Urolithiasis: Clinical Guidelines

List of Abbreviations

ACE – angiotensin-converting enzyme

URT – upper urinary tract

HPT – hyperparathyroidism

OAA – Other analgesics and antipyretics drug group

SWL — shock wave lithotripsy

GI – gastrointestinal tract

UTI — urinary tract infection

BMI – body mass index

CT – computed tomography

LKT – lithokinetic therapy

UPJ – ureteropelvic junction

IC – urolithiasis (urolithiasis disease)

MRI – magnetic resonance imaging

MRU – magnetic resonance urography

NC – nephrocalcinosis

NSAIDs – nonsteroidal anti-inflammatory drugs

PH – primary hyperoxaluria

RTA – renal tubular acidosis

PNL – percutaneous nephrolithotomy (nephrolithotripsy, nephrolitholapaxy)

PTH – parathyroid hormone

RCT – randomized controlled trial

GFR – glomerular filtration rate

US – ultrasound examination

URS – ureterorenoscopy

PCN – percutaneous nephrostomy

Pelvicalyceal system – pelvicalyceal system

PCPN – percutaneous puncture nephrostomy

IVU – excretory urography

FDA – Food and Drug Administration

HU – Hounsfield units

Terms and Definitions

“Stone street” — an accumulation of stone fragments in the ureter that fail to pass within a certain period and obstruct urine flow

Metaphylaxis of urolithiasis — a set of therapeutic and preventive measures aimed at preventing disease recurrence after surgical removal of a stone or after spontaneous passage of the calculus.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Urolithiasis (ICD, urolithiasis) is a chronic systemic disease resulting from metabolic disorders and/or environmental factors, manifested by the formation of stones (calculi) in the upper urinary tract.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Calculi should be subdivided into those formed due to infection (infectious); those not caused by infection (non-infectious); calculi arising from genetic disorders; and calculi formed during medication use (drug-induced).

Metabolic disturbance is one of the important factors in calculus formation. Determining the metabolic disturbance and analyzing the chemical composition of the calculus allows for determining the diagnostic and treatment tactics for the disease.

Depending on the cause of lithogenesis, calculi should be subdivided into infectious (formed due to the influence of an infectious agent), non-infectious (stone formation is not associated with infection activity), drug-induced (formed during medication use), and calculi arising from genetic disorders.

Chemical composition of urinary stones formed due to genetic disorders:

• Cystine (aminoaciduria characterized by impaired tubular reabsorption of dibasic amino acids: cystine, ornithine, arginine, and lysine);

• Xanthine (xanthinuria caused by hereditary xanthine oxidase enzyme deficiency);

• 2,8-dihydroxyadenine (hereditary adenine phosphoribosyltransferase deficiency leading to the accumulation of adenine, which is subsequently oxidized to 2,8-dihydroxyadenine).

• Chemical composition of infectious calculi:

• Magnesium ammonium phosphate (struvite);

• Carbonate apatite;

• Ammonium urate.

Chemical composition of non-infectious calculi:

• Calcium oxalate (whewellite, weddellite);

• Calcium phosphate (carbonate apatite, brushite);

• Uric acid.

Medicinal products contributing to urinary tract stone formation.

Compounds crystallizing in urine:

• Allopurinol**/oxypurinol;

• Amoxicillin**/ampicillin**;

• Ceftriaxone**;

• Ciprofloxacin**;

• Ephedrine;

• Indinavir;

• Magnesium trisilicate;

• Sulfonamide**;

• Triamterene.

Substances affecting urine composition:

• Acetazolamide**;

• Allopurinol**;

• Aluminum and magnesium hydroxide;

• Ascorbic acid**;

• Calcium;

• Furosemide**;

• Laxatives;

• Methoxyflurane;

• Vitamin D and its analogues.

Mineralogical composition of calculi

One of the important factors in calculus formation is metabolic disturbance. Identifying metabolic disturbances and analyzing the chemical composition of the calculus allows for determining the tactics of diagnosis and treatment.

In most cases, calculi are represented by a combination of several chemical compounds. An important aspect is determining the compound that makes up the majority of the calculus (Table 1).

Table 1 - Composition of the calculus

Risk groups for stone formation

The degree of risk for stone formation determines the likelihood of calculus formation, recurrence, or an increase in the size and number of calculi, as well as the need for medical treatment.

All children diagnosed with urolithiasis are at high risk for urolithiasis recurrence [76].

It is believed that the higher risk of stone formation recurrence compared to adults is due to a higher frequency of metabolic and genetic causes of stone formation, such as cystinuria and hyperoxaluria, and frequent association with congenital anomalies (e.g., hydronephrosis, megaureter, or vesicoureteral reflux, narrowing of the urinary tract caliber) [77,78].

Additional risk factors for stone formation in children:

• family history of the disease: presence of risk factors for urolithiasis, urological diseases, especially urolithiasis, in close relatives in the anamnesis;

• metabolic disorders of stone-forming substances;

• family living in an endemic region;

• maternal pregnancy history features: complicated pregnancy against the background of gestosis, use of antiviral and antibacterial drugs;

• nephrocalcinosis in the child and/or close relatives.

• decreased physical activity, forced recumbent position (limb immobilization, trauma consequences, etc.)

• restricted ordinary drinking water intake

• prolonged presence of drains or sutures in the lumen of the urinary tract (renal pelvis, ureter, urinary bladder)

Presence of urinary system anomalies in the child

• Calyceal diverticulum, calyceal cyst

• Ureteral stricture

• Pelviureteric junction (PUJ) obstruction

• Ureterocele

• Horseshoe kidney

• Neurogenic bladder dysfunction

• Vesicoureteral reflux

• Solitary kidney

Genetic causes of high risk for urolithiasis

• Cystinuria (types A, B, AB)

• Primary hyperoxaluria (PH types 1–3)

• Type 1 renal tubular acidosis (RTA)

• 2,8-dihydroxyadenine

• Xanthinuria

• Lesch-Nyhan syndrome

• Cystic fibrosis

• Idiopathic infantile hypercalcemia (types 1 and 2)

Appendix A3.3 presents some of the monogenic hereditary diseases leading to urolithiasis. These diseases are encountered more often than others in the practice of urologists, but currently about 80 monogenic forms of urolithiasis are described in the literature [1,2].

1.3 Epidemiology of the Disease or Condition

The analysis of the prevalence of urolithiasis in the Russian Federation from 2005 to 2020 showed that over time there is a clear trend towards an increase in the number of urolithiasis cases among the adult population. At the same time, the incidence among children remains stable. The reasons for this fact are being discussed and are not yet finally known.

The incidence of urolithiasis is endemic in nature. In the Russian Federation, the leading regions are Altai Krai, the Far East, and Yamalo-Nenets Autonomous Okrug. Among patients with urolithiasis, children account for about 1%. The incidence among adolescents is 50–100 cases per 100,000 population [3,4,5,6].

1.4 Features of Coding the Disease or Condition

N20.0 - Calculus of kidney

N20.1 - Calculus of ureter

N20.2 - Calculus of kidney with calculus of ureter

N20.9 - Urinary calculus, unspecified

Calculi of lower urinary tract (N21)

N21.0 - Calculus in bladder

N21.1 - Calculus in urethra

N21.8 - Other calculi of lower urinary tract

N21.9 - Calculus of lower urinary tract, unspecified

Urinary calculi in diseases classified elsewhere (N22)

Renal colic, unspecified (N23)

E79.8 - Other disorders of purine and pyrimidine metabolism (hereditary xanthinuria)

E79.9 - Disorder of purine and pyrimidine metabolism, unspecified

1.5 Classification of the disease or condition

Calculi can be classified according to the following criteria: size, location, radiological characteristics (calculus density), etiology, mineralogical composition, and risk of recurrence [1].

Calculus size

Calculus size is indicated in millimeters, specifying 1 or 2 dimensions. Based on the above, calculi can be divided into groups of < 5 mm, 5-10 mm, 10-20 mm, and > 20 mm.

Calculus location

Calculi are classified depending on their location within the anatomical structures of the urinary tract: upper, middle, or lower calyx group, renal pelvis, upper, middle, or distal ureter, and bladder.

Radiological characteristics

Calculi are also classified according to their radiological appearance on plain radiography (X-ray of the urinary system) (Table 2). When performing spiral computed tomography (CT), the Hounsfield unit (Hu) scale is used for classification. This X-ray attenuation scale is used for visual and quantitative assessment of the density of structures determined by computed tomography.

Table 2 - Radiological characteristics

1.6 Clinical presentation of the disease or condition

The leading manifestations of urolithiasis include pain, dysuria, hematuria, leukocyturia, and passage of urinary salt crystals and calculi. Only the last symptom is absolute. Pain is the most frequent symptom. Depending on the size, shape, location, and mobility of the stone, the pain can vary in character. Patients with kidney stones may experience vomiting and, sometimes, fever. An asymptomatic course of the disease is possible.

• When taking the medical history, the following should be considered:

- presence of risk factors for urolithiasis in close relatives, urological diseases, especially urolithiasis accompanied by metabolic disorders of stone-forming substances;

- presence of urinary tract anomalies in the child;

- family living in an endemic region;

- characteristics of the mother's pregnancy course;

- intake of medications promoting stone formation (see section 1.2);

- restriction of the child's mobility (trauma, musculoskeletal defects, neurological diseases);

- specific dietary habits (including food preferences).

2. Diagnostics, medical indications and contraindications for diagnostic methods

The diagnosis of urolithiasis is established based on the detection of calculi (clinically, based on spontaneous passage of the urolith and/or using instrumental diagnostic methods).

