nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.36485/1561-6274-2021-25-3-75-83nefr-1979Research ArticleПРОГРАММА НЕПРЕРЫВНОГО ПОСЛЕДИПЛОМНОГО ОБРАЗОВАНИЯ ПО НЕФРОЛОГИИPROGRAM ON CONTINUOUS POSTGRADUATE EDUCATION ON NEPHROLOGYСиндром Альпорта: современные представленияAlport syndrome: our knowledge updatehttps://orcid.org/0000-0002-3699-1884АксеноваМ. Е.AksenovaM. E.

 Аксенова Марина Евгеньевна, канд. мед. наук, ведущий научный сотрудник

125412, Москва, ул. Талдомская, д. 2.

Тел.: 8 495 4832183, 89166148139

 Marina E. Aksenova, MD, PhD, Leading Researcher

125412 Moscow, Taldomskaya str., 2

 Tel.: 8 495 4832183, 89166148139

maksyonova@pedklin.ruОтдел наследственных и приобретенных болезней почек имени профессора М.С. Игнатовой, НИКИ педиатрии имени академика Ю.Е. Вельтищева, Российский национальный исследовательский медицинский университет им. Н.И. ПироговаРоссияDepartment of Hereditary and Acquired Kidney Diseases named after Professor M.S. Ignatova, Scientific Research Institute of Pediatrics named after Academician Yu.E. Veltischev, Russian National Research Medical University named after N.I. PirogovRussian Federation2021220420212537583Copyright © Аксенова М.Е., 20212021Аксенова М.Е.Aksenova M.E.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/1979

Синдром Альпорта – мультисистемное заболевание, связанное с мутациями в генах COL4A3, COL4A4, COL4A5. Основным проявлением синдрома Альпорта является прогрессирующая нефропатия, приводящая к развитию почечной недостаточности, в том числе у женщин с Х-сцепленным вариантом наследования. Фенотипическая гетерогенность, неблагоприятный прогноз заболевания обуславливают необходимость его ранней диагностики путем внедрения генетического обследования пациентов с целью раннего назначения нефропротективной терапии, уменьшающей темпы прогрессирования нефропатии. В статье представлены: этиология, патогенез, генотип-фенотипические особенности синдрома Альпорта, экспертные клинические рекомендации по обследованию пациентов с персистирующей гломерулярной гематурией и ведению пациентов с синдромом Альпорта.

Alport syndrome is a progressive multisystem disease associated with variants in genes COL4A3, COL4A4, COL4A5.The syndrome is an important genetic cause of kidney failure, including women with X-linked disease. Given the unfavorable natural history of Alport nephropathy and benefit from early treatment with angiotensin-converting enzyme inhibition, it is necessary to change our diagnostic approach in patients with persistent glomerular hematuria and management of patients with Alport syndrome. This review presents the ethiology, pathogenesis, genotype and phenotype heterogeneity of the syndrome and expert clinical practice recommendations to enhancing early diagnosis and achieving optimal outcomes in Alport syndrome.

