urovestВестник урологииUrology Herald2308-6424Rostov State Medical University10.21886/2308-6424-2025-13-3-126-136urovest-1089Research ArticleОБЗОРЫ ЛИТЕРАТУРЫREVIEWS ARTICLEАктуальные аспекты терапии пациентов с цистиновым нефролитиазомCystine nephrolithiasis: contemporary approaches to patient managementhttps://orcid.org/0000-0003-4876-183XГелигВ. А.GeligV. A.

Виталий Аркадьевич Гелиг

Санкт-Петербург

Vitalii A. Gelig

St. Petersburg

vgelig@yandex.ruhttps://orcid.org/0000-0002-0236-3302ЛеоноваЕ. И.LeonovaE. I.

Елена Ивановна Леонова — канд. биол. наук.

Санкт-Петербург

Elena I. Leonova — Cand.Sc. (Biol)

St. Petersburg

e.leonova@spbu.ruhttps://orcid.org/0000-0002-7592-8167ГореловД. С.GorelovD. S.

Дмитрий Сергеевич Горелов

Санкт-Петербург

Dmitri S. Gorelov

St. Petersburg

dsgorelov@mail.ruhttps://orcid.org/0000-0003-3246-7337СеменякинИ. В.SemenyakinI. V.

Игорь Владимирович Семенякин — д-р мед. наук.

Москва

Igor V. Semenyakin — Dr.Sc.(Med)

Moscow

dr.semeniakin@gmail.comhttps://orcid.org/0000-0002-6255-0193ГаджиевН. К.GadzhievN. K.

Нариман Казиханович Гаджиев — д-р мед. наук.

Санкт-Петербург

Nariman K. Gadzhiev — Dr.Sc.(Med.)

St. Petersburg

nariman.gadjiev@gmail.comКлиника высоких медицинских технологий им. Н.И. Пирогова — Санкт-Петербургский государственный университетРоссияPirogov Clinic of Advanced Medical Technologies — St. Petersburg State UniversityRussian FederationЦентр трансгенеза и редактирования генома — Санкт-Петербургский государственный университетРоссияCentre for Transgenesis and Genome Editing — St. Petersburg State UniversityRussian FederationПервый Санкт-Петербургский государственный медицинский университет им. акад. И. П. ПавловаРоссияPavlov First St. Petersburg State Medical UniversityRussian FederationКлинико-диагностический центр «МЕДСИ»Россия«MEDSI» Clinical and Diagnostic CentreRussian FederationКлиника высоких медицинских технологий им. Н.И. Пирогова — Санкт-Петербургский государственный университет; Центр трансгенеза и редактирования генома — Санкт-Петербургский государственный университетРоссияPirogov Clinic of Advanced Medical Technologies — St. Petersburg State University; Centre for Transgenesis and Genome Editing — St. Petersburg State UniversityRussian Federation202530072025133126136Copyright © Гелиг В.А., Леонова Е.И., Горелов Д.С., Семенякин И.В., Гаджиев Н.К., 20252025Гелиг В.А., Леонова Е.И., Горелов Д.С., Семенякин И.В., Гаджиев Н.К.Gelig V.A., Leonova E.I., Gorelov D.S., Semenyakin I.V., Gadzhiev N.K.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.urovest.ru/jour/article/view/1089Введение

Введение. Цистинурия — редкое генетическое заболевание, при котором в моче многократно повышена концентрация цистина. Ввиду низкой растворимости цистина в моче пациенты с цистинурией на протяжении всей жизни имеют повышенный риск образования мочевых камней. Крайне высокая частота рецидивирования требует проведения профилактики. С учётом отсутствия у большинства практикующих урологов опыта ведения пациентов с цистиновым нефролитиазом ввиду крайне низкой распространённости заболевания актуальной задачей является разработка методических рекомендаций по проведению профилактики рецидива.

Цель исследования

Цель исследования. Обобщить данные мировой литературы по ведению пациентов с цистиновым нефролитиазом и представить алгоритм проведения профилактики заболевания.

Материалы и методы

Материалы и методы. Произведён систематический обзор литературы по зарубежным и отечественным научным базам данных с использованием ключевых слов: “cystine”, “cystine stones”, “cystinuria”, «цистин», «цистиновый нефролитиаз», «цистинурия». Проработаны 247 источников литературы, из которых в обзор включены 45.

