nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.36485/1561-6274-2022-26-3-19-29nefr-2135Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESАтипичный гемолитико-уремический синдром: эволюция лечения и влияние клинико-генетических характеристик на возможность отмены экулизумабаAtypical hemolytic-uremic syndrome: evolution of treatment and impact of clinical and genetic characteristics on possibility of eculizumab withdrawalhttps://orcid.org/0000-0002-7686-9816ПрокопенкоЕ. И.ProkopenkoE. I.

Елена Ивановна Прокопенко, д-р мед. наук

факультет усовершенствования врачей

кафедра трансплантологии, нефрологии и искусственных органов

129110

ул. Щепкина, д. 61/2

Москва

тел.: (495) 6845791

Elena I. Prokopenko, Doctor of Medical Sciences

Faculty of Advanced Medical Training

Department of Transplantology, Nephrology and Artificial Organs

129110

Shchepkina str., 61/2

Moscow

tel.: (495) 6845791

renalnephron@gmail.comМосковский областной научно-исследовательский клинический институт им. М. Ф. ВладимирскогоРоссияM. F. Vladimirsky Moscow Regional Research Clinical InstituteRussian Federation2022090920222631929Copyright © Прокопенко Е.И., 20222022Прокопенко Е.И.Prokopenko E.I.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/2135

   Атипичный гемолитико-уремический синдром (аГУС) – это редкий вариант тромботической микроангиопатии (ТМА), ассоциированный с неконтролируемой активацией альтернативного пути комплемента из-за мутаций генов, кодирующих регуляторные белки комплемента, или образования антител к некоторым из этих регуляторов. Триггерами клинической манифестации аГУС могут быть инфекции, сепсис, беременность, аутоиммунные заболевания, трансплантация органов и другие комплемент-активирующие состояния. Ранее единственным вариантом терапии аГУС была плазматерапия – инфузии свежезамороженной плазмы или плазмаобмен, однако эффективность плазматерапии была недостаточной. В настоящее время появилось таргетное лечение – препарат рекомбинантных гуманизированных моноклональных антител против белка комплемента С5 экулизумаб, показавший в ряде исследований высокую эффективность в достижении ремиссии аГУС, восстановлении почечной функции, профилактике ТМА при трансплантации почки. Долгое время оставался нерешенным вопрос об оптимальной продолжительности лечения и возможности отмены экулизумаба у пациентов с ремиссией. Было показано, что после отмены комплемент-блокирующей терапии рецидивы аГУС развивались у 20-35 % пациентов. В статье обсуждаются результаты большого числа публикаций, посвященных лечению экулизумабом и возможности его отмены, в том числе – французского проспективного открытого многоцентрового исследования, выявившего следующие факторы риска рецидива аГУС после отмены экулизумаба: наличие редких вариантов генов комплемента, женский пол, повышенный уровень в плазме растворимого C5b-9 в момент отмены препарата. У пациентов, не имевших редких генетических вариантов, риск рецидива составлял менее 5 %. В целом отмена экулизумаба после достижения полной ремиссии аГУС и восстановления функции почек при низком риске рецидива может обеспечить лучшую переносимость поддерживающего лечения, уменьшение частоты инфекционных осложнений и существенное снижение финансовой нагрузки на систему здравоохранения.

   Atypical hemolytic uremic syndrome (aHUS) is a rare variant of thrombotic microangiopathy (TMA) associated with uncontrolled activation of alternative complement pathway due to mutations in complement regulatory protein genes or antibodies formation to regulators. Clinical manifestations of aHUS can be triggered by infections, sepsis, pregnancy, autoimmune diseases, organ transplantation, and other complement-activating conditions. Previously, the only treatment option for aHUS was plasma therapy – fresh frozen plasma infusions or plasma exchange, but its effectiveness was insufficient. Currently, targeted treatment available – recombinant monoclonal antibodies against complement C5 protein – eculizumab with high efficiency in achieving aHUS remission, renal function recovery, and preventing TMA at kidney transplantation. For a long time, the question of the optimal duration of treatment and the possibility of eculizumab discontinuing remained unresolved. It was shown that aHUS relapses developed in 20-35 % of patients after discontinuation of complement-blocking therapy. The article presents an overview of a large number of studies of eculizumab treatment outcomes and the possibility of its withdrawal, including a French prospective multicenter study that identified risk factors for aHUS relapse after eculizumab discontinuation: the presence of rare variants of complement genes, female gender, increased soluble C5b-9 plasma level. In patients who did not have rare genetic variants, the risk of relapse was less than 5 %. In general, eculizumab discontinuation after achieving complete remission of aHUS and renal function recovery in patients with low risk of recurrence can provide better tolerability of maintenance treatment, and decrease the incidence of infectious complications and the financial burden on the healthcare system.