детисиндром Альпортаколлаген IV типагематурияхроническая болезнь почекингибиторы ангиотензин-превращающего ферментаchildrenAlport syndrometype iv collagenhematuriachronic kidney failureangiotensin converting enzyme inhibitorsReferencesGuthrie LG. Idiopathic or congenital, hereditary and family hematuria. Lancet1992;1:1243–1246. doi: 10.1001/jama.1902.02480220032009Guthrie LG. Idiopathic or congenital, hereditary and family hematuria. Lancet1992;1:1243–1246. doi: 10.1001/jama.1902.02480220032009Eason J, Smith GLM, Buchanan G. Hereditary and familial nephritis. Lancet1924;2:639–646Eason J, Smith GLM, Buchanan G. Hereditary and familial nephritis. Lancet1924;2:639–646Hurst AF. Hereditary familial congenital hemorrhagic nephritis occurring in 16 individuals in three operations. Guy Hosp Rep1923;73:368–370Hurst AF. Hereditary familial congenital hemorrhagic nephritis occurring in 16 individuals in three operations. Guy Hosp Rep1923;73:368–370Alport AC. Hereditary familial congenital haemorrhagic nephritis. Br Med J1927;1:504–506. doi: 10.1136/bmj.1.3454.504Alport AC. Hereditary familial congenital haemorrhagic nephritis. Br Med J1927;1:504–506. doi: 10.1136/bmj.1.3454.504Gast C, Pengelly RJ, Lyon M et al. Collagen (COL4A) mutations are the most frequent mutations underlying adult focal segmental glomerulosclerosis. Nephrol Dial Transplant 2016;31(6):961–970. doi: 10.1093/ndt/gfv325Gast C, Pengelly RJ, Lyon M et al. Collagen (COL4A) mutations are the most frequent mutations underlying adult focal segmental glomerulosclerosis. Nephrol Dial Transplant 2016;31(6):961–970. doi: 10.1093/ndt/gfv325Groopman EE, Marasa M, Cameron-Christie S et al. Diagnostic Utility of Exome Sequencing for Kidney Disease. N Engl J Med2019;10;380(2):142–151. doi: 10.1056/NEJMoa1806891Groopman EE, Marasa M, Cameron-Christie S et al. Diagnostic Utility of Exome Sequencing for Kidney Disease. N Engl J Med2019;10;380(2):142–151. doi: 10.1056/NEJMoa1806891Neild GH. Primary renal disease in young adults with renal failure. Nephrol Dial Transplant2010;25(4):1025–1032. doi:10.1093/ndt/gfp653Neild GH. Primary renal disease in young adults with renal failure. Nephrol Dial Transplant2010;25(4):1025–1032. doi:10.1093/ndt/gfp653Zhai Y, Liu X, Yang Q et al. IPDN-China promotes the development of pediatric dialysis in China. Pediatr Nephrol 2020;35(11):2163–2171. doi: 10.1007/s00467-020-04630-3Zhai Y, Liu X, Yang Q et al. IPDN-China promotes the development of pediatric dialysis in China. Pediatr Nephrol 2020;35(11):2163–2171. doi: 10.1007/s00467-020-04630-3Abrahamson D, Hudson B, Stroganova L et al. Cellular origins of type IV collagen networks in developing glomeruli. JASN 2009;20:1471–1479. doi: 10.1681/ASN.2008101086Abrahamson D, Hudson B, Stroganova L et al. Cellular origins of type IV collagen networks in developing glomeruli. JASN 2009;20:1471–1479. doi: 10.1681/ASN.2008101086Gosgrove D, Liu S. Collagen IV diseases: a focus on the glomerular basement membrane in Alport syndrome. Matrix Biol 2017;57–58:45–54. doi:10.1016/j.matbio.2016.08.005Gosgrove D, Liu S. Collagen IV diseases: a focus on the glomerular basement membrane in Alport syndrome. Matrix Biol 2017;57–58:45–54. doi:10.1016/j.matbio.2016.08.005Tsuji K, Suleiman H, Miner JH et al. Ultrastructural Characterization of the Glomerulopathy in Alport Mice by Helium Ion Scanning Microscopy (HIM). Sci Rep2017;7(1):11696. doi: 