Результаты

Результаты. Несмотря на неустранимую в настоящий момент генетическую причину цистинурии, профилактика камнеобразования существенно снижает частоту рецидивирования мочекаменной болезни у таких пациентов. Профилактика цистинового нефролитиаза представляет собой мультимодальное этапное лечение. Оно заключается в уменьшении концентрации цистина в моче за счёт применения диетических стратегий и повышении его растворимости в моче благодаря её ощелачиванию, а также в использовании цистин-связывающих препаратов. В данной статье приведён пошаговый алгоритм проведения профилактики цистинового нефролитиаза, основанный на клиническом течении заболевания и таких объективных показателях, как суточная экскреция цистина и pH мочи.

Заключение

Заключение. Существующие алгоритмы проведения профилактики цистинового нефролитиаза с использованием немедикаментозных и медикаментозных подходов доступны для применения в клинической практике и позволяют снизить частоту рецидивирования этого заболевания.

Introduction

Introduction. Cystinuria is a rare genetic disorder characterised by a markedly elevated concentration of cystine in the urine. Due to the low solubility of cystine in urine, patients with cystinuria face a lifelong increased risk of urinary stone formation. The exceptionally high recurrence rate necessitates the implementation of preventive measures. Given that most practising urologists have limited experience managing patients with cystine nephrolithiasis due to the disease’s rarity, the development of clinical guidelines for recurrence prevention represents a pressing need.

Objective

Objective. To summarize the world literature on managing patients with cystine nephrolithiasis and present an algorithm for preventing the disease.

Materials & methods

Materials & methods. A systematic review of the literature in foreign and domestic scientific databases was conducted using the keywords: “cystine”, “cystine stones”, “cystinuria”, “cystine”, “cystine nephrolithiasis”, “cystinuria”. Two hundred forty-seven sources of literature were processed, 45 of which were included in the review.

Results

Results. Despite the currently irreversible genetic cause of cystinuria, the implementation of stone prevention strategies significantly reduces the recurrence rate of urolithiasis in affected patients. Prevention of cystine nephrolithiasis involves a multimodal, stepwise treatment approach. This includes reducing urinary cystine concentration through dietary modifications and increasing its solubility by alkalinising the urine, as well as the use of cystine-binding agents. This article presents a step-by-step algorithm for the prevention of cystine nephrolithiasis, based on the clinical course of the disease and objective parameters such as 24-hour cystine excretion and urinary pH.

Conclusion

Conclusion. Current algorithms for preventing cystine nephrolithiasis, which combine both non-pharmacological and pharmacological strategies, are readily applicable in clinical practice and have been shown to effectively reduce the recurrence of this condition.