Additional information can be obtained by analyzing the combination of anamnestic and clinical data.

Determine the chemical composition of the stone(s) and the potential etiological basis of their formation based on laboratory test results (biochemical and, in some cases, molecular genetic analysis).

2.1 Complaints and Anamnesis

See the "Clinical Presentation" section

2.2 Physical Examination

During the physical examination, the patient's skin, sclerae should be inspected, pulse rate, volume, and rhythm assessed, blood pressure, respiratory rate, and body temperature measured.

Further examination should begin with superficial palpation and percussion of the abdominal cavity and retroperitoneal space. Palpation of the renal area is most commonly performed in the supine or lateral position. Tenderness upon examination indicates an inflammatory process in the renal parenchyma, perirenal tissue, or ureteral obstruction, provided there is no history of traumatic injury.

Deep palpation begins in painless areas and concludes with checking for Shchetkin-Blumberg, Pasternatsky, Ortner signs, etc. (Therapeutic visual inspection, Therapeutic palpation, Therapeutic auscultation, Therapeutic percussion, Heart rate measurement, Pulse examination, Blood pressure measurement on peripheral arteries, General thermometry)..

During the clinical examination, it is essential to pay attention to the patient's behavior: during renal colic, the patient is restless, cannot find a comfortable position, and tosses about. The "psoas sign" is frequently present.

The younger the child, the more pronounced the general symptoms of the pathological process, and the less distinct the local symptoms.

2.3 Laboratory Diagnostics

Patients with urolithiasis undergo urine and blood tests to determine the type of calculi, the presence of inflammation, and to assess renal function [1, 11, 16, 17, 22, 25, 27, 33, 34].

(LoE – C, GoR – 5)

Comment: the test is also performed dynamically; the frequency is determined individually.

(LoE – C, GoR – 5)

Comments: the frequency of testing during follow-up is determined by the clinical course of the disease. Nitrites can also be detected using test strips.

(GoR – C, LoE – 5)

Comment: the test may be ordered during follow-up as needed depending on the type of stones, as well as to monitor ongoing therapy [1, 38].

Testing can also be performed using test strips

(LoE – C, GoR – 5)

Comment: the test may also be performed during follow-up; the frequency is set individually.

Following surgery, no earlier than 2-3 days later 39, 40].

(LoE – C, GoR – 5)

Comments: in the presence of urinary tract infection, testing and treatment are carried out within the framework of relevant clinical guidelines.

Testing is also performed during follow-up; the frequency is determined individually.

(GoR – C, LoE – 5)

Comments: the scope and frequency of dynamic testing are determined individually depending on the clinical picture

(GoR – C, LoE – 5)

Comments: the frequency of follow-up tests is determined individually depending on the clinical picture (to assess inflammation).

(LoE – C, GoR – 5)

(LoE – C, GoR – 5)

• In cases of newly diagnosed urolithiasis, it is recommended to analyze the mineral composition of urinary stones (stone composition analysis using an analytical method such as X-ray diffraction or infrared spectroscopy) to determine the further examination plan and choose therapeutic tactics [11, 21, 24, 39].

(LoE – C, GoR – 5)

Comments: the test is performed if a substrate (calculus) is available.

If the test cannot be performed in the medical organization, the material should be sent for testing to a medical organization where the study can be performed.

• Repeat analysis of the mineral composition of urinary stones (calculi) is recommended in patients with: recurrence during medical prophylaxis; early recurrence after complete stone removal; late recurrence after a long period of stone-free status, as the composition of the calculus may change [11, 16].

(GoR – C, LoE – 5)

Comment: Cystine crystallization in urine occurs spontaneously due to its poor solubility. Cystine solubility depends exclusively on urine pH: at pH 6.0, the solubility limit is 133 mmol/L. However, routine cystine testing as part of urinary stone mineral composition analysis is impractical.

• When diagnosing cystine calculi, to clarify the diagnosis and choose therapeutic tactics, patients are recommended to undergo differentiation of cystine, cysteine, and drug-cysteine complexes to determine the further examination plan and therapeutic strategy. Various complexes formed as a result of treatment can only be differentiated using analytical methods based on high-performance liquid chromatography (complex determination of amino acid concentrations by high-performance liquid chromatography (HPLC)) [1, 21, 29].

(GoR – C, LoE – 5)

2.4 Instrumental Diagnostics

• As a primary diagnostic procedure for urolithiasis, all patients are recommended to undergo an ultrasound examination (US) of the urinary system (ultrasound of the kidneys, ultrasound of the ureters, ultrasound of the bladder) [9, 11, 17, 23].

(GoR – C, LoE – 5)

Comment: Ultrasound allows the detection of calculi in the calyces, renal pelvis, pelviureteric junction, and vesicoureteric junction, and allows the diagnosis of upper urinary tract (UUT) dilation. The examination is also performed during dynamic follow-up at a frequency determined individually.

Color Doppler ultrasound (duplex scanning of renal arteries) allows comparison of ureteric jets, the resistive index of arcuate arteries in both kidneys, and determination of the degree of obstruction.

(GoR – C, LoE – 5)

Comment:

If spiral CT is planned, this examination should not be prescribed. The frequency of the study is determined individually.

(GoR – C, LoE – 5)

Comments: in practice, excretory urography (EU) (intravenous urography) is usually performed first, and in case of insufficient informativeness, spiral computed tomography (CT) of the urinary system (spiral computed tomography of the kidneys and adrenal glands) is performed.

If possible, low-dose CT imaging is preferred.

Anesthetic management (including early postoperative care) – as clinically indicated.

(GoR – C, LoE – 5)

Comments: if possible, low-dose CT imaging is preferred. Anesthetic management (including early postoperative management) (General anesthesia) – as clinically indicated.

(GoR – C, LoE – 5)

Comment: computed tomography is currently the standard diagnostic method for acute flank pain. This method makes it possible to determine calculus density and the skin-to-stone distance—parameters that influence the efficacy of extracorporeal shock wave lithotripsy (ESWL).

However, the high radiation dose of the method must be taken into account, and its use in children should be restricted. Low-dose protocols should be used when possible.

Calculi containing uric acid and xanthine are radiolucent, but can be detected by computed tomography.

Calculi formed during indinavir therapy are not detected on spiral CT. Anesthetic management (including early postoperative management) (General anesthesia) – as clinically indicated.

(LoE – C, GoR – 5)

Comments: Anesthetic management (including early postoperative management) (General anesthesia) – as clinically indicated

Radionuclide renal studies (renal and urinary tract scintigraphy, renal and urinary tract scintigraphy with functional tests) are recommended to be used to determine renal function, detect obstruction, and determine its anatomical level as clinically indicated [11, 16, 22, 23].

(LoE – C, GoR – 5)

Comments: to determine nitrogen-excreting function (assess preservation of the renal parenchyma), renal and urinary tract scintigraphy (static renal scintigraphy) is preferred; to assess urodynamics (renal excretory function), dynamic renal and urinary tract scintigraphy with functional tests is performed.

• If stone removal is planned and the individual anatomical features of the pelvicalyceal system (PCS) are unknown, it is recommended to perform a contrast-enhanced study (computed tomography of the kidneys and upper urinary tracts with intravenous bolus contrast enhancement) [1, 10, 23, 25].

(GoR – C, LoE – 5)

Comment: spiral CT is preferred because it provides a three-dimensional image of the PCS, as well as measuring stone density and skin-to-stone distance. Excretory urography (intravenous urography) can also be performed. In the presence of an impacted stone, cystoscopy may be performed.

2.5 Other Procedures

Comments:

Appointments (examinations, consultations) with a geneticist are indicated for patients with multisystem organ involvement, early onset of the disease, a positive family history, or the detection of rarer chemical stone compositions upon analysis (e.g., cystine, xanthine, or 2,8-dihydroxyadenine stones).

Evaluation during medical genetic counseling includes patient examination, family history collection, instrumental, clinical-laboratory, and molecular-genetic studies.

Nephrolithiasis can be diagnosed both as part of syndromic forms of genetic diseases and monogenic ones: in Williams syndrome (OMIM 194050), Lesch-Nyhan syndrome (OMIM 308000), alkaptonuria (OMIM 203500), primary hyperoxaluria (OMIM 259900), cystinuria (OMIM 220100), X-linked recessive nephrolithiasis with renal failure (OMIM 310468), and others.

Comments: an anesthesiologist-resuscitologist, clinical pharmacologist, radiologist, ultrasound diagnostics physician; also, considering the likelihood of multiorgan involvement in genetically determined forms of urolithiasis and/or for the timely diagnosis of adverse reactions to therapy, consultations may be required with an ophthalmologist, dentist/pediatric dentist, otorhinolaryngologist, pediatric otorhinolaryngologist-audiologist, and others.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

Given the variety of causes of stone formation and the characteristics of renal calculi, treatment must be individualized. When choosing management tactics, in addition to the cause, it is necessary to take into account the size, localization, number of stones, presence/absence of pain/colic and/or urinary tract infection, as well as comorbid conditions [1]. Treatment includes conservative, surgical, and dietary measures. Currently, there is a need for high-quality studies to more accurately assess outcomes with various therapeutic methods [44].

3.1 Conservative Treatment

3.1.1 Renal colic

The objectives of treatment for renal colic are pain relief and, whenever possible depending on the clinical situation, removal of the calculus.

• At the first stage of treatment for renal colic, pain relief is recommended for all patients with urolithiasis [1, 23, 25, 27].

(GoR – C, LoE – 5)

(GoR – C, LoE – 5)

Comment: These drugs are significantly more effective than opioids in relieving pain during renal colic, and patients receiving OAAs or NSAIDs less frequently require further analgesia in the short term.

