nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.36485/1561-6274-2025-29-4-37-43XQQPWYnefr-2493Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESУролитиаз и основной белок мочиUrolithiasis and the major urinary proteinhttps://orcid.org/0000-0002-3756-0701ВерловН. А.VerlovN. A.

Верлов Николай Алекс андрович, канд. биол. наук

188300, Россия, г. Гатчина, Ленинградская обл., мкр. Орлова Роща, д. 1

+7(813)714-60-93

Nikolay A. Verlov, Ph.D.

188300, Russia, Leningradskaya oblast, Gatchina 1, mkr. Orlova roshcha

Phone: +7 (813) 714-60-93

verlov_na@pnpi.nrcki.ruhttps://orcid.org/0009-0008-0164-4832ДюсуповаК. Р.DyussupovaK. R.

Дюсупова Карина Рашидовна

197022, Россия, Санкт-Петербург, ул. Л. Толстого, д. 6–8Д, корп. 11

Karina R. Dyussupova

197022, Russia, Saint-Petersburg, 197022, Russia, St-Petersburg, L. Tolstoy st., 6-8, build 11

k.dyussupova@mail.ruhttps://orcid.org/0000-0002-2079-0439ЭмануэльВ. Л.EmanuelV. L.

Проф. Эмануэль Владимир Леонидович, д-р мед. наук

197022, Россия, Санкт-Петербург, ул. Л. Толстого, д. 6–8Д

Vladimir L. Emanuel

197022, Russia, St-Petersburg, L. Tolstoy st., 6-8, build 11

vladimirem1@gmail.comПетербургский институт ядерной физики им. Б.П. Константинова, Национальный исследовательский центр «Курчатовский институт»РоссияPetersburg Nuclear Physics Institute named by B.P.Konstantinov of National Research Centre «Kurchatov Institute»Russian FederationПервый Санкт-Петербургский государственный медицинский университет им. акад. И.П. ПавловаРоссияFirst Pavlov State Medical University of St. PetersburgRussian Federation2025260120262943743Copyright © Верлов Н.А., Дюсупова К.Р., Эмануэль В.Л., 20262026Верлов Н.А., Дюсупова К.Р., Эмануэль В.Л.Verlov N.A., Dyussupova K.R., Emanuel V.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/2493

Данное исследование посвящено изучению роли уромодулина в процессах кристаллообразования при уролитиазе и его значению в эволюции биологических функций организма. Авторы прослеживают эволюционное развитие механизмов поддержания гомеостаза, начиная с простейших форм жизни и заканчивая сложными организмами. Особое внимание уделяется формированию нефрона как ключевой структурно-функциональной единицы почки, обеспечивающей контроль и регуляцию состава межклеточной жидкости. Исследование подчеркивает уникальность ренального протеома, в частности, роль уромодулина и его изоформ в реализации специфических почечных функций. Отмечается чувствительность этой системы к внешним воздействиям, которые могут привести к развитию ренальных дисфункций и системным нарушениям. Работа открывает перспективы для разработки новых терапевтических подходов, направленных на модуляцию функций уромодулина и других компонентов ренального протеома, что может привести к инновационным стратегиям в профилактике и лечении уролитиаза и связанных с ним патологий.

The pathogenetic approach to metaphylaxis of urolithiasis is a widespread, socially significant healthcare issue due to the increasing incidence and, particularly, its recurrent nature, despite advances in pharmacotherapy and the application of lithotripsy. Pathological crystal genesis is viewed as a consequence of exceeding the solubility threshold of various urinary mineral components on one hand, and as a result of post-translational defects in the main proteome of urine formation – uromodulin (UMOD), which demonstrates a sanogenetic system in healthy individuals for maintaining biophysical homeostasis stability: the colloidal properties of urine. However, in addition to this, UMOD, by binding mannose-dependent pili of infectious agents, blocks bacterial contact with urothelial cells, given that urinary tract infection is a known factor in urolithiasis. By modeling the urine of healthy individuals through co-incubation with E. coli bacteria, a decrease in the concentration of polymerized uromodulin in urine has been demonstrated as a factor increasing the risk of calcium oxalate crystal formation.