цистинцистинуриянефролитиазмочекаменная болезньcystinecystinurianephrolithiasisurolithiasisРабота выполнена при поддержке Санкт-Петербургского государственного университета, проект ID 129658320The research was carried out with the support of St. Petersburg State University, project ID 129658320ReferencesBiyani CS, Cartledge JJ. Cystinuria—diagnosis and management. EAU-EBU Update Ser. 2006;4(5):175-183. DOI: 10.1016/j.eeus.2006.06.001Biyani CS, Cartledge JJ. Cystinuria—diagnosis and management. EAU-EBU Update Ser. 2006;4(5):175-183. DOI: 10.1016/j.eeus.2006.06.001Reinstatler L, Stern K, Batter H, Scotland KB, Ardekani GS, Rivera M, Chew BH, Eisner B, Krambeck AE, Monga M, Pais VM Jr. Conversion from Cystine to Noncystine Stones: Incidence and Associated Factors. J Urol. 2018;200(6):1285-1289. Erratum in: J Urol. 2019;201(3):629. DOI: 10.1016/j.juro.2018.07.047Reinstatler L, Stern K, Batter H, Scotland KB, Ardekani GS, Rivera M, Chew BH, Eisner B, Krambeck AE, Monga M, Pais VM Jr. Conversion from Cystine to Noncystine Stones: Incidence and Associated Factors. J Urol. 2018;200(6):1285-1289. Erratum in: J Urol. 2019;201(3):629. DOI: 10.1016/j.juro.2018.07.047Andreassen KH, Pedersen KV, Osther SS, Jung HU, Lildal SK, Osther PJ. How should patients with cystine stone disease be evaluated and treated in the twenty-first century? Urolithiasis. 2016;44(1):65-76. DOI: 10.1007/s00240-015-0841-xAndreassen KH, Pedersen KV, Osther SS, Jung HU, Lildal SK, Osther PJ. How should patients with cystine stone disease be evaluated and treated in the twenty-first century? Urolithiasis. 2016;44(1):65-76. DOI: 10.1007/s00240-015-0841-xEisner BH, Goldfarb DS, Baum MA, Langman CB, Curhan GC, Preminger GM, Lieske JC, Pareek G, Thomas K, Zisman AL, Papagiannopoulos D, Sur RL. Evaluation and Medical Management of Patients with Cystine Nephrolithiasis: A Consensus Statement. J Endourol. 2020;34(11):1103-1110. DOI: 10.1089/end.2019.0703Eisner BH, Goldfarb DS, Baum MA, Langman CB, Curhan GC, Preminger GM, Lieske JC, Pareek G, Thomas K, Zisman AL, Papagiannopoulos D, Sur RL. Evaluation and Medical Management of Patients with Cystine Nephrolithiasis: A Consensus Statement. J Endourol. 2020;34(11):1103-1110. DOI: 10.1089/end.2019.0703Shen L, Cong X, Zhang X, Wang N, Zhou P, Xu Y, Zhu Q, Gu X. Clinical and genetic characterization of Chinese pediatric cystine stone patients. J Pediatr Urol. 2017;13(6):629.e1-629.e5. DOI: 10.1016/j.jpurol.2017.05.021Shen L, Cong X, Zhang X, Wang N, Zhou P, Xu Y, Zhu Q, Gu X. Clinical and genetic characterization of Chinese pediatric cystine stone patients. J Pediatr Urol. 2017;13(6):629.e1-629.e5. DOI: 10.1016/j.jpurol.2017.05.021Servais A, Thomas K, Dello Strologo L, Sayer JA, Bekri S, Bertholet-Thomas A, Bultitude M, Capolongo G, Cerkauskiene R, Daudon M, Doizi S, Gillion V, Gràcia-Garcia S, Halbritter J, Heidet L, van den Heijkant M, Lemoine S, Knebelmann B, Emma F, Levtchenko E; Metabolic Nephropathy Workgroup of the European Reference Network for Rare Kidney Diseases (ERKNet) and eUROGEN. Cystinuria: clinical practice recommendation. Kidney Int. 2021;99(1):48-58. DOI: 10.1016/j.kint.2020.06.035Servais A, Thomas K, Dello Strologo L, Sayer JA, Bekri S, Bertholet-Thomas A, Bultitude M, Capolongo G, Cerkauskiene R, Daudon M, Doizi S, Gillion V, Gràcia-Garcia S, Halbritter J, Heidet L, van den Heijkant M, Lemoine S, Knebelmann B, Emma F, Levtchenko E; Metabolic Nephropathy Workgroup of the European Reference Network for Rare Kidney Diseases (ERKNet) and eUROGEN. Cystinuria: clinical practice recommendation. Kidney Int. 2021;99(1):48-58. DOI: 10.1016/j.kint.2020.06.035Bouzidi H, Daudon M. Cystinurie : du diagnostic à la surveillance thérapeutique [Cystinuria: from diagnosis to follow-up]. Ann Biol Clin (Paris). 