(GoR – C, LoE – 5)

Comment: the necessity of prescribing a drug from these groups should be evaluated, and upon making a positive decision, a drug with the fewest side effects should be chosen (e.g., tramadol**).

3.1.2 Prevention of recurrent renal colic

NSAIDs can relieve inflammation and reduce the risk of recurrent pain in patients with ureteral calculi that may pass spontaneously. OAAs and NSAIDs can have a negative impact on renal function in patients with stage 2 or higher CKD.

Recurrent episodes of renal colic are significantly less common in patients who received OAAs and NSAIDs during the first 7 days of treatment.

• If pain relief cannot be achieved with medicinal products, it is recommended to perform drainage using a ureteral stent (placement of a stent in the urinary tract) or percutaneous nephrostomy (PCN) (percutaneous puncture nephrostomy), or to remove the calculus (removal of ureteral stones) [1, 11, 16, 22, 25].

(LoE – C, GoR – 5)

Comments: in pediatric urology, placement of a puncture nephrostomy is technically difficult, which is why open pyelostomy or ureterostomy is mainly used in clinical practice.

3.1.3 Conservative treatment depending on calculus type

3.1.3.1 Hyperoxaluria and calcium-phosphate stones

Early diagnosis and correct patient management significantly affect the course of the disease.

(GoR – C, LoE – 5)

(LoE – C, GoR – 5)

Comments: maximum solubility of calcium oxalate is achieved at pH 6.2 – 6.8. Therapeutic doses of drugs for the treatment of nephrourolithiasis containing Potassium hydrogen carbonate + Citric acid + Sodium citrate are 0.1–0.15 g/kg (2–6 tablets) per day (according to the instructions – for children aged 12 years and older).

(GoR – C, LoE – 5)

(GoR – C, LoE – 5)

Comment: rarely used in pediatrics; the risk-benefit ratio should be evaluated.

• For the majority of patients with calcium-phosphate calculi in the presence of primary hyperparathyroidism, surgical treatment for therapeutic purposes is recommended [1].

(GoR – C, LoE – 5)

• If renal tubular acidosis is the cause, pharmacological therapy for this condition/disease for therapeutic purposes is recommended [1].

(GoR – C, LoE – 5)

(GoR – C, LoE – 5)

Comments: dietary measures regarding this type of hyperoxaluria have low efficacy. Early liver and kidney transplantation is most commonly used for type 1, and kidney transplantation for type 2. For type 3, transplantation is not performed due to preserved renal function.

Therapy with drugs for the treatment of nephrourolithiasis (Potassium hydrogen carbonate + Citric acid + Sodium citrate or Potassium sodium hydrogen citrate) is used for all types. For type 1, #pyridoxine** may also be used at a starting dose of 5 mg/kg/day, with a gradual dose increase, but not exceeding 20 mg/kg/day, and evaluation of results after at least 3 months [79]. A decrease in urinary oxalate levels by more than 30% from baseline is considered a positive response.

Currently, research continues on potential therapeutic methods for various types of primary hyperoxaluria, including various modalities of renal replacement therapy. Targeted therapy for type 1 hyperoxaluria has been approved by the FDA [51].

3.1.3.2 Struvite and infection calculi

(GoR – C, LoE – 5)

Comment: Even small residual fragments can become a focus for bacterial colonization and growth.

All patients with infectious calculi belong to the high-risk group for recurrence. Infectious calculi consist of struvite and/or carbonate apatite, and/or ammonium urate. Urinalysis and urine culture typically reveal the presence of urease-producing bacteria.

The most important species of urease-producing bacteria are:

- obligate urease-producing bacteria (> 98%): Proteus spp., Providencia rettgeri, Morganella morganii, Corynebacterium urealyticum, Ureaplasma urealyticum;

- facultative urease-producing bacteria: Enterobacter gergoviae, Klebsiella spp., Providencia stuartii, Serratia marcescens, Staphylococcus spp.

Approximately 0–5% of strains of Escherichia coli, Enterococcus, and Pseudomonas aerug. can produce urease.

3.1.3.3 Cystine calculi

(GoR – C, LoE – 5)

Comments: all patients with cystine calculi belong to the high recurrence risk group.

Table 4 - Body surface area

A variety of formulas are used to calculate body surface area (BSA). One of them is the Mosteller formula

(GoR – C, LoE – 5)

(GoR – C, LoE – 5)

Comment: Due to severe side effects, #penicillamine**, which forms soluble complexes with cystine, is used in pediatrics with limitations, under strict medical supervision and monthly monitoring of a complete (clinical) blood count and complete (clinical) urinalysis; the duration is determined individually due to the possibility of a prolonged effect developing.

3.1.3.4 2,8-Dihydroxyadenine and Xanthine Calculi

All patients with 2,8-dihydroxyadenine and xanthine calculi belong to the high recurrence risk group. Both types of calculi are rare. In general, diagnosis and specific prevention are similar to those for uric acid calculi.

Genetically determined deficiency of adenine phosphoribosyltransferase causes increased urinary excretion of poorly soluble 2,8-dihydroxyadenine.

(GoR – C, LoE – 5)

Comment: Patients with xanthine calculi generally show a significant decrease in serum uric acid levels. Currently, there are no drugs available to correct this condition.

3.1.3.4 Uratess

(GoR – C, LoE – 5)

(CRA – C, LE – 5)

3.2 Surgical Treatment

The initial approach for single, asymptomatic lower pole kidney stones with a high likelihood of spontaneous passage, particularly in patients with non-struvite and non-cystine stones <7 mm in size and no anatomical abnormalities, may be an expectant management strategy. Intervention may be required for stones located elsewhere, regardless of their size [1].

Effective methods for removing calculi in children currently include extracorporeal shock wave lithotripsy (ESWL) (Extracorporeal ureterolithotripsy, Extracorporeal nephrolithotripsy, Extracorporeal cystolithotripsy, Extracorporeal pyelolithotripsy, Extracorporeal calicolithotripsy), ureterolithotripsy with lithoextraction (transurethral endoscopic ureterolithotripsy, transurethral endoscopic laser ureterolithotripsy, transurethral ureterolithoextraction, contact cystolithotripsy), percutaneous nephrolithotripsy (percutaneous nephrolithotripsy with lithoextraction [nephrolitholapaxy]).

(LoE – C, GoR – 5)

Comment: Kidney calculi may remain asymptomatic, whereas ureteral calculi in most cases lead to acute pain resembling renal colic.

- calculi with a low probability of spontaneous passage;

- persistent pain despite adequate analgesia;

- persistent obstruction;

- impaired renal function (renal failure, bilateral obstruction, solitary kidney) in recurrent urinary tract infection or abnormal urinalysis findings (hematuria) [1].

(GoR – C, LoE – 5)

- calculus growth;

- calculi in patients with a high risk of stone formation;

- obstruction caused by calculi;

- infection;

- calculi accompanied by clinical manifestations (e.g., pain, hematuria);

- low probability of spontaneous stone passage;

- patient preferences;

- presence of comorbidities;

-  [1, 53, 59].

(GoR – C, LoE – 5)

Comments: When choosing a treatment method, the expected composition of the calculus, the anatomical features of the pelvicalyceal system, and the duration of stone presence should be considered.

(GoR – C, LoE – 5)

Comments: modern lithotripters are smaller in size and are often built into urological X-ray tables (e.g., Computerized Extracorporeal Lithotripter with X-ray television and ultrasound guidance systems). They allow performing not only ESWL but also other related diagnostic and auxiliary procedures.

The efficacy of ESWL depends on the lithotripter and the following factors:

- size, location (in the ureter, renal pelvis, or calyx), and structure (density) of the calculus

- patient body habitus

- characteristics of the ESWL procedure

Each of these factors has a major impact on the frequency of repeat treatment sessions and the outcome of ESWL.

Shock wave frequency

By reducing the shock wave frequency from 120 to 60–90 shock waves per minute, a higher stone-free rate is achieved.

Number of shock wave impulses, energy, and repeat ESWL sessions.

The number of shock wave impulses that can be used per session depends on the type of lithotripter and the shock wave energy. Tissue damage increases as the shock wave frequency increases; to prevent kidney injury, a low-power impulse should be used at the beginning of ESWL with subsequent gradual increase, thereby achieving vasoconstriction.

- hemorrhagic diathesis (conditions must be compensated for at least 24 hours before and 48 hours after ESWL)

- untreated urinary tract infections (UTIs)

- severe musculoskeletal deformities and severe obesity that prevent accurate targeting of the shock wave onto the calculus

- arterial aneurysm located near the calculus targeted by the shock wave, anatomical obstruction of the urinary tract distal to the calculus

to prevent complications [1]

(LoE – C, GoR – 5)

• All patients are recommended to squeeze the contact gel directly from the tube onto the lithotripter head, rather than applying it by hand, to minimize air bubbles and prevent a decrease in fragmentation efficiency [11, 17].

(RRR – C, LOR – 5)

Comment: good acoustic contact between the lithotripter head and the patient's skin is of great importance. Defects (air bubbles) in the contact gel reflect 99% of shock waves, reducing fragmentation efficiency.

• During the SWL (extracorporeal shock wave lithotripsy/nephrolithotripsy) procedure, it is recommended to always use imaging methods (fluoroscopy and/or ultrasound of the kidneys, ultrasound of the ureters) to determine the localization of the calculus in order to monitor the treatment process [1, 10, 11, 16].