10.1038/s41598-017-12064-5Tsuji K, Suleiman H, Miner JH et al. Ultrastructural Characterization of the Glomerulopathy in Alport Mice by Helium Ion Scanning Microscopy (HIM). Sci Rep2017;7(1):11696. doi: 10.1038/s41598-017-12064-5Lin X, Suh JH, Go G, Miner JH. Feasibility of repairing glomerular basement membrane defects in Alport syndrome. J Am Soc Nephrol2014;25(4):687–692. doi: 10.1681/ASN.2013070798Lin X, Suh JH, Go G, Miner JH. Feasibility of repairing glomerular basement membrane defects in Alport syndrome. J Am Soc Nephrol2014;25(4):687–692. doi: 10.1681/ASN.2013070798Zeisberg M, Neilson E. Mechanisms of tubulointerstitial fibrosis. JASN2010; 21:1819–1834. doi: 10.1681/ASN.2010080793Zeisberg M, Neilson E. Mechanisms of tubulointerstitial fibrosis. JASN2010; 21:1819–1834. doi: 10.1681/ASN.2010080793Wickman L, Hodgin JB, Wang SQ et al. Podocyte depletion in thin GBM and Alport syndrome. PLoS One 2016;11(5):e0155255. doi: 10.1371/journal.pone.0155255Wickman L, Hodgin JB, Wang SQ et al. Podocyte depletion in thin GBM and Alport syndrome. PLoS One 2016;11(5):e0155255. doi: 10.1371/journal.pone.0155255D’Agati VD. Podocyte growing pains in adaptive FSGS. JASN2017;28(10): 2825–2827. doi: 10.1681/ASN.2017060612D’Agati VD. Podocyte growing pains in adaptive FSGS. JASN2017;28(10): 2825–2827. doi: 10.1681/ASN.2017060612Аксенова МЕ, Конькова НЕ, Шагам ЛИ, Повилайтите ПЭ. Клиническое значение ультраструктурных изменений почечной ткани у детей с Х-сцепленным синдромом Aльпорта. Педиатрия2019;98(5):14–19Aksenova M, Konkova N, Shagam L, Povilaitite P. Clinical significance of renal tissue ultrastructal cahanges in children wirh X-linked Alport syndrome Pediatriya – Zhurnal im G.N. Speranskogo. 2019; 98(5):14–19 (In Russ.)Kashtan CE. Long-term management of Alport syndrome in pediatric patients.Pediatric Health Med Ther2013;4:41–45. doi:10.2147/PHMT.S35667Kashtan CE. Long-term management of Alport syndrome in pediatric patients.Pediatric Health Med Ther2013;4:41–45. doi:10.2147/PHMT.S35667Meehan DT, Delimont D, Dufek B et al. Endothelin-1 mediated induction of extracellular matrix genes in strial marginal cells underlies strial pathology in Alport mice.Hear Res2016;341:100–108. doi: 10.1016/j.heares.2016.08.003Meehan DT, Delimont D, Dufek B et al. Endothelin-1 mediated induction of extracellular matrix genes in strial marginal cells underlies strial pathology in Alport mice.Hear Res2016;341:100–108. doi: 10.1016/j.heares.2016.08.003Choi J, Na K, Bae S, Roh G. Anterior lens capsule abnormalities in Alport syndrome. Korean J Ophthalmol2005;19:84–89. doi: 10.3341/kjo.2005.19.1.84Choi J, Na K, Bae S, Roh G. Anterior lens capsule abnormalities in Alport syndrome. Korean J Ophthalmol2005;19:84–89. doi: 10.3341/kjo.2005.19.1.84Tan R, Colville D, Wang Y et al. Alport retinopathy results from “severe” COL4A5 mutations and predicts early renal failure. CJASN 2010; 5:34–38. doi: 10.2215/CJN.01030209Tan R, Colville D, Wang Y et al. Alport retinopathy results from “severe” COL4A5 mutations and predicts early renal failure. CJASN 2010; 5:34–38. doi: 10.2215/CJN.01030209Citirik M, Batman C, Men G et al. Electron microscopic examination of the anterior lens capsule in a case of Alport’s syndrome.Clin Exp Optom 2007; 90:367–370. doi: 10.1111/j.1444-0938.2007.00134.xCitirik M, Batman C, Men G et al. Electron microscopic examination of the anterior lens capsule in a case of