2007;65(5):473-481. (In French). PMID: 17913667Bouzidi H, Daudon M. Cystinurie : du diagnostic à la surveillance thérapeutique [Cystinuria: from diagnosis to follow-up]. Ann Biol Clin (Paris). 2007;65(5):473-481. (In French). PMID: 17913667DENT CE, Friedman M, Green H, Watson LC. Treatment of cystinuria. Br Med J. 1965;1(5432):403-408. PMID: 14237920DENT CE, Friedman M, Green H, Watson LC. Treatment of cystinuria. Br Med J. 1965;1(5432):403-408. PMID: 14237920Tiselius HG. New horizons in the management of patients with cystinuria. Curr Opin Urol. 2010;20(2):169-173. DOI: 10.1097/MOU.0b013e328333b674Tiselius HG. New horizons in the management of patients with cystinuria. Curr Opin Urol. 2010;20(2):169-173. DOI: 10.1097/MOU.0b013e328333b674Akakura K, Egoshi K, Ueda T, Nozumi K, Kotake T, Masai M, Ito H. The long-term outcome of cystinuria in Japan. Urol Int. 1998;61(2):86-89. DOI: 10.1159/000030294Akakura K, Egoshi K, Ueda T, Nozumi K, Kotake T, Masai M, Ito H. The long-term outcome of cystinuria in Japan. Urol Int. 1998;61(2):86-89. DOI: 10.1159/000030294Горбачевский П.Р., Парамонова Н.С., Юрага Т.М., Гресь Н.А. Нормальные значения экскреции аминокислот цистина, лизина и аргинина у здоровых детей и у пациентов с дисметаболической нефропатией. Нефрология. 2017;21(3):81-86. DOI: 10.24884/1561-6274-2017-3-81-86Gorbachevsky P.R., Paramonava N.S., Juraga T.M., Gres N.A. Refe­rence values of the amino acids cystine, lysine and arginine excretion in healthy children and in patients with dysmethabolic nephropathy. Nephrology (Saint-Petersburg). 2017;21(3):81-86. (In Russian). DOI: 10.24884/1561-6274-2017-3-81-86Pak CY, Fuller CJ. Assessment of cystine solubility in urine and of heterogeneous nucleation. J Urol. 1983;129(5):1066-1070. DOI: 10.1016/s0022-5347(17)52543-4Pak CY, Fuller CJ. Assessment of cystine solubility in urine and of heterogeneous nucleation. J Urol. 1983;129(5):1066-1070. DOI: 10.1016/s0022-5347(17)52543-4van Hoeve K, Vermeersch P, Regal L, Levtchenko E. Necessity of fractionated urine collection for monitoring patients with cystinuria. Clin Chem. 2011;57(5):780-781. DOI: 10.1373/clinchem.2010.161547van Hoeve K, Vermeersch P, Regal L, Levtchenko E. Necessity of fractionated urine collection for monitoring patients with cystinuria. Clin Chem. 2011;57(5):780-781. DOI: 10.1373/clinchem.2010.161547Rodman JS, Blackburn P, Williams JJ, Brown A, Pospischil MA, Peterson CM. The effect of dietary protein on cystine excretion in patients with cystinuria. Clin Nephrol. 1984;22(6):273-278. PMID: 6441658Rodman JS, Blackburn P, Williams JJ, Brown A, Pospischil MA, Peterson CM. The effect of dietary protein on cystine excretion in patients with cystinuria. Clin Nephrol. 1984;22(6):273-278. PMID: 6441658Gillion V, Saussez TP, Van Nieuwenhove S, Jadoul M. Extremely rapid stone formation in cystinuria: look out for dietary supplements! Clin Kidney J. 2021;14(6):1694-1696. DOI: 10.1093/ckj/sfab013Gillion V, Saussez TP, Van Nieuwenhove S, Jadoul M. Extremely rapid stone formation in cystinuria: look out for dietary supplements! Clin Kidney J. 2021;14(6):1694-1696. DOI: 10.1093/ckj/sfab013Jendle-Bengten C, Tiselius HG. Long-term follow-up of stone formers treated with a low dose of sodium potassium citrate. Scand J Urol Nephrol. 2000;34(1):36-41. DOI: 10.1080/003655900750016869Jendle-Bengten C, Tiselius HG. Long-term follow-up of stone formers treated with a low dose of sodium potassium citrate. Scand J Urol Nephrol. 