEI-5) are used for MET [117-120] A class effect of α-blockers in MET has been demonstrated in MAs
although this is an off-label indication [121-123]. However, there is contradictory evidence between these studies
and several well-designed, multicentre, placebo-controlled, double-blinded randomised studies showing limited,
or no, benefit using α-blockers, besides some advantage for distal ureteral stones > 5 mm [124-128]. Based
on studies with a limited number of patients [120, 121, 129, 130], no recommendation for the use of PDEI-5
or corticosteroids in combination with α-blockers in MET can be made. The panel concludes that MET using
α-blockers seems efficacious in the treatment of patients with distal ureteral stones > 5 mm who are amenable
to conservative management. Medical expulsive therapy in special situations is addressed in the relevant
chapters.
3.4.3.1 Summary of evidence and recommendations for medical expulsive therapy
Summary of evidence LE
Medical expulsive therapy seems to be efficacious for treating patients with ureteral stones who are
amenable to conservative management. The greatest benefit might be among those with > 5 mm
(distal) ureteral stones.
1a
Insufficient data exist to support the use of PDEI-5 or corticosteroids in combination with α-blockers as
an accelerating adjunct.
2a
Alpha-blockers increase stone expulsion rates in distal ureteral stones > 5 mm. 1a
A class effect of α-blockers has been demonstrated. 1a
Recommendation Strength rating
Offer α-blockers as medical expulsive therapy as one of the treatment options for (distal)
ureteral stones > 5 mm.*
Strong
* Alpha-blockers are an off-label treatment

17UROLITHIASIS - LIMITED UPDATE APRIL 2024
3.4.4 Chemolysis
Percutaneous irrigation chemolysis
Percutaneous chemolysis is rarely used nowadays, for practical reasons. Percutaneous irrigation chemolysis
may be an option for infection stones and theoretically also for uric acid stones. For dissolution of struvite
stones, Suby’s G solution (10% hemiacidrin; pH 3.5-4) can be used. The method has been described in case
series and literature reviews [131] .
Oral chemolysis
Stones composed of uric acid, but not sodium or ammonium urate stones, can be dissolved by oral chemolysis.
Prior stone analysis may provide information on stone composition. Urinary pH measurement and X-ray
characteristics can provide information on the type of stone.
Oral chemolysis is based on alkalinisation of urine by application of alkaline citrate or sodium
bicarbonate. The pH should be adjusted to 7.0-7.2. Chemolysis is more effective at a higher pH, which might,
however, promote calcium phosphate stone formation. Patients will need to adjust the dosage of alkalising
medication by self-monitoring the pH of their urine. A SR shows a complete or partial dissolution in 80.5%,
discontinuation rate of 10.2% with 15.7% requiring further intervention [132].
In the case of uric acid obstruction of the collecting system, oral chemolysis in combination with
urinary drainage is indicated. A combination of alkalinisation with tamsulosin can increase the frequency
of spontaneous passage of distal ureteral uric acid stones as shown in one RCT for stones > 5 mm [133].
Additional SWL might help to improve the results but evidence is weak [134] .
3.4.4.1 Summary of evidence and recommendations for chemolysis
Summary of evidence LE
Irrigation chemolysis has been used in limited clinical settings to dissolve struvite stones.3
Uric acid stones > 5mm can be dissolved based on oral alkalinisation of the urine above 7.0.3
For obstructing uric acid stones, a combination of oral chemolysis with tamsulosin is more effective
than each substance alone, particularly in stones > 8 mm.
1b
Recommendations (oral chemolysis of uric acid stones) Strength rating
Inform the patient how to monitor urine-pH by dipstick and to modify the dosage of alkalising
medication according to urine pH, as changes in urine pH are a direct consequence of such
medication.
Strong
Carefully monitor patients during/after oral chemolysis of uric acid stones. Strong
Combine oral chemolysis with tamsulosin in case of (larger) ureteral stones (if active
intervention is not indicated).
Weak
3.4.5 Extracorporeal shock wave lithotripsy (SWL)
The success of SWL depends on the efficacy of the lithotripter and the following factors:
• size, location (ureteral, pelvic, or calyceal), and composition (hardness) of the stones (Section 3.4.9.3);
• patient’s habitus (Section 3.4.10.3);
• performance of SWL (best practice, see below).
Each of these factors significantly influences the retreatment rate and outcome of SWL.
Best clinical practice
Stenting
Routine use of internal stents before SWL does not improve stone-free rates (SFRs), nor lowers the number of
auxiliary treatments. It may, however, reduce the formation of steinstrasse [135-138].
Pacemaker
Patients with a pacemaker can be treated with SWL, provided that appropriate technical precautions are taken.
Patients with implanted cardioverter defibrillators must be managed with special care (firing mode temporarily
reprogrammed during SWL treatment). However, this might not be necessary with new-generation lithotripters [139].
Shock wave rate
Lowering shock wave frequency from 120 to 60-90 shock waves/min improves SFRs [140-148]. Ultraslow

UROLITHIASIS - LIMITED UPDATE APRIL 2024 18
frequency of 30 shock waves/min may increase SFR [149]. Tissue damage increases with shock wave
frequency [150-153].
Number of shock waves, energy setting, and repeat treatment sessions
The number of shock waves that can be delivered at each session depends on the type of lithotripter and
shock wave power. There is no consensus on the maximum number of shock waves [154]. Starting SWL on a
lower energy setting with stepwise power (and SWL sequence) ramping can achieve vasoconstriction during
treatment [150], which prevents renal injury [155-157]. Animal studies [158] and a prospective randomised study
[159] have shown better SFRs (96% vs. 72%) using stepwise power ramping, but no difference has been found
for fragmentation or evidence of complications after SWL, irrespective of whether ramping was used [160, 161].
There are no conclusive data on the intervals required between repeated SWL sessions. However,
clinical experience indicates that repeat sessions are feasible (within one day for ureteral stones) [162] .
Improvement of acoustic coupling
Proper acoustic coupling between the cushion of the treatment head and the patient’s skin is important. Defects
(air pockets) in the coupling gel deflect 99% of shock waves [163]. Gentle swiping between the coupled therapy
head and the patient skin helps remove air bubbles and improves the coupling [164]. Ultrasound gel is probably
the most widely-used agent available as a lithotripsy coupling agent [165] .
Procedural control
Results of treatment are operator-dependent, and experienced clinicians obtain better results. During the
procedure, careful imaging control of localisation contributes to outcome quality [166].
Pain Control
Careful control of pain during treatment is necessary to limit pain-induced movements and excessive respiratory
excursions [167-170].
Antibiotic prophylaxis
No standard antibiotic prophylaxis before SWL is recommended. However, prophylaxis is recommended in the
case of internal stent placement ahead of anticipated treatments and in the presence of increased bacterial
burden (e.g., indwelling catheter, nephrostomy tube, or infectious stones) [62, 171, 172].
Medical therapy after extracorporeal shock wave lithotripsy
Despite conflicting results, most RCTs and several MAs support MET after SWL for ureteral or renal stones as
an adjunct to expedite expulsion and increase SFRs. Medical expulsion therapy might also reduce analgesic
requirements [173].
Post-treatment management
Mechanical percussion and diuretic therapy can significantly improve SFRs and accelerate stone passage after
SWL [174].
Complications of extracorporeal shock wave lithotripsy
Compared to percutaneous nephrolithotomy (PCNL) and ureteroscopy (URS), there are fewer overall
complications with SWL [175] (Table 3.8). In a Meta-Analysis of 115 RCT´s 18.43% of Clavien I–II complications
and 2.48% of Clavien III–IV complications occurred [175]. The relationship between SWL and hypertension or
diabetes is unclear. Published data are contradictory; however, no evidence exists supporting the hypothesis
that SWL may cause long-term adverse effects [176-182].
Table 3.8: Shock wave lithotripsy-related complications
Complications % Reference
Related to stone
fragments
Steinstrasse 4 [183-185]
Macroscopic
haematuria
17.2% [175]
Pain 12.1% [175]
Regrowth of residual
fragments
21 – 59 [186, 187]
Auxiliary procedure 6.9% [175]
Renal colic 2 – 4 [188]

19UROLITHIASIS - LIMITED UPDATE APRIL 2024
Infectious Bacteriuria in non-
infection stones
7.7 – 23 [186-189]
Sepsis 0.15% [175]
Tissue effect Renal Haematoma, symptomatic 0.21% [175]
Haematoma, asymptomatic 1.2% [175]
Cardiovascular Dysrhythmia 11 – 59 [186, 188]
Morbid cardiac events Case reports[186, 188]
Gastrointestinal Bowel perforation Case reports[190]
Liver, spleen haematoma Case reports[190-193]
3.4.5.1 Summary of evidence and recommendations for Shock wave lithotripsy

Summary of evidence LE
Stepwise power ramping prevents renal injury. 1b
Clinical experience has shown that repeat sessions are feasible (within one day for ureteral stones).4
Optimal shock wave frequency is 1.0 to 1.5 Hz. 1a
Proper acoustic coupling between the cushion of the treatment head and the patient’s skin is important.2
Careful imaging control of localisation of stone contributes to outcome of treatment. 2a
Careful control of pain during treatment is necessary to limit pain-induced movements and excessive
respiratory excursions.
1a
Antibiotic prophylaxis is recommended in the case of internal stent placement, infected stones, or
bacteriuria.
1a
Recommendations Strength rating
Ensure correct use of the coupling agent because this is crucial for effective shock wave
transportation.
Strong
Maintain careful fluoroscopic and/or ultrasonographic monitoring during shock wave
lithotripsy (SWL).
Strong
Use proper analgesia because it improves treatment results by limiting pain-induced
movements and excessive respiratory excursions.
Strong
Prescribe antibiotics prior to SWL in the case of infected stones or bacteriuria.Strong
3.4.6 Ureteroscopy (retrograde and antegrade)
The current standard for rigid ureteroscopes is a tip diameter of < 8 French (F). Rigid URS can be used for the
whole ureter [176]. However, technical improvements, as well as the availability of digital scopes, also favour the
use of flexible ureteroscopes in the ureter [194] .
Percutaneous antegrade removal of ureteral stones is a consideration in selected cases, i.e. large (>
15 mm), impacted proximal ureteral calculi in a dilated renal collecting system [195, 196], or when the ureter is
not amenable to retrograde manipulation [197].
Ureteroscopy for renal stones: Retrograde Intrarenal Surgery (RIRS)
Technical improvements including endoscope miniaturisation, improved deflection mechanism, enhanced
optical quality and tools, and introduction of disposables have led to an increased use of URS for both renal and
ureteral stones. Major technological progress has been achieved for RIRS. A systematic review addressing renal
stones > 2 cm showed a cumulative SFR of 91% with 1.45 procedures/patient; 4.5% of the complications were
> Clavien 3 [198, 199]. Digital scopes demonstrate shorter operation times due to the improvement in image
quality [200] .
Stones that cannot be extracted directly must be disintegrated. If it is difficult to access stones
within the lower renal pole that need disintegration it may help to displace them into a more accessible calyx
[201].

UROLITHIASIS - LIMITED UPDATE APRIL 2024 20
Best clinical practice in ureteroscopy
Access to the upper urinary tract
Most interventions are performed under general anaesthesia, although local or spinal anaesthesia is possible
[202]. Intravenous sedation is suitable for female patients with distal ureteral stones [203]. Smaller caliber (4.5/6
Fr) semi-rigid ureteroscope was associated with significantly higher SFR, lower rates of ureteric injury, and
shorter hospital stay [204] .
Antegrade URS is an option for large, impacted, proximal ureteral calculi [195, 205]. Reduction of
flexible ureteroscope diameter may provide similar vision, deflection, and manoeuvrability to standard flexible
ureteroscopes potentially with improved ureteric access [206]. Disposable ureteroscopes provide similar
safety and clinical effectiveness to reusable scopes. Concerns regarding cost-effectiveness and environmental
sustainability remain [204, 207-209].
Safety aspects
Fluoroscopic equipment must be available in the operating room. The Panel recommends placement of a safety
wire, even though some groups have demonstrated that URS can be performed without it [210-214]. Balloon and
plastic dilators should be available, if necessary.
Prior rigid URS can be helpful for optical dilatation followed by flexible URS, if necessary. If ureteral access is
not possible, insertion of a JJ stent followed by URS after seven to fourteen days offers an alternative [215].
Bilateral URS during the same session is feasible resulting in equivalent-to-lower SFRs, but slightly higher overall
complication rates (mostly minor, Clavien 1 and 2) [216, 217].
Difficult lower pole anatomy such as steep infundibulopelvic angle predisposes to failure during
RIRS [218]. A reusable flexible ureteroscope can be more helpful in reaching a difficult lower pole calyx [219].
Prolonged operative times are linked to increased complication rates in ureteroscopy, and efforts must be made
to keep it below 90 minutes [220] .
Ureteral access sheaths
Hydrophilic-coated ureteral access sheaths, which are available in different calibres (inner diameter from 9 F
upwards), can be inserted (via a guide wire) with the tip placed in the proximal ureter.
Ureteral access sheaths allow easy, multiple, access to the UUT and therefore significantly facilitate
URS. The use of ureteral access sheaths improves vision by establishing a continuous outflow, decreases
intrarenal pressure, and potentially reduces operating time [221, 222].
The insertion of ureteral access sheaths may lead to ureteral damage, the risk is lowest in pre-
stented systems [223]. No data on long-term side effects are available [198, 223]. Whilst larger cohort series
showed no difference in SFRs and ureteral damage (stricture rates of about 1.8%), they did show lower post-
operative infectious complications [224, 225]. Increasing sheath size directly determines higher grades of
ureteral injury rates but there is no difference in long-term stricture rates [226]. The use of a ureteral access
sheath is safe and can be useful for large and multiple renal stones or if long procedural time is expected [227].
Stone extraction
The aim of URS is complete stone removal. “Dust and go” strategies should be limited to the treatment of large
(renal) stones [228]. Stones can be extracted by endoscopic forceps or baskets. Only baskets made of nitinol
can be used for flexible URS [229] .
Intracorporeal lithotripsy
The most effective lithotripsy system is the holmium: yttrium-aluminum-garnet (Ho: YAG) laser, which is
currently the optimum standard for URS and flexible nephroscopy (Section 3.4.6), because it is effective in
all stone types [230, 231]. Compared to low-power lasers, high-power laser reduces procedural time although
the reported difference in clinical outcomes was non-significant and based on a low level of evidence [232].
The only RCT to date shows no clinical difference regarding stone-free rate or operative time [233]. Although
pulse-modulation in Ho: YAG lasers has demonstrated several in vitro benefits, a systematic review including 8
comparative studies and only one RCT showed no difference in stone-free rate, complication rate, or operative
time [234]. The two available RCTs on the subject both found a shorter operative time, without conferring a
difference in success rate [235, 236]. Thulium fiber laser (TFL) for stone disease has a promising role and offers
good clinical outcomes, which seem to be comparable to Ho: YAG laser (holmium) laser [237-239]. With the
limited reports of clinical use available to date, a meta-analysis could not demonstrate the superiority of TFL
over Ho: YAG, although the operative time to achieve this stone-free rate seems to be shorter with the use of
TFL [240]. More comparative clinical studies are however needed between these two modalities. When a laser
is not available, pneumatic and US systems can be used with high disintegration efficacy in rigid URS [241,
242]. However, stone migration into the kidney is a common problem, which can be prevented by the placement

21UROLITHIASIS - LIMITED UPDATE APRIL 2024
of special anti-migration tools proximal to the stone [243]. Medical expulsion therapy following Ho: YAG laser
lithotripsy increases SFRs and reduces colic episodes [244].
Stenting before and after URS
Routine stenting is not necessary before URS. Despite a complete lack of RCTs on this subject, a meta-analysis
has been performed, demonstrating that pre-stenting may improve the stone-free rate of ureteroscopic
treatment of renal stones, but not of ureteral stones [245]. Although it may facilitate ureteroscopic management
of stones and increase success in access sheath placement, intra-operative complications were not significantly
different [245, 246]. One should also consider that pre-stenting also causes the patient to experience stent-
related symptoms during the time the stent is indwelling, prior to a procedure.
Randomised prospective trials have found that routine stenting after uncomplicated URS (complete stone
removal) is not necessary; stenting might be associated with higher postoperative morbidity and costs [247].
Smaller diameter ureteric stents may reduce urinary symptoms and patient‑reported pain [248]. A ureteral
catheter with a shorter indwelling time (one day) may also be used, with similar results [249].
Stents should be inserted in patients who are at increased risk of complications (e.g., ureteral
trauma, residual fragments, bleeding, perforation, UTIs, or pregnancy), and in all doubtful cases, to avoid
stressful emergencies. The ideal duration of stenting is not known. Most urologists favour one to two weeks
after URS. Alpha-blockers reduce the morbidity of ureteral stents and increase tolerability [250].
Medical expulsive therapy before and after ureteroscopy
Medical expulsion therapy before URS might reduce the risk for intra-operative ureteral dilatation, protect against
ureteral injury when using access sheaths and increase stone-free rates four weeks after URS [251, 252] .
Medical expulsion therapy following Ho: YAG laser lithotripsy accelerates the spontaneous passage of
fragments and reduces episodes of colic [244] .
Complications of ureteroscopy
The overall complication rate after URS is 4-25% [253, 254]. Most complications are minor and do not
require intervention. There is evidence suggesting a risk of post-operative urosepsis of up to 5% [255, 256].
Ureteral avulsion and strictures are rare (< 1%). Previous perforations, pre-operative positive urine cultures,
comorbidities, and longer operation time are the most important risk factor for complications [220, 257, 258].
Infectious complications following URS can be minimised using prophylactic antibiotics, limiting stent dwell
and procedural time, identification and treatment of UTI, and planning in patients with large stone burden and
multiple comorbidities [259].
High intrarenal pressure (IRP) predisposes to URS complications, and measures should be used to reduce IRP.
Currently, there are no accurate ways to measure the intra-operative IRP [260].
3.4.6.1 Summary of evidence and recommendations for retrograde URS, RIRS and antegrade ureteroscopy
Summary of evidence LE
In uncomplicated URS, a post-procedure stent need not be inserted. 1a
In URS, pre-stenting has been shown to improve outcomes for renal stones. 1a
An α-blocker can reduce stent-related symptoms and colic episodes. 1a
The most effective lithotripsy system for flexible ureteroscopy is the Ho: YAG laser. 2a
Pneumatic and US systems can be used with high disintegration efficacy in rigid URS. 2a
Percutaneous antegrade removal of proximal ureter stones, or laparoscopic ureterolithotomy are
feasible alternatives to retrograde ureteroscopy, in selected cases.
1b
Pre-treatment of patients undergoing URS with an α-blocker one week prior to the procedure reduces
the need for active dilatation and increases the stone free rate.
1a
Recommendations Strength rating
Use holmium: yttrium-aluminum-garnet (Ho: YAG) or Thulium fiber laser (TFL) laser
lithotripsy for (flexible) ureteroscopy (URS).
Strong
Perform stone extraction only under direct endoscopic visualisation of the stone.Strong

UROLITHIASIS - LIMITED UPDATE APRIL 2024 22
Do not insert a stent in uncomplicated cases. Strong
Offer medical expulsive therapy for patients suffering from stent-related symptoms and after
Ho: YAG laser lithotripsy to facilitate the passage of fragments.
Strong
Use percutaneous antegrade removal of ureteral stones as an alternative when shock
wave lithotripsy (SWL) is not indicated or has failed, and when the upper urinary tract is not
amenable to retrograde URS.
Strong
Use flexible URS (even for stones > 2 cm) in cases where percutaneous nephrolithotomy or
SWL are not an option. However, in this case, there is a higher risk that a follow-up procedure
and placement of a ureteral stent may be needed.
Strong
3.4.7 Percutaneous nephrolithotomy
Percutaneous nephrolithotomy remains the standard procedure for large renal calculi. Different rigid and flexible
endoscopes are available, and the selection is mainly based on the surgeon’s own reference. Standard access
tracts are 24-30 F. Smaller access sheaths, < 18 F, were initially introduced for paediatric use, but are now
increasingly utilized in the adult population [261, 262].
Contraindications
Patients receiving anticoagulant therapy must be monitored carefully pre-and post-operatively. Anti-coagulant
therapy must be discontinued before PCNL [263].
Other important considerations include:
• untreated UTI;
• tumour in the presumptive access tract area;
• potential malignant kidney tumour;
• pregnancy (Section 3.4.14.1).
Best clinical practice
Intracorporeal lithotripsy
Several methods for intracorporeal lithotripsy during PCNL are available. Ultrasonic, pneumatic, and combined
systems are most commonly used for rigid nephroscopy, whilst the laser is increasingly used for miniaturised
and flexible instruments [264] .
Pre-operative imaging
Pre-procedural imaging evaluations are summarised in Section 3.3.1. In particular, US or CT of the kidney
and the surrounding structures can provide information regarding interposed organs within the planned
percutaneous path (e.g., spleen, liver, large bowel, pleura, and lung).
Positioning of the patient
Both prone and supine positions are equally safe. A meta-analysis including twelve studies and a total of 1,290
patients treated, showed a similar SFR but a lower operative time for supine PCNL [265]. The supine position
allows simultaneous retrograde access to the collecting system, using a flexible ureteroscope [266]. The
combination of PCNL and RIRS may be a good alternative for the treatment of complex renal stones compared
to standard PCNL; however, the existing evidence is of low-quality [265, 267].
Puncture
Although fluoroscopy is still the most common intra-operative imaging method, the use of US as an additional
or only means of puncture guidance provides advantages according to two meta-analyses including eight
randomised controlled trials. Additional to the expected reduced radiation exposure with the use of ultrasound
the meta-analyses also demonstrated a lower complication rate [268, 269]. Pre-operative CT or intra-operative
US allows identification of the tissue between the skin and kidney and lowers the incidence of visceral injury. As
an additional aid to increase puncture accuracy, the calyceal puncture may be done under direct visualisation
using simultaneous flexible URS [270-272] .
Dilatation
Dilatation of the percutaneous access tract can be achieved using a metallic telescopic, single (one-shot or
serial) dilator, or balloon dilatator. During PCNL, safety and effectiveness are similar for different tract dilatation
methods [273]. Although there are papers demonstrating that single-step dilation is equally effective as other
methods and that US only can be used for the dilatation, the difference in outcomes is most likely related to
surgeon experience rather than to the technology used [273, 274]. A meta-analysis of the most commonly used