Alport’s syndrome.Clin Exp Optom 2007; 90:367–370. doi: 10.1111/j.1444-0938.2007.00134.xColville D, Savige J. Alport syndrome. A review of the ocular manifestations. Ophthalmic Genet 1997;18:161–173. PMID: 9457747Colville D, Savige J. Alport syndrome. A review of the ocular manifestations. Ophthalmic Genet 1997;18:161–173. PMID: 9457747Wilson M, Trivedi R, Biber J, Golub R. Anterior capsule rupture and subsequent cataract formation in Alport syndrome. J AAPOS2006; 10:182–183. doi:10.1016/j.jaapos.2005.09.008Wilson M, Trivedi R, Biber J, Golub R. Anterior capsule rupture and subsequent cataract formation in Alport syndrome. J AAPOS2006; 10:182–183. doi:10.1016/j.jaapos.2005.09.008Díez-del Hoyo F, Sanz-Ruiz R, Díez-Villanueva P et al. A novel cardiovascular presentation of Alport Syndrome: spontaneous coronary artery dissection. Int J Cardiol2014;177(3):e133–134. doi: 10.1016/j.ijcard.2014.09.065Díez-del Hoyo F, Sanz-Ruiz R, Díez-Villanueva P et al. A novel cardiovascular presentation of Alport Syndrome: spontaneous coronary artery dissection. Int J Cardiol2014;177(3):e133–134. doi: 10.1016/j.ijcard.2014.09.065Kashtan C, Segal Y, Flinter F et al. Aortic abnormalities in males with Alport syndrome. Nephrol Dial Transplant 2010;25(11):3554–3560. doi: 10.1093/ndt/gfq271Kashtan C, Segal Y, Flinter F et al. Aortic abnormalities in males with Alport syndrome. Nephrol Dial Transplant 2010;25(11):3554–3560. doi: 10.1093/ndt/gfq271Earl T, Khan L, Hagau D, Fernandez A. The spectrum of aortic pathology in Alport syndrome: a case report and review of the literature. Am J Kidney Dis2012;60(5):821–822. doi: 10.1053/j.ajkd.2012.06.024Earl T, Khan L, Hagau D, Fernandez A. The spectrum of aortic pathology in Alport syndrome: a case report and review of the literature. Am J Kidney Dis2012;60(5):821–822. doi: 10.1053/j.ajkd.2012.06.024Zhang Y, Ding J, Zhang H et al. Effect of heterozygous pathogenic COL4A3 or COL4A4 variants on patients with X-linked Alport syndrome. Mol Genet Genomic Med 2019;7:e647. doi: 10.1002/mgg3.647Zhang Y, Ding J, Zhang H et al. Effect of heterozygous pathogenic COL4A3 or COL4A4 variants on patients with X-linked Alport syndrome. Mol Genet Genomic Med 2019;7:e647. doi: 10.1002/mgg3.647Mencarelli MA, Heidet L, Storey H et al. Evidence of digenic inheritance in Alport syndrome. J Med Genet 2015;52(3):163–174. doi: 10.1136/jmedgenet-2014-102822Mencarelli MA, Heidet L, Storey H et al. Evidence of digenic inheritance in Alport syndrome. J Med Genet 2015;52(3):163–174. doi: 10.1136/jmedgenet-2014-102822Kashtan CE, Ding J, Garosi G et al. Alport syndrome: a unified classification of genetic disorders of collagen IV α345: a position paper of the Alport Syndrome Classification Working Group. Kidney Int2018;93(5):1045–1051. doi: 10.1016/j.kint.2017.12.018Kashtan CE, Ding J, Garosi G et al. Alport syndrome: a unified classification of genetic disorders of collagen IV α345: a position paper of the Alport Syndrome Classification Working Group. Kidney Int2018;93(5):1045–1051. doi: 10.1016/j.kint.2017.12.018Jais JP, Knebelmann B, Giatras I et al. X-linked Alport syndrome: natural history and genotype-phenotype correlations in girls and women belonging to 195 families: a "European Community Alport Syndrome Concerted Action" study. J Am Soc Nephrol2003;14(10):2603–2610. doi: 10.1097/01.asn.0000090034.71205.74Jais JP, Knebelmann B, Giatras I et al. X-linked Alport