2000;34(1):36-41. DOI: 10.1080/003655900750016869Nagamori S, Wiriyasermkul P, Guarch ME, Okuyama H, Nakagomi S, Tadagaki K, Nishinaka Y, Bodoy S, Takafuji K, Okuda S, Kurokawa J, Ohgaki R, Nunes V, Palacín M, Kanai Y. Novel cystine transporter in renal proximal tubule identified as a missing partner of cystinuria-related plasma membrane protein rBAT/SLC3A1. Proc Natl Acad Sci U S A. 2016;113(3):775-780. DOI: 10.1073/pnas.1519959113Nagamori S, Wiriyasermkul P, Guarch ME, Okuyama H, Nakagomi S, Tadagaki K, Nishinaka Y, Bodoy S, Takafuji K, Okuda S, Kurokawa J, Ohgaki R, Nunes V, Palacín M, Kanai Y. Novel cystine transporter in renal proximal tubule identified as a missing partner of cystinuria-related plasma membrane protein rBAT/SLC3A1. Proc Natl Acad Sci U S A. 2016;113(3):775-780. DOI: 10.1073/pnas.1519959113Chillarón J, Font-Llitjós M, Fort J, Zorzano A, Goldfarb DS, Nunes V, Palacín M. Pathophysiology and treatment of cystinuria. Nat Rev Nephrol. 2010;6(7):424-434. DOI: 10.1038/nrneph.2010.69Chillarón J, Font-Llitjós M, Fort J, Zorzano A, Goldfarb DS, Nunes V, Palacín M. Pathophysiology and treatment of cystinuria. Nat Rev Nephrol. 2010;6(7):424-434. DOI: 10.1038/nrneph.2010.69Claes DJ, Jackson E. Cystinuria: mechanisms and management. Pediatr Nephrol. 2012;27(11):2031-2038. DOI: 10.1007/s00467-011-2092-6Claes DJ, Jackson E. Cystinuria: mechanisms and management. Pediatr Nephrol. 2012;27(11):2031-2038. DOI: 10.1007/s00467-011-2092-6Гаджиев Н.К., Бровкин С.С., Григорьев В.Е., Дмитриев В.В., Малхасян В.А., Шкарупа Д.Д., Писарев А.В., Мазуренко Д.А., Обидняк В.М., Попов С.В., Тагиров Н.С., Король В.Д., Петров С.Б. Метафилактика мочекаменной болезни в смартфоне, или mHealth по-русски. Педиатр. 2016;(7):84-91. DOI: 10.17816/PED7384-91Gadzhiev N.K., Brovkin S.S., Grigoryev V.E., Dmitriev V.V., Malkhasyan V.A., Shkarupa D.D., Pisarev A.V., Mazurenko D.A., Obidnyak V.M., Popov S.V., Tagirov N.S., Korol V.D., Petrov S.B. Metaphylaxis Of Stone Disease In Smartphone Or Russian mHEALTH. Pediatrician (St. Petersburg). 2016;7(3):84-91. (In Russian). DOI: 10.17816/PED7384-91Siener R, Bitterlich N, Birwé H, Hesse A. The Impact of Diet on Urinary Risk Factors for Cystine Stone Formation. Nutrients. 2021;13(2):528. DOI: 10.3390/nu13020528Siener R, Bitterlich N, Birwé H, Hesse A. The Impact of Diet on Urinary Risk Factors for Cystine Stone Formation. Nutrients. 2021;13(2):528. DOI: 10.3390/nu13020528Гаджиев Н.К., Гелиг В.А., Кутина А.В., Горгоцкий И.A., Kapпищeнкo А.И., Горелов Д.С., Семенякин И.В., Закуцкий А.Н., Кулешов О.В., Шкарупа Д.Д. Кислотно-основное состояние (pH) мочи: механизм регуляции и его роль в метафилактике мочекаменной болезни. Вестник урологии. 2022;10(4):120-140. DOI: 10.21886/2308-6424-2022-10-4-120-140Gadzhiev N.K., Gelig V.A., Kutina A.V., Gorgotsky I.A., Karpishchenko A.I., Gorelov D.S., Semenyakin I.V., Zakutsky A.N., Kuleshov O.V., Shkarupa D.D. Urinary pH: its regulation and relevance in urolithiasis metaphylaxis. Urology Herald. 2022;10(4):120-140. DOI: 10.21886/2308-6424-2022-10-4-120-140Sterrett SP, Penniston KL, Wolf JS Jr, Nakada SY. Acetazolamide is an effective adjunct for urinary alkalization in patients with uric acid and cystine stone formation recalcitrant to potassium citrate. Urology. 2008;72(2):278-281. DOI: 10.1016/j.urology.2008.04.003Sterrett SP, Penniston KL, Wolf JS Jr, Nakada SY. Acetazolamide is an effective adjunct for urinary alkalization in patients with uric acid and cystine stone formation recalcitrant to potassium citrate. Urology. 2008;72(2):278-281. DOI: 10.1016/j.urology.2008.04.003Dolin DJ, Asplin JR, Flagel L, Grasso M, Goldfarb DS. Effect of cystine-binding thiol drugs on urinary cystine capacity in patients with cystinuria. J Endourol. 