(GoR – C, LoE – 5)

(LoE – C, GoR – 5)

(LoE – C, GoR – 5)

(RRR – C, LOR – 5)

Comment: In some cases, stenting (placement of a stent in the urinary tract) does not ensure efficient outflow of purulent and mucous discharge, which leads to an increased risk of obstructive pyelonephritis.

In case of fever and obstruction, urgent PCNL (percutaneous nephrostomy) is performed [1]

• When calculi are localized in the lower calyx, it is recommended to perform PCNL even if the calculus size exceeds 1.5 cm to increase treatment efficacy [1, 11, 16, 23, 25].

(LoE – C, GoR – 5)

Comment: When the stone is located in the lower calyces after SWL, the stone-free rate is lower than for other localizations. This is due to the fact that fragments often remain in the calyx and lead to recurrent stone formation.

Treatment of urolithiasis patients using SWL may be ineffective in the presence of the following factors:

• acute angle between the infundibulum and the renal pelvis

• long calyx

• narrow infundibulum

«Steinstrasse» – a complication whose appearance must be avoided; if present, maximum attention must be paid to it due to the high risk of renal function loss and renal colic.

«Steinstrasse» may be asymptomatic or accompanied by flank pain, fever, nausea, and vomiting, or bladder irritation, signs of inflammation in the complete blood count, and elevated procalcitonin levels. The main danger lies in ureteral obstruction and a high risk of renal failure [7, 21].

• If «steinstrasse» is asymptomatic, it is recommended to start treatment with conservative methods – lithokinetice therapy significantly facilitates stone passage and reduces the need for endoscopic surgery [12, 21]. If spontaneous passage of «steinstrasse» is unlikely, other treatments are recommended - stent placement or PCNL (ureteral SWL or stent placement (bladder catheterization / percutaneous nephrostomy, placement of a stent in the upper urinary tract (polymeric ureteral stent****)) [1, 11, 25].

(LoE – C, GoR – 5)

Comment: In most cases, lithokinetice therapy alone is not sufficiently effective.

- SWL is prescribed both in the presence and absence of symptoms, provided there is no urinary tract infection (UTI) and large stone fragments are present (technique

- SWL: avoid the formation of large fragments)

- Ureteroscopy in the treatment of «steinstrasse» is not inferior in efficacy to SWL.

- PCNL is indicated in cases where ureteral obstruction is accompanied by clinical manifestations with or without UTI.

(LoE – C, GoR – 5)

Comments: there are several methods of contact stone fragmentation.

• When performing percutaneous nephrolithotomy (PCNL), it is recommended to use ultrasonic, laser, or pneumatic lithotripters for effective therapy [1, 11, 16, 25].

(LoE – C, GoR – 5)

Comment: Any PCNL is performed with urinary tract stenting or nephrostomy.

Any stent placement must be accompanied by urinary catheterization

In complicated cases, multiple nephrostomies can be placed (into each calyx)

• For hard kidney stones, it is recommended to selectively (where possible) use laser (holmium) contact lithotripsy for effective treatment [1, 59].

(LoE – C, GoR – 5)

Comment: percutaneous nephrolithotripsy (PCNL) is the «gold standard» in the treatment of pediatric patients with staghorn and large kidney stones. PCNL is preferred when choosing a surgical treatment method with the highest possible success rate (over 80%) in a single session and a reduction in hospital stay (up to 3–4 days).

• For children in the middle (4–12 years) and younger (1–3 years) age groups, it is recommended to prefer the use of miniature instruments (mini-percutaneous nephrolithotripsy to increase treatment efficacy (16 Ch. catheter, protective sheath), ultra-mini-percutaneous nephrolithotripsy (12 Ch. catheter, protective sheath) [58, 61, 62].

(RRR – C, LOR – 3)

Comments: this technique is very effective; however, if the pediatric urologist-andrologist/urologist lacks sufficient experience, damage to surrounding tissues is possible. Training specialists in PCNL takes a long period of practice in specialized hospitals, starting with performing interventions in adult patients.

• When performing contact lithotripsy using a rigid nephroscope, it is recommended to use ultrasonic, pneumatic, and holmium lithotripters. Among flexible instruments, the holmium laser is considered the most effective device [1, 11, 16, 22, 25].

(LoE – C, GoR – 5)

• Percutaneous nephrolithotripsy (PCNL) is recommended for:

o staghorn calculi;

o large kidney stones (over 2 cm in adolescents and up to 1.5 cm in children of the younger (1–3 years) and middle (4–12 years) age groups;

o high stone density (over 1500 HU);

o stone localization in the lower calyx (>1–1.5 cm);

o multiple kidney stones;

o large stones of the upper ureter (over 1 cm);

o ineffectiveness of extracorporeal shock wave lithotripsy [1, 11, 16, 22, 25, 54, 59].

(LoE – C, GoR – 5)

• PCNL is not recommended for:

o acute urinary tract infection;

o atypical interposition of the intestine (in the path of access to the calculus);

o tumor in the intended access path to the calculus;

o potentially malignant renal tumor;

o contraindications to general anesthesia, including blood clotting disorders

to prevent complications [1, 11, 16, 22, 25, 59]

(LoE – C, GoR – 5)

Comment: if pus is present during the puncture of the pelvicalyceal system, the surgical intervention is divided into two stages:

1 – drainage of the pelvicalyceal system via nephrostomy (percutaneous puncture nephrostomy under ultrasound guidance), antibacterial therapy according to urine culture.

2 – PCNL after conservative treatment in 2–4 weeks.

Standardly, PCNL is performed in the prone position, however, in rare cases, it can be performed in the supine position.

(LoE – C, GoR – 5)

Comment: preoperative imaging (ultrasound, plain and excretory urograms, or CT (see subsection 2.4)) provides information on stone localization, the structure of the pelvicalyceal system, and organs located along the intended access path to the pelvicalyceal system (e.g., spleen, liver, colon, pleura, lung).

The access is established in such a way as to ensure the maximum probability of removing the largest possible volume of the calculus from adjacent organs, enable visual inspection and manipulation in the pelviureteric junction area, and create safe conditions for the surgery.

• If PNL facilities and experience are lacking, it is recommended to consider transferring the patient to a specialized urolithiasis treatment clinic; if PNL is contraindicated, it is recommended to selectively use contact ureteronephrolithotripsy (the procedure is not included in the current Nomenclature) in order to select and provide adequate treatment [1, 59, 63].

(GoR – C, LoE – 5)

Comments: the purpose of contact ureteronephrolithotripsy is to perform ureteronephroscopy (UNS) and complete removal of calculi. Calculi can be extracted using endoscopic forceps or baskets (lithotripter basket). Forceps allow safely releasing a calculus if it gets stuck in the ureter, but extraction takes longer than with baskets (lithotripter basket). Using baskets (lithotripter basket) without a range of laser and other lithotripters is a dangerous manipulation and is often accompanied by ureteral trauma up to avulsion.

However, ureteronephrolithotripsy (the procedure is not included in the current Nomenclature) does not allow adequate visualization of the pelvicalyceal system and is accompanied by a high risk of ureteral trauma during ureteroscopy; this type of surgical intervention should be used strictly according to indications in rare cases.

The practice of leading Russian clinics makes it possible to remove almost all calculi using minimally invasive surgical interventions (PNL, SWL, CULT, UNS); open surgical interventions are currently indicated in isolated, individual cases. If it is impossible to remove kidney and ureteral calculi, it is necessary to consider transferring patients to centers equipped with the full range of capabilities for minimally invasive surgical interventions. [11, 16, 22, 25].

Calculi that cannot be extracted whole during URS should preferably be pre-fragmented to achieve extractability [1, 10, 16, 25, 29, 55, 59].

(LoE – C, GoR – 5)

(LoE – C, GoR – 5)

Comment: nevertheless, preliminary stenting (placement of a stent in the urinary tract) facilitates ureteroscopy, increases the stone-free rate, and reduces the complication rate.

Stents should be placed in patients with an increased risk of complications (e.g., residual fragments, bleeding, perforation, UTI), as well as in all doubtful cases to avoid emergency stressful situations.

In practice, most pediatric urologist-andrologists/urologists prefer to place a stent for 1-2 weeks after URS. Dynamically, patients should undergo a plain abdominal X-ray of the urinary system (X-ray of kidneys and urinary tract), CT (spiral computed tomography of kidneys and adrenal glands), or ultrasound (ultrasound examination of kidneys, ultrasound examination of ureters, ultrasound examination of the bladder).

(GoR – C, LoE – 5)

Comment: The advancement of SWL and endourological surgeries (URS and PNL) has led to a significant reduction in indications for open stone removal surgery;

(GQR-C; LoE-5)

Comment: including, for example, in cases of:

o ineffectiveness of previous SWL and/or PNL, as well as ureteroscopic surgery;

o pelviureteric junction obstruction;

o ureteral stricture;

o concomitant diseases;

o non-functioning lower pole (after partial nephrectomy);

o non-functioning kidney (after radical nephrectomy);

PNL can be successfully performed for complex stones located in a renal diverticulum, in an abnormally positioned kidney, in obese patients, pelvic contractures, lower limb deformities, provided the physician has sufficient experience.

(GoR – C, LoE – 5)

Comment: this allows the removal of large staghorn calculi using multiple small radial nephrotomies without impairing renal function.

o presence of complex-shaped stones;

o ineffectiveness of previous SWL and/or endourological surgeries;

o anatomical anomalies;

o severe obesity;

(GoR – C, LoE – 5)

o need for surgical intervention for concomitant diseases;

o ineffectiveness of other non-invasive or minimally invasive surgeries performed.