syndrome: natural history and genotype-phenotype correlations in girls and women belonging to 195 families: a "European Community Alport Syndrome Concerted Action" study. J Am Soc Nephrol2003;14(10):2603–2610. doi: 10.1097/01.asn.0000090034.71205.74Savige J, Colville D, Rheault M et al. Alport Syndrome in Women and Girls. Clin J Am Soc Nephrol2016 Sep 7;11(9):1713–1720. doi: 10.2215/CJN.00580116.Savige J, Colville D, Rheault M et al. Alport Syndrome in Women and Girls. Clin J Am Soc Nephrol2016 Sep 7;11(9):1713–1720. doi: 10.2215/CJN.00580116.Aksenova M, Shagam L, Konkova N, Dlin V. X-linked Alport syndrome in females: experience of one center. Pediatr Nephrol 2018;33:1913. doi:10.1007/s00467-018-4028-xAksenova M, Shagam L, Konkova N, Dlin V. X-linked Alport syndrome in females: experience of one center. Pediatr Nephrol 2018;33:1913. doi:10.1007/s00467-018-4028-xSavige J, Storey H, Il Cheong H et al. X-Linked and Autosomal Recessive Alport Syndrome: Pathogenic Variant Features and Further Genotype-Phenotype Correlations.PLoS One 2016;11(9):e0161802. doi: 10.1371/journal.pone.0161802Savige J, Storey H, Il Cheong H et al. X-Linked and Autosomal Recessive Alport Syndrome: Pathogenic Variant Features and Further Genotype-Phenotype Correlations.PLoS One 2016;11(9):e0161802. doi: 10.1371/journal.pone.0161802Kamiyoshi N, Nozu K, Fu XJ et al. Genetic, clinical and pathologic backgrounds of patients with autosomal dominant Alport syndrome.Clin J Am Soc Nephrol2016;11(8):1441–1449. doi: 10.2215/CJN.01000116Kamiyoshi N, Nozu K, Fu XJ et al. Genetic, clinical and pathologic backgrounds of patients with autosomal dominant Alport syndrome.Clin J Am Soc Nephrol2016;11(8):1441–1449. doi: 10.2215/CJN.01000116Fallerini C, Baldassarri M, Trevisson E et al. Alport syndrome: impact of digenic inheritance in patients management. Clin Genet2017;92(1):34–44. doi: 10.1111/cge.12919Fallerini C, Baldassarri M, Trevisson E et al. Alport syndrome: impact of digenic inheritance in patients management. Clin Genet2017;92(1):34–44. doi: 10.1111/cge.12919Bekheirnia MR, Reed B, Gregory MC et al. GenotypePhenotype correlation in X-linked Alport Syndrome. J Am Soc Nephrol2010(21):876–883. doi:10.1681/ASN.2009070784Bekheirnia MR, Reed B, Gregory MC et al. GenotypePhenotype correlation in X-linked Alport Syndrome. J Am Soc Nephrol2010(21):876–883. doi:10.1681/ASN.2009070784Kashtan CE. Alport syndrome and the X chromosome: implications of a diagnosis of Alport syndrome in females. Nephrol Dial Transplant 2007;22(6):1499–1505. doi: 10.1093/ndt/gfm024Kashtan CE. Alport syndrome and the X chromosome: implications of a diagnosis of Alport syndrome in females. Nephrol Dial Transplant 2007;22(6):1499–1505. doi: 10.1093/ndt/gfm024Żurowska AM, Bielska O, Daca-Roszak P et al. Mild Xlinked Alport syndrome due to the COL4A5 G624D variant originating in the Middle Ages is predominant in Central/East Europe and causes kidney failure in midlife. Kidney Int 2020;10:S0085–2538(20)31410-1. doi: 10.1016/j.kint.2020.10.040Żurowska AM, Bielska O, Daca-Roszak P et al. Mild Xlinked Alport syndrome due to the COL4A5 G624D variant originating in the Middle Ages is predominant in Central/East Europe and causes kidney failure in midlife. Kidney Int 2020;10:S0085–2538(20)31410-1. doi: 10.1016/j.kint.2020.10.040Gao E, Yang X, Si N et al. Novel COL4A5 Splicing Mutation Causes Skipping of Exon 14 in a Chinese