2005;19(3):429-432. DOI: 10.1089/end.2005.19.429Dolin DJ, Asplin JR, Flagel L, Grasso M, Goldfarb DS. Effect of cystine-binding thiol drugs on urinary cystine capacity in patients with cystinuria. J Endourol. 2005;19(3):429-432. DOI: 10.1089/end.2005.19.429DeBerardinis RJ, Coughlin CR 2nd, Kaplan P. Penicillamine therapy for pediatric cystinuria: experience from a cohort of American children. J Urol. 2008;180(6):2620-2623. DOI: 10.1016/j.juro.2008.08.057DeBerardinis RJ, Coughlin CR 2nd, Kaplan P. Penicillamine therapy for pediatric cystinuria: experience from a cohort of American children. J Urol. 2008;180(6):2620-2623. DOI: 10.1016/j.juro.2008.08.057Kumar V, Singh AP, Wheeler N, Galindo CL, Kim JJ. Safety profile of D-penicillamine: a comprehensive pharmacovigilance analysis by FDA adverse event reporting system. Expert Opin Drug Saf. 2021;20(11):1443-1450. DOI: 10.1080/14740338.2021.1956460Kumar V, Singh AP, Wheeler N, Galindo CL, Kim JJ. Safety profile of D-penicillamine: a comprehensive pharmacovigilance analysis by FDA adverse event reporting system. Expert Opin Drug Saf. 2021;20(11):1443-1450. DOI: 10.1080/14740338.2021.1956460Joly D, Rieu P, Méjean A, Gagnadoux MF, Daudon M, Jungers P. Treatment of cystinuria. Pediatr Nephrol. 1999;13(9):945-950. DOI: 10.1007/s004670050736Joly D, Rieu P, Méjean A, Gagnadoux MF, Daudon M, Jungers P. Treatment of cystinuria. Pediatr Nephrol. 1999;13(9):945-950. DOI: 10.1007/s004670050736Rezaee ME, Rule AD, Pais VM Jr. What are the main challenges to the pharmacological management of cystinuria? Expert Opin Pharmacother. 2020;21(2):131-133. DOI: 10.1080/14656566.2019.1691522Rezaee ME, Rule AD, Pais VM Jr. What are the main challenges to the pharmacological management of cystinuria? Expert Opin Pharmacother. 2020;21(2):131-133. DOI: 10.1080/14656566.2019.1691522Prot-Bertoye C, Lebbah S, Daudon M, Tostivint I, Bataille P, Bridoux F, Brignon P, Choquenet C, Cochat P, Combe C, Conort P, Decramer S, Doré B, Dussol B, Essig M, Gaunez N, Joly D, Le Toquin-Bernard S, Méjean A, Meria P, Morin D, N’Guyen HV, Noël C, Normand M, Pietak M, Ronco P, Saussine C, Tsimaratos M, Friedlander G, Traxer O, Knebelmann B, Courbebaisse M; French Cystinuria Group. CKD and Its Risk Factors among Patients with Cystinuria. Clin J Am Soc Nephrol. 2015;10(5):842-851. DOI: 10.2215/CJN.06680714Prot-Bertoye C, Lebbah S, Daudon M, Tostivint I, Bataille P, Bridoux F, Brignon P, Choquenet C, Cochat P, Combe C, Conort P, Decramer S, Doré B, Dussol B, Essig M, Gaunez N, Joly D, Le Toquin-Bernard S, Méjean A, Meria P, Morin D, N’Guyen HV, Noël C, Normand M, Pietak M, Ronco P, Saussine C, Tsimaratos M, Friedlander G, Traxer O, Knebelmann B, Courbebaisse M; French Cystinuria Group. CKD and Its Risk Factors among Patients with Cystinuria. Clin J Am Soc Nephrol. 2015;10(5):842-851. DOI: 10.2215/CJN.06680714Prot-Bertoye C, Lebbah S, Daudon M, Tostivint I, Jais JP, Lillo-Le Louët A, Pontoizeau C, Cochat P, Bataille P, Bridoux F, Brignon P, Choquenet C, Combe C, Conort P, Decramer S, Doré B, Dussol B, Essig M, Frimat M, Gaunez N, Joly D, Le Toquin-Bernard S, Méjean A, Meria P, Morin D, N’Guyen HV, Normand M, Pietak M, Ronco P, Saussine C, Tsimaratos M, Friedlander G, Traxer O, Knebelmann B, Courbebaisse M; French Cystinuria Group. Adverse events associated with currently used medical treatments for cystinuria and treatment goals: results from a series of 442 patients in France. BJU Int. 2019;124(5):849-861. DOI: 10.1111/bju.14721Prot-Bertoye C, Lebbah S, Daudon M, Tostivint I, Jais JP, Lillo-Le