23UROLITHIASIS - LIMITED UPDATE APRIL 2024
tract dilation methods suggested that one-step dilation would allow for a shorter operative time and reduced
complication rate, including haemoglobin loss and transfusion rate [275].
Choice of instruments
Several meta-analyses on mini-PCNL (12-22 F) vs. standard PCNL (> 22 F) have identified that both techniques
allow for a similar SFR. Patients treated with mini-PCNL had reduced blood loss and transfusion rates, as well
as a shorter hospital stay, without a significant difference in overall complication rates [262, 276-278]. However,
it is important to note that the level of evidence was downgraded due to heterogeneity of data related to tract
sizes used and types of stones treated. There is some evidence for using suction during PCNL to reduce intra-
renal pressure and increase SFR [279] .
Post-operative drainage
The decision on whether, or not, to place a nephrostomy tube or a double J stent at the conclusion of the PCNL
procedure depends on several factors, including:
• presence of residual stones;
• likelihood of a second-look procedure;
• significant intra-operative blood loss/ bleeding from the percutaneous tract;
• urine extravasation;
• ureteral obstruction;
• potential persistent bacteriuria due to infected stones;
• solitary kidney;
• bleeding diathesis;
• planned percutaneous chemolitholysis.
Small-bore nephrostomies seem to have advantages in terms of postoperative pain [262, 280, 281]. Tubeless
PCNL is performed without a nephrostomy tube and is associated with reduced post-operative pain and hospital
stay [282]. When neither a nephrostomy tube nor a ureteral stent is introduced, the procedure is known as a
totally tubeless PCNL [283]. In uncomplicated cases, the latter procedure results in a shorter hospital stay, with
no disadvantages reported [284].
As reported in the above section on the drainage of an infected or obstructed system [110-
112] (section 3.4.2), the quality of life may be slightly lower with a DJ stent in comparison to a short-term
nephrostomy tube after PCNL. This should be weighed against the shorter hospital stay with a DJ stent [285].
Complications of percutaneous nephrolithotomy
A systematic review of almost 12,000 patients shows the incidence of complications associated with PCNL;
fever 10.8%, transfusion 7%, thoracic complication 1.5%, sepsis 0.5%, organ injury 0.4%, embolisation 0.4%,
urinoma 0.2%, and death 0.05% [286].
Perioperative fever can occur, even with a sterile pre-operative urinary culture and peri-operative
antibiotic prophylaxis, because the renal stones themselves may be a source of infection. The evidence
demonstrates that a stone culture or urine culture taken directly from the renal pelvis is more predictive of post-
operative SIRS or sepsis. Whenever possible a urine culture from the renal pelvis and/or stone culture should be
taken at the time of PCNL [287].
Intra-operative renal stone or renal pelvic urine culture may be more indicative of the causative
organism for sepsis; therefore, helping to select the most suitable postoperative antibiotics [287-289]. Although
this data is weak, there is limited retrospective data indicating that increased pressures during mPCNL may
contribute to febrile complications [290-292]. This contrasts with the previously mentioned meta-analyses
on mini vs standard PCNL that do not identify a difference in complication rate between the two procedures
[262, 276-278]. Bleeding after PCNL may be treated by briefly clamping the nephrostomy tube. Super-selective
embolic occlusion of the arterial branch may become necessary in the case of severe bleeding. Several
meta-analyses have demonstrated that the use of tranexamic acid reduces bleeding complications and the
transfusion rate of PCNL [293-295]. However, the transfusion rate in the control group of the meta-analyses was
in the range of 10-12%.
Depending on the stone burden and the patient’s anatomy, multiple tracts may be necessary to
render the patient stone free in one session of PCNL. While this is a generally accepted practice, it should be
highlighted that this comes with an increased risk of postoperative complications including pleural damage,
infections, and the need for transfusion [296].
To reduce post-operative pain after PCNL, a peripheral nerve block can be performed at the intercostal nerve,
paravertebral region, erector spinae, or quadratus lumborum. Such a block may significantly reduce the need
for post-operative opioid analgesics [297, 298]. Current evidence shows that a quadratus lumborum block or

UROLITHIASIS - LIMITED UPDATE APRIL 2024 24
infiltration of a local anaesthetic around the nephrostomy tube may reduce post-operative pain and opioid
consumption after PCNL [299, 300].
3.4.7.1 Summary of evidence and recommendations for endourology techniques for renal stone removal
Summary of evidence LE
Imaging of the kidney with US or CT can provide information regarding inter-positioned organs within
the planned percutaneous path (e.g., spleen, liver, large bowel, pleura, and lung).
3
Both prone and supine positions are equally safe with equivalent SFR. 1a
Percutaneous nephrolithotomy performed with small instruments tends to be associated with
significantly lower blood loss, but the duration of procedure tended to be significantly longer. There are
no significant differences in SFR or any other complications.
1a
In uncomplicated cases, a totally tubeless PCNL results in a shorter hospital stay, with no increase in
complication rate.
1a
Peri-operative use of tranexamic acid may reduce bleeding complications and transfusion rates.1a
Urine cultures taken directly from the renal pelvis, or a stone culture are more predictive of post-PCNL
sepsis than a pre-operative midstream urine culture.
1a
Recommendations Strength rating
Perform pre-procedural computed tomography (CT) imaging, including contrast medium
when indicated or retrograde study when starting the procedure, to assess stone
comprehensiveness and anatomy of the collecting system to ensure safe access to the renal
stone.
Strong
Perform a tubeless (without nephrostomy tube) or totally tubeless (without nephrostomy
tube and ureteral stent) percutaneous nephrolithotomy (PCNL) procedure, in uncomplicated
cases.
Strong
Take a stone culture or urine culture directly from the renal pelvis at time of PCNL, if
possible.
Strong
3.4.8 General recommendations and precautions for stone removal
3.4.8.1 Antibiotic therapy
Urinary tract infections should always be treated if stone removal is planned. In patients with clinically
significant infection and obstruction, drainage should be performed for several days before starting stone
removal. A urine culture or urinary microscopy should be performed before treatment [301].
Peri-operative antibiotic prophylaxis
The available evidence for prevention of infection following URS and percutaneous stone removal, remains
limited [302]. Administration of a single dose of prophylactic antibiotics prior to ureteroscopy was found to be
sufficient [302-304]. In a review of a large database of patients undergoing PCNL, it was found that in patients
with negative baseline urine culture, antibiotic prophylaxis significantly reduced the rate of postoperative fever
and other complications [305]. Based on three meta-analyses, pooling data from small series with varying
quality an extended course of pre-operative prophylactic antibiotics prior to PCNL compared to a single dose
before anaesthesia significantly reduced post-operative sepsis and fever in patients with an a priori increased
risk of infection [288, 306, 307]. In an RCT including only moderate to high-risk infection patients (patients with
pre-operative stents/nephrostomy or positive urine culture), a seven-day course of pre-operative antibiotics
reduced the risk of post-PCNL sepsis threefold in comparison to a two-day course [308]. In studies that did
not specify the risk of the patient population, a single dose of antibiotic prophylaxis administered at induction
was equivalent to an extended pre-operative course [307, 309]. In contrast to this, a prolonged course of post-
operative antibiotics was not superior to a single dose pre-operatively [288, 307] .
As national and regional antibiotic resistance patterns can differ significantly, the choice of antibiotic
prophylaxis should be tailored to institutional or regional antimicrobial susceptibility [304] .

25UROLITHIASIS - LIMITED UPDATE APRIL 2024
Recommendations Strength rating
Obtain a urine culture or perform urinary microscopy before any treatment is planned.Strong
Exclude or treat urinary tract infections prior to stone removal. Strong
Offer peri-operative antibiotic prophylaxis to all patients undergoing endourological
treatment.
Strong
3.4.8.2 Antithrombotic therapy and stone treatment
Patients with a bleeding disorder, or receiving antithrombotic therapy, should be referred to an internist for
appropriate therapeutic measures before deciding on stone management [310-314]. In patients with an
uncorrected bleeding disorder, the following are at elevated risk of haemorrhage or perinephric haematoma
(PNH) (high-risk procedures):
• SWL (hazard ratio of PNH up to 4.2 during anti-coagulant/anti-platelet medication) [315]
• PCNL;
• percutaneous nephrostomy;
• laparoscopic surgery;
• open surgery [310].
Shock wave lithotripsy is feasible and safe after correction of the underlying coagulopathy [316, 317]. In
the case of an uncorrected bleeding disorder or continued antithrombotic therapy, URS, in contrast to SWL
and PCNL, might offer an alternative approach since it is associated with less morbidity [318-320]. Despite
the appropriate cessation of anti-platelet agents, following standardised protocols, prolonged haematuria in
tube drainage after PCNL has been reported [321]. Only data on flexible URS are available which support the
superiority of URS in the treatment of proximal ureteral stones [322, 323]. Although URS is safe in patients with
bleeding disorders or anticoagulation, an individualised patient approach is necessary [320].
Table 3.9: Risk stratification for bleeding [312-314, 324]
Low-risk bleeding procedures • Cystoscopy
• Flexible cystoscopy
• Ureteral catheterisation
• Extraction of ureteral stent
• Ureteroscopy
High-risk bleeding procedures • Shock wave lithotripsy
• Percutaneous nephrostomy
• Percutaneous nephrolithotomy
Table 3.10: Suggested strategy for antithrombotic therapy in stone removal [312-314]
(In collaboration with a cardiologist/internist weigh the risks and benefits of discontinuation of therapy, vs.
delaying elective surgical procedures).
Medication/AgentBleeding risk of
planned procedure
Risk of thromboembolism
Low risk Intermediate riskHigh risk
Warfarin
Dabigatran
Rivaroxaban
Apixaban
Low-risk procedureMay be continuedBridging therapyBridging therapy
High-risk procedureMay be temporarily
discontinued at
appropriate interval.
Bridging therapy
is strongly
recommended.
Bridging therapyBridging therapy

UROLITHIASIS - LIMITED UPDATE APRIL 2024 26
Aspirin Low-risk procedureContinue Continue Elective surgery:
postpone.
Non-deferrable
surgery: continue.
High-risk procedureDiscontinue Elective surgery:
postpone.
Non-deferrable
surgery: continue, if
it is possible.
Elective surgery:
postpone.
Non-deferrable
surgery: continue.
Thienopyridine
agents (P2Y12
receptor inhibitors)
Low-risk procedureDiscontinue
five days before
intervention.
Resume within
24-72 hours with a
loading dose.
Continue Elective surgery:
postpone.
Non-deferrable
surgery: continue.
High-risk procedureDiscontinue
five days before
intervention and
resume within 24-72
hours with a loading
dose.
Elective surgery:
postpone.
Non-deferrable
surgery: discontinue
five days before
procedure and
resume within 24-72
hours with a loading
dose.
Bridging therapy
-glycoprotein IIb/IIIa
inhibitors if aspirin is
discontinued.
Elective surgery:
postpone.
Non-deferrable
surgery: discontinue
five days before
procedure and
resume within 24-72
hours, with a loading
dose.
Bridging therapy
-glycoprotein IIb/IIIa
inhibitors.
3.4.8.2.1 Summary of evidence and recommendations for antithrombotic therapy and stone treatment
Summary of evidence LE
Active surveillance is indicated in patients at high risk for thrombotic complications in the presence of
an asymptomatic calyceal stone.
4
The temporary discontinuation, or bridging of antithrombotic therapy in high-risk patients, should be
discussed with the internist.
3
Retrograde (flexible) URS stone removal is associated with less morbidity in patients when antithrombotic
therapy cannot be discontinued.
2a
Recommendations Strength rating
Offer active surveillance to patients at high risk of thrombotic complications in the presence
of an asymptomatic calyceal stone.
Weak
Decide on temporary discontinuation, or bridging of antithrombotic therapy in high-risk
patients, in consultation with the internist.
Strong
Retrograde (flexible) URS is the preferred intervention if stone removal is essential and
antithrombotic therapy cannot be discontinued since it is associated with less morbidity.
Strong
3.4.8.3 Obesity
A high BMI can pose a higher anaesthetic risk and a lower success rate after SWL and PCNL and may influence
the choice of treatment [325].
3.4.8.4 Stone composition
Stones composed of brushite, calcium oxalate monohydrate, or cystine are particularly hard, as well as
homogeneous stones with a high density on NCCT [326, 327]. Percutaneous nephrolithotomy or RIRS and URS
are alternatives for removal of large SWL-resistant stones.

27UROLITHIASIS - LIMITED UPDATE APRIL 2024
Recommendations Strength rating
Consider the stone composition before deciding on the method of removal, based on patient
history, former stone analysis of the patient or Hounsfield unit on unenhanced computed
tomography.
Strong
Attempt to dissolve radiolucent stones. Strong
3.4.8.5 Contraindications of procedures
Contraindications of extracorporeal SWL
There are several contraindications to the use of extracorporeal SWL, including:
• pregnancy, due to the potential effects on the foetus [328] ;
• bleeding disorders, which should be compensated for at least 24 hours before and 48 hours after
treatment [329] ;
• uncontrolled UTIs;
• severe skeletal malformations and severe obesity, which prevent targeting of the stone;
• arterial aneurysm in the vicinity of the stone [330];
• anatomical obstruction distal to the stone.
Contraindications of URS
Apart from general problems, for example with general anaesthesia or untreated UTIs, URS can be performed in
all patients without any specific contraindications.
Contraindications of PCNL
Patients receiving anti-coagulant therapy must be monitored carefully pre- and post-operatively. Anti-coagulant
therapy must be discontinued before PCNL [320]. Other important contraindications include:
• untreated UTI;
• tumour in the presumptive access tract area;
• potential malignant kidney tumour;
• pregnancy (Section 3.4.14.1).
General contraindication for endourological procedures
Endourological interventions do not adversely affect renal function although care must be taken in those with
poor pre-operative renal function, diabetes and hypertension [331]. However, a meta-analysis, based on low
quality evidence, suggests that patients with impaired renal function and stone disease, may in fact benefit from
the procedure to preserve or increase their renal function [332].
3.4.9 Specific stone management of ureteral stones
3.4.9.1 Conservative treatment/observation
There are only limited data regarding spontaneous stone passage according to stone size [333, 334].
Spontaneous stone passage was reported for 49-52% of upper ureteral stones, 58-70% of mid ureteral stones
and 68-83% of distal ureteral stones. Considering stone size almost 75% of stones < 5 mm and 62% of stones
≥ 5 mm passed spontaneously, with an average time to stone expulsion about 17 days (range 6-29 days)
[333, 335]. Considering both size and location, stones of <5mm in the distal ureteral have a 89% chance of
spontaneous passage, while 71% of stones <5mm located in the upper ureter still pass spontaneously [333]. The
Panel is aware of the fact that spontaneous stone expulsion decreases with increasing stone size and that there
are differences between individual patients.
3.4.9.2 Pharmacological treatment, medical expulsive therapy
Medical expulsive therapy should only be used in informed patients if active stone removal is not indicated.
Treatment should be discontinued if complications develop (infection, refractory pain, deterioration of renal
function). In the case of known uric acid stones in the distal ureter, a combination of alkalinisation with
tamsulosin can increase the frequency of spontaneous passage. For details see Sections 3.4.3 and 3.4.4.
3.4.9.3 Indications for treatment of ureteral stones
Indications for removal of ureteral stones are [176, 334, 336]:
• stones with a low likelihood of spontaneous passage;
• persistent pain despite adequate analgesic medication;
• persistent obstruction;
• renal insufficiency (renal failure, bilateral obstruction, or single kidney).

UROLITHIASIS - LIMITED UPDATE APRIL 2024 28
3.4.9.4 Selection of procedure for removal of ureteral stones
The selection of the procedure depends on many factors, including stone-related factors, such as size, location,
and density, as well as patient-related factors, such as body habitus, urinary anatomy, bleeding disorders, and
other potential comorbidities. These and their influence on the outcomes of each of the procedures should be
considered when counselling patients.
As previously mentioned in this guideline, CT imaging can provide useful information that may influence the choice
of treatment. A meta-analysis outlines that increasing stone density, stone burden, skin-to-stone distance, and
hydronephrosis can negatively impact the success of the shockwave lithotripsy [337].
Overall, SFRs after URS or SWL for ureteral stones are comparable. However, larger stones achieve earlier stone-
free status with URS.
A large multi-center non-inferiority trial compared URS to SWL for ureteral stones. When excluding patients that
had spontaneously passed their stone prior to treatment, SWL could not be considered non-inferior to URS with
only 12% of patients needing further intervention after URS in comparison to 26% in the SWL arm [253]. In contrast
to the success of SWL, comparative data on the outcomes of URS depending on patients’ BMI has shown URS to
be as effective and safe in obese and morbidly obese patients as in non-obese patients [338].
The Panel performed a systematic review to assess the benefits and harms of URS compared to SWL [339].
Compared with SWL, URS was associated with a significantly greater SFR of up to four weeks, but the difference
was not significant at three months in the included studies. Ureteroscopy was associated with fewer retreatments
and the need for secondary procedures but with a higher need for adjunctive procedures, higher complication
rates, and longer hospital stay. Counterbalancing for URS’s higher SFRs, SWL is associated with lower morbidity.
Success rates and complications of URS are not impacted by previous unsuccessful SWL [340]. Clavien-Dindo
grade complications were if reported, less frequent in patients treated with SWL [175].
Apart from the treatment modality, the timing of treatment may also be of importance. Primary or emergent
ureteroscopy appears to be a safe and feasible procedure for patients presenting with renal colic due to an
obstructive ureteral stone [341], without however increasing the stone-free rate. These results however are
based mainly on low level of evidence reports and should be interpreted with caution [341]. Similarly, SWL can be
performed in the acute setting or electively allowing a trial of spontaneous passage. In contrast to acute URS, SWL
in the acute setting does provide an increased stone-free rate and reduced need for auxiliary procedures [342].
For large proximal ureteral stones, a percutaneous antegrade approach may provide better stone-free results than
a retrograde ureteroscopic approach [343].
Bleeding disorder
Ureteroscopy can be performed in patients with bleeding disorders, with a moderate increase in complications
(see also Section 3.4.8.2) [320] .
3.4.9.4.1  Summary of evidence and recommendations for selection of procedure for active removal of ureteral
stones
Summary of evidence LE
Observation is feasible in informed patients who develop no complications (infection, refractory pain,
deterioration of renal function).
2a
Medical expulsive therapy seems to be efficacious for treating patients with ureteral stones who are
amenable to conservative management. The greatest benefit might be among those with > 5 mm
(distal) stones.
1a
Compared with SWL, URS was associated with significantly greater SFRs up to four weeks, but the
difference was not significant at three months in the included studies.
1a
Ureteroscopy was associated with fewer retreatments and need for secondary procedures, but with a
higher need for adjunctive procedures, greater complication rates and longer hospital stay.
1a
In the case of severe obesity, URS is a more promising therapeutic option than SWL. 2b

29UROLITHIASIS - LIMITED UPDATE APRIL 2024
Recommendations Strength rating
If active removal is not indicated (Section 3.4.9.3) in patients with newly diagnosed small*
ureteral stones, observe patient initially with periodic evaluation.
Strong
Offer α-blockers as medical expulsive therapy as one of the treatment options for (distal)
ureteral stones > 5 mm**.
Strong
Inform patients that ureteroscopy (URS) has a better chance of achieving stone-free status
with a single procedure.
Strong
Inform patients that URS has higher complication rates when compared to shock wave
lithotripsy.
Strong
Use URS as first-line therapy for ureteral (and renal) stones in cases of severe obesity.Strong
*See stratification data [176].
** Alpha-blockers are an off-label treatment for this indication
Figure 3.1: Treatment algorithm for ureteral stones (if stone removal is indicated)
SWL = shock wave lithotripsy; URS = Ureteroscopy.
3.4.10 Specific stone management of renal stones
The natural history of small, non-obstructing asymptomatic calculi is not well defined, and the risk of
progression is unclear. There is still no consensus on the follow-up duration, timing, and type of intervention. In
an RCT patients with small asymptomatic renal stones, who were not treated actively, had a higher incidence of
relapse [344].
3.4.10.1 Conservative treatment (observation)
Observation of renal stones, especially in calyces, depends on their natural history (Section 3.4.10.3). The
recommendations provided are not supported by high-level literature [345]. There is a prospective trial
supporting annual observation for asymptomatic inferior calyceal stones, < 10 mm. In case stone growth is
detected, the follow-up interval should be lowered [346]. Intervention is advised for growing stones > 5 mm
[347]. In a systematic review of patients with asymptomatic renal stones on active surveillance spontaneous
stone passage rates varied from 3-29%, symptom development from 7-77%, stone growth from 5-66%, surgical
intervention from 7-26% [345].
Proximal ureteral stone
> 10 mm
1. URS (ante- or retrograde)
2. SWL
< 10 mm SWL or URS
Distal ureteral stone
> 10 mm
1. URS
2. SWL
< 10 mm SWL or URS
Diagnosis Treatment Follow-up

UROLITHIASIS - LIMITED UPDATE APRIL 2024 30
3.4.10.2 Pharmacological treatment of renal stones
Dissolution therapy seems to be an option for uric acid stones. See sections 3.4.4. and 3.4.8.4.
3.4.10.3 Indications for stone removal of renal stones
Indications for the removal of renal stones include:
• stone growth;
• stones in high-risk patients for stone formation;
• obstruction caused by stones;
• infection;
• symptomatic stones (e.g., pain or haematuria) [348] ;
• patient preference;
• comorbidity;
• the social situation of the patient (e.g., profession or traveling);
3.4.10.4 Selection of procedure for active removal of renal stones
For general recommendations and precautions see Section 3.4.8.
3.4.10.4.1 Stones in the renal pelvis or upper/middle calyces
Shock wave lithotripsy, PCNL and RIRS are available treatment modalities for renal calculi. While PCNL efficacy
is hardly affected by the stone size, the SFRs after SWL or URS are inversely proportional to stone size [253,
349-355]. Although multiple treatments or sessions may be needed shock wave lithotripsy achieves good
SFRs for stones up to 20 mm, except for those at the lower pole [351, 356, 357]. When SWL is considered,
stones with density > 1,000 HU (and with high homogeneity) on non-contrast-enhanced CT are less likely to
be disintegrated [43]. Endourology is considered an alternative because of the reduced need for repeated
procedures and consequently a shorter time until stone-free status is achieved. For stones > 10 mm, mPCNL
achieves a higher SFR than RIRS or SWL, but carries a higher risk of bleeding and is associated with a longer
hospital stay; however, there is a high degree of heterogeneity among the included studies [353, 355]. Stones

> 20 mm should be treated primarily by PCNL, because SWL often requires multiple treatments, and is
associated with an increased risk of ureteral obstruction (colic or steinstrasse) with a need for adjunctive
procedures (Figure 3.2) [358]. Retrograde renal surgery cannot be recommended as first-line treatment for
stones > 20 mm in uncomplicated cases as SFRs decrease, and staged procedures will be required [359-361].
However, it may be a first-line option in patients where PCNL is not an option or contraindicated or in selected
patients [362]. The combination of PCNL and RIRS may be a good alternative for the treatment of complex renal
stones compared to standard PCNL; however, the level of the existing evidence is low [265].
3.4.10.4.2 Stones in the lower renal pole
The stone clearance rate after SWL seems to be lower for stones in the inferior calyx than for other intra-renal
locations. Although the disintegration efficacy of SWL is not limited compared to other locations, the fragments
often remain in the calyx and cause recurrent stone formation. The reported SFR of SWL for lower pole calculi
is 25-95%. The preferential use of endoscopic procedures is supported by some current reports, even for stones

< 1 cm [350, 352, 356, 358, 361, 363-370].
The following can impair successful stone treatment by SWL [371-377]:
• steep infundibular-pelvic angle;
• long calyx;
• long skin-to-stone distance;
• narrow infundibulum;
• shock wave-resistant stones (calcium oxalate monohydrate, brushite, or cystine).
Further anatomical parameters cannot yet be established. Supportive measures such as inversion,
vibration or hydration may facilitate stone clearance (See 3.4.5 SWL) [174, 378, 379]. If there are negative
predictors for SWL, PCNL and RIRS might be reasonable alternatives, even for smaller calculi [363]. Retrograde
renal surgery seems to have comparable efficacy to SWL [350, 356, 358, 380]. Clinical experience has suggested
a higher SFR of RIRS compared to SWL but at the expense of greater invasiveness. Depending on operator
skills, stones up to 3 cm can be treated by RIRS [362, 381]. However, staged procedures are frequently required.
Although mini-PCNL has the highest success rate for the treatment of lower pole stones up to 2 cm, it comes at
the expense of a higher complication rate and longer hospital stay [355] .
In complex stone cases, open or laparoscopic approaches are possible alternatives although they are
infrequently used.