Family with Alport Syndrome. Kidney Dis2020;6(1):43–49. doi:10.1159/000502798Gao E, Yang X, Si N et al. Novel COL4A5 Splicing Mutation Causes Skipping of Exon 14 in a Chinese Family with Alport Syndrome. Kidney Dis2020;6(1):43–49. doi:10.1159/000502798Bu L, Chen J, Nelson AC et al. Somatic Mosaicism in a Male Patient With X-linked Alport Syndrome. Kidney Int Rep 2019;4(7):1031–1035. doi: 10.1016/j.ekir.2019.03.005Bu L, Chen J, Nelson AC et al. Somatic Mosaicism in a Male Patient With X-linked Alport Syndrome. Kidney Int Rep 2019;4(7):1031–1035. doi: 10.1016/j.ekir.2019.03.005Kamura M, Yamamura T, Omachi K et al. Trimerization and Genotype-Phenotype Correlation of COL4A5 Mutants in Alport Syndrome. Kidney Int Rep 2020;5(5):718–726. doi:10.1016/j.ekir.2020.01.008Kamura M, Yamamura T, Omachi K et al. Trimerization and Genotype-Phenotype Correlation of COL4A5 Mutants in Alport Syndrome. Kidney Int Rep 2020;5(5):718–726. doi:10.1016/j.ekir.2020.01.008Daga S, Fallerini C, Furini S et al. Non-collagene genes role in digenic Alport syndrome. BMC Nephrol2019;20(1):70. doi:10.1186/s12882-019-1258-5Daga S, Fallerini C, Furini S et al. Non-collagene genes role in digenic Alport syndrome. BMC Nephrol2019;20(1):70. doi:10.1186/s12882-019-1258-5Mohammad M, Nanra R, Colville D et al. A female with X-linked Alport syndrome and compound heterozygous COL4A5 mutations. Pediatr Nephrol2014;29(3):481–485. doi: 10.1007/s00467-013-2682-6Mohammad M, Nanra R, Colville D et al. A female with X-linked Alport syndrome and compound heterozygous COL4A5 mutations. Pediatr Nephrol2014;29(3):481–485. doi: 10.1007/s00467-013-2682-6Li Y, Groopman EE, D'Agati V et al. Type IV Collagen Mutations in Familial IgA Nephropathy. Kidney Int Rep2020;5(7):1075–1078. doi:10.1016/j.ekir.2020.04.011Li Y, Groopman EE, D'Agati V et al. Type IV Collagen Mutations in Familial IgA Nephropathy. Kidney Int Rep2020;5(7):1075–1078. doi:10.1016/j.ekir.2020.04.011Tishler PV, Rosner B. The genetics of Alport syndrome. Birth Defects1974(10):93. PMID: 4470916Tishler PV, Rosner B. The genetics of Alport syndrome. Birth Defects1974(10):93. PMID: 4470916Flinter FA, Cameron JS, Chantler C et al. Genetics of classic Alport’s syndrome. Lancet1988;2:1005–1007. doi: 10.1016/s0140-6736(88)90753-2Flinter FA, Cameron JS, Chantler C et al. Genetics of classic Alport’s syndrome. Lancet1988;2:1005–1007. doi: 10.1016/s0140-6736(88)90753-2Hanson H, Storey H, Pagan J, Flinter F. The Value of Clinical Criteria in Identifying Patients with X-Linked Alport Syndrome. Clin J Am Soc Nephrol2011;6(1):198–203. doi: 10.2215/CJN.00200110Hanson H, Storey H, Pagan J, Flinter F. The Value of Clinical Criteria in Identifying Patients with X-Linked Alport Syndrome. Clin J Am Soc Nephrol2011;6(1):198–203. doi: 10.2215/CJN.00200110Savige J, Gregory M, Gross O et al. Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. J Am Soc Nephrol2013;24(3):364–375. doi: 10.1681/ASN.2012020148JSavige J, Gregory M, Gross O et al. Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. J Am Soc Nephrol2013;24(3):364–375. doi: 10.1681/ASN.2012020148JOhtsubo H, Morisada N, Kaito H et al. Alport-like glomerular basement membrane changes with renal-coloboma syndrome. Pediatr Nephrol2012;27(7):1189–1192. doi: 10.1007/s00467-012-2125-9Ohtsubo H, Morisada N, Kaito H et al. Alport-like glomerular basement membrane changes with renal-coloboma syndrome. Pediatr Nephrol2012;27(7):1189–1192. doi: 10.1007/s00467-012-2125-9Han KH, Lee H, Kang HG et al. Renal manifestations of patients with MYH9-related disorders. Pediatr Nephrol 2011;26(4):549–555. doi: 10.1007/s00467-010-1735-3Han KH, Lee H, Kang HG et al. Renal manifestations of patients with MYH9-related disorders. Pediatr Nephrol 2011;26(4):549–555. doi: 10.1007/s00467-010-1735-3Gross O, Licht C, Anders HJ et al. Early angiotensinconverting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy. Kidney Int2012(5):494–501. doi: 10.1038/ki.2011.407Gross O, Licht C, Anders HJ et al. Early angiotensinconverting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy. Kidney Int2012(5):494–501. doi: 10.1038/ki.2011.407Yamamura T, Horinouchi T, Nagano C et al. Genotype-phenotype correlations influence the response to angiotensin-targeting drugs in Japanese patients with male X-linked Alport syndrome. Kidney Int2020(6):1605–1614. doi: 10.1016/j.kint.2020.06.038Yamamura T, Horinouchi T, Nagano C et al. Genotype-phenotype correlations influence the response to angiotensin-targeting drugs in Japanese patients with male X-linked Alport syndrome. Kidney Int2020(6):1605–1614. doi: 10.1016/j.kint.2020.06.038Weinstock BA, Feldman DL, Fornoni A et al. Workshop Participants. Clinical trial recommendations for potential Alport syndrome therapies. Kidney Int 2020(6):1109–1116. doi: 10.1016/j.kint.2020.02.029Weinstock BA, Feldman DL, Fornoni A et al. Workshop Participants. Clinical trial recommendations for potential Alport syndrome therapies. Kidney Int 2020(6):1109–1116. doi: 10.1016/j.kint.2020.02.029Kashtan CE, Gross O. Clinical practice recommendation for the diagnosis and management of Alport syndrome in children, adolescents, and young adults – an update for 2020.Pediatr Nephrol2021(3):711–719. doi:10.1007/s00467-020-04819-6Kashtan CE, Gross O. Clinical practice recommendation for the diagnosis and management of Alport syndrome in children, adolescents, and young adults – an update for 2020.Pediatr Nephrol2021(3):711–719. doi:10.1007/s00467-020-04819-6Kashtan CE, Ding J, Gregory M et al. Clinical practice recommendations for the treatment of Alport Syndrome: a statement of the Alport Syndrome Research Collaborative. Pediatr Nephrol 2013;28(1):5–11. doi: 10.1007/s00467-012-2138-4Kashtan CE, Ding J, Gregory M et al. Clinical practice recommendations for the treatment of Alport Syndrome: a statement of the Alport Syndrome Research Collaborative. Pediatr Nephrol 2013;28(1):5–11. doi: 10.1007/s00467-012-2138-4Gross O, Tönshoff B, Weber LT et al. German Pediatric Nephrology (GPN) Study Group and EARLY PRO-TECT Alport Investigators. A multicenter, randomized, placebo-controlled, double-blind phase 3 trial with open-arm comparison indicates safety and efficacy of nephroprotective therapy with ramipril in children with Alport's syndrome. Kidney Int2020(6):1275–1286. doi: 10.1016/j.kint.2019.12.015Gross O, Tönshoff B, Weber LT et al. German Pediatric Nephrology (GPN) Study Group and EARLY PRO-TECT Alport Investigators. A multicenter, randomized, placebo-controlled, double-blind phase 3 trial with open-arm comparison indicates safety and efficacy of nephroprotective therapy with ramipril in children with Alport's syndrome. Kidney Int2020(6):1275–1286. doi: 10.1016/j.kint.2019.12.015Gross O, Beirowski B, Koepke ML et al. Preemptive ramipril therapy delays renal failure and reduces