(GoR – C, LoE – 5)

Comment: the method is associated with fewer postoperative complications compared to open surgery; however, currently, given the experience with PNL and contact ureterolithotripsy (transurethral endoscopic ureterolithotripsy/transurethral endoscopic laser ureterolithotripsy), laparoscopic techniques are unnecessary and can be used extremely rarely.

During the surgery, a urinary tract stent or nephrostomy (ultrasound-guided percutaneous puncture nephrostomy) is placed, along with a urinary catheter (ureteral catheterization).

3.3 Other Treatment

3.3.1 Chemolysis

Oral chemolysis of calculi or their fragments can be an effective therapy. It can be used in addition to extracorporeal shock wave lithotripsy (SWL), percutaneous nephrolithotomy (PNL), ureterorenoscopy (URS), or open surgery to facilitate the passage of small residual fragments.

Percutaneous chemolysis is rarely used (possible for struvite calculi) and has a low level of evidence.

The results of oral chemolysis as a 1st-line therapy become apparent only after several weeks; therefore, in urgent situations, it is usually prescribed in addition to endourological treatment methods.

The duration of oral chemolysis is determined individually, ranging from 1 to several months, with an average of 6 months.

(LoE – C, GoR – 5)

Comment: Oral litholysis (chemolysis) is only possible for uric acid stones: radiolucent on plain radiography (plain KUB radiography [kidneys, ureters, bladder]), CT density ≤ 600 HU, history of uric acid stones. Uric acid-containing calculi (urate stones) are generally amenable to chemolysis, with the exception of sodium urate and ammonium urate [1].

(LoE – C, GoR – 5)

Comment: This treatment method is effective and is carried out in combination with urinary tract drainage. The effect is possible with full adherence of the parents/relatives/patient to the attending physician's recommendations [1, 7, 8, 18, 24]. The treatment is based on urine alkalinization using potassium sodium hydrogen citrate or potassium bicarbonate + citric acid + sodium citrate (citrate mixtures) or baking soda. The urine pH level should be maintained within 7.0 — 7.2. The dose of the alkalinizing agent is selected individually. The urine pH level must be measured using test strips at regular intervals throughout the day.

3.1.2 Complementary and alternative medicine (CAM) methods in the treatment of urolithiasis in children

CAM methods involve a combination of various therapeutic approaches not fully based on traditional medicine principles. These methods do not replace the main treatment listed above.

Nevertheless, CAM methods used in addition to standard guidelines can improve mutual understanding (compliance) between the patient and their parents and the specialist in achieving disease control by optimizing the patient's environment during prolonged courses of conventional treatment until complete recovery is achieved. Alternative/complementary treatment does not replace conventional treatment.

When deciding on complementary treatment, it is necessary to weigh the potential benefits and risks, including clarifying the absence of allergic reactions (e.g., to herbal components) and taking into account the specific features of the disease.

The efficacy of herbal medicine in urolithiasis is primarily due to a mild diuretic effect [80, 81].

Positive effects may also be associated with litholytic and spasmolytic activity, as well as an inhibitory effect on crystal crystallization and aggregation. Molecular mechanisms may be related to the antioxidant, anti-inflammatory, and antimicrobial properties of plant components [81]

(Recommendation Grade B, Evidence Level 2)

Comments: there are few publications on the use of herbal medicine in children with urolithiasis, and while there are reports of positive effects of this CAM modality in children with urolithiasis, further research is required.

In the Russian Federation, the most commonly used preparation is Centaury herb + Lovage roots + Rosemary leaves. This preparation (in the form of drops or tablets) may be prescribed to children over 6 years of age at an age-appropriate dosage, provided there is no sensitivity to plants of the Apiaceae family (including anise and fennel) or to anethole (a component of essential oils in plants such as anise and fennel).

Data also exist on the efficacy of edible plants and plant parts, though further studies are needed for definitive recommendations [87].

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Sanatorium-resort treatment for patients with kidney and ureteral stones is performed in the absence of urodynamic disorders no earlier than 6 months after surgical intervention. Sanatorium-resort treatment is carried out at climatic and balneological resorts with mineral drinking waters.

Comment 1: Sanatorium-resort treatment includes balneotherapy using mineral waters for internal and external use, adequate physical activity, climatotherapy, medical nutrition, hardware physical therapy, and psychological correction.

Comment 2: Sanatorium-resort institutions under the jurisdiction of the Russian Ministry of Health admit children aged 4 to 14 years inclusive, including those accompanied by a legal representative, and children aged 15 to 18 years unaccompanied. If a sanatorium-resort institution has a specialized children's department, children aged 7 to 14 years inclusive are admitted without being accompanied by a legal representative, unless accompaniment is required for medical indications.

Comment 3: Sanatorium-resort treatment does not replace the main treatment listed above. Selective internal administration of mineral water is recommended [88, 89, 91, 92, 93].

Recommendation Grade C, Evidence Level 5.

Comment: For internal administration, low- or medium-mineralized mineral waters are used at a dose of 3–5 ml per 1 kg of the child's body weight (i.e., up to 100 ml per dose for children aged 6–10 years, and up to 200 ml for those aged 11–14 years), 3 times a day, 30 minutes before meals throughout the entire stay at the sanatorium.

Recommendation Grade C, Evidence Level 5.

Comment: Resort climatotherapy begins with Regimen I (sparing, weak). In the warm months of the year, a transfer to Regimen II (sparing-toning) is possible after 3–5 days.

Recommendation Grade C, Evidence Level 5.

Comment 1: The tasks of physical therapy are to improve the excretory function of the kidneys and urine outflow; general strengthening of the body and improvement of metabolism. Special exercises for the abdominal, back, and pelvic floor muscles reduce the tone of the smooth muscles of the ureters. Such exercises include various torso bends and turns, and sudden changes in body position. These exercises alternate with muscle relaxation and diaphragmatic breathing. An important feature of physical therapy sessions is the frequent change of starting positions (standing, sitting, kneeling, lying prone, supine, or on the side). The duration of the session is 30–45 minutes. Physical therapy is prescribed as a course of 10 procedures, every other day.

Comment 2: therapeutic dosed walking is carried out according to Regimen I with a route length of 500 m on a flat grass-covered surface at a pace of 60–70 steps per minute.

LoE C, GoR 5

Comment: Mineral baths are prescribed according to the traditional method: temperature 37°C, duration 5–8 minutes for children aged 7–10 years and 8–12 minutes for those aged 11–14 years, with a course of 6–8 procedures for the younger age group and 8–10 for the older group. Sodium chloride baths are administered at a concentration of 10 g/l.

Recommendation Grade – C, Evidence Level – 5

Comment: the most effective techniques are amplipulse therapy, low-frequency magnetotherapy, laser therapy, and ultrasound therapy when applied to the lumbar region (kidney projection area) and the anterior abdominal wall (projection area of the affected ureter).

Level of Reliability of Evidence – C, Grade of Recommendation – 5

Comment: The main goals of psychotherapy are to relieve and reduce neurotic manifestations and to mobilize the sick child's willpower to strictly follow medical prescriptions.

5. Prevention and Dispensary Observation

5.1 Prevention

Urolithiasis is not a contraindication to vaccination with any type of vaccine (Order of the Russian Ministry of Health No. 1122n dated 06.12.2021 “On Approval of the National Schedule of Preventive Vaccinations and the Schedule of Preventive Vaccinations by Epidemiological Indications”, Methodological Guidelines MU 3.3.1.1095–02. Medical Contraindications to Preventive Vaccinations with National Immunization Schedule Preparations). Routine immunization of a patient with urolithiasis is carried out in accordance with the national schedule of preventive vaccinations during a period of stable underlying disease.

5.2 Principles of Metaphylaxis, Dynamic Monitoring, and Clinical Follow-up

Patients at high risk of recurrent stone formation require prevention (metaphylaxis), including medical treatment and, as a rule, general preventive measures (including adherence to an appropriate diet and fluid intake regimen).

Comment:

- Drugs for the treatment of urolithiasis (Alkaline citrates)

Among the drugs used in urology (alkalinizing agents), the most common are: Potassium sodium hydrogen citrate, Potassium bicarbonate + Citric acid + Sodium citrate. The doses of medications for the treatment of nephrourolithiasis (alkaline citrates) in children are 0.1–0.15 mg/kg/day

Drugs for the treatment of urolithiasis (Alkaline citrates) are prescribed:

- for the correction of hypocitraturia;

- for urine alkalinization;

- to inhibit the crystallization and aggregation of calcium oxalate (primary hyperoxaluria type 1);

- to inhibit calcium phosphate aggregation.

- #Allopurinol^**

#Allopurinol** is used to prevent the recurrence of calcium oxalate calculi, as a link between hyperuricosuria and the formation of such calculi has been established, as well as calculi composed of uric acid, ammonium urate, and 2,8-dihydroxyadenine (in children, 1–3 mg/kg/day) [1].

- #Pyridoxine^**

It is possible to prescribe #pyridoxine** to reduce oxalate excretion in patients with primary hyperoxaluria type 1 (starting dose 5 mg/kg/day, maximum 20 mg/kg/day) [1].

5.2.1 General principles of management of children with urolithiasis

Currently, there is no consensus on whether, when, how, and how often patients with urolithiasis should undergo follow-up after successful treatment. This is mainly due to the high heterogeneity of urolithiasis among patients and the lack of comparative studies regarding follow-up versus no follow-up.

Comments: children belong to the high-risk group for recurrent stone formation. It should be taken into account that, in addition to stone removal surgery, treatment requires a thorough investigation of metabolism and environmental factors in each individual case.