31UROLITHIASIS - LIMITED UPDATE APRIL 2024
3.4.10.5 Summary of evidence and recommendations for the management of renal stones
Summary of evidence LE
It is still debatable whether renal stones should be treated, or whether annual follow-up is sufficient for
asymptomatic calyceal stones that have remained stable for six months.
4
Although the question of whether asymptomatic calyceal stones should be treated is still unanswered,
stone growth, de novo obstruction, associated infection, and acute and/or chronic pain are indications
for treatment.
3
Percutaneous nephrolithotomy is indicated in renal stones > 2 cm as primary option. 1a
Recommendations Strength rating
Offer active treatment for renal stones in case of stone growth, de novo obstruction,
associated infection, and acute and/or chronic pain.
Weak
Evaluate stone composition before deciding on the method of removal, based on patient
history, former stone analysis of the patient or Hounsfield unit (HU) on unenhanced
computed tomography.
Strong
Perform percutaneous nephrolithotomy (PCNL) as first-line treatment of larger stones > 2 cm.Strong
Treat larger stones (> 2 cm) with flexible ureteroscopy or shock wave lithotripsy (SWL), in
cases where PCNL is not an option. However, in such instances there is a higher risk that a
follow-up procedure and placement of a ureteral stent may be needed.
Strong
Perform PCNL or retrograde intrarenal surgery for the lower pole, even for stones > 1 cm, as
the efficacy of SWL is limited (depending on favourable and unfavourable factors for SWL).
Strong
Perform PCNL or retrograde intrarenal surgery for the lower pole, even for stones > 1 cm, as
the efficacy of SWL is limited (depending on favourable and unfavourable factors for SWL).
Strong
Figure 3.2: Treatment algorithm for renal stones (if/when active treatment is indicated)
Kidney stone
(all but lower pole stone 10-20 mm)
> 20 mm
1. PCNL
2. RIRS or SWL
10-20 mm SWL or Endouro logy*
10-20 mm
SWL or Endourology*
1. Endourology*
2. SWL
< 10 mm
1. SWL or RIRS
2. PCNL
Lower pole stone
(> 20 mm and < 10 mm: as above)
Unfavourable
factors for SWL**
No
Yes
Diagnosis Treatment Follow-up
*The term ‘Endourology’ encompasses all PCNL and URS interventions.
PCNL = percutaneous nephrolithotomy; RIRS = retrograde intrarenal surgery; SWL = shock wave lithotripsy; URS =
ureteroscopy

UROLITHIASIS - LIMITED UPDATE APRIL 2024 32
3.4.11 Laparoscopy and open surgery
Advances in SWL and endourological surgery (URS and PCNL) have significantly decreased the indications for
open or laparoscopic stone surgery [382-387]. There is a consensus that most complex stones, including partial
and complete staghorn stones, should be approached primarily with PCNL. Additionally, a combined approach
with PCNL and RIRS may also be an appropriate alternative. However, if percutaneous approaches are not
likely to be successful, or if multiple endourological approaches have been performed unsuccessfully; open or
laparoscopic surgery may be a valid treatment option [388-392].
Few studies have reported laparoscopic stone removal. These procedures are usually reserved for
special cases. When expertise is available, laparoscopic ureterolithotomy can be performed for large proximal
ureteral stones as an alternative to URS or SWL [393, 394]. These more invasive procedures have yielded high
SFRs and lower auxiliary procedure rates [196, 205, 389]. A systematic review showed no difference in the post-
operative phase for stented or unstented laparoscopic ureterolithotomy [389].
Laparoscopic pyelolithotomy could be offered for solitary stones > 2 cm located in the renal pelvis
as an alternative to PCNL [390]. In addition, in selected cases with an extrarenal and dilated pelvis, RLP can be
considered as an alternative management of staghorn calculi [395].
A few studies with limited numbers of patients have reported using robotic surgery in the treatment
of urinary stones [391]. Open surgery should be considered as the last treatment option after all other
possibilities have been explored.
Studies on laparoscopy should be interpreted with caution due to their low design and quality of
evidence.
3.4.11.1 Recommendation for laparoscopy and open surgery
Recommendation Strength rating
Offer laparoscopic or open surgical stone removal in rare cases in which shock wave
lithotripsy, retrograde or antegrade ureteroscopy and percutaneous nephrolithotomy fail, or
are unlikely to be successful.
Strong
3.4.12 Steinstrasse
Steinstrasse is an accumulation of stone fragments or stone gravel in the ureter and may interfere with the
passage of urine [396]. Steinstrasse occurs in 4% of cases of SWL [175, 183], and the major factor in the
development of steinstrasse formation is stone size [397].
A major problem of steinstrasse is ureteral obstruction, which may be silent in up to 23% of cases. A MA
including eight RCTs (n = 876) suggested a benefit of stenting before SWL in terms of steinstrasse formation
but did not result in a benefit on SFRs or less auxiliary treatments [136]. When steinstrasse is asymptomatic,
conservative treatment is an initial option. Medical expulsion therapy increases stone expulsion and reduces the
need for endoscopic intervention [398, 399]. Ureteroscopy and SWL are effective in the treatment of steinstrasse
[185, 400]. In the event of UTI or fever, the urinary system should be decompressed, preferably by percutaneous
nephrostomy [113, 401] .
3.4.12.1 Summary of evidence and recommendations for steinstrasse
Summary of evidence LE
Medical expulsion therapy increases the stone expulsion rate of steinstrasse. 1b
Ureteroscopy is effective for the treatment of steinstrasse. 3
Only low-level evidence is available, supporting SWL or URS for the treatment of steinstrasse.4
Recommendations Strength rating
Treat steinstrasse associated with urinary tract infection (UTI)/fever preferably with
percutaneous nephrostomy.
Weak
Treat steinstrasse when large stone fragments are present with shock wave lithotripsy or
ureteroscopy (in absence of signs of UTI).
Weak

33UROLITHIASIS - LIMITED UPDATE APRIL 2024
3.4.13 Management of patients with residual stones
Following initial treatment with SWL, URS or PCNL, residual fragments may remain and require additional
intervention [347, 402-405]. Most of these studies indicate that initial imaging is performed on the first day or
the first week after treatment. However, false positive results from dust or residual fragments, that will pass
spontaneously without causing any stone-related event, might lead to over-treatment. Therefore, imaging at four
weeks seems most appropriate [406-408]. Compared to US, KUB and IVU, NCCT scan has a higher sensitivity to
detect small residual fragments after definitive treatment of ureteral or kidney stones [409, 410] .
A SR/MA examining residual fragments following any treatment has demonstrated that around a third of
patients with either dust or fragments </= 4 mm experience disease progression and re-intervention within
three years, whilst a third have spontaneous passage within two years regardless of imaging modality follow-
up. For fragments > 4 mm, there are fewer studies, but these suggest low spontaneous passage rates and high
intervention rates [411].
Although NCCT has the highest sensitivity to detect residual fragments, this must be balanced to the exposure
to ionising radiation when compared with KUB and US. Recurrence risk in patients with residual fragments after
treatment of infection stones is higher than for other stones [412].
3.4.13.1 Recommendation for management of patients with residual stones
Recommendation Strength rating
Treat residual fragments > 4 mm. Weak
3.4.14 Management of specific patient groups
3.4.14.1 Management of urinary stones and related problems during pregnancy
Clinical management of a pregnant patient with urolithiasis is complex and demands close collaboration
between the patient, radiologist, obstetrician, and urologist [64]. For diagnostic imaging see Section 3.3.1.
Patients with urolithiasis may be at increased risk of developing adverse maternal or neonatal outcomes [413] .
Conservative approaches for symptomatic hydronephrosis as well as for ureteric calculi are the
preferred initial management option in pregnant patients [414, 415] .
If spontaneous passage does not occur, or if complications develop (e.g., intractable symptoms, severe
hydronephrosis, spontaneous renal fornix rupture [416] or induction of premature labour), placement of a
ureteral stent or a percutaneous nephrostomy tube is necessary as it is more effective than conservative
treatment for symptom relief [417-419] .
In the treatment of renal stones during pregnancy, when a stent is necessary, PCNL versus ureteral stent
placement does not confer a significant difference in rates of adverse pregnancy events. However, ureteral
stent placement was associated with a lower incidence of hospital admissions, emergency department visits,
exchange procedures, and new UTIs or pyelonephritis [420] .
Ureteroscopy has become a reasonable alternative in these situations [408, 421]. When compared to temporary
ureteral JJ stenting until after delivery, ureteroscopy resulted in fewer needs for stent exchanges, less irritative
LUTS and better patient satisfaction [422, 423].
Non-urgent ureteroscopy in pregnant women is best performed during the second trimester, by an experienced
urologist. Counselling of the patient should include access to neonatal and obstetric services [72] .
Although feasible, percutaneous removal of renal stones during pregnancy remains an individual decision and
should be performed only in experienced centres [424]. Pregnancy remains an absolute contraindication for
SWL.

UROLITHIASIS - LIMITED UPDATE APRIL 2024 34
3.4.14.1.1  Summary of evidence and recommendation for the management of urinary stones and related
problems during pregnancy
Summary of evidence LE
Stent insertion seems to be more effective than conservative treatment in the management of
symptomatic moderate-to-severe hydronephrosis during pregnancy.
1a
Ureteroscopy is a reasonable alternative to avoid long-term stenting/drainage. 1b
There is a higher tendency for stent encrustation during pregnancy. 3
Recommendation Strength rating
Treat all uncomplicated cases of urolithiasis in pregnancy conservatively (except when there
are clinical indications for intervention).
Strong
3.4.14.2 Management of stones in patients with urinary diversion
Aetiology
Patients with urinary diversion are at high risk for stone formation in the renal collecting system and ureter or in
the conduit or continent reservoir [425, 426] . Metabolic factors (hypercalciuria, hyperoxaluria and hypocitraturia),
infection with urease-producing bacteria, foreign bodies, mucus secretion, and urinary stasis are responsible
for stone formation [427] (section 3.1.3). One study has shown that the risk for recurrent upper tract stones in
patients with urinary diversion subjected to PCNL was 63% at five years [428].
Management
Smaller upper-tract stones can be treated effectively with SWL [429, 430]. In most cases, endourological
techniques are necessary to achieve stone-free status [431]. In individuals with long, tortuous conduits or with
invisible ureter orifices, a retrograde endoscopic approach might be difficult or impossible [432].
For stones in the conduit, a trans-stomal approach can be used to remove all stone material (along with the foreign
body) using standard techniques, including intracorporeal lithotripsy and flexible endoscopes. Trans-stomal
manipulations in continent urinary diversion must be performed carefully to avoid disturbance of the continence
mechanism [433].
Before considering any percutaneous approach in these cases, CT should be undertaken to assess
the presence of overlying bowel, which could make this approach unsafe [434], and if present, a surgical approach
should be considered.
Prevention
Recurrence risk is high in patients with urinary diversion [428]. Metabolic evaluation and close follow-up are
necessary to obtain the risk parameters for effective long-term prevention. Preventive measures include medical
management of metabolic abnormalities, appropriate therapy of urinary infections, and hyper-diuresis or regular
irrigation of continent reservoirs [435] .
3.4.14.2.1  Summary of evidence and recommendation for the management of stones in patients with urinary
diversion
Summary of evidence LE
The choice of access depends on the feasibility of orifice identification in the conduit or bowel
reservoir. Whenever a retrograde approach is impossible, percutaneous access with antegrade
ureteroscopy is the alternative.
4
Recommendation Strength rating
Perform percutaneous lithotomy to remove large renal stones in patients with urinary
diversion, as well as for ureteral stones that cannot be accessed via a retrograde approach,
or that are not amenable to shock wave lithotripsy.
Strong

35UROLITHIASIS - LIMITED UPDATE APRIL 2024
3.4.14.3 Management of stones in patients with neurogenic bladder
Aetiology, clinical presentation, and diagnosis
Patients with neurogenic bladder develop urinary calculi because of additional risk factors such as bacteriuria,
hydronephrosis, VUR, renal scarring and lower urinary tract reconstruction [436, 437]. The most common
causes are urinary stasis and infection (Section 3.1.3). Indwelling catheters and surgical interposition of bowel
segments for treatment of bladder dysfunction both facilitate UTI. Although calculi can form at any level of the
urinary tract, they occur more frequently in the bladder; especially if bladder augmentation has been performed
[438, 439].
Diagnosis of stones may be difficult and delayed in the absence of clinical symptoms due to
sensory impairment and vesicourethral dysfunction. Difficulties in self-catheterisation should lead
to suspicion of bladder calculi. Imaging studies are needed (US, CT) to confirm the clinical diagnosis prior to
surgical intervention.
Management
Management of calculi in patients with neurogenic bladder is similar to that described in Section 3.3. Any
surgery in these patients must be performed under general anaesthesia because of the impossibility of using
spinal anaesthesia. Bone deformities often complicate positioning on the operating table [440]. The risk of stone
formation after augmentation cystoplasty in immobile patients with sensory impairment can be significantly
reduced by irrigation protocols [435] .
For efficient long-term stone prevention in patients with neurogenic bladder, correction of the
metabolic disorder, appropriate infection control, and restoration of normal storing/voiding function of the
bladder are needed.
3.4.14.3.1  Summary of evidence and recommendation for the management of stones in patients with
neurogenic bladder
Summary of evidence LE
Patients undergoing urinary diversion and/or suffering from neurogenic bladder dysfunction are at risk
for recurrent stone formation.
3
3.4.14.4 Management of stones in patients with transplanted kidneys
Stones in transplanted kidneys can either be transplanted or present de novo allograft stones. Usually, they are
detected by routine US examination, followed by NCCT in cases of unclear diagnosis [441] .
Aetiology
Transplant patients depend on their solitary kidneys for renal function. Impairment causing urinary stasis/
obstruction, therefore, requires immediate intervention or drainage of the transplanted kidney. Stones in kidney
allografts have an incidence of 2% [441]. Risk factors for de novo stone formation in these patients are multi-fold:
• Immunosuppression increases the infection risk, resulting in recurrent UTIs.
• Hyper-filtration, excessively alkaline urine, renal tubular acidosis (RTA), and increased serum calcium
caused by persistent tertiary hyperparathyroidism [442] are biochemical risk factors.
Management
Selecting the appropriate technique for stone removal in a transplanted kidney is difficult, although
management principles are like those applied in other single renal units [443-445]. Additional factors such as
transplant function, coagulative status, and anatomical alterations due to the iliac position of the organ, directly
influence the surgical strategy.
For large or ureteral stones, careful percutaneous access and subsequent antegrade endoscopy are
more favourable. The introduction of small flexible ureteroscopes and the holmium laser has made URS a valid
treatment option for transplant calculi; however, one must be aware of potential injury to adjacent organs [444,
446, 447]. Retrograde access to transplanted kidneys can be difficult due to the anterior location of the ureteral
anastomosis, and ureteral tortuosity [448-450]. Treatment of donor stones may be needed pre-transplant and
increases the pool available for renal transplants. Post-transplant stone disease may also need treatment to
maintain the allograft function. A systematic review evaluating the outcomes of pre- vs. post-transplant URS
demonstrated a 100% SFR with an overall 7.5% complication rate, compared to a SFR of 60-100% with an overall
complication rate of 12.9% for post-transplant URS; most complications were Clavien 1 [451]. A SR shows that
SWL is also a safe and effective option for de novo stones after transplantation, with an overall SFR of 81% and
a complication rate of 17.2% [452].

UROLITHIASIS - LIMITED UPDATE APRIL 2024 36
3.4.14.4.1  Summary of evidence and recommendation for the management of stones in patients with
transplanted kidneys
Summary of evidence LE
Conservative treatment for small asymptomatic stones is only possible under close surveillance and in
absolutely compliant patients.
3
Shock wave lithotripsy for small calyceal stones is an option with minimal risk of complication, but
localisation of the stone can be challenging.
3
Recommendation Strength rating
Offer patients with transplanted kidneys any of the contemporary management options,
including shock wave lithotripsy, flexible ureteroscopy and percutaneous nephrolithotomy.
Strong
3.4.14.5 Special problems in stone removal
Table 3.11: Special problems in stone removal [453]
Calyceal diverticulum
stones
•
•
•
SWL, PCNL [454] (if possible) or RIRS [454, 455] .
Can also be removed using laparoscopic retroperitoneal surgery [456, 457] .
Patients may become asymptomatic due to stone disintegration (SWL),
whilst well-disintegrated stone material remains in the original position due
to narrow calyceal neck.
Horseshoe kidneys •
•
•
Can be treated in line with the options described above [458-460].
Passage of fragments after SWL might be poor.
Acceptable SFRs (up to 76%) with low major complication rates (2.4%) can
be achieved with flexible ureteroscopy [458-460].
Stones in pelvic kidneys• SWL, RIRS, PCNL or laparoscopic surgery [461].
Stones formed in a
continent reservoir
•Each stone must be considered and treated individually.
Patients with obstruction of
the UPJ
•
•
When outflow abnormality requires correction, stones can be removed by
PCNL together with percutaneous endopyelotomy or open/laparoscopic
reconstructive surgery.
URS together with endopyelotomy with Ho:YAG laser [462] .
3.4.15 Management of stones in children
The true incidence of nephrolithiasis in children remains unclear due to the global lack of large epidemiological
studies. Data derived from nationwide epidemiological studies, studies performed in different counties
worldwide [463] and large-scale databases [464, 465] indicate that the incidence and prevalence of paediatric
urinary stone disease have increased over the last few decades. Although boys are most commonly affected in
the first decade of life [466] the greatest increase in incidence has been seen in older female adolescents [463].
Stone composition is similar in children as in adults, with a predominance of calcium oxalate stones. Compared
to historical data, metabolic abnormalities responsible for stone formation are less commonly identified in
children nowadays [467-469]. Hypocitraturia, low urine volume and hypercalciuria predominate [84, 467-469].
Age may affect the predominant metabolic abnormality with hypercalciuria and hypocitraturia being the
most common disorder present in children < 10 and > 10 years old, respectively [469]. Genetic or systemic
diseases (e.g., cystinuria or nephrocalcinosis) contributing to stone formation are relatively frequent in children
accounting for less than 17% of the identifying causes [467, 470]. The role of diet remains unclear in children,
although there is some evidence that children are drinking less water and taking greater daily amounts of
sodium than is recommended [471-473] .
For diagnostic procedures see Section 3.3.3.2, for acute decompression see Section 3.4.2. and for metabolic
evaluation see Chapter 4.
3.4.15.1 Clinical presentation
Children with urinary stones can be asymptomatic or present with non-specific symptoms that necessitate a
high index of suspicion for proper diagnosis. Symptoms are age-dependent with infants presenting with crying,

37UROLITHIASIS - LIMITED UPDATE APRIL 2024
irritability and vomiting in 40% of cases [474] while in older children flank pain, micro or gross haematuria and
recurrent UTIs are more common [475].
3.4.15.2 Conservative management
There is a lack of evidence on conservative management of paediatric stones with evidence for ureteric calculi
coming from the placebo arms of medical expulsive trials, while evidence for renal stones comes from small
cohort studies, either on primary stones [476, 477] or residual fragments remained after SWL, RIRS or PCNL
[478]. Expectant management for single, asymptomatic lower-pole renal stones could be the initial approach
with increased odds of stone passage, especially in patients with non-struvite, non-cystine stones < 7 mm, with
no anatomic abnormalities [476]. Intervention may be needed for stones located elsewhere independently of
their size [476-478].
3.4.15.3 Medical expulsive therapy in children
There are limited studies on MET as off-label expulsive therapy for children with ureteral stones up to