уролитиазпротеомуромодулинбиофизический гомеостазколлоидные свойства мочиurolithiasisbiocrystallomicsproteomeuromodulinbiophysical homeostasiscolloidal properties of urineE. colicalcium oxalateРабота выполнена в рамках государственного задания по теме «Изучение молекулярных и клеточных компонентов патогенеза социально-значимых заболеваний для разработки методов ранней диагностики и лечения» (регистрационный номер №121060200125-2).supported by the Ministry of Science and Higher Education of the Russian Federation (Project No. № 121060200127-6).ReferencesThe National Medical Research Centre of Radiology of Ministry of health of Russian Federation et al. The incidence of urolithiasis in the Russian Federation from 2005 to 2020. ECU 2022;15(2):10–17. https://doi.org/10.29188/2222-8543-2022-15-2-10-17The National Medical Research Centre of Radiology of Ministry of health of Russian Federation et al. The incidence of urolithiasis in the Russian Federation from 2005 to 2020. ECU 2022;15(2):10–17. https://doi.org/10.29188/2222-8543-2022-15-2-10-17Li S, Huang X, Liu S et al. Trends in the Incidence and DALYs of Urolithiasis From 1990 to 2019: Results From the Global Burden of Disease Study 2019. Front Public Health 2022;10(825541). https://doi.org/10.3389/fpubh.2022.825541Li S, Huang X, Liu S et al. Trends in the Incidence and DALYs of Urolithiasis From 1990 to 2019: Results From the Global Burden of Disease Study 2019. Front Public Health 2022;10(825541). https://doi.org/10.3389/fpubh.2022.825541Borumandnia N et al. Longitudinal trend of urolithiasis incidence rates among world countries during past decades. BMC Urol 2023;23(1):166. https://doi.org/10.1186/s12894-023-01336-0Borumandnia N et al. Longitudinal trend of urolithiasis incidence rates among world countries during past decades. BMC Urol 2023;23(1):166. https://doi.org/10.1186/s12894-023-01336-0Allam EAH. Urolithiasis unveiled: pathophysiology, stone dynamics, types, and inhibitory mechanisms: a review. Afr J Urol 2024;30(1):34. https://doi.org/10.1186/s12301-024-00436-zAllam EAH. Urolithiasis unveiled: pathophysiology, stone dynamics, types, and inhibitory mechanisms: a review. Afr J Urol 2024;30(1):34. https://doi.org/10.1186/s12301-024-00436-zO’Kell AL, Grant DC, Khan SR. Pathogenesis of calcium oxalate urinary stone disease: species comparison of humans, dogs, and cats. Urolithiasis 2017;45(4):329–336. https://doi.org/10.1007/s00240-017-0978-xO’Kell AL, Grant DC, Khan SR. Pathogenesis of calcium oxalate urinary stone disease: species comparison of humans, dogs, and cats. Urolithiasis 2017;45(4):329–336. https://doi.org/10.1007/s00240-017-0978-xAlexander RT et al. Kidney Stones and Cardiovascular Events: A Cohort Study. Clinical Journal of the American Society of Nephrology 2014;9(3):506–512. https://doi.org/10.2215/cjn.04960513Alexander RT et al. Kidney Stones and Cardiovascular Events: A Cohort Study. Clinical Journal of the American Society of Nephrology 2014;9(3):506–512. https://doi.org/10.2215/cjn.04960513Наточин ЮВ. Нефрология и фундаментальная наука. Нефрология 2012;16(1):9–21. https://doi.org/10.24884/1561-6274-2012-16-1-9-21Natochin YuV. Nephrology and fundamental science. Nephrology (Saint-Petersburg) 2012;16(1):9–21.