тромботическая микроангиопатияатипичный гемолитико-уремический синдромактивация комплементаэкулизумаботмена экулизумабаthrombotic microangiopathyatypical hemolytic uremic syndromecomplement activationeculizumabeculizumab withdrawalReferencesFakhouri F., Zuber J., Frémeaux-Bacchi V., Loirat C. Haemolytic uraemic syndrome. Lancet 2017;38:817–824. doi: 10.1016/S0140-6736(17)30062-4Fakhouri F., Zuber J., Frémeaux-Bacchi V., Loirat C. Haemolytic uraemic syndrome. Lancet 2017;38:817–824. doi: 10.1016/S0140-6736(17)30062-4Bezdíčka M., Pavlíček P., Bláhová K. et al. Various phenotypes of disease associated with mutated DGKE gene. Eur J Med Genet 2020; 63 (8): 103953. doi: 10.1016/j.ejmg.2020.103953Bezdíčka M., Pavlíček P., Bláhová K. et al. Various phenotypes of disease associated with mutated DGKE gene. Eur J Med Genet 2020; 63 (8): 103953. doi: 10.1016/j.ejmg.2020.103953Raina R., Krishnappa V., Blaha T. et al. Atypical hemolytic-uremic syndrome: an update on pathophysiology, diagnosis, and treatment. Ther Apher Dial 2019; 23 (1): 4–21. doi: 10.1111/1744-9987.12763Raina R., Krishnappa V., Blaha T. et al. Atypical hemolytic-uremic syndrome: an update on pathophysiology, diagnosis, and treatment. Ther Apher Dial 2019; 23 (1): 4–21. doi: 10.1111/1744-9987.12763Warwicker P., Donne R. L., Goodship J. A. et al. Familial relapsing haemolytic uraemic syndrome and complement factor H deficiency. Nephrol Dial Transplant 1999; 14 (5): 1229–1233. doi: 10.1093/ndt/14.5.1229Warwicker P., Donne R. L., Goodship J. A. et al. Familial relapsing haemolytic uraemic syndrome and complement factor H deficiency. Nephrol Dial Transplant 1999; 14 (5): 1229–1233. doi: 10.1093/ndt/14.5.1229Fremeaux-Bacchi V., Kemp E. J., Goodship J. A. et al. The development of atypical haemolytic-uraemic syndrome is influenced by susceptibility factors in factor H and membrane cofactor protein: evidence from two independent cohorts. J Med Genet 2005; 42 (11): 852–856. doi: 10.1136/jmg.2005.030783Fremeaux-Bacchi V., Kemp E. J., Goodship J. A. et al. The development of atypical haemolytic-uraemic syndrome is influenced by susceptibility factors in factor H and membrane cofactor protein: evidence from two independent cohorts. J Med Genet 2005; 42 (11): 852–856. doi: 10.1136/jmg.2005.030783Goicoechea de Jorge E., Harris C. L., Esparza-Gordillo J. et al. Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome. Proc Natl Acad Sci USA 2007; 104 (1): 240–245. doi: 10.1073/pnas.0603420103Goicoechea de Jorge E., Harris C. L., Esparza-Gordillo J. et al. Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome. Proc Natl Acad Sci USA 2007; 104 (1): 240–245. doi: 10.1073/pnas.0603420103Fremeaux-Bacchi V., Miller E. C., Liszewski M. K. et al. Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome. Blood 2008;112 (13): 4948–4952. doi: 10.1182/blood-2008-01-133702Fremeaux-Bacchi V., Miller E. C., Liszewski M. K. et al. Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome. Blood 2008;112 (13): 4948–4952. doi: 10.1182/blood-2008-01-133702Osborne A. J., Breno M., Borsa N. G. et al. Statistical validation of rare complement variants provides insights into the molecular basis of atypical hemolytic uremic syndrome and C3 glomerulopathy. J Immunol 2018; 200 (7): 2464–2478. doi: 10.4049/jimmunol.1701695Osborne A. J., Breno M., Borsa N. G. et al. Statistical validation of rare complement variants provides insights into the molecular basis of atypical hemolytic uremic syndrome and C3 glomerulopathy. J Immunol 2018; 200 (7): 2464–2478. doi: 10.4049/jimmunol.1701695Strobel S., Hoyer P. F., Mache C. J. Functional analyses indicate a pathogenic role of factor H autoantibodies in atypical haemolytic uraemic syndrome. Nephrol Dial Transplant 2010; 25: 136–144. doi:10.1093/ndt/gfp388Strobel