10 mm which show conflicting outcomes. Several systematic reviews and meta-analyses, including six RCTs
and one conference abstract of an RCT, have been performed, all unanimously reporting that the use of alpha-
blockers for distal ureteric stones increases the stone-free or stone expulsion rate [479-481]. The use of alpha-
blockers also reduces the stone expulsion time and decreases pain episodes and analgesia demand with the
disadvantage of more side-effects such as headache and nasal congestion [480, 481].
3.4.15.4 Extracorporeal shock wave lithotripsy
Shock wave lithotripsy is still the first-line treatment for most ureteral stones in children. However, it is less likely
to be successful for stones > 10 mm in diameter, impacted stones, calcium oxalate monohydrate or cystine
stones, or for stones in children with unfavourable anatomy and in whom localisation is difficult [482].
Studies on extracorporeal SWL in children suggest an overall SFR of 70-90%, retreatment rate of
4-50% and need for auxiliary procedures in 4-12.5% of cases [483-487]. A MA of fourteen studies reporting on
1,842 paediatric patients treated with SWL found significantly higher SFR for stones < 10 mm than for stones
> 10 mm and higher retreatment rates as the stone size increased [482]. For best clinical practice see Section
3.4.5. A MA on slow SWL vs. rapid SWL for renal stones revealed very low-quality evidence about the effects
of SWL on SFRs, serious adverse events or complications of treatment and secondary procedures for residual
fragments [479]. Shock wave lithotripsy is well tolerated; however, good treatment outcomes are more likely to
require the administration of general anaesthesia to children. With improvements in modern (second and third-
generation) lithotripters, successful treatment using intravenous sedation, patient-controlled analgesia or no
medication at all has been increasingly performed in a select population of older, co-operative children [488].
Based on the results of a MA which compared SWL to dissolution therapy for intra-renal stones, and SWL
to ureteroscopy with holmium laser or pneumatic lithotripsy for renal and distal ureteric stones, no firm
conclusions can be drawn about the effects of SWL on SFR, serious adverse events or complications
of treatment and secondary procedures for residual fragments [479]. When SWL was compared to mini-
percutaneous nephrolithotomy for lower pole renal stones 1-2 cm in size SWL resulted in lower SFRs (RR: 0.88,
95% CI: 0.80 - 0.97; moderate-quality evidence) and higher rates of secondary procedures (RR: 2.50, 95% CI: 1.01
- 6.20; low-quality evidence); however, SWL showed less severe adverse events (RR: 0.13, 95% CI: 0.02 - 0.98;
low-quality evidence) [489].
3.4.15.5 Endourological procedures
Rigid/semi-rigid ureteroscopy
In recent years ureteroscopy is increasingly used in children with ureteral stones [490]. Ureteroscopy proved to
be effective with SFR of 81-98% [491-493], retreatment rates of 6.3%-10% [494] and complication rates of 1.9-
23% [491-493, 495]. Similar to adults, routine stenting is not necessary before URS. Pre-stenting may facilitate
URS, increase SFR and decrease complication rates [496, 497].
Flexible ureteroscopy/retrograde intrarenal surgery
Retrograde intra-renal surgery with flexible ureteroscopes (FURS) has become an efficacious treatment modality
for paediatric renal stones. Studies report SFRs of 76-100%, retreatment rates of 0-19% and complication rates
of 0-28% [498-501]. Younger age, cystine composition [502], large stone diameter [501] and lack of pre-stenting
predispose to FURS failure in children [496]. A large global study across eight centres shows an SFR of 75.5%;
although complications were minor, they were higher in patients < 5 years of age [503].
Although high-level evidence is lacking to support a strong recommendation [479], FURS may be a particularly
effective treatment option for lower calyceal stones in the presence of unfavourable factors for SWL [493, 499,
504].

UROLITHIASIS - LIMITED UPDATE APRIL 2024 38
For large and complex kidney stones RIRS has a significantly lower SFR compared to PCNL (71% vs. 95%), but
is associated with less radiation exposure, lower complication rates, and a shorter hospital stay [505]. Similarly,
retrospective data indicate that RIRS may achieve lower SFRs compared to micro percutaneous surgery in
favour of shorter operative time, shorter fluoroscopy time, and less hospitalisation time [506, 507]. A published
MA confirmed these results [508] .
Percutaneous nephrolithotomy
Indications for PCNL in children are like those in adults and include renal stones > 2 cm, or smaller stones resistant
to SWL and ureteroscopic treatment. Reported SFRs with paediatric PCNL are 71.4-95% after a single session
[505-507, 509, 510] with an overall complication rate of 20% [511]. A high degree of hydronephrosis, increased
number of tracts and operative time [512], and large tract size [510, 513-515] are associated with increased blood
loss. Child age [514] and stone burden [510] predispose to the use of larger instruments during PCNL in children.
The miniaturisation of equipment increases the opportunity to perform tubeless PCNL in appropriately selected
children, which can reduce the length of hospital stay and post-operative pain [516, 517]. A systematic review on
the role of mini-PCNL showed an initial and overall SFR of 87.9% and 97% respectively, with no conversions to
standard PCNL, and a complication rate of 19%, with a mean transfusion rate of 3.3% [503].
Concerns have been raised regarding the possible adverse effects of PCNL on the renal parenchyma
of the developing child. However, focal damage is only reported in 5% of cases [518]. Using pre- and post-
PCNL dimercaptosuccinic acid (DMSA) scans, Cicekbilek et al. demonstrated that PCNL tracts between 12-24
Charrière in size did not cause significant harm to paediatric kidneys [509] .
3.4.15.6 Open and laparoscopic/robot-assisted stone surgery
With the advances in SWL, PCNL and RIRS, very few cases of paediatric urolithiasis require open surgery. Data
extracted from the National Inpatient Sample (NIS) databases for 2001-2014 showed that in the USA incisional
procedures (mainly nephrolithotomy, pyelolithotomy and ureterotomy) were performed in 2.6% of hospitalised
patients (52% aged 15-17 years) who required surgical intervention for urinary stones [519]. Laparoscopy for the
management of paediatric renal and ureteric stones is a safe and effective procedure when specific indications
are followed. Stone-free rates of 100% were reported when laparoscopic pyelolithotomy was applied for a

≥ 1 cm single stone located in an extra-renal pelvis [520], or when laparoscopic ureterolithotomy was applied
to impacted ureteric stones ≥ 1.5 cm, or to ureteric stones that were refractory to SWL or URS [521]. There are
extremely limited data available on the efficacy and complications of robot-assisted laparoscopic management
of paediatric urolithiasis [522] .
3.4.15.7 Special considerations on recurrence prevention
All paediatric stone formers need metabolic evaluation and recurrence prevention with respect to the detected
stone type. Children are in the high-risk group for stone recurrence (See Chapter 4).
3.4.15.8 Summary of evidence and recommendations for the management of stones in children
Summary of evidence LE
In children, MET could increase the rate of stone expulsion, reduce the stone expulsion time, and
decrease pain episodes/analgesia demand, but it has a higher incidence of side effects.
1b
In children, the indications for SWL, URS and PCNL are similar to those in adults. 1b
Children with renal stones of a diameter up to 20 mm (~300 mm
2
) are ideal candidates for SWL. 1b
Ureteroscopy has become the treatment of choice for larger distal ureteral stones in children.1a
In children, the indications for PCNL are similar to those in adults. 1a
Mini-PCNL is safe and effective in children. 1b
Recommendations Strength rating
Offer children with single ureteral stones less than 10 mm shock wave lithotripsy (SWL) if
localisation is possible or ureteroscopy as first-line option.
Strong
Ureteroscopy is a feasible alternative for ureteral stones not amenable to SWL. Strong
Offer children with renal stones with a diameter of up to 20 mm (~300 mm
2
) SWL. Strong
Offer children with renal pelvic or calyceal stones with a diameter > 20 mm (~300 mm
2
)
percutaneous nephrolithotomy.
Strong
Retrograde renal surgery is a feasible alternative for renal stones smaller than 20 mm in all
locations.
Weak

39UROLITHIASIS - LIMITED UPDATE APRIL 2024
3.5 Radiation exposure and protection during endourology
The diagnosis and treatment of nephrolithiasis are associated with high levels of ionising radiation exposure to
patients [523, 524]. Currently, there are no studies estimating the lifetime radiation exposure of stone formers or
the subsequent risk of malignancy development. The radiation exposure of endourologists has been extensively
studied. Still, there are no studies assessing the risk of radiation-induced malignancies in urologists or operating
theatre staff members [525-527] .
Current evidence from atomic bomb patients [528, 529], retrospective epidemiological data on medical exposure
[530, 531], and modelling studies [532, 533] suggest an age and dose-dependent risk of secondary malignancy
from ionising radiation.
The International Commission on Radiological Protection (ICRP) recommends a maximum annual occupational
exposure of 50mSv [534]. However, the risk of radiation-induced malignancy follows a stochastic model having
no known safe threshold of exposure. Taking this into consideration as well as the length of a urologist’s career
the upper limit of 50mSv is still highly concerning.
Table 3.12 shows the EAU Urolithiasis guidelines panel recommended protection methods to reduce radiation
exposure to patients, surgical, anaesthesiologic, and nursing staff.
Table 3.12 Radiation protection measures
Limit studies or intervention involving radiation exposure to those that are strictly medically necessary.
Implement a patient electronic record of medical imaging.
Make use of imaging studies with lower radiation doses (US, KUB, digital tomosynthesis, low-dose and ultra-
low dose CT scan).
Create and follow a precise radiation exposure protection protocol in your department.
Act in accordance with the as low as reasonably achievable (ALARA) principle.
Measure and report fluoroscopy time to the operative surgeon (use dosimeters and perform monthly
calculations).
Technical measures to reduce radiation exposure include:
• Reducing fluoroscopy time;
• Limiting time adjacent to patient;
• Using low-dose radiation; Irradiating only to observe motion;
• Intra-operative use of pulsed fluoroscopy;
• Reduced fluoroscopy pulse rate;
• Collimated fields;
• Avoid digital image acquisition and rely on last image hold and instant replay technology.
Use radiation protection instruments (chest, pelvic and thyroid shields, lead or lead-free gloves, protective
glasses, lead protection under the operating table between the x-ray source and the surgeon).
The radiation protection instruments must be cared for appropriately as any damage decreases effectiveness
and increases exposure risk. They should be monitored and measured regularly to ensure integrity.
Proper surgeon and operating room setup should be observed (follow the inverse square law, use the x-ray
source underneath the patient’s body, decrease the x-ray source to patient distance, reduce magnification,
avoid field overlap by not turning the C-arm in extreme angles, operate in the standing rather than the seated
position).
The availability of fluoroscopy is mandatory for endourological procedures. There is an increasing interest
in fluoroless and fluoroscopy-free operations in urology. Several RCTs have been published showing a good
outcome in means of stone-free and complication rates [166, 270, 535-537]. These trials have been limited to
non-complex cases and they were not sufficiently powered to show the non-inferiority of fluoroscopy in PCNL
[270, 525] or the superiority of ultrasound in URS [213, 214] .

UROLITHIASIS - LIMITED UPDATE APRIL 2024 40
4. METABOLIC EVALUATION AND RECURRENCE

PREVENTION
4.1 General metabolic considerations for patient work-up
4.1.1 Evaluation of patient risk
After stone passage, every patient should be assigned to a low- or high-risk group (Table 3.3) for stone formation
(Figure 4.1).
Reliable stone analysis by infrared spectroscopy or X-ray diffraction and basic metabolic evaluation is
mandatory for all stone formers.
Only high-risk stone formers require specific metabolic evaluation. Stone type is the deciding factor for further
diagnostic tests. The different stone types include:
• calcium oxalate;
• calcium phosphate;
• uric acid;
• ammonium urate;
• struvite (and infection stones);
• cystine;
• xanthine;
• 2,8-Dihydroxyadenine;
• drug stones;
• stones of unknown composition.
Figure 4.1: Assignment of patients to low- or high-risk groups for stone formation
STONE
Stone analysis
known
Stone analysis
unknown
Basic evaluation
(Section 3.3.2.3)
Investigating a patient
with unknown 
composition (Table 3.1)
Specific metabolic
evaluation
General preventive
measures
Stone specific
recurrence prevention
Low-risk
stone former
High-risk
stone former
Risk factors
Present
no  yes
Diagnosis Treatment Follow-up

41UROLITHIASIS - LIMITED UPDATE APRIL 2024
4.1.2 Urine sampling
Specific metabolic evaluation requires the collection of two consecutive 24-hour urine samples [63, 538,
539]. The collecting bottles should be prepared with 1 g thymol per liter or stored at < 8°C during collection to
reduce bacterial proliferation [63]. Pre-analytical errors can be minimised by carrying out urinalysis immediately
after collection. Alternatively, boric acid (10 g powder per urine container) can also be used, but this prevents
the correct determination of pH [63]. The collecting method should be chosen in close cooperation with the
laboratory. A pH < 5.5 in a 24-hour urine indicates hyper acidic urine (acidic arrest) [540-542]. In the course of
alkalinising therapy for cystinuria and uric acid stones, urine pH should be assessed during the collection of
freshly voided urine at different times throughout the day using sensitive pH dipsticks or a pH-meter [23, 63,
543]. A consensus statement stated that RTA is suspected if 24-hour urine pH is > 6.2 and fasting second-
morning spot urine pH is > 5.8 [544, 545].
Spot urine samples are an alternative sampling method, particularly when 24-hour urine collection is difficult, for
example, in non-toilet-trained children [546]. Spot urine studies normally link the excretion rates to the creatinine
[547], but these are of limited use because the results may vary with collection time and patients’ sex, body
weight, and age.
4.1.3 Timing of specific metabolic work-up
For the initial specific metabolic work-up, the patient should stay on a self-determined diet under normal daily
conditions and should ideally be stone-free for at least twenty days [548]. Follow-up studies are necessary for
patients taking medication for recurrence prevention [549]. The first follow-up 24-hour urine measurement is
suggested eight to twelve weeks after starting pharmacological prevention of stone recurrence. This enables
diet and/or drug dosage to be adjusted if urinary risk factors have not normalised, with further 24-hour urine
measurements, if necessary. Once urinary parameters have been normalised, it is sufficient to perform a
24-hour urine evaluation every twelve months. On this issue, the Panel realises that there is only very limited
published evidence.
4.1.4 Reference ranges of laboratory values
Tables 4.1-4.4 provide the internationally accepted reference ranges for the different laboratory values in serum
and urine.
Table 4.1: Normal laboratory values for blood parameters in adults [23, 549]
Blood parameter Reference range
Creatinine 50-100 μmol/L
Sodium 135-145 mmol/L
Potassium 3.5-5.5 mmol/L
Calcium 2.0-2.5 mmol/L (total calcium)
1.12-1.32 mmol/L (ionised calcium)
Uric acid 119-380 μmol/L
Chloride 98-112 mmol/L
Phosphate 0.81-1.29 mmol/L
Blood gas analysis pH 7.35-7.45
pO
2 80-90 mmHg
pCO
2 35-45 mmHg
HCO
3 22-26 mmol/L
BE BE ± 2 mmol/L
BE = base excess (loss of buffer base to neutralise acid); HCO = bicarbonate; pCO = partial pressure of carbon
dioxide; PO = partial pressure of oxygen.
4.1.5 Risk indices and additional diagnostic tools
Several risk indices have been developed to describe the crystallisation risk for calcium oxalate or calcium
phosphate in the urine [550-553]. However, clinical validation of these risk indices for recurrence prediction or
therapy improvement is ongoing.

UROLITHIASIS - LIMITED UPDATE APRIL 2024 42
Table 4.2: Laboratory values for urinary parameters in adults
Urinary Parameters Reference ranges and limits for medical attention
pH Consistently fasting morning spot urine pH > 5.8 and
> 6.2 in 24-hr collection (suspicious of renal tubular
acidosis) [544, 545]
Consistently > 7.0 (suspicious of infection)
Consistently < 5.5 in morning urine and in 24-hr
collection (suspicious of acidic arrest) [540, 554]
Specific weight Specific weight > 1.010
Creatinine 7-13 mmol/day (females), 13-18 mmol/day (males)
Calcium > 5.0 mmol/day (see Fig. 4.2)
> 8.0 mmol/day (see Fig. 4.2)
Oxalate > 0.5 mmol/day (suspicious of enteric hyperoxaluria)
>1.0 mmol/day (suspicious of primary hyperoxaluria)
Uric acid > 4.0 mmol/day (females), 5 mmol/day (males)
Citrate < male < 1.7 mmol/day, female < 1.9 mmol/day
Magnesium < 3.0 mmol/day
Inorganic phosphate > 35 mmol/day
Ammonium > 50 mmol/day
Cystine > 0.8 mmol/day
Table 4.3: Normal values for spot urine samples: creatinine ratios (solute/creatinine) in children [555]
Parameter/Patient age Ratio of solute to creatinine Units
Calcium mol/mol mg/mg
< 12 months < 2.0 0.81
1-3 years < 1.5 0.53
1-5 years < 1.1 0.39
5-7 years < 0.8 0.28
> 7 years < 0.6 0.21
Oxalate mol/mol mg/mg
0-6 months < 325-360 288-260
7-24 months < 132-174 110-139
2-5 years < 98-101 80
5-14 years < 70-82 60-65
> 16 years < 40 32
Citrate mol/mol g/g
0-5 years > 0.25 0.42
> 5 years > 0.15 0.25
Magnesium* mol/mol g/g
> 0.63 > 0.13
Uric acid
> 2 years < 0.56 mg/dL (33 μmol/L) per GFR (ratio x plasma creatinine)
* There is low-level evidence regarding the importance of magnesium.

43UROLITHIASIS - LIMITED UPDATE APRIL 2024
Table 4.4: Solute excretion in 24-hour urine samples in children [556, 557]*
Calcium/24 Citrate/24 hour Cystine/24 hour Oxalate/24 hour Urate/24 hour
All age groupsBoys Girls < 10 years> 10 yearsAll age
groups
< 1 year1-5 years> 5 years
< 0.1 mmol/kg/
24 h
> 1.9 mmol/
1.73 m2/24 h
> 1.6 mmol/
1.73 m2/24 h
< 55 μmol/
1.73 m2/24 h
< 200 μmol/
1.73 m2/24 h
< 0.5 mmol/
1.73 m2/24 h
< 70 μmol/
kg/24 h
< 65 mμmol/
kg/24 h
< 55 μmol/
kg/24 h
< 4 mg/kg/24 h> 365 mg/
1.73 m2/24 h
> 310 mg/
1.73 m2/24 h
< 13 mg/
1.73 m2/24 h
< 48 mg/
1.73 m2/24 h
< 45 mg /
1.73 m2/24 h
< 13 mg/
kg/24 h
< 11 mg/
kg/24 h
< 9.3 mg/
kg/24 h
*24 h urine parameters are diet and gender-dependent and may vary geographically.
4.2 General considerations for recurrence prevention
All stone formers, independent of their individual risk, should follow the preventive measures in Table 4.5. The
main focus is the normalisation of dietary habits and lifestyle risks. Stone formers at high risk need specific
prophylaxis for recurrence, which is usually pharmacological treatment based on stone analysis and urinary risk
profile.
Table 4.5: General Preventive Measures
Fluid intake (drinking advice) Fluid amount: 2.5-3.0 L/day
Water is the preferred fluid
Diuresis: 2.0-2.5 L/day
Specific weight of urine: < 1,010 g/day
Nutritional advice for a balanced diet Balanced diet*
Rich in vegetables and fibre
Normal calcium content: 1-1.2 g/day
Limited NaCl content: 4-5 g/day
Limited animal protein content: 0.8-1.0 g/kg/day
Lifestyle advise to normalise general risk factorsRetain a normal BMI level
Adequate physical activity
Balancing of excessive fluid loss
Reduce the intake of alcohol containing fluids
Reduce the intake of sodas and calorie-containing
fluids
Caution: Protein requirements are age dependent; therefore, protein restriction in childhood should be handled
carefully.
* Avoid excessive consumption of vitamin supplements.
4.2.1 Fluid intake
An inverse relationship between high fluid intake and stone formation has been repeatedly demonstrated [556-
560]. The beneficial effect of fruit juices is mainly determined by the presence of citrate or bicarbonate [561].
Citrus fruit juices seem to protect against stone disease either by increasing urinary citrate levels or by having
an alkalinising effect on it [562]. However, if potassium is present, both pH and citrate are increased [563,
564]. One large moderate-quality RCT randomly assigned men with more than one past renal stone of any type
and soft drink consumption of at least 160 mL/day to reduced soft drink intake or no treatment. Although the
intervention significantly reduced the risk for symptomatic recurrent stones (RR: 0.83; CI: 0.71-0.98), the level of
evidence for this outcome is low because the results were from only one trial [565]. An analysis of 3 Channing’s
cohorts (194,095 participants) over a median follow-up of more than eight years has shown that consumption
of sugar-sweetened soda and punch is associated with a higher risk of stone formation, whereas consumption
of coffee, tea, beer, wine, and orange juice is associated with a lower risk [566], whereas consumption of tea
and coffee does not seem to increase the risk of stones disease [567]. However, the intake of fluids should
be considered within a holistic approach to health. Some of them contain calories or alcohol that may be
detrimental to health. Therefore, water should be the preferred fluid.