(In Russ.) https://doi.org/10.24884/1561-6274-2012-16-1-9-21Luo W, Zhou Y, Gao C et al. Urolithiasis, Independent of Uric Acid, Increased Risk of Coronary Artery and Carotid Atherosclerosis: A Meta-Analysis of Observational Studies. BioMed Research International 2020;2020(1):1–11. https://doi.org/10.1155/2020/1026240Luo W, Zhou Y, Gao C et al. Urolithiasis, Independent of Uric Acid, Increased Risk of Coronary Artery and Carotid Atherosclerosis: A Meta-Analysis of Observational Studies. BioMed Research International 2020;2020(1):1–11. https://doi.org/10.1155/2020/1026240Tamborino F, Cicchetti R, Mascitti M et al. Pathophysiology and Main Molecular Mechanisms of Urinary Stone Formation and Recurrence. JMS 2024;25(5):3075. https://doi.org/10.3390/ijms25053075Tamborino F, Cicchetti R, Mascitti M et al. Pathophysiology and Main Molecular Mechanisms of Urinary Stone Formation and Recurrence. JMS 2024;25(5):3075. https://doi.org/10.3390/ijms25053075Argade S et al. An evaluation of Tamm–Horsfall protein glycans in kidney stone formers using novel techniques. Urolithiasis 2015;43(4):303–312. https://doi.org/10.1007/s00240-015-0775-3Argade S et al. An evaluation of Tamm–Horsfall protein glycans in kidney stone formers using novel techniques. Urolithiasis 2015;43(4):303–312. https://doi.org/10.1007/s00240-015-0775-3Armstrong JA. Urinalysis in Western culture: A brief history. Kidney International 2007;71(5):384–387. https://doi.org/10.1038/sj.ki.5002057Armstrong JA. Urinalysis in Western culture: A brief history. Kidney International 2007;71(5):384–387. https://doi. org/10.1038/sj.ki.5002057Bolodeoku J, Olukoga A, Donaldson D. Historical perspectives on health Origins of blood analysis in clinical diagnosis. Journal of the Royal Society for the Promotion of Health 1998;118(4):231–236. https://doi.org/10.1177/146642409811800409Bolodeoku J, Olukoga A, Donaldson D. Historical perspectives on health Origins of blood analysis in clinical diagnosis. Journal of the Royal Society for the Promotion of Health 1998;118(4):231–236. https://doi.org/10.1177/146642409811800409Olukoga AO, Bolodeoku J, Donaldson D. Laboratory Instrumentation in Clinical Biochemistry: An Historical Perspective. J R Soc Med 1997;90(10):570–577. https://doi.org/10.1177/146642409811800409Olukoga AO, Bolodeoku J, Donaldson D. Laboratory Instrumentation in Clinical Biochemistry: An Historical Perspective. J R Soc Med 1997;90(10):570–577. https://doi.org/10.1177/146642409811800409Billman GE. Homeostasis: The Underappreciated and Far Too Often Ignored Central Organizing Principle of Physiology. Front Physiol 2020;11:200. https://doi.org/10.3389/fphys.2020.00200Billman GE. Homeostasis: The Underappreciated and Far Too Often Ignored Central Organizing Principle of Physiology. Front Physiol 2020;11:200. https://doi.org/10.3389/fphys.2020.00200Oghoverere AB, Igho OE. Comparative histochemical study of the kidney of six mammalian species. J Med Scie 2019;51(1):11–23. https://doi.org/10.19106/jmedscie/005101201902Oghoverere AB, Igho OE. Comparative histochemical study of the kidney of six mammalian species. J Med Scie 2019;51(1):11–23. https://doi.org/10.19106/jmedscie/005101201902Ivanova LA et al. Matrix is everywhere: extracellular DNA is a link between biofilm and mineralization in Bacillus cereus planktonic lifestyleю npj Biofilms Microbiomes 2023;9(1):9. https://doi.org/10.1038/s41522-023-00377-5Ivanova LA et al. Matrix is everywhere: extracellular DNA is a link between biofilm and mineralization in Bacillus cereus planktonic lifestyleю npj Biofilms Microbiomes 2023;9(1):9. https://doi.org/10.1038/s41522-023-00377-5Santucci L, Candiano G, Brushi M et al. Urinary proteome in a snapshot: normal urine and glomerulonephritis. JN 2013;26(4):610–616. https://doi.org/10.5301/jn.5000233Santucci L, Candiano G, Brushi M et al. Urinary proteome in a snapshot: normal urine and glomerulonephritis. JN 