S., Hoyer P. F., Mache C. J. Functional analyses indicate a pathogenic role of factor H autoantibodies in atypical haemolytic uraemic syndrome. Nephrol Dial Transplant 2010; 25: 136–144. doi:10.1093/ndt/gfp388Kim J. J., McCulloch M., Marks S. D. et al. The clinical spectrum of hemolytic uremic syndrome secondary to complement factor H autoantibodies. Clin Nephrol 2015; 83: 49–56. doi:10.5414/CN107777Kim J. J., McCulloch M., Marks S. D. et al. The clinical spectrum of hemolytic uremic syndrome secondary to complement factor H autoantibodies. Clin Nephrol 2015; 83: 49–56. doi:10.5414/CN107777Iorember F., Nayak A. Deficiency of CFHR plasma proteins and autoantibody positive hemolytic uremic syndrome: treatment rationale, outcomes, and monitoring. Pediatr Nephrol 2021; 36 (6): 1365–1375. doi: 10.1007/s00467-020-04652-xIorember F., Nayak A. Deficiency of CFHR plasma proteins and autoantibody positive hemolytic uremic syndrome: treatment rationale, outcomes, and monitoring. Pediatr Nephrol 2021; 36 (6): 1365–1375. doi: 10.1007/s00467-020-04652-xNoris M., Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med 2009 22; 361 (17): 1676–1687. doi: 10.1056/NEJMra0902814Noris M., Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med 2009 22; 361 (17): 1676–1687. doi: 10.1056/NEJMra0902814Sinha A., Gulati A., Saini S. et al. Prompt plasma exchanges and immunosuppressive treatment improves the outcomes of antifactor H autoantibody-associated hemolytic uremic syndrome in children. Kidney Int 2014; 85 (5): 1151–1160. doi: 10.1038/ki.2013.373Sinha A., Gulati A., Saini S. et al. Prompt plasma exchanges and immunosuppressive treatment improves the outcomes of antifactor H autoantibody-associated hemolytic uremic syndrome in children. Kidney Int 2014; 85 (5): 1151–1160. doi: 10.1038/ki.2013.373Brocklebank V., Johnson S., Sheerin Th. P. et al. Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland. Kidney Int 2017; 92 (5): 1261–1271. doi: 10.1016/j.kint.2017.04.028Brocklebank V., Johnson S., Sheerin Th. P. et al. Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland. Kidney Int 2017; 92 (5): 1261–1271. doi: 10.1016/j.kint.2017.04.028Zipfel P. F., Mache C., Muller D. et al. European DEAP-HUS Study Group. DEAP-HUS: deficiency of CFHR plasma proteins and autoantibody-positive form of hemolytic uremic syndrome. Pediatr Nephrol 2010; 25: 2009–2019. doi: 10.1007/s00467-010-1446-9Zipfel P. F., Mache C., Muller D. et al. European DEAP-HUS Study Group. DEAP-HUS: deficiency of CFHR plasma proteins and autoantibody-positive form of hemolytic uremic syndrome. Pediatr Nephrol 2010; 25: 2009–2019. doi: 10.1007/s00467-010-1446-9Jiang H., Fan M. N., Yang M. et al. Association among complement factor H autoantibodies, deletions of CFHR, and the risk of atypical hemolytic uremic syndrome. Int J Environ Res Public Health 2016; 13 (12): 1209–1221. doi: 10.3390/ijerph13121209Jiang H., Fan M. N., Yang M. et al. Association among complement factor H autoantibodies, deletions of CFHR, and the risk of atypical hemolytic uremic syndrome. Int J Environ Res Public Health 2016; 13 (12): 1209–1221. doi: 10.3390/ijerph13121209Carrillo-Carrasco N., Venditti C. P. Combined methylmalonic acidemia and homocystinuria, cblC type. II. Complications, pathophysiology, and outcomes. J Inherit Metab Dis 2012; 35: 103–114. doi: 10.1007/s10545-011-9365-xCarrillo-Carrasco N., Venditti C. P. Combined methylmalonic acidemia and homocystinuria, cblC type. II. Complications, pathophysiology, and outcomes. J Inherit Metab Dis 2012; 35: 103–114. doi: 10.1007/s10545-011-9365-xLemaire M., Frémeaux-Bacchi V., Schaefer F. et al. Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome. Nat Genet 2013; 45: 531–536. doi: 10.1038/ng.2590Lemaire M., Frémeaux-Bacchi V., Schaefer F. et al. Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome. Nat Genet 2013; 45: 531–536. doi: 10.1038/ng.2590Challis R. C., Ring T., Xu Y. et al. Thrombotic microangiopathy in inverted formin 2-mediated renal disease. J Am Soc Nephrol 2017; 28: 1084–1091. doi: 10.1681/ASN.2015101189Challis R. C., Ring T., Xu Y. et al. Thrombotic microangiopathy in inverted formin 2-mediated renal disease. J Am Soc Nephrol 2017; 28: 1084–1091. doi: 10.1681/ASN.2015101189Lemaire M., Noone D., Lapeyraque A.-L. et al. Clin J Am Soc Nephrol 2021; 16 (6): 942–956. doi: 10.2215/CJN.11830720Lemaire M., Noone D., Lapeyraque A.-L. et al. Clin J Am Soc Nephrol 2021; 16 (6): 942–956. doi: 10.2215/CJN.11830720Fremeaux-Bacchi V., Fakhouri F., Garnier A. et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol 2013; 8 (4): 554–562. doi: 10.2215/CJN.04760512Fremeaux-Bacchi V., Fakhouri F., Garnier A. et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol 2013; 8 (4): 554–562. doi: 10.2215/CJN.04760512Bu F., Borsa N. Gh., Jones M. B. et al. High-throughput genetic testing for thrombotic microangiopathies and C3 glomerulopathies. J Am Soc Nephrol 2016; 27 (4): 1245–1253. doi: 10.1681/ASN.2015040385Bu F., Borsa N. Gh., Jones M. B. et al. High-throughput genetic testing for thrombotic microangiopathies and C3 glomerulopathies. J Am Soc Nephrol 2016; 27 (4): 1245–1253. doi: 10.1681/ASN.2015040385Bu F., Zhang Yu., Wang K. et al. Genetic analysis of 400 patients refines understanding and implicates a new gene in atypical hemolytic uremic syndrome. J Am Soc Nephrol 2018; 29 (12): 2809–2819. doi: 10.1681/ASN.2018070759Bu F., Zhang Yu., Wang K. et al. Genetic analysis of 400 patients refines understanding and implicates a new gene in atypical hemolytic uremic syndrome. J Am Soc Nephrol 2018; 29 (12): 2809–2819. doi: 10.1681/ASN.2018070759El Karoui K., Boudhabhay I., Petitprezet F. et al. Impact of hypertensive emergency and complement rare variants on presentation and outcome of atypical hemolytic uremic syndrome. Haematologica 2019; 104 (12): 2501–2511. doi: 10.3324/haematol.2019.216903.El Karoui K., Boudhabhay I., Petitprezet F. et al. Impact of hypertensive emergency and complement rare variants on presentation and outcome of atypical hemolytic uremic syndrome. Haematologica 2019; 104 (12): 2501–2511. doi: 10.3324/haematol.2019.216903.Campistol J. M., Arias M., Ariceta G. et al. An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document. Nefrologia 2015; 35 (5): 421–447. doi: 10.1016/j.nefro.2015.07.005Campistol J. M., Arias M., Ariceta G. et al. An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document. Nefrologia 2015; 35 (5): 421–447. doi: 10.1016/j.nefro.2015.07.005Karpman D., Loos S., Tati R., Arvidsson I. Haemolytic uraemic syndrome. J Intern Med 2017; 281 (2): 123–148. doi: 10.1111/joim.12546Karpman D., Loos S., Tati R., Arvidsson I. Haemolytic uraemic syndrome. J Intern Med 2017; 281 (2): 123–148. doi: 10.1111/joim.12546Noris M., Caprioli J., Bresin E. et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 2010; 5 (10): 1844–1859. doi: 10.2215/CJN.02210310Noris M., Caprioli J., Bresin E. et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 2010; 5 (10): 1844–1859. doi: 10.2215/CJN.02210310van Hoeve K., Vandermeulen C., Van Ranst M. et al. Occurrence of atypical HUS associated with influenza B. Eur J Pediatr 2017; 176 (4): 449–454. doi: 10.1007/s00431-017-2856-5van Hoeve K., Vandermeulen C., Van Ranst M. et al. Occurrence of atypical HUS associated with influenza B. Eur J Pediatr 2017; 176 (4): 449–454. doi: 10.1007/s00431-017-2856-5Togarsimalemath S. K., Si-Mohammed A., Puraswani M. et al. Gastrointestinal pathogens in anti-FH antibody positive and negative Hemolytic Uremic Syndrome. Pediatr