UROLITHIASIS - LIMITED UPDATE APRIL 2024 44
Diet
A common-sense approach to diet should be taken, that is, a mixed, balanced diet with contributions from all
food groups, without any excesses [557, 568, 569]. Sufficient calcium intake is needed especially in vegetarian
and vegan diets [570] .
Fruit, vegetables and fibre: Fruit and vegetable intake should be encouraged because of the beneficial effects of
fiber, although the role of the latter in preventing stone recurrences is debatable [571-574]. The alkaline content
of a vegetarian diet also increases urinary pH. In addition, fruits and vegetables have a high-water content and
can significantly contribute to fluid intake.
Oxalate: Excessive intake of oxalate-rich products should be limited or avoided to prevent high oxalate load
[575], particularly in patients who have high oxalate excretion.
Vitamin C: Although vitamin C is a precursor of oxalate, its role as a risk factor in calcium oxalate stone
formation remains controversial [576]. However, it seems wise to advise calcium oxalate stone formers to avoid
excessive intake.
Animal protein: Animal protein should not be consumed in excess [577, 578] and limited to 0.8-1.0 g/kg body
weight. Excessive consumption of animal protein has several effects that favour stone formation, including
hypocitraturia, low urine pH, hyperoxaluria, and hyperuricosuria.
Calcium intake: Calcium should not be restricted, unless there are strong reasons for doing so, due to the inverse
relationship between dietary calcium and stone formation [572, 579]. The daily requirement for calcium is 1,000
to 1,200 mg [23]. Calcium supplements are not recommended except in enteric hyperoxaluria when additional
calcium should be taken with meals to bind intestinal oxalate [557, 575, 577, 580]. Older adults who do not have
a history of renal stones but who take calcium supplements should ensure adequate fluid intake since it may
prevent increases in urine calcium concentration, and thereby reduce or eliminate any increased risk of renal
stones formation associated with calcium supplement use [581].
Sodium: Daily sodium (NaCl) intake should not exceed 4-5g [23]. High intake adversely affects urine composition:
• Calcium excretion is increased by reduced tubular re-absorption;
• urinary citrate is reduced due to loss of bicarbonate;
• increased risk of sodium urate crystal formation.
Calcium stone formation can be reduced by restricting sodium and animal protein [577, 578]. A positive
correlation between sodium consumption and the risk of first-time stone formation has been confirmed only in
women [579]. There have been no prospective clinical trials on the role of sodium restriction as an independent
variable in reducing the risk of stone formation.
Urate: Intake of purine-rich food should be restricted in patients with hyperuricosuric calcium oxalate [582, 583]
and uric acid stones. Intake should not exceed 500 mg/day [23].
4.2.2 Lifestyle
Lifestyle factors may influence the risk of stone formation, for example, those causing obesity [584], diabetes
mellitus [585] , and metabolic syndrome [586] .
4.2.3 Summary of evidence and recommendation for recurrence prevention
Summary of evidence LE
Increasing water intake reduces the risk of stone recurrence. 1a
Recommendation Strength rating
Advise patients that a generous intake of fluids, preferably water, is to be maintained,
allowing for a 24-hour urine volume > 2.5 L.
Strong

45UROLITHIASIS - LIMITED UPDATE APRIL 2024
4.3 Stone-specific metabolic evaluation and pharmacological recurrence prevention
4.3.1 Introduction
Pharmacological treatment is necessary in patients at high risk for stone formation or for associated systemic
conditions. The ideal drug should halt stone formation, have no side effects, and be easy to administer. Each of
these aspects is important to achieve good compliance. Table 4.6 highlights the most important characteristics
of commonly used medication.
Table 4.6: Pharmacological substances used for stone prevention - characteristics, specifics, and dosage.
Agent Rationale Dose Specifics and side
effects
Stone type Ref
Alkaline citratesAlkalinisation
Hypocitraturia
Inhibition of
calcium oxalate
crystallisation
3.25-9.75 g/d
(10-30 mmol/d)
Children:
0.1-0.15 g/kg/d
Daily dose for
alkalinisation depends
on urine pH.
Calcium oxalate
Uric acid
Cystine
[587-592]
Allopurinol Hyperuricosuria
Hyperuricaemia
100-300 mg/d
Children:
1-3 mg/kg/d
100 mg in isolated
hyperuricosuria.
Renal insufficiency
demands dose
correction.
Contraindicated in
acute gout pregnancy,
and breastfeeding.
Allergies from trivial
to very severe forms,
xanthine stone
formation.
Calcium oxalate
Uric acid
Ammonium urate
2,8-Dihydroxyadenine
[557, 593-
596]
Calcium Enteric
hyperoxaluria
Up to 2,000
mg/d depending
on oxalate
excretion
Intake 30 min before
meals.
Calcium oxalate [577, 579,
580, 597]
Captopril Cystinuria
Active decrease
of urinary cystine
levels
75-150 mg Second-line option
in case of significant
side effects of
tiopronin.
Cystine [598, 599]
Febuxostat Hyperuricosuria
Hyperuricaemia
80-120 mg/d Contraindicated in
acute gout, pregnancy
and breastfeeding.
Xanthine stone
formation.
Calcium oxalate
Uric acid
[600, 601]
L-Methionine Acidification 600-1,500 mg/dHypercalciuria, bone
demineralisation,
systemic acidosis.
No long-term therapy.
Infection stones
Ammonium urate
Calcium phosphate
[587, 602]
Magnesium Isolated
Hypomagnesuria
Enteric
hyperoxaluria
200-400 mg/d
Children:
6 mg/kg/d
Renal insufficiency
demands dose
correction.
Diarrhoea, chronic
alkali losses,
hypocitraturia.
Calcium oxalate [603, 604]
(Low level
of
evidence)
Sodium bicarbonateAlkalinisation
Hypocitraturia
4.5 g/d Daily dose for
alkalinisation depends
on urine pH
Calcium oxalate
Uric acid, Cystine
[605]

UROLITHIASIS - LIMITED UPDATE APRIL 2024 46
Pyridoxine Primary
hyperoxaluria
Initial dose
5 mg/kg/d
Max. 20 mg/kg/d
Sensory peripheral
neuropathy
Calcium oxalate [606]
Thiazide
(Hydro-
chlorothiazide*)
Hypercalciuria 25-50 mg/d
Children:
0.5-1 mg/kg/d
Risk for hypotension
diabetes,
hyperuricaemia,
hypokalaemia,
hypocitraturia.
Calcium oxalate
Calcium phosphate
[583, 587-
596, 598-
616]
Tiopronin Cystinuria
Increase in
solubility of levels
Initial dose
800 mg/d
Avg. 2,000 mg/d**
Children:
Initial dose in
patients > 20kg is
15 mg/kg/day.
Avoid dosages >
50mg/kg/day
Risk for
proteinuria.
Cystine [617-620]
* Patients on hydrochlorothiazide should be advised to get their skin checked on a regular basis as they have a
higher risk of developing a non-melanoma skin cancer (NMSC) and some forms of melanoma. In patients with a
history of skin cancer, the indication for treatment with hydrochlorothiazide should be thoroughly reviewed [621-
623].
**  No information is available on maximum dose and patients may be initiated on a very low dose if they have
previously had reactions to tiopronin or penicillamine. For all patients, dosage should be titrated according to the
frequency of stone episodes, side effects, and renal function under expert supervision with close monitoring.
4.4 Calcium oxalate stones
The criteria for identification of calcium oxalate stone formers with a high risk of recurrences and comorbidities
are listed in section 3.1.3.
4.4.1 Diagnosis
Blood analysis requires measurement of creatinine, sodium, potassium, chloride, ionised calcium (or total
calcium + albumin), phosphate, uric acid; and, in the case of increased calcium levels, parathyroid hormone
(PTH) and vitamin D. Urinalysis requires measurement of urine volume, urine pH, specific weight, calcium,
oxalate, uric acid, citrate, sodium, and magnesium. Figure 4.2 summarises the diagnostic steps for calcium
oxalate stones.

47UROLITHIASIS - LIMITED UPDATE APRIL 2024
Figure 4.2 Diagnostic algorithm for Calcium Oxalate stones
Calcium oxalate stone
HypercalciuriaHypocitraturiaHyperoxaluriaHyperuricosuriaHypomagnesuria
Persistent
low urine
volume
No
metabolic
abnor-
mality
Normo-
calcemi a
Hyper-
calcemi a
Normo-
calcemi a
+
Meta-
bolic
acidosis
Meta-
bolic
Acidosis
Hypo-
kalemia
Idio-
pathic
DietaryEntericPrimary
Hyper-
uricemia
Normou -
ricemia
Poor
dietary
intake
Reduced
intestinal
absorption
(chronic
diarrhea)
Diarrheal
states
Idiopathic
hyper-
calciuria
(commo -
nest)
Granulo-
matous
diseases
(rare)
Vitamin D
excess
Primary
Hyperpara-
thyroidis m
Granulo -
matous
diseases
Vitamin D
excess
Malignancy
Hyper-
thyroidis m
Distal
renal
Tubular
Acidosis
Type
1, 2
Small bowe l
resection
Bariatric
Surgery
Fat malab-
sorption
Gout
High dietary
purine
intake
Myeloprolif
erative
disorders
Hemolytic
anaemia
Low
Calcium
intake
High intake
of oxalate-
rich foods
Excess vit
C intake
(>5mmol/
day)
Diagnosis
Treatment
Follow-up

UROLITHIASIS - LIMITED UPDATE APRIL 2024 48
4.4.2 Interpretation of results and aetiology
The most common metabolic abnormalities associated with calcium stone formation are hypercalciuria, which
affects 30-60% of adult stone formers, and hyperoxaluria (26-67%), followed by hyperuricosuria (15-46%),
hypomagnesuria (7-23%), and hypocitraturia (5-29%). However, ranges tend to differ based on ethnicity [624].
• Elevated levels of ionised calcium in serum (or total calcium and albumin) require assessment of intact
PTH to confirm or exclude suspected hyperparathyroidism (HPT).
• Consistently low pH (< 5.5) or 24-hour urine pH < 5.5 may promote co-crystallisation of uric acid and
calcium oxalate.
• Similarly, increased uric acid excretion (> 4 mmol/day in adults or > 12 mg/kg/day in children) can act as a
promoter.
• A pH > 6.2 in a 24-hour urine collection may indicate RTA provided UTI has been excluded. An ammonium
chloride loading test confirms distal RTA (Section 4.6.5).
• Hypercalciuria may be associated with normocalcemia (idiopathic hypercalciuria, or granulomatous
diseases) or hypercalcemia (hyperparathyroidism, granulomatous diseases, vitamin D excess, or
malignancy).
• Hypocitraturia (male < 1.7 mmol/d, female < 1.9 mmol/d) may be idiopathic or secondary to metabolic
acidosis or hypokalaemia.
• Oxalate excretion > 0.5 mmol/day in adults confirms hyperoxaluria (see Table 4.3 for the values in
children).
oprimary hyperoxaluria (oxalate excretion mostly > 1 mmol/day), appears in three genetically
determined forms;
osecondary hyperoxaluria (oxalate excretion > 0.5 mmol/day, usually < 1 mmol/day), occurs due to
intestinal hyperabsorption of oxalate or extreme dietary oxalate intake;
omild hyperoxaluria (oxalate excretion 0.45-0.85 mmol/day), commonly found in idiopathic calcium
oxalate stone formers.
• Hypomagnesuria (< 3.0 mmol/day) may be related to poor dietary intake or to reduced intestinal absorption
(chronic diarrhoea).

49UROLITHIASIS - LIMITED UPDATE APRIL 2024
Figure 4.3: Therapeutic algorithm for calcium oxalate stones
1
Be aware of excess calcium excretion.
2
tid = three times/day (24h).
3
No magnesium therapy for patients with renal insufficiency.
4
 There is no evidence that combination therapy (thiazide + citrate) or (thiazide + allopurinol) is superior to
thiazide therapy alone [588, 625].
5
Febuxostat 80 mg/d.
* Low evidence (see text)
** Calciuria is a continuous variable and treatment may be adjusted to clinical need even when below the
threshold indicated.
*** Patients on hydrochlorothiazide should be advised to get their skin checked on a regular basis as they have
a higher risk of developing NMSC and some forms of melanoma. In patients with a history of skin cancer, the
indication for treatment with hydrochlorothiazide should be thoroughly reviewed [621-623].
Basic evaluatio n
24 h urine collectio n
Alkaline citrate
3-10 g/d
or
sodium
bicarbonate
1.5 g tid
2,4
5-8 mmol/d**
8 mmol/d
Male < 1.7
mmol/d
Female < 1.9
mmol/d
> 0.5 mmol/d
(enteric)
> 1 mmol/d
(primary)
> 4 mmol/d
Hyperuricosuria
and
Hyperuricaemia
> 380 :mol/L
< 3 mmol/d
Hydrochloro-
thiazide***
initially 25 mg/d
up to 50 mg/d
chlorthalidone
25 mg/d
indapamide
2.5 mg/d
Alkaline
citrate
3-10 g/ d
Calcium
1000 to 2000 mg/d
depending on oxalate
excretion
1
and
magnesium*
200-400 mg/d
Pyridoxin e
initial 5 mg/kg/d
up to
20 mg/kg/d
Alkaline citrate
3-10 g/d
or
sodium
bicarbonate
1.5 g tid
2
plus/o r
allopurinol
100 mg/d
Alkaline citrate
3-10 g/d
plus
allopurinol
100-300 mg/d
4,5
Magnesium
200-400 mg/d
3
Hypercalcuria
Hypocitraturia
Hyperoxaluri a
Hyperuricosuria
Hypomagnesuria *
Diagnosis
Treatment
Follow-up
Calcium oxalate stone

UROLITHIASIS - LIMITED UPDATE APRIL 2024 50
4.4.3 Specific treatment
General preventive measures are recommended for fluid intake and diet. Hyperoxaluric stone formers should
consume foods with low oxalate content, whereas hyperuricosuric stone formers benefit from daily dietary
reduction of purine. Figure 4.3 summarises the pharmacological treatment of calcium oxalate stones [557,
564, 587-590, 593, 594, 596, 600, 603-605, 609-616, 624, 626-629]. There is only low-level evidence for
the efficacy of preventing stone recurrence based on pre-treatment stone composition examination and
biochemistry measures, or on-treatment biochemistry measures [557]. One RCT concluded that treatment with
hydrochlorothiazide (HCTZ) does not differ substantially from placebo in the prevention of stone recurrence
of kidney stones in patients at high risk for recurrence [630]. However, the study was not powered to show any
difference of HCTZ over placebo [631]. In fact, the study’s main objective based on the author’s protocol [631],
was to investigate the existence of a dose-response relationship, i.e., a linear trend for three different doses of
HCTZ (12.5, 25 mg, and 50 mg/day) on stone recurrence, and this was shown. In addition, the hypercalciuria
levels in the population enrolled in the study were significantly lower than the threshold the EAU guidelines
recommend being administered to patients (Figure 4.3).
4.4.4 Summary of evidence and recommendations for pharmacological treatments for patients with
specific abnormalities in urine composition (based on 24-hour urine samples)
Summary of evidence LE
Alkaline citrates can reduce stone formation. 1a
Thiazides reduces calciuria. 1a
Oxalate restriction is beneficial if hyperoxaluria is present. 2b
Alkaline citrates can reduce stone formation in enteric hyperoxaluria. 4
Calcium supplement can reduce stone formation in enteric hyperoxaluria. 2
A diet reduced in fat and oxalate can be beneficial in reducing stone formation. 3
Alkaline citrates and sodium bicarbonate can be used if hypocitraturia is present. 1b
Allopurinol is first-line treatment of hyperuricosuria. 1a
Febuxostat is second-line treatment of hyperuricosuria. 1b
Avoid excessive intake of animal protein in hyperuricosuria. 1b
Restricted intake of salt is beneficial if there is high urinary sodium excretion. 1b
Recommendations Strength rating
Prescribe thiazide or alkaline citrates or both in case of hypercalciuria*. Strong
Advise oxalate restriction if hyperoxaluria is present. Weak
Offer alkaline citrates in enteric hyperoxaluria. Weak
Offer calcium supplement in enteric hyperoxaluria. Strong
Advise reduced dietary fat and oxalate in enteric hyperoxaluria. Weak
Prescribe alkaline citrates or sodium bicarbonate in case of hypocitraturia. Strong
Prescribe allopurinol in case of hyperuricosuria. Strong
Offer febuxostat as second-line treatment of hyperuricosuria. Strong
Avoid excessive intake of animal protein in hyperuricosuria. Strong
Advise restricted intake of salt if there is high urinary sodium excretion. Strong
* Patients on hydrochlorothiazide should be advised to get their skin checked on a regular basis as they have a
higher risk of developing an NMSC and some forms of melanoma. In patients with a history of skin cancer, the
indication for treatment with hydrochlorothiazide should be thoroughly reviewed [621-623].
4.5 Calcium phosphate stones [557, 587, 596, 609, 610, 614, 632]
Some calcium phosphate stone formers are at high risk of recurrence. Further information on identifying high-
risk patients is provided in section 3.1.3.

51UROLITHIASIS - LIMITED UPDATE APRIL 2024
Calcium phosphate mainly appears in two completely different minerals: carbonate apatite and
brushite. Carbonate apatite crystallisation occurs at a pH > 6.8 and may be associated with infection. Brushite
crystallises at an optimum pH of 6.5-6.8 at high urinary concentrations of calcium (> 8 mmol/day) and
phosphate (> 35 mmol/day). Its occurrence is not related to UTI. Possible causes of calcium phosphate stones
include HPT, RTA, and UTI; each of which requires different therapy.
4.5.1 Diagnosis
Diagnosis requires blood analysis for creatinine, sodium, potassium, chloride, ionised calcium (or total calcium
+ albumin), phosphate, and PTH (in the case of increased calcium levels). Urinalysis includes measurement of
volume, urine pH, specific weight, calcium, phosphate, and citrate.
4.5.2 Interpretation of results and aetiology
General preventive measures are recommended for fluid intake and diet. The diagnostic and therapeutic
algorithm for calcium phosphate stones is shown in Figure 4.4.
Figure 4.4: Diagnostic and therapeutic algorithm for calcium phosphate stones
HPT = hyperparathyroidism; RTA = renal tubular acidosis; UTI = urinary tract infection.
* Patients on hydrochlorothiazide should be advised to get their skin checked on a regular basis as they have
a higher risk of developing NMSC and some forms of melanoma. In patients with a history of skin cancer, the
indication for treatment with hydrochlorothiazide should be thoroughly reviewed [621-623].
4.5.3 Pharmacological therapy [557, 587, 596, 609, 610, 614, 632]
Hyperparathyroidism and RTA are common causes of calcium phosphate stone formation. Most patients
with primary HPT require surgery. Renal tubular acidosis can be corrected pharmacologically including with
bicarbonate or alkaline citrate therapy. If primary HPT and RTA have been excluded, pharmacotherapy for
calcium phosphate calculi depends on the effective reduction of urinary calcium levels using thiazides. For
infection-associated calcium phosphate stones, it is important to consider the guidance given for infection
stones.
Calcium phosphate
stones
Carbonate
apatite
stones
Hypercalciuria
Brushite stones
Basic evaluation
Elevated calcium
Exclude HPT
Exclude HPT Exclude RT A
Hydrochlorothiazide*
initially 25 mg/d
up to 50 mg/d
Hypercalciuria
> 8 mmol/d
Hydrochlorothiazide*
initially 25 mg/d
up to 50 mg/d
chlorthalidone 25 mg/d
indapamide 2.5 mg/d
Basic evaluation
Urinary pH
> 6.5-6.8
Exclude conditions
causing stones.
Act consequently
RTA, UTI,
treatment with
Acetazolamide,
Topiramate,
Zonisamide
Diagnosis Treatment Follow-up
Exclude
conditions
preventing
stones
Treatment with
bicarbonate,
alkine citrate,
vegetarian-
vegan diet
Exclude
Metabolic
alkalosis,
respiratory
acidosis
If none of the
previous
Adjust urinary
pH between 5,8
and 6,2 with
L-methionine
200-500mg TID

UROLITHIASIS - LIMITED UPDATE APRIL 2024 52
4.5.4 Summary of evidence and recommendation for the management of calcium phosphate Stones
Summary of evidence LE
Thiazide decreases calciuria. 1a
Recommendation Strength rating
Prescribe thiazide in case of hypercalciuria > 8 mmol/24 hours. Strong
4.6 Disorders and diseases related to calcium stones
4.6.1 Hyperparathyroidism [633-636]
Primary HPT is responsible for an estimated 5% of all calcium stone formation. Renal stones occur in
approximately 20% of patients with primary HPT. Elevated levels of PTH significantly increase calcium turnover,
leading to hypercalcemia, hypercalciuria, and bone disease. Serum calcium may be mildly elevated and serum
PTH may be within the upper normal limits, therefore, repeated measurements may be needed; preferably
with the patient fasting. Stones of HPT patients may contain both calcium oxalate and calcium phosphate.
Nephrocalcinosis and CKD may also occur.
If HPT is suspected, neck exploration should be performed to confirm the diagnosis. If surgery is
contraindicated, primary HPT can be treated with cinacalcet.
4.6.2 Granulomatous Diseases [637]
Granulomatous diseases, such as sarcoidosis, may be complicated by hypercalcemia and hypercalciuria
secondary to increased calcitriol production. The latter is independent of PTH control, leading to increased
calcium absorption in the gastrointestinal tract and suppression of PTH. Treatment focuses on the activity of
the granulomatous diseases and may require steroids, hydroxychloroquine, or ketoconazole. Treatment should
be reserved for a specialist.
4.6.3 Primary Hyperoxaluria [606]
Patients with primary hyperoxaluria (PH) should be referred to a specialised center, as successful management
requires an experienced interdisciplinary team. The main therapeutic aim is to reduce endogenous oxalate
production, which is increased in patients with PH. In approximately one-third of patients with PH type I,
pyridoxine therapy normalises or significantly reduces urinary oxalate excretion. The goal of adequate urine
dilution is achieved by adjusting fluid intake to 3.5-4.0 L/day in adults (children 1.5 L/m
2
body surface area) and
following a circadian drinking regimen.
Therapeutic options for preventing calcium oxalate crystallisation include hyper-diuresis, alkaline
citrates, magnesium, and Lumasiran, an RNAi agent, a new treatment for reducing the synthesis of oxalate of PH
type 1 [638].
Treatment regimens are:
• pyridoxine in PH type I: 5-20 mg/kg/day according to urinary oxalate excretion and patient tolerance;
• alkaline citrate: 3.25-9.75 g/day in adults, 0.1-0.15 mq/kg/day in children;
• magnesium: 200-400 mg/day (no magnesium in the case of renal insufficiency).
• Lumasiran: Subcutaneous injection with dose and timing adjusted according to body weight and duration
of treatment:
oInitial Dose: Bodyweight < 10 kg: 6 mg/kg; Bodyweight 10-20 kg: 6 mg/kg; Bodyweight > 20 kg: 3 mg/
kg; once per month for three months subcutaneous injection.
oMaintenance starting one month after initial doses: Bodyweight < 10 kg: 3 mg/kg 1-mal monthly;
Bodyweight 10-20 kg: 6 mg/kg every three months, Bodyweight > 20 kg: 3 mg/kg [639]

53UROLITHIASIS - LIMITED UPDATE APRIL 2024
4.6.3.1 Summary of evidence and recommendation for the management of primary hyperoxaluria
Summary of evidence LE
Pyridoxine can reduce the urinary oxalate excretion in primary hyperoxaluria type 1. 3
Lumasiran can reduce the urinary oxalate excretion in primary hyperoxaluria type 1. 1b
Recommendation Strength rating
Prescribe pyridoxine for primary hyperoxaluria type 1. Strong
Prescribe Lumasiran for primary hyperoxaluria type 1 if not responsive to pyridoxine.Strong
4.6.4 Enteric hyperoxaluria [575, 580, 640-642]
Enteric hyperoxaluria is a particularly problematic condition in patients with intestinal malabsorption of
fat. This abnormality is associated with a high risk of stone formation and is seen after intestinal resection
and malabsorptive bariatric surgery, as well as in Crohn’s disease and pancreas insufficiency. In addition to
hyperoxaluria, these patients usually present with hypocitraturia due to loss of alkali. Urine pH is usually low,
as are urinary calcium and urine volume. All these abnormalities contribute to high levels of supersaturation
with calcium oxalate, crystalluria, stone formation, and less frequently to nephrocalcinosis and CKD. Specific
preventive measures are:
• restricted intake of oxalate-rich foods [575] ;
• restricted fat intake [575];
• calcium supplementation at mealtimes to enable calcium oxalate complex formation in the intestine [580,
640-642];
• sufficient fluid intake to balance the intestinal loss of water caused by diarrhoea;
• alkaline citrates to raise urinary pH and citrate.
Summary of evidence LE
Alkaline citrates can be beneficial to replace citrate loss and raise urine pH. 3
Calcium supplements with meals enable calcium oxalate complex formation in the intestine.2b
Reduction in dietary fat and oxalate can be beneficial in intestinal malabsorption. 3
Recommendations Strength rating
Prescribe alkaline citrates for enteric hyperoxaluria. Weak
Advise patients to take calcium supplements with meals. Strong
Advise patients to follow a diet with a low fat and oxalate content. Weak
4.6.5 Renal tubular acidosis [557, 596, 643, 644]
Renal tubular acidosis is caused by severe impairment of proton (type I) or bicarbonate handling (type II) along
the nephron. Kidney stone formation occurs in patients with distal RTA type I. Figure 4.5 outlines the diagnosis
of RTA type I. Table 4.7 shows acquired and inherited causes of RTA.