Louët A, Pontoizeau C, Cochat P, Bataille P, Bridoux F, Brignon P, Choquenet C, Combe C, Conort P, Decramer S, Doré B, Dussol B, Essig M, Frimat M, Gaunez N, Joly D, Le Toquin-Bernard S, Méjean A, Meria P, Morin D, N’Guyen HV, Normand M, Pietak M, Ronco P, Saussine C, Tsimaratos M, Friedlander G, Traxer O, Knebelmann B, Courbebaisse M; French Cystinuria Group. Adverse events associated with currently used medical treatments for cystinuria and treatment goals: results from a series of 442 patients in France. BJU Int. 2019;124(5):849-861. DOI: 10.1111/bju.14721Cohen TD, Streem SB, Hall P. Clinical effect of captopril on the formation and growth of cystine calculi. J Urol. 1995;154(1):164-166. PMID: 7776415Cohen TD, Streem SB, Hall P. Clinical effect of captopril on the formation and growth of cystine calculi. J Urol. 1995;154(1):164-166. PMID: 7776415Biyani CS, Palit V, Daga S. The Use of Captopril-Angiotensin Converting Enzyme (ACE) Inhibitor for Cystinuria During COVID-19 Pandemic. Urology. 2020;141:182-183. DOI: 10.1016/j.urology.2020.04.057Biyani CS, Palit V, Daga S. The Use of Captopril-Angiotensin Converting Enzyme (ACE) Inhibitor for Cystinuria During COVID-19 Pandemic. Urology. 2020;141:182-183. DOI: 10.1016/j.urology.2020.04.057Fattah H, Hambaroush Y, Goldfarb DS. Cystine nephrolithiasis. Transl Androl Urol. 2014;3(3):228-233. DOI: 10.3978/j.issn.2223-4683.2014.07.04Fattah H, Hambaroush Y, Goldfarb DS. Cystine nephrolithiasis. Transl Androl Urol. 2014;3(3):228-233. DOI: 10.3978/j.issn.2223-4683.2014.07.04Dello Strologo L, Laurenzi C, Legato A, Pastore A. Cystinuria in children and young adults: success of monitoring free-cystine urine levels. Pediatr Nephrol. 2007;22(11):1869-1873. DOI: 10.1007/s00467-007-0575-2Dello Strologo L, Laurenzi C, Legato A, Pastore A. Cystinuria in children and young adults: success of monitoring free-cystine urine levels. Pediatr Nephrol. 2007;22(11):1869-1873. DOI: 10.1007/s00467-007-0575-2Гаджиев Н.К., Горелов Д.С., Акопян Г.Н., Гелиг В.А., Иванов А.О., Петров С.Б., Крюкова Н.Ю., Рева С.А., Пономарева Ю.А., Аль-Шукри А.С., Мищенко А.А., Когай М.А., Васильев В.Н., Чернышева Д.Ю., Обидняк В.М., Макарьин В.А., Писарев А.В., Закуцкий А.Н., Кузьмин И.В., Амдий Р.Э., Корнеев И.А., Аль-Шукри С.Х. «Школы пациентов» с мочекаменной болезнью и заболеваниями предстательной железы. Вестник урологии. 2020;8(1):110-120. DOI: 10.21886/2308-6424-2020-8-1-110-120Gadjiev N.K., Gorelov D.S., Akopyan G.N., Gelig V.A., Ivanov A.O., Petrov S.B., Kryukova N.U., Reva S.A., Ponomareva Yu.A., Al-Shukri A.S., Mischenko A.A., Kogai M.A., Vasiliev V.N., Chernysheva D.Yu., Obidnyak V.M., Makar’in V.A., Pisarev A.V., Zakuckij A.N., Kuzmin I.V., Amdiy R.E., Korneye I.A., Al-Shukri S.H. «Schools for Patients» with Urolithiasis and Prostatic Diseases. Urology Herald. 2020;8(1):110-120. DOI: 10.21886/2308-6424-2020-8-1-110-120Daga S, Palit V, Forster JA, Biyani CS, Joyce AD, Dimitrova AB. An Update on Evaluation and Management in Cystinuria. Urology. 2021;149:70-75. DOI: 10.1016/j.urology.2020.12.025Daga S, Palit V, Forster JA, Biyani CS, Joyce AD, Dimitrova AB. An Update on Evaluation and Management in Cystinuria. Urology. 