2013;26(4):610–616. https://doi.org/10.5301/jn.5000233Deen WM. What determines glomerular capillary permeability? J Clin Invest 2004;114(10):1412–1414. https://doi.org/10.1172/jci200423577Deen WM. What determines glomerular capillary permeability? J Clin Invest 2004;114(10):1412–1414. https://doi.org/10.1172/jci200423577Rodewald R, Karnovsky MJ. Porous substructure of the glomerular slit diaphragm in the rat and mouse. The Journal of Cell Biology 1974;60(2):423–433. https://doi.org/10.1083/jcb.60.2.423Rodewald R, Karnovsky MJ. Porous substructure of the glomerular slit diaphragm in the rat and mouse. The Journal of Cell Biology 1974;60(2):423–433. https://doi.org/10.1083/jcb.60.2.423Tojo A, Kinugasa S. Mechanisms of Glomerular Albumin Filtration and Tubular Reabsorption. International Journal of Nephrology 2012;2012:1–9. https://doi.org/10.1155/2012/481520Tojo A, Kinugasa S. Mechanisms of Glomerular Albumin Filtration and Tubular Reabsorption. International Journal of Nephrology 2012;2012:1–9. https://doi.org/10.1155/2012/481520Graham RC, Karnovsky MJ. Glomerular permeability. The Journal of Experimental Medicine 1966;124(6):1123–1134. https://doi.org/10.1084/jem.124.6.1123Graham RC, Karnovsky MJ. Glomerular permeability. The Journal of Experimental Medicine 1966;124(6):1123–1134. https://doi.org/10.1084/jem.124.6.1123Наточин ЮВ. Почка: орган выделения или сохранения? Успехи физиологических наук 2019;50(4):14–25. https://doi.org/10.1134/S0301179819040064Natochin YuV. Kidney: excretion or preservation organ? Progress in physiological science 2019;50(4):14–25. (In Russ.) https:// doi.org/10.1134/S0301179819040064Seriki AS. Role of the Kidneys in the Regulation of Intra-and Extra-Renal Blood Pressure. Ann Clin Hypertens 2018;2:048–058. https://doi.org/10.29328/journal.ach.1001011Seriki AS. Role of the Kidneys in the Regulation of Intra-and Extra-Renal Blood Pressure. Ann Clin Hypertens 2018;2:048–058. https://doi.org/10.29328/journal.ach.1001011Hall JE, Hall ME. Guyton and Ha ll Textbook Of Medical Physiology. 14th ed. Elsevier, Philadelphia, 2021;1184Hall JE, Hall ME. Guyton and Ha ll Textbook Of Medical Physiology. 14th ed. Elsevier, Philadelphia, 2021;1184Srivastava R, Micanovic R, El-Achkar TM et al. An Intricate Network of Conserved DNA Upstream Motifs and Associated Transcription Factors Regulate the Expression of Uromodulin Gene. Journal of Urology 2014;192(3):981–989. https://doi.org/10.1016/j.juro.2014.02.095Srivastava R, Micanovic R, El-Achkar TM et al. An Intricate Network of Conserved DNA Upstream Motifs and Associated Transcription Factors Regulate the Expression of Uromodulin Gene. Journal of Urology 2014;192(3):981–989. https:// doi.org/10.1016/j.juro.2014.02.095Tokonami N, Takata T, Beyeler J et al. Uromodulin is expressed in the distal convoluted tubule, where it is critical for regulation of the sodium chloride cotransporter NCC. Kidney International 2018;94(4):701–715. https://doi.org/10.1016/j.kint.2018.04.021Tokonami N, Takata T, Beyeler J et al. Uromodulin is expressed in the distal convoluted tubule, where it is critical for regulation of the sodium chloride cotransporter NCC. Kidney International 2018;94(4):701–715. https://doi.org/10.1016/j.kint.2018.04.021Izzedine H, Lescure FX, Bonnet F. HIV medication-based urolithiasis. Clin Kidney J 2014;7(2):121–126. https://doi.org/10.1093/ckj/sfu008Izzedine H, Lescure FX, Bonnet F. HIV medication-based urolithiasis. Clin Kidney J 2014;7(2):121–126. https://doi.org/10.1093/ckj/sfu008

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