UROLITHIASIS - LIMITED UPDATE APRIL 2024 54
Figure 4.5: Diagnosis of renal tubular acidosis
BGA = blood gas analysis; RTA = renal tubular acidosis.
** An alternative ammonium chloride loading test using 1-day NH4Cl load with 0.05 g/kg body weight might
provide similar results and may be better tolerated by the patient [645]. A second alternative in these cases could
be the furosemide/fludrocortisone acidification test [646].
Renal tubular acidosis can be acquired or inherited. Reasons for acquired RTA can be chronic obstructive
uropathy, recurrent pyelonephritis, acute tubular necrosis, renal transplantation, analgesic nephropathy,
sarcoidosis, Sjögren syndrome and other autoimmune diseases, medullary sponge kidney, liver cirrhosis,
sickle cell anaemia, idiopathic hypercalciuria, and primary parathyroidism; it may also be drug-induced (e.g.,
amphotericin B, foscarnet, lithium, zonisamide, and other carbonic anhydrase inhibitors).
Table 4.7: Inherited causes of renal tubular acidosis
Type - inheritance Gene/gene product/function Phenotype
Autosomal dominant SLC4A1/AE1/Cl-bicarbonate
exchanger
Hypercalciuria, hypokalaemia,
rickets/osteomalacia
Autosomal recessive with hearing
loss
ATP6V1B1/B1 sub-unit of vacuolar
H-ATPase/proton secretion
Hypercalciuria, hypokalaemia,
rickets/osteomalacia
Autosomal recessive ATP6V0A4/A4 sub-unit of vacuolar
H-ATPase/proton secretion
Hypercalciuria, hypokalaemia,
rickets/osteomalacia
Very rarely biallelic causative variants in FOXI1 and WDR72 genes have also been identified. The main
therapeutic aim of RTA treatment is restoring a normal acid-base equilibrium. Despite the alkaline pH of urine
in RTA, alkalinisation using alkaline citrates or sodium bicarbonate is important for normalising the metabolic
changes (intracellular acidosis) responsible for stone formation (Table 4.8) and bone demineralisation. The
alkali load reduces tubular re-absorption of citrate, which in turn normalises citrate excretion. Therapeutic
success can be monitored by venous blood gas analysis (base excess: ± 2.0 mmol/L) in complete RTA. If
Ammonium chloride 
loading test**
(NH4CI 0.1 g/kg body weight)
Except for patients with 
clinically confirmed 
metabolic acidosis
Urine pH < 5.4
RTA excluded
Urine pH > 5.4
RTA
Normal bicarbonate 
in BGA
RTA - incomplete
Urinary pH
constantly > 5.8
RTA Type I
possible
Low bicarbonate 
in BGA
RTA - complete
Diagnosis Treatment Follow-up

55UROLITHIASIS - LIMITED UPDATE APRIL 2024
excessive calcium excretion (> 8 mmol/day) persists after re-establishing acid-base equilibrium, thiazides may
lower urinary calcium excretion.
Table 4.8: Pharmacological treatment of renal tubular acidosis
Biochemical risk factor Indication for pharmacological
therapy
Medication
Hypercalciuria Calcium excretion > 8 mmol/dayHydrochlorothiazide*,
- in adults: 25 mg/day initially, up to
50 mg/day
- in children: 0.5-1 mg/kg/day
Alternatives in adults:
Chlorthalidone 25 mg/d
Indapamide 2.5 mg/d
Inadequate urine pH Citrate excretion male < 1.7 mmol/
day, female < 1.9 mmol/day
Alkaline citrate, 3.25-9.75 g/day
divided in three doses
OR
Sodium bicarbonate, 1.5 g, three
times daily
* Patients on hydrochlorothiazide should be advised to get their skin checked on a regular basis as they have
a higher risk of developing NMSC and some forms of melanoma. In patients with a history of skin cancer, the
indication treatment with hydrochlorothiazide should be thoroughly reviewed [621-623].
4.6.5.1 Summary of evidence and recommendations for the management of tubular acidosis
Summary of evidence LE
Alkaline citrates can be beneficial in distal renal tubular acidosis. 2b
Thiazides are beneficial for hypercalciuria. 1a
Recommendations Strength rating
Prescribe alkaline citrates for distal renal tubular acidosis. Strong
Address normalization of bicarbonatremia and citraturia with alkaline citrate Strong
Prescribe thiazides for hypercalciuria. Strong
4.6.6 Nephrocalcinosis [647]
Nephrocalcinosis (NC) refers to increased calcium crystal deposition within the renal cortex or medulla and
occurs alone or in combination with renal stones. There are various metabolic causes. The main causes
are HPT, primary and enteric hyperoxalurias, genetic and acquired RTA, medullary sponge kidney, vitamin D
metabolic disorders, sarcoidosis, idiopathic hypercalciuria and hypocitraturia, and genetic disorders, including
Dent’s disease and Bartter’s syndrome. The many causes of NC mean there is no single standard therapy.
Therapeutic attention must focus on the underlying metabolic or genetic disease, on the frequent association
with CKD while minimising the biochemical risk factors.
4.6.6.1 Diagnosis
Diagnosis requires the following blood analysis: PTH (in the case of increased calcium levels), vitamin D and
metabolites, vitamin A, sodium, potassium, magnesium, chloride, and bicarbonate. Urinalysis should investigate
urine pH profile at different times of the day daily urine volume, specific weight of urine, and levels of calcium,
oxalate, phosphate, uric acid, magnesium, and citrate [545].
4.7 Uric acid and ammonium urate stones
All uric acid and ammonium urate stone formers are considered to be at high risk of recurrence [23]. Uric acid
nephrolithiasis is responsible for approximately 10% of renal stones [648] and is associated with hyperuricosuria or
low urinary pH. Hyperuricosuria may be a result of dietary excess, endogenous overproduction (enzyme defects),
myeloproliferative disorders, chemotherapy drugs, gout or catabolism [542]. Low urinary pH may be caused by
decreased urinary ammonium excretion (insulin resistance, gout, Autosomal dominant polycystic kidney disease
[ADPKD]), increased endogenous acid production (insulin resistance, metabolic syndrome, or exercise-induced
lactic acidosis), increased acid intake (high animal protein intake), or increased base loss (diarrhoea) [542].

UROLITHIASIS - LIMITED UPDATE APRIL 2024 56
Ammonium urate stones are extremely rare, comprising < 1% of all types of urinary stones. They are
associated with UTI, malabsorption (inflammatory bowel disease and ileostomy diversion or laxative abuse),
phosphate deficiency, hypokalemia, and malnutrition. Suggestions on uric acid and ammonium urate
nephrolithiasis are based on level 3 and 4 evidence. Chronic kidney disease is frequently observed.
4.7.1 Diagnosis
Figure 4.6 shows the diagnostic algorithm for uric acid stones and figure 4.7 shows the therapeutic algorithm
for uric acid and ammonium urate stones. Blood analysis requires measurement of creatinine and uric acid
levels. Urinalysis requires measurement of urine volume, urine pH, specific weight of urine, and uric acid level.
Urine culture is needed in the case of ammonium urate stones.
4.7.2 Interpretation of results
Uric acid and ammonium urate stones form under completely different biochemical conditions. Low urine pH
promotes uric acid crystallisation.
Hyperuricosuria is defined as uric acid excretion > 4 mmol/day and day and > 5 mmol/day in adult females and
males, respectively, or > 0.12 mmol/kg/day in children. Hyperuricaemia may be present, but there is only weak
evidence for its association with stone formation [649].
Hyperuricosuric calcium oxalate stone formation can be distinguished from uric acid stone formation by
urinary pH, which is usually > 5.5 in calcium oxalate stone formation and < 5.5 in uric acid stone formation
and occasional absence of hyperuricosuria in patients with pure uric acid stones [650, 651]. Ammonium urate
crystals form in urine at pH > 6.5, high uric acid concentration in urine when ammonium is present [652, 653].
4.7.3 Specific treatment
General preventive measures are recommended for fluid intake and diet. Hyperuricosuric stone formers benefit
from purine reduction in their daily diet. Figure 4.6 describes pharmacological treatment [23, 648, 650-660]. For
uric acid stones, allopurinol may change the stone composition distribution in patients with gout to a pattern
similar to that in stone formers without gout [661].
Figure 4.6: Diagnostic algorithm for uric acid stones
ADPKD = autosomal dominant polycystic kidney disease; G6P = glucose-6 phosphate dehydrogenase; HGPT
= hypoxanthine guanine phosphoribosyl transferase; PRPS = phosphoribosyl-pyrophosphate synthetase
superactivity; XO = xanthine oxidase.

Hyperuricosuria Low urinary pH Low urine volume
Uric Acid Nephrolithiasis
1) Gout
2) High dietary purine
intake
3) Myeloproliferative
disorders
4) Haemolytic
anaemia
5) Chemotherapy-
induced tumour lysis
1) HGPT
deficiency
2) PRPS
overactivity
3) G6P
deficiency
4) XO
deficiency
1) Insulin
resistance
2) Gout
3) ADPKD
1) Insulin
resistance
2) Metabolic
syndrome
Exercise-induced
Lactic Acidosis
1) Probenecid
2) High-dose
salicylates
3) Radiocontrast
agents
4) Losartan
Uricosuric drugs
Urate over-
production
URAT 1
mutations
Hypouricemic
hyperuricosuria
High animal-
protein intake
Enzymatic
deficiencies
Increased acid
intake
Increased
base loss
Decreased
urinary
ammonium
excretion
Increased
endogenous acid
production
Chronic Dehydration
Excessive Respiration /
Exercise
Chronic Diarrhoea
Diarrhoea
Diagnosis Treatment Follow-up

57UROLITHIASIS - LIMITED UPDATE APRIL 2024
Figure 4.7: Therapeutic algorithm for uric acid- and ammonium urate stones
1
d: day.
2
tid: three times a day.
3
A higher pH may lead to calcium phosphate stone formation.
4
In patients with high uric acid excretion, allopurinol may be helpful.
4.7.4 Summary of evidence and recommendations for the management of uric acid- and ammonium urate
stones
Summary of evidence LE
Alkaline citrates can be beneficial to alkalinise the urine in uric acid stone formers. 3
Allopurinol can be beneficial in hyperuricosuric urate stone formers. 1b
Recommendations Strength rating
Prescribe alkaline citrates to alkalinise the urine in uric acid stone formers. Strong
Prescribe allopurinol in hyperuricosuric urate stone formers. Strong
4.8 Struvite and infection stones
All infection-stone formers are deemed at high risk of recurrence. Struvite stones represent 2-15% of the stones
sent for analysis. Stones that contain struvite may originate de novo or grow on pre-existing stones, which are
infected with urea-splitting bacteria [662]. There are several factors predisposing patients to struvite stone
formation (Table 4.9) [663]. Several studies have reported that urinary metabolic alterations can be disclosed in
36-81% of patients with mixed struvite stones [664-669].
Uric acid- and urate-
containing stones
Ammonium
urate stones
Urate acid stone
Basic evaluation  Basic evaluation
"Uric acid arrest"
Urine pH < 6
Alkaline citrate
3-10 g/d
1
or
Sodium
bicarbonate
1.5 g tid
2
Urine
pH > 6.5
Hyperuricosuria
Allopurinol
100 mg/d
Antibiotics
Correction
of factors
predisposing
amm.urate 
stone
formation
4
Allopurinol
100-300 mg/d
Dose depends 
on targeted
urine pH
Chemolitholysis
urine pH 6.5-7.2
3
Prevention
urine pH 6.2-6.8
> 4.0 mmol/d
> 4.0 mmol/d
and
Hyperuricaemia
> 380 mol
UTI 
L-methionine
200-500 mg tid
Target urine-pH
5.8-6.2
Diagnosis Treatment Follow-up

UROLITHIASIS - LIMITED UPDATE APRIL 2024 58
4.8.1 Diagnosis
Blood analysis requires measurement of creatinine, and urinalysis requires repeat urine pH measurements and
urine culture. In cases of mixed struvite stones, the search for metabolic abnormalities in 24-hour urine after
stone removal and infection control is suggested.
4.8.2 Interpretation
Infection stones contain the following minerals: struvite and/or carbonate apatite and/or ammonium urate.
Urine culture typically provides evidence for urease-producing bacteria, which increase ammonia ions and
develop alkaline urine (Table 4.10). Carbonate apatite starts to crystallise at a urine pH level of 6.8. Struvite only
precipitates at pH > 7.2 [670, 671]. A mixed struvite stone, i.e., containing a high percentage of calcium oxalate
and carbonate apatite, suggests the over-infection of a “metabolic” calcium oxalate or calcium phosphate stone
[669]. Proteus mirabilis accounts for more than half of all urease positive UTIs [672, 673].
4.8.3 Specific treatment
General preventive measures are recommended for fluid intake and diet. Specific measures include complete
surgical stone removal [663], short- or long-term antibiotic treatment [674], and urinary acidification using
methionine [602] or ammonium chloride [675]. For persistent infections/colonisation, acetohydroxamic acid may
be an option [676, 677] (Figure 4.8); however, it is not licensed/available in all European countries.
Eradication of infection after complete stone removal is desirable. The evidence regarding the
duration of post-operative antibiotic administration is inconclusive.
Summary of evidence LE
Removing the stone material as completely as possible with surgery can reduce ongoing infection.3
Antibiotics are beneficial after complete stone removal. 3
Ammonium chloride, 1 g, two or three times daily, can ensure urinary acidification to prevent recurrent
infection.
3
Methionine, 200-500 mg, one to three times daily, can be used as an alternative to ammonium chloride,
to ensure urinary acidification.
3
Treatment of underlying metabolic abnormalities reduces recurrence of mixed struvite stones.3
Urease inhibitors in case of severe infection are occasionally used (if licensed). 1b
Recommendations Strength rating
Surgically remove the stone material as completely as possible. Strong
Prescribe antibiotics in case of persistent bacteriuria. Strong
Prescribe ammonium chloride, 1 g, two or three times daily to ensure urinary acidification.Weak
Prescribe methionine, 200-500 mg, one to three times daily, as an alternative, to ensure
urinary acidification.
Weak
Table 4.9: Factors predisposing to struvite stone formation.
• Neurogenic bladder
• Spinal cord injury/paralysis
• Continent urinary diversion
• Ileal conduit
• Foreign body
• Stone disease
• Indwelling urinary catheter
• Urethral stricture
• Benign prostatic hyperplasia
• Bladder diverticulum
• Cystocele
• Calyceal diverticulum
• UPJ obstruction
Table 4.10: Most important species of urease-producing bacteria
Obligate urease-producing bacteria (> 98%)
• Proteus spp.
• Providencia rettgeri
• Morganella morganii
• Corynebacterium urealyticum
• Ureaplasma urealyticum

59UROLITHIASIS - LIMITED UPDATE APRIL 2024
Facultative urease-producing bacteria
• Enterobacter gergoviae
• Klebsiella spp.
• Providencia stuartii
• Serratia marcescens
• Staphylococcus spp.
CAUTION:  0-5% of Escherichia coli, Enterococcus spp. and Pseudomonas aeruginosa strains may produce
urease.
Figure 4.8: Diagnostic and therapeutic algorithm for infection stones.
1
Discussed with uric acid stones.
2
Acetohydroxamic acid.
* When nationally available.
bid = twice a day; tid = three times a day; AHA = acetohydroxamic acid.
4.9 Cystine stones
Cystine stones account for 1-2% of all urinary stones in adults and 6-8% of the stones reported in paediatric
studies [678, 679] . All cystine stone formers are deemed at high risk of recurrence and CKD [680, 681].
4.9.1 Diagnosis
Blood analysis includes measurement of creatinine, and urinalysis includes measurement of urine volume, pH
profile, specific weight, and cystine. Since the disease may be asymptomatic, siblings of cystinuric patients
should be investigated for cystinuria [682] .
Interpretation
• Cystine is poorly soluble in urine and crystallises spontaneously within the physiological urinary pH range.
• Cystine solubility depends strongly on urine pH: at pH 6.0, the limit of solubility is 1.33 mmol/L.
Infection stones
(Struvite carbon apatite
Ammonium urate
1
)
Urease
producing
bacteria
Treatment
Urinary pH
(Carbon apatite > 6.8
Struvite > 7.2)
Short or
long course
Percutaneous
chemolysis may
be a useful
adjunct
Ammonium
chloride
1 g bid or tid
Methionine
200-500 mg
1-3 times/d
AHA
2
15 mg/kg/day
Antibiotics
Complete
surgical
removal
is mandatory
Urease
inhibition*
Urine
acidification
Basic evaluation
Diagnosis Treatment Follow-up

UROLITHIASIS - LIMITED UPDATE APRIL 2024 60
• Routine analysis of cystine is not suitable for therapeutic monitoring.
• Regardless of the phenotype or genotype of the cystinuric patient, the clinical manifestations are the same
[683].
• There is no role for genotyping patients in the routine management of cystinuria [684, 685] .
• Reductive therapy targets the disulphide binding in the cystine molecule. For therapy monitoring, it is
important to differentiate between cystine, cysteine, and drug-cysteine complexes. However, available
methods to monitor cystinuria treatment which may be able to differentiate between the different
complexes formed by therapy are cumbersome [686, 687] non accurate, including high-performance liquid
chromatography (HPLC) [63].
• Quantitative 24-hour urinary cystine excretion confirms the diagnosis in the absence of stone analysis.
• Levels above 0.125 mmol/day (30 mg/day) are considered abnormal [688, 689].
4.9.2 Specific treatment
General preventative measures for fluid intake and diet are recommended. A diet low in methionine may
theoretically reduce urinary excretion of cystine; however, patients are unlikely to comply sufficiently with such
a diet. A restricted intake of sodium is more easily achieved and is more effective in reducing urinary cystine.
Patients are usually advised to avoid sodium consumption > 2 g/day (5 g NaCl) [690]. A high level of diuresis
is of fundamental importance, aiming for a 24-hour urine volume of > 3 L [683, 690-692]. A considerable fluid
intake evenly distributed throughout the day is necessary.
4.9.2.1 Pharmacological treatment of cystine stones
The main therapeutic option for avoiding cystine crystallisation is to maintain urine pH > 7.5, to improve cysteine
solubility, and ensure appropriate hydration with a minimum of >3 L/day in adults, or 1.5 L/m2 body surface
area in children [683, 690-692]. Home monitoring of the urine pH is suggested because of the possibility of self-
adjusting alkaline treatment keeping the urine pH within range [63].
Free cystine concentration can be decreased by reductive substances, which act by splitting the
disulphide binding of cystine.
Tiopronin is currently the best choice for cystine reduction. However, side effects often lead to
treatment termination, for example when nephrotic syndrome develops or when there is poor compliance,
especially with long-term use. After carefully considering the risk of early tachyphylaxis, putting into place a dose-
escape phenomenon for long-term use, and recurrence risk, tiopronin is recommended at cystine levels > 3.0
mmol/day (720 mg/day) or in the case of recurring stone formation, notwithstanding other preventive measures
[683, 690-692]. Spot measurement of urine protein should be performed at baseline and during follow-up.
Figure 4.9: Metabolic management of cystine stones [693]
Cystine Stones
Basic evaluation
Appropriate hydration with
> 3.5 L/d in adults and
1.5 L/m
2
body surface in
children
and
adjust urine pH
between 7.5 and 8.0
with
alkaline citrates or
sodium bicarbonate
Cystine excretion
< 3 mmol/d
Cystine excretion
> 3 mmol/d
Possible add. treatment
with tiopronin
(depending on recurrence)
Additional treatment with
tiopronin 250 mg/d up to
2,000 mg/d max. dos.
Diagnosis Treatment Follow-up