The main directions of stone formation prevention and outpatient treatment are the correction of metabolic disorders of stone-forming substances in the blood and urine, sanitation of the urinary tract, and normalization of urine pH values.

Treatment and follow-up for each patient should be developed individually depending on age, chemical type of urolithiasis, and the nature of comorbidities [1,4,7,8,14,17,18,21].

Comments: initial and follow-up consultations are indicated by a pediatrician/general practitioner (family physician), nephrologist, pediatric urologist-androloist/urologist, dentist, ophthalmologist, otolaryngologist, geneticist, etc.

Frequency depends on the clinical situation.

The follow-up plan includes:

Laboratory tests:

o general (clinical) urinalysis (every 3 months and as indicated);

o general general-medical blood biochemistry analysis (every 3 months during the first year of follow-up, then every 6 months and as indicated);

o ultrasound examination of the urinary system (kidney ultrasound, ureter ultrasound, bladder ultrasound) (every 3 months during the first year of follow-up, then every 6 months and as indicated);

o radiological examination: X-ray of the kidneys and urinary tract, excretory urography (intravenous urography) (as indicated, including as part of postoperative studies);

o microbiological (cultural) analysis of urine for aerobic and facultatively anaerobic opportunistic microorganisms, with determination of microorganism susceptibility to antimicrobial drugs. The examination should be repeated after the course of therapy. In the absence of microbial growth, antibiotic therapy should be discontinued and a control analysis scheduled (frequency is determined individually, according to the clinical situation);

Urine pH measurement (determination of urine hydrogen ion (pH) concentration) (1 time every 3 months during the first year of follow-up for 3–5 days). Keeping a urine acidity diary.

Comment: families with children having genetic forms of urolithiasis are recommended to undergo genetic counseling to determine genetic risk. The risk of re-birth of a child with genetic forms of urolithiasis depends on the type of inheritance. In families with a child affected by a genetic disorder, prenatal and preimplantation diagnostics can be performed. For this purpose, parents should be referred to specialized diagnostic laboratories and medical centers.

Pediatric patients diagnosed with urolithiasis are recommended to undergo an additional examination to detect metabolic disorders, including [1, 11, 16, 17, 22, 25, 27, 33, 34]:

- general medical blood biochemistry analysis determining the levels of ionized calcium, total calcium, sodium, magnesium, inorganic phosphorus, chlorine, creatinine, urea, uric acid, potassium in the blood, and the level of 25-OH vitamin D in the blood;

- 24-hour urine biochemistry analysis: calcium (study of calcium levels in urine); oxalates (study of oxalate levels in urine – service is absent in the current Nomenclature); citrate (study of citrate levels in urine – service is absent in the current Nomenclature); phosphorus (study of phosphorus levels in urine), uric acid (study of uric acid levels in urine), sulfate (study of sulfate levels in urine – service is absent in the current Nomenclature), creatinine (study of creatinine levels in urine), magnesium (study of total magnesium levels in urine – service is absent in the current Nomenclature), phosphates (study of phosphorus levels in urine), potassium (study of potassium levels in urine), chlorides (study of chloride levels in urine), sodium (study of sodium levels in urine); cystine (study of cystine levels in urine – service is absent in the current Nomenclature) (if cystine stone formation is suspected), 24-hour urine volume (diuresis) (determination of urine volume);

- determination of parathyroid hormone levels in the blood in patients with elevated calcium levels (ionized calcium in the blood) (see section 2.3).

(LoE – C, GoR – 5)

Comments: collection of 24-hour urine samples should be carried out no earlier than 20 days from the moment of stone passage or removal in order to increase the reliability of the results. It is advisable to perform the 24-hour urine analysis twice with an interval of one week to increase the reliability of the results. After submitting the midstream urine sample to the laboratory, it is advisable to perform a blood biochemistry analysis on the same day to more adequately reflect the metabolic status. The study may be prescribed during dynamic monitoring, as well as to monitor ongoing therapy. The frequency is set individually [38, 65, 67, 68]. If collecting 24-hour urine is impossible due to the child's age, biochemical analysis of a morning urine sample may be performed. In biochemical analysis of a morning urine sample, the excretion level of lithogenic substances is usually calculated based on the creatinine concentration. It should be noted that this method has limited application, as results may vary depending on the patient's gender, body weight, and the child's age.

• In cases of newly diagnosed urolithiasis, it is recommended to analyze the mineral composition of urinary stones (analysis of stone composition using an analytical method (e.g., X-ray diffraction or infrared spectroscopy)) to determine the further examination plan and therapeutic tactics [11, 21, 24, 39].

(LoE – C, GoR – 5)

• Repeat analysis of stone composition is recommended for patients: with recurrence during medical prophylaxis; with early recurrence after complete stone removal; with late recurrence after a long period of stone-free status, as the stone composition may change [11, 16, 21]. (GRL – C, LEL – 5)

(LoE – C, GoR – 5)

(LoE – C, GoR – 5)

• To clarify the diagnosis and choose the therapeutic strategy, patients with suspected or diagnosed cystine stones are recommended to undergo high-performance liquid chromatography (comprehensive determination of amino acid concentrations by high-performance liquid chromatography (HPLC)) to differentiate between cystine, cysteine, and drug-cysteine complexes [1, 21, 29].

(GoR – C, LoE – 5)

5.2.2 Diet therapy and lifestyle recommendations

(GoR – C, LoE – 5)

Comment: There is an inverse relationship between stone formation and high fluid intake. Patients at risk of stone formation are recommended to maintain a high diuresis and abundant fluid intake. It is preferable to use drinking water that complies with state standards, at least 1.2–2.5 liters per day depending on age and weight (according to Rospotrebnadzor data). In cases of high physical exertion in a child or specific weather conditions (hot climate), the daily water intake volume may be increased.

• All pediatric patients diagnosed with urolithiasis are recommended a dietary calcium intake ranging from 700 to 1300 mg per day, depending on the patient's age [12, 21, 69, 74].

(GoR – C, LoE – 5)

Comments: physiological daily norm of calcium intake depending on age: children under 3 years: 700 mg, from 4 to 10 years: 1000 mg, from 10 to 16 years: 1300 mg, over 16 years: 1000 mg per day.

(GoR – C, LoE – 5)

Comments: although vitamin C is a source of endogenous oxalate formation, opinions on its role as a risk factor for calcium oxalate stone formation remain controversial. Nevertheless, it is advisable to recommend that patients at risk for calcium oxalate stones avoid excessive vitamin C intake

High amounts of oxalates are found, for example, in beets (greens, roots, chard), spinach, purslane, rhubarb, sorrel, turnip greens, dandelion, endive, kale, nuts (peanuts, pecans), etc. Chocolate and cola, which are often consumed by children, also have a fairly high oxalate content, and although there is currently no convincing evidence regarding the efficacy of dietary restriction alone (only cases combining dietary therapy and #pyridoxine** intake have been studied), such restriction should nevertheless be assumed to be effective in the treatment and prevention of recurrent stone formation in children with hyperoxaluria [50, 64]

(GoR – C, LoE – 5)

Comments: currently, the mechanism of action of vegetables and fruits in preventing recurrent stone formation remains unclear; however, the high potassium content in these foods helps increase urine pH, and the high fiber content has a beneficial effect on metabolism.

• All patients with urolithiasis are recommended to avoid excessive dietary animal protein, but not less than 0.8–1.0 g/kg/day, in order to reduce stone formation risk factors [1].

(GoR – C, LoE – 5)

Comments: Excessive animal protein in the diet leads to the appearance of pro-lithogenic factors such as hypocitraturia, low urine pH, hyperoxaluria, and hyperuricosuria. In children, dietary animal protein restrictions should be recommended individually and with caution due to the nutritional needs of the growing body.

(GoR – C, LoE – 5)

(GoR – C, LoE – 5)

Comment: sodium intake should be no more than 200–1300 mg/day

Increased sodium intake adversely affects urine composition. Calcium excretion increases due to decreased tubular reabsorption; urinary citrate concentration decreases due to bicarbonate loss; and the risk of sodium urate crystal formation increases.

The likelihood of calcium stone formation can be reduced by restricting sodium and animal protein intake.

• The consumption of food, especially rich in purines, is recommended to be restricted in patients at risk of calcium oxalate stones caused by hyperuricosuria, as well as in patients at risk of uric acid stones, to prevent stone formation [1].

(GoR – C, LoE – 5)

(Strength of Recommendation – C, Quality of Evidence – 5

Comments: The results of some studies indicate that the risk of stone formation depends on lifestyle factors, for example, it increases with overweight and obesity, as well as with arterial hypertension.

6. Organization of Medical Care

Children with urolithiasis may be provided with any type, conditions, and forms of medical care stipulated by the legislation of the Russian Federation, as needed.

Patients with urolithiasis must be under dispensary surveillance (active clinical monitoring), receiving primary health care in outpatient settings. The primary condition for providing care to a patient with urolithiasis must be ensuring continuous monitoring, anti-relapse treatment, and timely hospitalization.

The child is monitored by a pediatrician / general practitioner (family doctor), urologist / pediatric urologist, nephrologist, with the participation, if necessary, of a geneticist, hematologist / pediatric oncologist-hematologist, otorhinolaryngologist, dentist, dietitian, and other specialists as needed.

Indications for planned hospitalization:

1) Kidney stones requiring surgical intervention;

2) Ureteral stones requiring surgical intervention;

3) Patient's social status requiring the removal of asymptomatic urinary tract stones.

Indications for emergency hospitalization:

1) Infectious complications of urolithiasis;

2) Uncontrolled pain syndrome caused by urinary tract stones;

3) Complete obstruction of the upper urinary tract by a stone;

Indications for patient discharge from the hospital:

1) Restoration of urine outflow from the kidney;

2) Absence of signs of systemic inflammation;

3) Absence of risk of urolithiasis complications.