renal fibrosis in COL4A3-knockout mice with Alport syndrome. Kidney Int2003 Feb;63(2):438–446. doi: 10.1046/j.1523-1755.2003.00779.xGross O, Beirowski B, Koepke ML et al. Preemptive ramipril therapy delays renal failure and reduces renal fibrosis in COL4A3-knockout mice with Alport syndrome. Kidney Int2003 Feb;63(2):438–446. doi: 10.1046/j.1523-1755.2003.00779.xАксенова МЕ, Конькова НЕ, Тутельман КМ. Уровень артериального давления и прогрессирование патологии почек у детей с Х-сцепленным синдромом Альпорта. Нефрология 2020;24(6):78–84. doi:10.36485/1561-6274-2020-24-6-78-84Aksenova ME, Konkova NE, Tutelman KM. Blood pressure level and progression of renal disease in children with Х-linked Alport syndrome. Nephrology (Saint-Petersburg)2020;24(6):78–84. (In Russ.). doi:10.36485/1561-6274-2020-24-6-78-84Yamamura T, Horinouchi T, Adachi T et al. Development of an exon skipping therapy for X-linked Alport syndrome with truncating variants in COL4A5. Nat Commun2020;2;11(1):2777. doi: 10.1038/s41467-020-16605-xYamamura T, Horinouchi T, Adachi T et al. Development of an exon skipping therapy for X-linked Alport syndrome with truncating variants in COL4A5. Nat Commun2020;2;11(1):2777. doi: 10.1038/s41467-020-16605-xGuo J, Song W, Boulanger J et al. Dysregulated Expression of microRNA-21 and Disease-Related Genes in Human Patients and in a Mouse Model of Alport Syndrome. Hum Gene Ther 2019;30(7):865–881. doi: 10.1089/hum.2018.205Guo J, Song W, Boulanger J et al. Dysregulated Expression of microRNA-21 and Disease-Related Genes in Human Patients and in a Mouse Model of Alport Syndrome. Hum Gene Ther 2019;30(7):865–881. doi: 10.1089/hum.2018.205A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Alport Syndrome – CARDINAL (CARDINAL). [Internet]. Available from: https://clinicaltrials.gov/ct2/show/NCT03019185A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Alport Syndrome – CARDINAL (CARDINAL). [Internet]. Available from: https://clinicaltrials.gov/ct2/show/NCT03019185Mabillard H, Sayer JA. SGLT2 inhibitors – a potential treatment for Alport syndrome. Clin Sci (Lond) 2020;28;134(4):379–388. doi: 10.1042/CS20191276Mabillard H, Sayer JA. SGLT2 inhibitors – a potential treatment for Alport syndrome. Clin Sci (Lond) 2020;28;134(4):379–388. doi: 10.1042/CS20191276Davenport AP, Kuc RE, Southan C, Maguire JJ. New drugs and emerging therapeutic targets in the endothelin signaling pathway and prospects for personalized precision medicine. Physiol Res2018;67(Suppl 1):S37–S54. doi: 10.33549/physiolres.933872Davenport AP, Kuc RE, Southan C, Maguire JJ. New drugs and emerging therapeutic targets in the endothelin signaling pathway and prospects for personalized precision medicine. Physiol Res2018;67(Suppl 1):S37–S54. doi: 10.33549/physiolres.933872Torra R, Furlano M. New therapeutic options for Alport syndrome. Nephrol Dial Transplant2019;34(8):1272–1279. doi:10.1093/ndt/gfz131Torra R, Furlano M. New therapeutic options for Alport syndrome. Nephrol Dial Transplant2019;34(8):1272–1279. doi:10.1093/ndt/gfz131Omachi K, Miner JH. Alport Syndrome Therapeutics: Ready for Prime-Time Players. Trends Pharmacol Sci2019; 40(11): 803–806. doi: 10.1016/j.tips.2019.07.012Omachi K, Miner JH. Alport Syndrome Therapeutics: Ready for Prime-Time Players. Trends Pharmacol Sci2019; 40(11): 803–806. doi: 10.1016/j.tips.2019.07.012

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