61UROLITHIASIS - LIMITED UPDATE APRIL 2024
4.9.3 Summary of evidence and recommendations for the management of cystine stones
Summary of evidence LE
Increasing fluid intake so that 24-hour urine volume exceeds 3 L is used to dilute the cystine.3
Alkaline citrates 3-10 mmol two or three times daily can be used to achieve pH > 7.5. 3
Tiopronin, 250-2,000 mg/day can be used to reduce stone formation in patients with cysteine excretion,
> 3 mmol/day, or when other measures are insufficient.
3
Recommendations Strength rating
Therapeutic measures
Urine dilution
Advise patients to increase their fluid intake so that 24-hour urine volume exceeds 3 L.
Strong
Alkalinisation
Prescribe potassium citrate 3-10 mmol two or three times daily, to achieve pH > 7.5
Strong
Complex formation with cystine
For patients with cystine excretion, > 3 mmol/day, or when other measures are insufficient:
prescribe in addition to other measures tiopronin, 250-2,000 mg/day.
Strong
4.10 2,8-Dihydroxyandenine stones and xanthine stones
All 2,8-Dihydroxyadenine and xanthine stone formers are at high risk of recurrence. Both stone types are rare.
Diagnosis and specific prevention are similar to those for uric acid stones [23].
4.10.1 2,8-Dihydroxyadenine stones
A genetically determined defect of adenine phosphoribosyl transferase causes high urinary excretion of poorly
soluble 2,8-Dihydroxyadenine [694]. High-dose allopurinol or febuxostat are important options but should be
given with regular monitoring [695] .
4.10.2 Xanthine stones
Patients who form xanthine stones usually show decreased levels of serum uric acid. There is no available
pharmacological intervention.
4.10.3 Fluid intake and diet
Recommendations for general preventive measures apply. Pharmacological intervention is difficult; therefore,
high fluid intake ensures optimal specific weight levels of urine < 1.010 (urine specific gravity). A purine-reduced
diet decreases the risk of spontaneous crystallisation in urine.
4.11 Drug-induced stones
Drug stones are induced by pharmacological treatment [587, 696] (Table 4.11). Two types exist:
• stones formed by crystallised compounds of the drug;
• stones formed due to unfavourable changes in urine composition under drug therapy.
Table 4.11: Compounds that cause drug stones.
Active compounds crystallising in urine Substances impairing urine composition
• Allopurinol/oxypurinol
• Amoxicillin/ampicillin
• Ceftriaxone
• Quinolones
• Ephedrine
• Indinavir and other HIV-protease inhibitors
• Magnesium trisilicate
• Sulphonamides
• Triamterene
• Acetazolamide
• Aluminium magnesium hydroxide
• Ascorbic acid
• Calcium
• Laxatives
• Losartan
• Methoxyflurane
• Orlistat
• Vitamin D
• Topiramate
• Zonisamide

UROLITHIASIS - LIMITED UPDATE APRIL 2024 62
4.12 Matrix Stones
Pure matrix stones are extremely rare with less than 70 cases described in the literature. They are more
prevalent in females. The main risk factors are recurrent UTIs, especially due to P. mirabilis or E. coli, previous
surgery for stone disease, chronic renal failure, and haemodialysis. Complete endourological removal, frequently
via the percutaneous approach, is critical. Given the rarity of matrix calculi a specific prophylactic regimen to
minimise recurrence cannot be recommended. Eliminating infections and prophylactic use of antibiotics are
most commonly proposed [697].
4.13 Unknown stone composition [16]
An accurate medical history is the first step towards identifying risk factors as summarised in sections 3.1.3 and
4.13.1 and Fig. 4.1.
Diagnostic imaging begins with a US examination of both kidneys to establish whether the patient is stone-free.
Stone detection by the US should be followed by KUB and unenhanced multislice CT in adults to differentiate
between calcium-containing and non-calcium stones.
Blood analysis may demonstrate severe metabolic and organic disorders, such as renal insufficiency,
HPT or other hypercalcaemic states and hyperuricaemia. In children with GFR lower than 30 ml/min, oxalaemia
should also be checked.
Urinalysis is performed routinely with a dipstick test as described above. A urine culture is required
if there are signs of infection. Urine pH < 5.5 in 24-hour urine collection indicates hyper-acidic urine, which could
promote uric acid crystallisation. Urine pH > 6.2 in 24-hour urine collection may indicate RTA if UTI is excluded
[642, 644].
Microscopy of urinary sediment can help to discover rare stone types because crystals of
2,8-dihydroxyadenine, cystine, and xanthine are pathognomonic for the corresponding disease. In cases in
which the presence of cystine is doubtful, a cyanide nitroprusside colorimetric qualitative test can be used to
detect the presence of cystine in urine, with a sensitivity of 72% and specificity of 95%. False-positive results
are possible in patients with Fanconi’s syndrome or homocystinuria or in those taking various drugs, including
ampicillin or sulfa-containing medication [698, 699].
Following this programme, the most probable stone type can be assumed, and specific patient
evaluation can follow. Further metabolic investigations will depend on the presence of risk factors
(see section 3.1.3) and on the results of previous investigations. However, if any expulsed stone material is
available, it should be analysed for diagnostic confirmation or correction.
4.13.1 Recommendations for investigations for the assessment of patients with stones of unknown
composition [17, 23, 62, 587]
Recommendations Strength rating
Investigation Rationale for investigation
Take a medical history • Stone history (former stone events, family history)
• Dietary habits
• Medication chart
Strong
Perform diagnostic imaging • Ultrasound in the case of a suspected stone
• Un-enhanced helical computed tomography
•  Determination of Hounsfield units provides
information about the possible stone composition
Strong
Perform a blood analysis • Creatinine
• Calcium (ionised calcium or total calcium + albumin)
• Uric acid
Strong
Perform a urinalysis • pH measurement
•  Dipstick test: leukocytes, erythrocytes, nitrites
• Protein, specific weight
• Urine cultures
• Microscopy of urinary sediment (morning urine)
• Cyanide nitroprusside test (cystine exclusion)

Further examinations depend on the results of the
investigations listed above.
Strong

63UROLITHIASIS - LIMITED UPDATE APRIL 2024
5. FOLLOW-UP OF URINARY STONES
There is no consensus in the urological literature on whether, when, how, and how often stone patients should
be followed up after definitive treatment (extracorporeal shock wave lithotripsy, ureteroscopy, percutaneous
nephrolithotripsy, medical chemoprophylaxis). This is mainly attributed to the high heterogeneity of stone
disease among patients and to the lack of comparative studies regarding follow-up versus no follow-up.
The EAU Urolithiasis Guidelines Panel performed a systematic review questioning the benefits and harms of
scheduled imaging and metabolic follow-up for patients who underwent definitive treatment for upper urinary
tract stone disease [411] . Based on the results a consensus was reached regarding the frequency of the follow-
up for stone-free patients (the general population and the high-risk patients), patients with residual fragments ≤
4 mm, and patients with residual fragments > 4 mm (Figures 5.1 and 5.2).
Stone-free patients could be discharged after two years (radiopaque stones) or after three years (radiolucent
stones) as 80% of them will remain stone-free thereafter. Increasing the safety margin for remaining stone-
free up to 90%, the patients should be followed up to five years. Most stone-free patients in the general
population remained stone-free during the first year, while < 40% of patients with metabolic abnormalities not
on medication remained stone-free after three years of follow-up. Therefore, a more extensive follow-up is
proposed for patients with metabolic abnormalities.
Patients with fragments ≤ 4 mm showed a spontaneous expulsion rate of 17.9-46.5% during the first year. At
49 months of follow-up disease progression rate was 9-34%, the intervention rate 17-29%, and the spontaneous
passage rate 21-34%.
Patients with residual stone fragments > 4 mm had only 9% of spontaneous expulsion at three years. These
patients should be offered further definitive treatment since intervention rates are high (24-100%). For those on
follow-up close surveillance is needed.
Insufficient data exist for high-risk patients, but current literature dictates that patients who are adherent to
targeted medical treatment seem to experience less stone growth or re-growth of residual fragments and may
be discharged after 36-48 months of non-progressive disease on imaging (Figure 5.1).
Proposed imaging consists of plain X-ray KUB and/or US, based on stone characteristics and clinicians’
preferences. Computed tomography scan should be reserved for symptomatic disease or pre-operative imaging,
to avoid extensive radiation exposure [411].
The information on stone composition can be used to counsel patients to set expectations and help plan the
need for follow up and medical stone management [700].

UROLITHIASIS - LIMITED UPDATE APRIL 2024 64
Figure 5.1: Follow-up duration of Urinary stone patients after treatment.
* Not enough data about subgroup analysis of radiolucent and radiopaque stones.
**According to patient preference or symptomatic disease.
***Patients with diagnosed metabolic abnormalities.
****Lifelong follow-up is advised but data are available for up to ten years.
Stone free patientsHigh-risk patients***
Patients with residual
fragments
Follow-up of stone-disease
patients after treatment
80% "safety margin"
2 years X-ray
Follow-up for
radiopaque
stones
80% "safety margin"
3 years X-ray +/- US
Follow-up for
radiolucent stones
≤ 4 mm or dust
Follow-up for 4
years or
intervention**
On medical treatment
Follow-up for 4 years
and consider discha rge
for non-progressive
disease
Not on medical
treatment
Follow-up for at least 4
years - strongly consider
follow-up until 10 years
due to high-risk of
recurrence****
90% "safety margin"
Follow-up for 5
years*
> 4 mm
Schedule
re-intervention
Diagnosis
Treatment
Follow-up

65UROLITHIASIS - LIMITED UPDATE APRIL 2024
Figure 5.2: Consensus on follow-up frequency and imaging modality to use after treatment
Stone free = No stone fragments on postoperative imaging (i.e. no stone fragments on CT/KUB/US).
High-Risk = Known biochemical abnormality (i.e.: hypercalciuria, hypocitraturia, hyperuricosuria, RTA, or high-risk
stone type such as struvite [See table 3.6]).
Imaging = plain film KUB &/or kidney ultrasonography (KUS) based on clinicians’ preference and stone
characteristics. Consider CT if the patient is symptomatic or if intervention is planned.
* Clinicians may choose the imaging-only pathway in patients with fragments ≤ 2 mm.
a Treatment monitoring for side effects, intolerance, and compliance.
+ Panel recommends reintervention however close follow up may be considered for some patients at high risk for
reintervention based on clinicians’ preference.
Counsel on
imaging  vs.
discha rge
ImagingImaging
ImagingImagingImagingImagingImagingImagingImagin g
ImagingImagingImagingImagin g
X
X
ImagingImagingX
X
Counsel on
imaging  vs.
discha rge
Counsel on
imaging  vs.
discha rge
Imaging
+
Metabolic
+
Treatment
monitoring
a
Imagin g
+
Metabolic
+
Treatment
monitoring
a
Imaging
+
Metabolic
+
Treatment
monitoring
a
Imaging
+
Metabolic
+
Treatment
monitoring
a
Imaging
+
Metabolic
+
Treatment
monitoring
a
Imagin g
+
Metabolic
+
Treatment
monitoring
a
6
Months
12
Months
18
Months
24
Months
36
Months
48
Months
60
Months
Follow-up
afer
treatment
Stone-free
Residual
fragments
Fragments
> 4mm
+
Fragments
≤ 4mm*
High-ris k
General
population
High-ris k
Low-risk
Diagnosis
Treatment
Follow-up

UROLITHIASIS - LIMITED UPDATE APRIL 2024 66
6. BLADDER STONES
6.1 Prevalence, aetiology, and risk factors of bladder stones
Bladder stones constitute only approximately 5% of all urinary tract stones [701] yet are responsible for 8% of
urolithiasis-related mortalities in developed nations [702]. The incidence is higher in developing countries [703].
The prevalence of bladder stones is higher in males, with a reported male-to-female ratio between 10:1 and 4:1
[704, 705]. The age distribution is bimodal: incidence peaks at three years in children in developing countries
[704, 706], and 60 years in adulthood [705].
The aetiology of bladder stones is typically multi-factorial [705]. Bladder stones can be classified as primary,
secondary, or migratory [707] .
Primary or endemic bladder stones occur in the absence of other urinary tract pathology, typically seen in
children in areas with poor hydration, recurrent diarrhoea, and a diet deficient in animal protein [708].
Secondary bladder stones occur in the presence of other urinary tract abnormalities, which include bladder
outlet obstruction (BOO), neurogenic bladder dysfunction, chronic bacteriuria, foreign bodies (including
catheters), bladder diverticula, and bladder augmentation or urinary diversion. In adults, BOO is the most
common predisposing factor for bladder stone formation and accounts for 45-79% of vesical calculi [705, 709-
712].
Migratory bladder stones are those that have passed from the upper urinary tract where they formed and may
then serve as a nidus for bladder stone growth. Patients with bladder calculi are more likely to have a history of
upper tract stones and risk factors for their formation [713].
A wide range of metabolic urinary abnormalities can pre-dispose to calculi anywhere in the urinary tract, which
is covered in more detail in Section 4. Metabolic Evaluation and Recurrence Prevention. There is a paucity of
studies on the specific metabolic abnormalities that predispose to bladder stones.
Bladder stones will form in 3-4.7% of men undergoing surgery for benign prostatic obstruction (BPO) [714, 715],
19-39% and 36-67% of motor-incomplete and motor-complete spinal cord injury patients, respectively [716], and
2.2% of patients with long-term catheters [717]. Two research groups have identified that a larger intravesical
protrusion of the prostrate is an independent risk factor for bladder stone formation in patients with BPH
undergoing TURP [718, 719]. Kim and colleagues additionally found older age and a lower Qmax to be predictive
of bladder stones [718] .
In men with chronic urinary retention secondary to BPO, the 24-hour urine of 27 men with bladder stones had
a higher uric acid supersaturation (2.2 vs. 0.6 mmol/L, p < 0.01), lower magnesium (106 vs. 167 mmol/L, p =
0.01) and lower pH (5.9 vs. 6.4, p = 0.02) than the 21 men without bladder stones [713]. It is therefore likely
that patients with these conditions who form bladder stones also have an abnormal urine composition which
predisposes them to bladder stone formation.
The metabolic abnormalities which predispose patients to form secondary bladder stones are poorly
understood. Stone analysis of 86 men with a BPO-related bladder stone demonstrated that 42% had calcium-
based stones (oxalate, phosphate), 33% had magnesium ammonium phosphate, 10% had mixed stones and 14%
had urate stones [705]. Similar findings were reported in more recent studies [720-722] and it is therefore likely
that multiple metabolic factors predispose patients to secondary bladder stone formation.
Low urine volume (poor hydration) is the most consistently demonstrable abnormality [723-725].
As an outlet obstruction is more often absent in children than in adults, the aetiology is most likely quite
different in this population. Twenty-four-hour urine analysis in children with endemic bladder stones is reported
in two studies. Of 57 children in Pakistan, 89.5% had hypocitraturia, 49% had a low urine volume, 44% had
hyperoxaluria and 42% had hypocalciuria [723]. Of 61 children in India, stone formers had higher urine calcium
and uromucoid concentrations than controls [724]. One study from Thailand compared 24-hour urine analyses
from children from a rural area with a high prevalence of bladder stones with those from an urban area: rural
children had lower urine volumes and, despite equal calcium, oxalate, and uric acid concentrations, crystalluria
with uric acid and calcium oxalate crystals was more prevalent in rural children [725].

67UROLITHIASIS - LIMITED UPDATE APRIL 2024
Table 6.1 Bladder stones classified by aetiology.
Type of bladder stonePrimary Secondary Migratory
Cause/Associations Occur in the absence
of other urinary tract
pathology, typically in
children in areas with
poor hydration, recurrent
diarrhoea, and a diet
deficient in animal protein
BOO (e.g., BPO, urethral
stricture)
Form in the upper urinary
tract, then passed into
the bladder where they
may be a nidus for stone
growth
Neurogenic bladder
dysfunction
Chronic bacteriuria
Foreign bodies (including
catheters)
Bladder diverticula
Bladder augmentation
Urinary diversion
BOO = Bladder Outlet Obstruction; BPO = Benign Prostatic Obstruction.
6.2 Presentation
The symptoms are most associated with bladder stones are urinary frequency, haematuria (which is typically
terminal) and dysuria or suprapubic pain, which are worst towards the end of micturition. Sudden movement
and exercise may exacerbate these symptoms. Detrusor over-activity is found in over two-thirds of adult male
patients with vesical calculi and is significantly more common in patients with larger stones (> 4 cm). However,
recurrent UTIs may be the only symptom [710, 711] .
In children, symptoms may also include pulling of the penis, difficulties in micturition, urinary retention, enuresis,
and rectal prolapse (resulting from straining due to bladder spasms). Bladder stones may also be an incidental
finding in 10% of cases [708, 726].
6.3 Diagnostic evaluation
6.3.1 Diagnostic investigations for bladder stones
Plain X-ray of KUB has a reported sensitivity of 21%-78% for cystoscopically detected bladder stones in adults
[710, 727]. Larger (> 2.0 cm) stones are more likely to be radiopaque [727]. However, plain X-ray provides
information on radio-opacity which may guide treatment and follow-up (see Section 3.2.3 X-ray characteristics,
for further information).
Ultrasound has a reported sensitivity and specificity of 20-83% and 98-100%, respectively for the detection
of bladder stones in adults [728, 729]. Computed tomography and cystoscopy have a higher sensitivity for
detecting bladder stones than US or X-ray in adults [728, 729]. No study compares cystoscopy and CT for the
diagnosis of bladder stones. Cystoscopy has the advantage of detecting other potential causes for a patient’s
symptoms (e.g., bladder cancer), whilst CT can also assess upper tract urolithiasis (see also section 3.2.3 X-ray
characteristics) [730].
There is a paucity of evidence for the investigation of bladder stones, particularly in children [83, 731]. See also
Section 3.3 Diagnostic evaluation, for further information on diagnostic imaging for urolithiasis. The principle of
ALARA should be applied, especially in children [732].
6.3.2 Diagnosing the cause of bladder stones
The cause of the bladder stone should be considered prior to bladder stone treatment as eliminating the
underlying cause will reduce recurrence rates [733]. The following should be performed where possible prior to
(or at the time of) bladder stone treatment:
• physical examination of external genitalia, and peripheral nervous system (including digital rectal
examination, peri-anal tone, and sensation in men);
• uroflowmetry and post-void residual urine assessment;
• urine dipstick to include pH ± culture;
• metabolic assessment (see also section 3.3.2.3) including: serum (creatinine, (ionised) calcium, uric acid,
sodium, potassium, blood cell count);
• urine pH;
• stone analysis: in first-time formers using a valid procedure (X-ray diffraction or infrared spectroscopy).

UROLITHIASIS - LIMITED UPDATE APRIL 2024 68
The following investigations should also be considered for selected patients:
• upper tract imaging (in patients with a history of urolithiasis or loin pain);
• cysto-urethroscopy or urethrogram.
6.4 Disease Management
6.4.1 Conservative treatment and Indications for active stone removal
Migratory bladder stones in adults may typically be left untreated, especially asymptomatic small stones. Rates
of spontaneous stone passage are unknown, but data on ureteric stones suggest stones < 1 cm are likely to
pass in the absence of BOO, bladder dysfunction, or long-term catheterisation (see section 3.4.9 Specific stone
management of ureteral stones).
Primary and secondary bladder stones are usually symptomatic and are unlikely to pass
spontaneously: active treatment of such stones is therefore indicated.
6.4.2 Medical management of bladder stones
There is a paucity of evidence on chemolitholysis of bladder stones. However, guidance on the medical
management of urinary tract stones in section 3.4.9 Specific stone management of ureteral stones, can be
applied to urinary stones in all locations. Uric acid stones can be dissolved by oral urinary alkalinisation when a
PH > 6.5 is consistently achieved, typically using alkaline citrate or sodium bicarbonate. Regular monitoring is
required during therapy (see section 3.4.4 Chemolysis). Irrigation chemolysis is also possible using a catheter;
however, this is time-consuming may cause chemical cystitis and is therefore not commonly employed [734,
735].
6.4.3 Bladder stone interventions
Minimally invasive techniques for the removal of bladder stones have been widely adopted to reduce the risk
of complications and shorten hospital stay and convalescence. Bladder stones can be treated with open,
laparoscopic, robotic-assisted laparoscopic, endoscopic (transurethral or percutaneous) surgery or ESWL [736] .
6.4.3.1 Suprapubic cystolithotomy
Open suprapubic cystolithotomy is very effective but is associated with a need for catheterisation and longer
hospital stay in both adults and children compared to all other stone removal modalities [736]. In children, a
non-randomised study found that, if the bladder was closed meticulously in two layers, “tubeless” (drain-less
and catheter-less) cystolithotomy was associated with a significantly shorter length of hospital stay compared
with traditional cystolithotomy, without significant differences regarding late or intra-operative complications
provided that children with prior UTI, recurrent stones, or with previous surgery for anorectal malformation (or
other relevant surgery) were excluded [737].
6.4.3.2 Transurethral cystolithotripsy
In both adults and children, transurethral cystolithotripsy provides high SFRs and appears to be safe, with a very
low risk of unplanned procedures and major post-operative and late complications [736].
6.4.3.2.1 Transurethral cystolithotripsy in adults
In adults, a meta-analysis of four RCTs including 409 patients demonstrated that transurethral cystolithotripsy
has a shorter hospital stay and convalescence with less pain, but equivalent SFR and complications compared
to percutaneous cystolithotripsy [736]. Transurethral cystolithotripsy with a nephroscope was quicker than
percutaneous cystolithotripsy in three RCTs, although transurethral cystolithotripsy with a cystoscope was
slower than percutaneous cystolithotripsy [736].
Rates of urethral strictures following transurethral procedures were not robustly reported: studies report rates
between 2.9% and 19.6% during a follow up period of 12 – 24 months [720, 736, 738] .
One small RCT demonstrated a shorter duration of catheterisation, hospital stay and procedure with
transurethral cystolithotripsy than open cystolithotomy with similar SFR [736]. Meta-analysis of five RCTs found
significantly shorter procedure duration for transurethral cystolithotripsy using a nephroscope vs. cystoscope
with similar SFRs, hospital stay, convalescence, pain, and complications [739]. Two retrospective studies
(n=188) reported that using a resectoscope or nephroscope was associated with a shorter procedure duration
(p < 0.05) than a cystoscope for transurethral cystolithotripsy [740, 741]. This suggests that transurethral
cystolithotripsy is quicker when using a continuous flow instrument.