It is necessary to inform the patient with an indication for surgical treatment of urolithiasis in detail about all existing treatment methods and their complications in order to raise awareness and assist in making a decision on the choice of surgical method.

Modern clinical practice for the treatment of urolithiasis includes many options for surgical techniques to rid patients of urinary tract stones with potentially equivalent efficacy of the final result. However, each operation differs in the frequency of complication risks, stone-free rates, and the degree of invasiveness. Often, the choice of surgery depends on the doctor's preferences, which leads to a lack of patient awareness regarding the pros and cons of a particular operation and, thereby, impairs treatment adherence. The working group considers it necessary to inform the patient in detail about all existing methods of urolithiasis treatment and their complications.

The organization of dietary nutrition for patients during inpatient treatment in medical organizations is carried out in accordance with Appendix 3 of the Order of the Russian Ministry of Health dated September 23, 2020, No. 1008n "On Approval of the Procedure for Providing Patients with Therapeutic Nutrition"

7. Additional Information

7.1 Prognosis

With timely and correct treatment, it is relatively favorable. After surgical treatment, long-term anti-relapse treatment is indicated, taking into account the chemical composition of the stones, urine pH, presence of urinary infection, and renal function status. In case of concomitant pyelonephritis, anti-inflammatory therapy is performed.

7.2 Complications

Complications of urolithiasis

• pyelonephritis

• hypertension

• hydronephrosis

• pyonephrosis

• anuria

• acute renal failure

• chronic kidney disease

Complications of surgical treatment of urolithiasis

Complications of ESWL

Related to stone fragments:

• «steinstrasse» (stone street);

• growth of residual fragments;

• renal colic

• urinary tract obstruction

• pyonephrosis.

Infectious:

• bacteriuria in non-infectious stones;

• sepsis.

Renal tissue injury:

• clinically significant hematoma;

• asymptomatic hematoma.

Cardiovascular complications:

• arrhythmia.

Gastrointestinal complications:

• intestinal perforation;

• liver or spleen hematoma.

«Steinstrasse»

Complications of percutaneous nephrolithotripsy

• intraoperative or postoperative bleeding

• urinary tract perforation

• loss of percutaneous access

• urinary leakage

• injury to adjacent organs

URS Complications

Intraoperative:

• mucosal injury;

• ureteral and renal pelvicalyceal system perforation;

• urinary leakage

• ureteral avulsion, injury to the ureteral orifice;

• stent migration;

• significant bleeding;

Early complications manifest as persistent hematuria and renal colic. Late complications include ureteral stricture and persistent vesicoureteral reflux.

Criteria for Evaluating the Quality of Medical Care

Quality assessment criteria for primary health care in children with urolithiasis (ICD-10 codes: N20, N21, N22, N23)

Quality assessment criteria for specialized medical care in children with urolithiasis (ICD-10 codes: N20, N21, N22, N23)

References

Appendix A1. Working Group Composition

Akopyan A.V., Candidate of Medical Sciences, pediatric urologist-andrologist at the Federal Scientific and Clinical Center for Children and Adolescents of the Federal Medical-Biological Agency of Russia, member of the Union of Pediatricians of Russia

Anokhin N.V. – Candidate of Medical Sciences, Senior Researcher at the Urolithiasis Department, Lopatkin Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Centre of Radiology of the Russian Ministry of Health

Apakina A.V., member of the Union of Pediatricians of Russia (participation in the initial version of the document)

Apkhanova T.V., Doctor of Medical Sciences, National Medical Research Centre for Rehabilitation and Balneology of the Russian Ministry of Health

Baranov A.A. - Academician of the Russian Academy of Sciences, Professor, Doctor of Medical Sciences; Honorary President of the Union of Pediatricians of Russia, Advisor to the Head of the Research Institute of Pediatrics and Child Health of the Clinical Research Center No. 2 of the Petrovsky National Research Centre of Surgery, Professor at the Department of Pediatrics and Pediatric Rheumatology, Sechenov First Moscow State Medical University of the Russian Ministry of Health (Sechenov University), Chief freelance pediatric specialist of the Russian Ministry of Health

Bakanov M.I., Professor, Doctor of Medical Sciences, member of the Union of Pediatricians of Russia (participation in the initial version of the document)

Borisova S.A., Candidate of Medical Sciences, member of the Union of Pediatricians of Russia (participation in the initial version of the document)

Borovik T.Э., Professor, Doctor of Medical Sciences, Head of the Laboratory of Nutrition for Healthy and Sick Children at the National Medical Research Center for Children's Health of the Russian Ministry of Health, member of the Association of Medical Geneticists (AMG)

Vardak A.B. Candidate of Medical Sciences, pediatric urologist-andrologist at the Pediatric Uroandrology Department, Lopatkin Research Institute of Urology and Interventional Radiology - branch of the National Medical Research Centre of Radiology of the Russian Ministry of Health

Vashakmadze N.D. - Doctor of Medical Sciences, Head of the Department of Orphan Diseases and Prevention of Disabling Conditions at the Research Institute of Pediatrics and Child Health of the Clinical Research Center No. 2 of the Petrovsky National Research Centre of Surgery, Professor at the Department of Faculty Pediatrics, Pediatric Faculty of the Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Russian Ministry of Health (Pirogov University), member of the Union of Pediatricians of Russia

Vishnyova E.A. – Sc.D. in Medicine, Professor of the Russian Academy of Sciences, Deputy Head of the Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Centre of Surgery; Professor at the Department of Faculty Pediatrics, Faculty of Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University (Pirogov University) of the Russian Ministry of Health; Member of the Union of Pediatricians of Russia

Vorobyova L.E., Member of the Union of Pediatricians of Russia (participation in the initial version of the document)

Dvoryakovskaya G.M. Ph.D. in Medicine, Member of the Union of Pediatricians of Russia (participation in the initial version of the document)

Dvoryakovskiy I.V., Sc.D. in Medicine, Professor, Member of the Union of Pediatricians of Russia (participation in the initial version of the document)

Demin N.V., Ph.D. in Medicine, Senior Researcher, Research Institute of Emergency Pediatric Surgery and Trauma, Moscow Healthcare Department

Zhurkova N.V. – Ph.D. in Medicine, Leading Researcher, Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Centre of Surgery; Member of the Union of Pediatricians of Russia, Member of the Association of Medical Geneticists (AMG)

Zakharova E.Yu. – Sc.D. in Medicine, Head of the Laboratory of Inherited Metabolic Diseases, Academician N.P. Bochkov Research Centre for Medical Genetics; Member of the Russian Society of Medical Geneticists, Member of the Society for the Study of Inborn Errors of Metabolism (SSIEM)

Zelikovich E.I., Sc.D. in Medicine, Professor (participation in the initial version of the document)

Zokirov N.Z., Sc.D. in Medicine, Head of the Department, Academy of Postgraduate Education under the Federal Scientific and Clinical Centre of the Federal Medical and Biological Agency (FSCC FMBA of Russia); Federal Scientific and Clinical Centre of Children and Adolescents of the FMBA of Russia; Member of the Union of Pediatricians of Russia

Zorkin S.N., Sc.D. in Medicine, Professor, Head of the Centre of Pediatric Urology and Andrology, Head of the Urology Department with Groups of Reproductology and Transplantation, Acting Head of the Department of Pediatric Organ Transplantation, Professor at the Department of Pediatric Surgery and Urology-Andrology, I.M. Sechenov First Moscow State Medical University; Deputy Chairman of the Interregional Public Organization of Pediatric Urologists and Andrologists, Member of the Association of Pediatric Surgeons of Russia, Member of the Union of Pediatricians of Russia (participation in the initial version of the document)

Konstantinova O.V. – Sc.D. in Medicine, Chief Researcher, Urolithiasis Department, N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Centre for Radiology of the Russian Ministry of Health

Konchugova T.V., DSc, Professor, Chief Research Scientist at the Department of Physiotherapy and Reflexology, National Medical Research Center for Rehabilitation and Balneology of the Ministry of Health of Russia

Kutafina E.K., Ph.D. in Medicine, Member of the Union of Pediatricians of Russia (participation in the initial version of the document)

Kutsev S.I. – Academician of the Russian Academy of Sciences, Sc.D. in Medicine, Director of the Academician N.P. Bochkov Research Centre for Medical Genetics, President of the Association of Medical Geneticists (AMG)

Mazo A.M., Ph.D. in Medicine, Member of the Union of Pediatricians of Russia (participation in the initial version of the document)

Margieva T.V., Ph.D. in Medicine, Chief Specialist, Methodological Centre for Specialist Accreditation, I.M. Sechenov First Moscow State Medical University (Sechenov University) of the Russian Ministry of Health, Nephrologist, Member of the Union of Pediatricians of Russia

Marukhnenko D.V. – Ph.D. in Medicine, Professor, Head of the Pediatric Uroandrology Department, N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Centre for Radiology of the Russian Ministry of Health

Mayansky N.A., Sc.D. in Medicine, Member of the Union of Pediatricians of Russia (participation in the initial version of the document)

Namazova-Baranova L.S. Academician of the Russian Academy of Sciences, Sc.D. in Medicine, Professor, President of the Union of Pediatricians of Russia; Past President of EPA/UNEPSA; Head of the Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Centre of Surgery; Head of the Department of Faculty Pediatrics, Faculty of Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University (Pirogov University) of the Russian Ministry of Health; Chief freelance pediatric specialist in preventive medicine of the Russian Ministry of Health