2021;149:70-75. DOI: 10.1016/j.urology.2020.12.025Hu L, Yang Y, Aloysius H, Albanyan H, Yang M, Liang JJ, Yu A, Shtukenberg A, Poloni LN, Kholodovych V, Tischfield JA, Goldfarb DS, Ward MD, Sahota A. l-Cystine Diamides as l-Cystine Crystallization Inhibitors for Cystinuria. J Med Chem. 2016;59(15):7293-7298. DOI: 10.1021/acs.jmedchem.6b00647Hu L, Yang Y, Aloysius H, Albanyan H, Yang M, Liang JJ, Yu A, Shtukenberg A, Poloni LN, Kholodovych V, Tischfield JA, Goldfarb DS, Ward MD, Sahota A. l-Cystine Diamides as l-Cystine Crystallization Inhibitors for Cystinuria. J Med Chem. 2016;59(15):7293-7298. DOI: 10.1021/acs.jmedchem.6b00647Yang Y, Albanyan H, Lee S, Aloysius H, Liang JJ, Kholodovych V, Sahota A, Hu L. Design, synthesis, and evaluation of l-cystine diamides as l-cystine crystallization inhibitors for cystinuria. Bioorg Med Chem Lett. 2018;28(8):1303-1308. DOI: 10.1016/j.bmcl.2018.03.024Yang Y, Albanyan H, Lee S, Aloysius H, Liang JJ, Kholodovych V, Sahota A, Hu L. Design, synthesis, and evaluation of l-cystine diamides as l-cystine crystallization inhibitors for cystinuria. Bioorg Med Chem Lett. 2018;28(8):1303-1308. DOI: 10.1016/j.bmcl.2018.03.024Zee T, Bose N, Zee J, Beck JN, Yang S, Parihar J, Yang M, Damodar S, Hall D, O’Leary MN, Ramanathan A, Gerona RR, Killilea DW, Chi T, Tischfield J, Sahota A, Kahn A, Stoller ML, Kapahi P. α-Lipoic acid treatment prevents cystine urolithiasis in a mouse model of cystinuria. Nat Med. 2017;23(3):288-290. DOI: 10.1038/nm.4280Zee T, Bose N, Zee J, Beck JN, Yang S, Parihar J, Yang M, Damodar S, Hall D, O’Leary MN, Ramanathan A, Gerona RR, Killilea DW, Chi T, Tischfield J, Sahota A, Kahn A, Stoller ML, Kapahi P. α-Lipoic acid treatment prevents cystine urolithiasis in a mouse model of cystinuria. Nat Med. 2017;23(3):288-290. DOI: 10.1038/nm.4280Chi T. Lipoic Acid Supplement for Cystine Stone (ALA). Accessed on 8 January 2023. URL:https://clinicaltrials.gov/ct2/show/NCT02910531Chi T. Lipoic Acid Supplement for Cystine Stone (ALA). Accessed on 8 January 2023. URL:https://clinicaltrials.gov/ct2/show/NCT02910531Cil O, Perwad F. α-Lipoic Acid (ALA) Improves Cystine Solubility in Cystinuria: Report of 2 Cases. Pediatrics. 2020;145(5):e20192951. DOI: 10.1542/peds.2019-2951Cil O, Perwad F. α-Lipoic Acid (ALA) Improves Cystine Solubility in Cystinuria: Report of 2 Cases. Pediatrics. 2020;145(5):e20192951. DOI: 10.1542/peds.2019-2951Stoller M.L. Long Term Clinical Efficacy of Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitor in Cystinurics. Accessed on 8 January 2023. URL:https://clinicaltrials.gov/ct2/show/NCT05058859eStoller M.L. Long Term Clinical Efficacy of Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitor in Cystinurics. Accessed on 8 January 2023. URL:https://clinicaltrials.gov/ct2/show/NCT05058859eBai Y, Tang Y, Wang J, Wang X, Wang Z, Cao D, Han P, Wang J. Tolvaptan treatment of cystine urolithiasis in a mouse model of cystinuria. World J Urol. 2021;39(1):263-269. DOI: 10.1007/s00345-020-03166-3Bai Y, Tang Y, Wang J, Wang X, Wang Z, Cao D, Han P, Wang J. Tolvaptan treatment of cystine urolithiasis in a mouse model of cystinuria. World J Urol. 2021;39(1):263-269. DOI: 10.1007/s00345-020-03166-3Nelson CP, Kurtz MP, Venna A, Cilento BG Jr, Baum MA. Pharmacological Dilutional Therapy Using the Vasopressin Antagonist Tolvaptan for Young Patients With Cystinuria: A Pilot Investigation. Urology. 2020;144:65-70. DOI: 10.1016/j.urology.2020.07.002Nelson CP, Kurtz MP, Venna A, Cilento BG Jr, Baum MA. Pharmacological Dilutional Therapy Using the Vasopressin Antagonist Tolvaptan for Young Patients With Cystinuria: A Pilot Investigation. Urology. 2020;144:65-70. DOI: 10.1016/j.urology.2020.07.002Peek JL, Wilson MH. Gene therapy for kidney disease: targeting cystinuria. Curr Opin Nephrol Hypertens. 2022;31(2):175-179. DOI: 10.1097/MNH.0000000000000768Peek JL, Wilson MH. Gene therapy for kidney disease: targeting cystinuria. Curr Opin Nephrol Hypertens. 2022;31(2):175-179. DOI: 10.1097/MNH.0000000000000768

The authors declare that there are no conflicts of interest present.