69UROLITHIASIS - LIMITED UPDATE APRIL 2024
6.4.3.2.1.1 Lithotripsy modalities used during transurethral cystolithotripsy in adults.
When considering lithotripsy modalities for transurethral cystolithotripsy, the Panel’s systematic review found
very low-quality evidence from five non-randomised studies (n=385) which found no difference in SFR between
modalities (mechanical, laser, pneumatic, ultrasonic, electrohydraulic lithotripsy [EHL] or washout alone) [736].
Unplanned procedures and major postoperative complications were low-rate events and were not significantly
different between lithotripsy modalities, although one non-randomised study (NRS) suggested these might be
higher with EHL or mechanical lithotripsy than pneumatic or ultrasonic lithotripsy [742]. All outcomes had very
low-quality evidence (GRADE) [736]. High-powered lasers seem to reduce lithotripsy time. Laser lithotripsy was
faster than pneumatic lithotripsy (MD 16.6 minutes; CI: 23.51-9.69, p < 0.0001) in one NRS (n=62); however, a
laser was used with a resectoscope and the pneumatic device with a cystoscope [743]. The same conclusion
was stated in a meta-analysis of ten RCTs with high heterogeneity and small sample sizes in some of the
included RCTs [744]. Continuous vs. intermittent irrigating instruments may affect the operation time more
significantly than the choice of lithotripsy device [736].
6.4.3.2.1.2 Transurethral cystolithotripsy in children
In children, three NRS suggest that transurethral cystolithotripsy has a shorter hospital stay and catheterisation
time than open cystolithotomy, but similar stone-free and complication rates [745]. One small quasi-RCT found
a shorter procedure time using laser vs. pneumatic lithotripsy for < 1.5 cm bladder stones with no difference
in SFR or other outcomes [746]. Another RCT (n=73) found shorter procedure time using pneumatic vs. laser
therapy for bladder stones ≤ 1.5 cm with similar SFRs and higher (minor) complication rates for pneumatic
lithotripsy [747] .
6.4.3.3 Percutaneous cystolithotripsy
6.4.3.3.1 Percutaneous cystolithotripsy in adults:
One NRS found a shorter duration of procedure and catheterisation and less blood loss for percutaneous,
compared with open surgery in adult male patients with urethral strictures; all patients in both groups were
rendered stone-free [722].
Meta-analysis of four RCTs comparing transurethral and percutaneous cystolithotripsy found a shorter hospital
stay for transurethral cystolithotripsy over percutaneous surgery. Transurethral cystolithotripsy was quicker
when using a nephroscope. There were no significant differences in SFRs, major postoperative complications, or
re-treatment [736] .
6.4.3.3.2 Percutaneous cystolithotripsy in children:
In children, three NRS suggest that percutaneous cystolithotripsy has a shorter hospital stay and catheterisation
time, but a longer procedure duration and more peri-operative complications than open cystolithotripsy; SFRs
were similar [726, 736, 745, 748] .
A systematic review identified four non-randomised studies comparing percutaneous and transurethral
cystolithotripsy and found similar SFRs, but that transurethral surgery offers shorter duration of catheterisation
and hospital stay [726, 745] in contrast, a transurethral approach may need a longer operative time and shows
a higher post-operative stricture rate [748]. One small NRS found a non-significant increased risk of unplanned
procedures (within 30 days of primary procedure) and major postoperative complications for percutaneous
operations compared with transurethral procedures; however, age and stone size determined which intervention
children underwent and all patients were rendered stone-free [726]. One RCT compared 48 boys < 14 years
undergoing transurethral lithotripsy vs. 49 boys undergoing percutaneous lithotripsy with comparable success
and complication rates; however, PCCL had a shorter operative time and less need for stone disintegration [749].
6.4.3.4 Extracorporeal shock wave lithotripsy
Extracorporeal SWL is the least invasive therapeutic procedure [736].
6.4.3.4.1 Shock wave lithotripsy in adults
In adults, one RCT compared SWL with transurethral cystolithotripsy in 100 patients with ≤ 2 cm bladder
stones presenting with acute urinary retention. Stone-free rate after one SWL session favoured transurethral
cystolithotripsy (86% vs. 98%, p = 0.03); however, following up to three sessions of SWL, there was no significant
difference in SFR (94% vs. 98%, p = 0.3) [736, 750].
Two NRS compared transurethral cystolithotripsy vs. SWL and found no significant difference in SFR (97.0% vs.
93.9%, p=0.99, 97.7% vs. 89.7% p=0.07) despite larger stones in transurethral cystolithotripsy patients (4.2 vs.
2.5 cm, p=0.014; and 3.6 vs. 2.6 cm [p value not reported]) [751, 752].

UROLITHIASIS - LIMITED UPDATE APRIL 2024 70
Length of hospital stay appeared to favour SWL in all three studies (0 vs. 1 day, 4.8 vs. 0 days, p=0.02, 0.8 vs. 2.4
days, respectively) [750-752]. No significant differences in major post-operative or intra-operative complications
were reported in any study [750-752] .
One NRS compared SWL vs. open cystolithotomy in just 43 patients. Stone sizes were not comparable (2.5 vs.
7.4 cm, p < 0.001). Stone-free rates were not significantly different (93.9% vs. 100%, p=0.50). Length of stay
favored SWL. There was no significant difference in intra-operative or major post-operative complications [751] .
6.4.3.4.2 Shock wave lithotripsy in children
One large NRS found lower SFR for SWL than both transurethral cystolithotripsy and open cystolithotomy,
despite treating smaller stones with SWL. However, the length of hospital stays favoured SWL over open
cystolithotomy, although this appeared to be comparable between SWL and transurethral cystolithotripsy [753] .
6.4.3.5 Laparoscopic cystolithotomy
Laparoscopic cystolithotomy has been described in adults and is typically performed in combination with simple
prostatectomy using either traditional laparoscopy or with robotic assistance [754, 755]. A SR found no studies
comparing laparoscopic surgery with other procedures [736].
6.4.4 Treatment for bladder stones secondary to bladder outlet obstruction in adult men
Bladder stones in men aged over 40 years may be caused by BPO, the management of which should also be
considered. Bladder stones were traditionally an indication for a surgical intervention for BPO: a doctrine that
has been questioned by studies. One prospective study reports urodynamics (cystometrogram) findings in
46 men aged > 60 years before and after bladder stone treatment [711]. Only 51% of men had BOO while 10%
had detrusor under-activity. Eighteen percent of men had a completely normal urodynamic study and 68%
had detrusor over-activity. There was no significant difference between pre- and post-bladder stone removal
urodynamic findings [711] .
One NRS compared 64 men undergoing transurethral cystolithotripsy with either transurethral resection of the
prostate (TURP) or medical management for BPO (α-blocker with or without 5-alpha reductase inhibitor). After
28 months of follow-up, no men on medication had had a recurrence, but 34% underwent TURP: a high post-
void residual urine volume predicted the need for subsequent TURP [756]. Another observational study of 23
men undergoing cystolithotripsy and commencing medical management for BPO found 22% developed a BPO-
related complication, including 17% who had recurrent stones [733]. One RCT comparing cystolithotripsy with
concomitant TURP to cystolithotripsy with medical management of bladder outlet obstruction with Tamsulosin
and finasteride demonstrated that both groups had a significantly improved QMax, IPSS, and PVR at follow-up,
although the TURP group had a longer procedure and catheterisation time [757]. Large prostates and a high PVR
(> 190 ml) were predictive of needing a TURP over time in the medical management cohort, although this was
based on only a small number of patients.
Large studies support the safety of performing BPO and bladder stone procedures during the same operation
with no difference in major complications compared to a BPO procedure alone [758-760]. An observational
study on 2,271 patients undergoing TURP found no difference in complications except UTIs, which occurred
slightly more frequently in patients with simultaneously treated bladder stones: 0% vs. 0.6%, p=0.044 [758]. An
observational study of 321 men undergoing Holmium laser enucleation of the prostate (HoLEP) found a higher
rate of early post-operative incontinence (26.8% vs. 12.5%, p=0.03) in men having concomitant transurethral
cystolithotripsy, but no difference in long-term continence rates [760]. Another larger multicenter observational
study of 963 patients undergoing HoLEP found no significant differences in the frequency of complications in
patients with (n=54 [5.6%]) or without concomitant transurethral cystolithotripsy [761] .
6.4.5 Special situations
6.4.5.1 Neurogenic bladder and stone formation
A study of 2,825 spinal cord injury patients over eight years found a 3.3% incidence of bladder stones: 2% with
CISC, 6.6% with an indwelling urethral catheter, 11% with a suprapubic catheter, and 1.1% in patients voiding
using reflex micturition [766]. However, another study of 457 spinal cord injury patients for six months found no
difference in bladder stones between urethral and suprapubic catheterisation [765]. Spinal cord injury patients
with an indwelling urethral catheter are six times more likely to develop bladder stones than patients with normal
micturition [764, 766].

71UROLITHIASIS - LIMITED UPDATE APRIL 2024
The risk of stone recurrence after complete removal in spinal cord injury patients is 16% per year [765]. An RCT
of 78 spinal cord injury patients who perform CISC found a significant reduction in bladder stone formation
when twice weekly manual bladder irrigations were performed for six months (49% vs. 0%, p = < 0.0001), as well
as less symptomatic UTIs (41% vs. 8%; p = 0.001) [767]. However, this study excluded patients who developed
autonomic dysreflexia during bladder irrigations. The irrigation volume used was not reported.
6.4.5.2 Bladder Augmentation
The incidence of vesical calculus formation after bladder augmentation is 2-44% in adults [768-777], and 4-53%
in children [777-791]. Following cystoplasty, stones form after 24-31 months in adults [769, 771, 776], and after
25-68 months in children [782, 785, 786, 790, 792-794]. The reported cumulative incidence of bladder stone
formation after ten years is 28-36% and after twenty years is 41% [777, 795].
Risk factors for bladder stone formation after augmentation include excess mucus production, incomplete
bladder emptying, non-compliance with CIC or bladder irrigations, bacteriuria or urinary tract infections (due
to urease-producing bacteria), foreign bodies (including staples, mesh, non-absorbable sutures), drainage by
vesico-entero-cystostomy (Mitrofanoff or Monti) [435, 769, 772, 774, 775, 782, 786, 789, 795] and voiding by
CISC compared with those voiding spontaneously [773]. Gastric segment augmentation confers a lower risk of
bladder stones than ileal or colonic segment cystoplasty [778, 782, 786, 789] .
In previous stone formers, the rate of recurrence is 15-44% in adults [769-771, 773, 776], and 19-56% in children
[435, 777, 778, 782, 784-787, 789, 794]. The risk of recurrence is greatest during the first two years, at about 12%
per patient per year, with the risk decreasing with time [794] .
Daily, or three-times-weekly bladder irrigations reduce the incidence of bladder stones following bladder
augmentation or continent urinary diversion [435, 772]. A randomised study found that daily bladder irrigation
with 240 mL of saline reduced stone recurrences (p< 0.0002, p=0.0152) and symptomatic UTIs (p < 0.0001, p <
0.0001) compared to 60mL or 120mL [772]. The frequency of bladder irrigations required is unclear.
6.4.5.3 Urinary diversion
The incidence of stone formation after urinary diversion with an ileal or colon conduit is 0-3% [796, 797]. The
incidence of stone formation is 0-34% in orthotopic ileal neobladders (Hautmann, hemi-Kock, Studer, T-pouch
or w-neobladder) [433, 773, 797-805], and 4-6% in orthotopic sigmoid neobladders (Reddy) [802, 806]. The risk
of pouch stone formation is 4-43% in adults with an ileocaecal continent cutaneous urinary diversion (Indiana,
modified Indiana, Kock, or Mainz I) [425, 773, 796, 797, 805, 807]. The average interval from construction of
the urinary diversion to stone detection is 71-99 months [801, 808]. In children, the incidence of neobladder
stone formation is 30% after Mainz II diversion (rectosigmoid reservoir) [779], and 27% after Kock ileal reservoir
construction [791].
6.4.5.4 Treatment of stones in patients with bladder augmentation or urinary diversion
Stones may be removed by open or endoscopic surgery in patients with bladder augmentation or diversion
[784]. However, often access cannot be obtained through a continent vesico-entero-cystostomy without
damaging the continence apparatus; hence a percutaneous or open approach is typically preferred [784].
No studies comparing outcomes following procedures for stones in reconstructed or augmented bladders
were found. Two observational studies indicate that percutaneous lithotomy can be safely performed with
US or CT guidance in patients with reconstructed or augmented bladders [809, 810] and is proposed to offer
similar advantages over open surgery to those for percutaneous native bladder surgery. Stone recurrence after
successful removal has been reported to be 10-42% [809, 810], but appears to be unrelated to the modality used
for stone removal [776, 782, 786, 787, 789, 794] .

UROLITHIASIS - LIMITED UPDATE APRIL 2024 72
Figure 6.1 Management of Bladder stones
* Lithotripsy modality at surgeon’s discretion (e.g., mechanical, laser, pneumatic, ultrasonic).
† Prefer “tubeless” procedure (without placing a catheter or drain) for children with primary bladder stones and
no prior infection, surgery, or bladder dysfunction where open cystolithotomy is indicated.
** Stone analysis should be sent for all first-time stone formers and in patients who develop a recurrence under
pharmacological prevention, early recurrence after interventional therapy with complete stone clearance or
late recurrence after a prolonged stone-free period (see main Urolithiasis guideline).
†† Use an alkaline citrate or sodium bicarbonate with frequent urine pH monitoring and dose titration to achieve a
consistent pH > 6.5.
BOO = Bladder Outlet Obstruction, TUCL = Trans-urethral cystolithotripsy, PCCL = Percutaneous cystolithotripsy,
SWL = Shock-wave Lithotripsy.
6.5 Bladder stones follow-up
There are no studies examining the merits of differing follow-up modalities or frequencies following
conservative, medical, or operative treatment of bladder stones in adults or children. Identification and
prevention of the cause of bladder stone formation will be crucial to prevent recurrence (see section 6.3.2
Diagnosing the cause of bladder stones).
Consider concomitant treatment
for:
• BOO
• Chronic urinary retention
 (e.g., intermitent self-
 catheterisation)
• Pre-disposing metabolic
 factors
Investigations for cause:
• physical examination
• uroflowmetry and post-void
 residual
• urine dipstick (inc. pH±
 culture)
• serum tests
In selected patients, consider:
• upper tract imaging (if history
 of urolithiasis or loin pain)
• cysto-urethroscopy or
 urethrogram
Surgical Tr eatment:
1. TUCL*
2. PCCL*
 If TUCL is not possible or
 advisable (e.g., urethral
 stricture, young child)
3. Open cystolithotomy
†
 Consider as first-line
 treatment in selected cases,
 e.g., very large stones
4. SWL, laparoscopic
 cystolithotomy 
Radio-opaque
Bladder stone diagnosed on
imaging or cystoscopy
X-ray KUB
Radio-lucent
(or other factors
suggesting uric
acid calculi)
Ofer oral
chemolitholysis
††
Ultrasound
Stone analysis** Failure Success
Diagnosis Treatment Follow-up

73UROLITHIASIS - LIMITED UPDATE APRIL 2024
In adults, there is a paucity of evidence on dietary modification or medical treatment for the prevention of
bladder stone recurrence. Recommendations in the EAU Guideline on Urolithiasis, based on evidence from
upper tract stones, constitute the best available recommendations, especially for migratory bladder stones (see
Section 4 Metabolic Evaluation and Recurrence Prevention).
Where it is possible to address the cause of secondary bladder stones (e.g., treatment of BPO), it is unclear
whether metabolic intervention would offer any significant additional benefit in preventing stone recurrence.
However, especially where the secondary cause cannot be addressed (e.g., indwelling catheter, neuropathic
bladder, bladder augmentation, or urinary diversion); metabolic interventions are likely to reduce bladder stone
recurrence rates.
Regular bladder irrigation reduces the chances of bladder stone recurrence in adults and children with bladder
augmentation or continent cutaneous urinary diversion and adults with spinal cord injury who perform CISC (see
section 6.4.5 Special Situations) [767, 772, 797].
In children with primary (endemic) bladder stones maintenance of hydration, avoidance of diarrhoea, and a
mixed cereal diet with milk and Vitamins A and B supplements, with the addition of eggs, meat, and boiled cows’
milk after one year of age are recommended to prevent a recurrence [723] .
Finally, there are contradictory reports on a possible association between bladder calculi and the future
development of bladder cancer [811-813]. The need for follow-up with regular cystoscopy therefore remains
controversial.
6.6 Summary of evidence and recommendations for the treatment of bladder stones
Summary of evidence LE
The incidence of bladder stones peaks at three years in children (endemic/primary stones in developing
countries) and 60 years in adults.
2c
In adults, BOO is the most common pre-disposing factor for bladder stone formation. 2c
Of men undergoing surgery for BPO, 3-4.7% form bladder stones. 2b
Primary (endemic) bladder stones typically occur in children in areas with poor hydration, recurrent
diarrhoea, and a diet deficient in animal protein. The following measures are proposed to reduce their
incidence: maintenance of hydration, avoidance of diarrhoea, and a mixed cereal diet with milk and
Vitamins A and B supplements; with the addition of eggs, meat, and boiled cows’ milk after one year of
age.
5
Endoscopic bladder stone treatments (trans-urethral or percutaneous) are associated with comparable
SFRs, but a shorter length of hospital stay, duration of procedure and duration of catheterisation
compared to open cystolithotomy in adults.
1a
Stone-free rates are lower in patients treated with SWL than those treated with open or endoscopic
procedures in both adults and children.
2a
Transurethral cystolithotripsy is associated with a shorter length of hospital stay, less pain and a
shorter convalescence period than percutaneous cystolithotripsy in adults.
1b
Transurethral cystolithotripsy with a nephroscope is quicker than when using a cystoscope with no
difference in SFR in adults.
1a
Mechanical, pneumatic and laser appear equivalent lithotripsy modalities for use in endoscopic bladder
stone treatments in adults and children.
2a
Open cystolithotomy without a retropubic drain or urethral catheter (“tubeless”) is associated with a
shorter length of hospital stay than traditional cystolithotomy and can be performed safely in children
with primary stones and no prior bladder surgery or infections.
2b
Bladder stone removal with concomitant treatment for BOO is associated with no significant difference
in major post-operative complications when compared to BOO treatment alone in adults. However,
concomitant bladder stone treatment does increase the rates of short-term post-operative incontinence
and UTI.
2b
The incidence of bladder stone formation in spinal cord injury patients is 19-67% over time. The
absolute annual risk of stone formation in spinal cord injury patients is significantly higher with an
indwelling catheter compared to those voiding with CISC or spontaneously.
2b

UROLITHIASIS - LIMITED UPDATE APRIL 2024 74
The incidence of bladder stone formation after bladder augmentation or vesico-entero-cystostomy is
between 2-53% in adults and children.
2b
The risk of bladder stone formation in spinal cord injury, bladder augmentation or continent urinary
diversion patients is reduced by performing regular bladder irrigation.
2b
Recommendations Strength rating
Use ultrasound (US) as first-line imaging with symptoms suggestive of a bladder stone. Strong
Use cystoscopy or computed tomography (CT), or kidney-ureter-bladder X-Ray (KUB) to
investigate adults with persistent symptoms suggestive of a bladder stone if US is negative.
Strong
All patients with bladder stones should be examined and investigated for the cause of
bladder stone formation, including:
• uroflowmetry and post-void residual;
• urine dipstick, pH, ± culture;
• metabolic assessment and stone analysis (see sections 3.3.2.3 and 4.1 of the
Urolithiasis guidelines for further details).
In selected patients, consider:
• upper tract imaging (in patients with a history of urolithiasis or loin pain);
• cysto-urethroscopy or urethrogram.
Weak
Offer oral chemolitholysis for radiolucent or known uric acid bladder stones in adults.Weak
Offer adults with bladder stones transurethral cystolithotripsy where possible. Strong
Perform transurethral cystolithotripsy with a continuous flow instrument in adults

(e.g., nephroscope or resectoscope) where possible.
Weak
Offer adults percutaneous cystolithotripsy where transurethral cystolithotripsy is not
possible or advisable.
Strong
Suggest open cystolithotomy as an option for very large bladder stones in adults and
children.
Weak
Offer children with bladder stones transurethral cystolithotripsy where possible. Weak
Offer children percutaneous cystolithotripsy where transurethral cystolithotripsy is not
possible or is associated with a high risk of urethral stricture (e.g., young children, previous
urethral reconstruction, and spinal cord injury).
Weak
Open, laparoscopic, and extracorporeal shock wave lithotripsy are alternative treatments
where endoscopic treatment is not advisable in adults and children.
Weak
Prefer “tubeless” procedure (without placing a catheter or drain) for children with primary
bladder stones and no prior infection, surgery, or bladder dysfunction where open
cystolithotomy is indicated.
Weak
Individualise imaging follow up for each patient as there is a paucity of evidence. Factors
affecting follow up will include:
• whether the underlying functional predisposition to stone formation can be treated (e.g.,
TURP);
• metabolic risk.
Weak
Recommend regular irrigation therapy with saline solution to adults and children with bladder
augmentation, continent cutaneous urinary reservoir or neuropathic bladder dysfunction, and
no history of autonomic dysreflexia, to reduce the risk of stone recurrence.
Weak

75UROLITHIASIS - LIMITED UPDATE APRIL 2024
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8. CONFLICT OF INTEREST
All members of the Urolithiasis Guidelines Panel have provided disclosure statements of all relationships that
they have that might be perceived as a potential source of a conflict of interest. This information is publicly
accessible through the European Association of Urology website: http://www.uroweb.org/guidelines/. This
guidelines document was developed with the financial support of the European Association of Urology. No
external sources of funding and support have been involved. The EAU is a non-profit organisation and funding
is limited to administrative assistance and travel and meeting expenses. No honoraria or other reimbursements
have been provided.
9. CITATION INFORMATION
The format in which to cite the EAU Guidelines will vary depending on the style guide of the journal in which the
citation appears. Accordingly, the number of authors or whether, for instance, to include the publisher, location,
or an ISBN number may vary.
The compilation of the complete Guidelines should be referenced as:
EAU Guidelines. Edn. presented at the EAU Annual Congress Paris 2024. ISBN 978-94-92671-23-3.
If a publisher and/or location is required, include:
EAU Guidelines Office, Arnhem, the Netherlands. http://uroweb.org/guidelines/compilations-of-all-guidelines/
References to individual guidelines should be structured in the following way:
Contributors’ names. Title of resource. Publication type. ISBN. Publisher and publisher location, year.