Prosyannikov M.Yu. – Sc.D. in Medicine, Head of the Urolithiasis Department, N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Centre for Radiology of the Russian Ministry of Health; Professor at the Department of Biomedical Security, Bauman Moscow State Technical University

Repina S.A. – Ph.D. in Medicine, Medical Geneticist, Department of Medical Care Organization, Academician N.P. Bochkov Research Centre for Medical Genetics, Member of the Association of Medical Geneticists (AMG)

Rudin Yu.E., MD, PhD, Professor, Head of the Pediatric Urology Group at the Department of General and Reconstructive Urology at the Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Radiological Center of the Russian Ministry of Health

Svetlichnaya D.V. – Medical Geneticist, Moscow Regional Research Clinical Institute named after M.F. Vladimirsky (MONIKI), Member of the Association of Medical Geneticists (AMG)

Selimzyanova L.R. – Ph.D. in Medicine, Head of the Department of Standardization and Study of Evidence-Based Medicine, Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Centre of Surgery; Associate Professor at the Department of Pediatrics and Pediatric Rheumatology, I.M. Sechenov First Moscow State Medical University (Sechenov University) of the Russian Ministry of Health; Associate Professor at the Department of Faculty Pediatrics, Faculty of Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University (Pirogov University) of the Russian Ministry of Health; Member of the Union of Pediatricians of Russia

Smirnova O.Ya. – Medical Geneticist, Senior Researcher, Department of Standardization and Study of Evidence-Based Medicine, Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Centre of Surgery; Member of the Union of Pediatricians of Russia, Member of the Association of Medical Geneticists

Khodova T.V., DSc, Head of the N.K. Krupskaya Children's Sanatorium, North-Caucasian Federal Research and Clinical Center of the FMBA of Russia

Tsygin A.N. Sc.D. in Medicine, Professor, Member of the Union of Pediatricians of Russia (participation in the initial version of the document)

Tsygina E.N., Sc.D. in Medicine, Member of the Union of Pediatricians of Russia (participation in the initial version of the document)

Shakhnovsky D.S., Member of the Union of Pediatricians of Russia (participation in the initial version of the document)

Yakovlev M.Yu., Sc.D. in Medicine, National Medical Research Centre for Rehabilitation and Balneology of the Russian Ministry of Health

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Pediatric urologists-andrologists;

2. Pediatricians;

3. Pediatric surgeons;

4. General practitioners (family physicians);

5. Medical students;

6. Residents and interns.

Methods used for evidence collection/selection: electronic database search.

Description of methods used to assess the quality and strength of evidence: the evidence base for the recommendations includes publications from the Cochrane Library, EMBASE, MEDLINE, and PubMed databases. Search depth: 5 years.

Methods used to assess the quality and strength of evidence:

• expert consensus;

• assessment of significance in accordance with the rating scheme.

Methods used for evidence analysis:

• reviews of published meta-analyses;

• systematic reviews with evidence tables.

Description of methods used for evidence analysis

When selecting publications as potential sources of evidence, the methodology used in each study is examined to ensure its validity. The result of this examination affects the level of evidence assigned to the publication, which in turn affects the strength of the recommendations.

To minimize potential bias, each study was evaluated independently. Any discrepancies in evaluations were discussed by the full panel of authors. If a consensus could not be reached, an independent expert was involved.

Evidence tables: compiled by the authors of the clinical guidelines.

Methods used to formulate the recommendations: expert consensus.

Good Practice Points (GPPs)

Recommended good clinical practice is based on the clinical experience of the authors of these guidelines.

Economic analysis

Cost analysis was not performed, and pharmacoeconomic publications were not analyzed.

Recommendation validation method

• External expert review.

• Internal expert review.

Description of the recommendation validation method

The draft of these recommendations was reviewed by independent experts who were primarily asked to comment on how comprehensible the interpretation of the evidence underlying the recommendations is.

Feedback was obtained from primary care physicians regarding the readability of these guidelines and their assessment of the importance of the proposed recommendations as a tool for daily practice.

All comments received from the experts were thoroughly systematized and discussed by the members of the working group (authors of the recommendations). Each item was discussed individually.

Consultation and peer review

The draft recommendations were reviewed by independent experts who were primarily asked to comment on the clarity and accuracy of the interpretation of the evidence base underlying the recommendations.

Working Group

For the final revision and quality control, the recommendations were re-evaluated by the members of the working group, who concluded that all comments and feedback from the experts had been taken into account and the risk of bias in the development of the recommendations was minimized.

Table 1. Scale for assessing levels of reliable evidence (LRE) for diagnostic methods (diagnostic interventions)

Table 2. Scale for assessing the levels of evidence (LE) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Scale for grading levels of recommendation certainty (LRC) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision — at least once every three years, as well as upon the emergence of new evidence-based medicine data regarding the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

Care delivery pathways:

1. Order of the Ministry of Health and Social Development of the Russian Federation No. 366n dated April 16, 2012, "On Approval of the Procedure for Providing Pediatric Care"

2. Order of the Russian Ministry of Health No. 562n dated October 31, 2012, "On Approval of земля the Procedure for Providing Medical Care in the Profile 'Pediatric Surgery'"

Other documents:

1. Order of the Russian Ministry of Health No. 1094n dated November 24, 2021, "On Approval of the Procedure for Prescribing Medicinal Products, Prescription Form Templates for Medicinal Products, the Procedure for Issuing These Forms, Their Accounting and Storage, Prescription Form Templates Containing Prescriptions for Narcotic Drugs or Psychotropic Substances, the Procedure for Their Manufacture, Distribution, Registration, Accounting and Storage, as well as the Rules for Issuing Prescription Forms, Including in the Form of Electronic Documents"

2. International Statistical Classification of Diseases and Related Health Problems (ICD-10);

3. Order of the Ministry of Health of the Russian Federation No. 1183n dated December 20, 2012, "On Approval of the Nomenclature of Positions for Medical and Pharmaceutical Workers".

4. Order of the Ministry of Health of the Russian Federation No. 541n dated July 23, 2010. Unified Qualification Handbook of Positions of Managers, Specialists and Employees, Section: Qualification Characteristics of Healthcare Workers' Positions.

5. Federal Law No. 489-FZ dated December 25, 2018, "On Amendments to Article 40 of the Federal Law 'On Compulsory Medical Insurance in the Russian Federation' and the Federal Law 'On the Fundamentals of Protecting the Health of Citizens in the Russian Federation' Regarding Clinical Guidelines".

6. Order of the Russian Ministry of Health No. 103n dated February 28, 2019, "On Approval of the Procedure and Deadlines for the Development of Clinical Guidelines, Their Revision, the Standard Template of Clinical Guidelines and Requirements for Their Structure, Composition and Scientific Validity of Information Included in Clinical Guidelines".

7. Order of the Russian Ministry of Health No. 804n dated October 13, 2017, "On Approval of the Nomenclature of Medical Services".

8. Order of the Russian Ministry of Health No. 1008n dated September 23, 2020, "On Approval of the Procedure for Providing Patients with Medical Nutrition"

9. Order of the Russian Ministry of Health No. 321n dated June 7, 2018, "On Approval of Lists of Medical Indications and Contraindications for Sanatorium-Resort Treatment" (Registered with the Ministry of Justice of Russia on July 2, 2018, No. 51503). Access mode: https://rg.ru/2018/07/04/minzdrav-prikaz-321-site-dok.html

10. Letter of the Ministry of Health and Social Development of the Russian Federation No. 14-5/10/2-4265 dated May 29, 2009, "On Referring Children for Sanatorium-Resort Treatment to Sanatorium-Resort Institutions under the Jurisdiction of the Ministry of Health and Social Development of Russia"

Appendix A3.2 Examples of diagnoses

o Bilateral nephrolithiasis. Primary hyperoxaluria type I. Nephrocalcinosis, stage 2. Chronic kidney disease, stage 1–2.

o Left kidney stone. Calcium oxalate urolithiasis. Secondary calculous pyelonephritis in clinical and laboratory remission stage. Chronic kidney disease stage 1.

Appendix A3.3 Genetic causes of urolithiasis

Appendix A3.4 Decoding of notes

** – a medicinal product included in the Order of the Government of the Russian Federation No. 2406-r dated October 12, 2019 (as amended on June 9, 2023) "On Approval of the List of Vital and Essential Drugs, as well as Lists of Medicinal Products for Medical Use and the Minimum Assortment of Medicinal Products Required for the Provision of Medical Care"

# - The use of a medicinal product in accordance with indications (characteristics) not specified in its instructions for use (off-label) is carried out by decision of the medical commission subject to the signed informed voluntary consent (pursuant to Federal Law No. 323-FZ of November 21, 2011, as amended).

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

Urolithiasis is a concept that unites a large group of syndromes and diseases heterogeneous in etiology and pathogenesis, one of the clinical and morphological manifestations of which is the formation of calculi in the urinary system organs, affecting both males and females.

The prognosis of urolithiasis with timely and proper treatment is relatively favorable. Following surgical treatment, long-term anti-relapse therapy is indicated, taking into account the chemical composition of the stones, urine pH, presence of urinary tract infection, and renal function status.

The results of some studies indicate that the risk of stone formation depends on lifestyle-related factors, such as physical inactivity, overweight and obesity, living in a hot climate, and insufficient intake of clean water or water containing excessive amounts of salts.

The main areas for the prevention of stone formation and outpatient treatment are the correction of metabolic disorders of stone-forming substances. Adherence to stone prevention regimens ensures a favorable prognosis and improves the quality of life of children with urolithiasis, preventing disability.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Not used