Res 2018; 84 (1): 118–124. doi: 10.1038/s41390-018-0009-9Togarsimalemath S. K., Si-Mohammed A., Puraswani M. et al. Gastrointestinal pathogens in anti-FH antibody positive and negative Hemolytic Uremic Syndrome. Pediatr Res 2018; 84 (1): 118–124. doi: 10.1038/s41390-018-0009-9Abe T., Sasaki A., Ueda T. et al. Complement-mediated thrombotic microangiopathy secondary to sepsis-induced disseminated intravascular coagulation successfully treated with eculizumab: A case report. Medicine (Baltimore) 2017; 96 (6): e6056. doi: 10.1097/MD.0000000000006056Abe T., Sasaki A., Ueda T. et al. Complement-mediated thrombotic microangiopathy secondary to sepsis-induced disseminated intravascular coagulation successfully treated with eculizumab: A case report. Medicine (Baltimore) 2017; 96 (6): e6056. doi: 10.1097/MD.0000000000006056So S., Fischer E., Gangadharan Komala M., Bose B. Postpartum atypical hemolytic uremic syndrome: Evaluating thrombotic microangiopathy in the pregnant woman. Obstet Med 2021; 14 (2): 105–108. doi: 10.1177/1753495X20926043So S., Fischer E., Gangadharan Komala M., Bose B. Postpartum atypical hemolytic uremic syndrome: Evaluating thrombotic microangiopathy in the pregnant woman. Obstet Med 2021; 14 (2): 105–108. doi: 10.1177/1753495X20926043Portoles J., Huerta A., Arjona E. et al. Characteristics, management and outcomes of atypical haemolytic uraemic syndrome in kidney transplant patients: a retrospective national study. Clin Kidney J 2020 13; 14 (4): 1173–1180. doi: 10.1093/ckj/sfaa096Portoles J., Huerta A., Arjona E. et al. Characteristics, management and outcomes of atypical haemolytic uraemic syndrome in kidney transplant patients: a retrospective national study. Clin Kidney J 2020 13; 14 (4): 1173–1180. doi: 10.1093/ckj/sfaa096Mir T. H. Thrombotic microangiopathy (aHUS/iTTP) reported so far in Covid-19 patients: The virus alone or an omnium gatherum of mechanisms and etiologies? Crit Rev Oncol Hematol 2021; 162: 103347. doi: 10.1016/j.critrevonc.2021.103347Mir T. H. Thrombotic microangiopathy (aHUS/iTTP) reported so far in Covid-19 patients: The virus alone or an omnium gatherum of mechanisms and etiologies? Crit Rev Oncol Hematol 2021; 162: 103347. doi: 10.1016/j.critrevonc.2021.103347Ville S., Le Bot S., Chapelet-Debout A. et al. Atypical HUS relapse triggered by COVID-19. Kidney Int 2021; 99 (1): 267–268. doi: 10.1016/j.kint.2020.10.030Ville S., Le Bot S., Chapelet-Debout A. et al. Atypical HUS relapse triggered by COVID-19. Kidney Int 2021; 99 (1): 267–268. doi: 10.1016/j.kint.2020.10.030Ikushima E., Hisahara M., Nishijima T. et al. Atypical Hemolytic Uremic Syndrome following Acute Type A Aortic Dissection. Case Rep Hematol 2020 Mar 3; 2020: 2467953. doi: 10.1155/2020/2467953Ikushima E., Hisahara M., Nishijima T. et al. Atypical Hemolytic Uremic Syndrome following Acute Type A Aortic Dissection. Case Rep Hematol 2020 Mar 3; 2020: 2467953. doi: 10.1155/2020/2467953Hanna R. M., Hasnain H., Abdelnour L. et al. Atypical hemolytic uremic syndrome in a patient with protein-losing enteropathy. J Int Med Res 2019; 47 (8): 4027–4032. doi: 10.1177/0300060519864808Hanna R. M., Hasnain H., Abdelnour L. et al. Atypical hemolytic uremic syndrome in a patient with protein-losing enteropathy. J Int Med Res 2019; 47 (8): 4027–4032. doi: 10.1177/0300060519864808Fujisawa M., Kato H., Yoshida Y. et al. Clinical characteristics and genetic backgrounds of Japanese patients with atypical hemolytic uremic syndrome. Clin Exp Nephrol 2018; 22 (5): 1088–1099. doi: 10.1007/s10157-018-1549-3Fujisawa M., Kato H., Yoshida Y. et al. Clinical characteristics and genetic backgrounds of Japanese patients with atypical hemolytic uremic syndrome. Clin Exp Nephrol 2018; 22 (5): 1088–1099. doi: 10.1007/s10157-018-1549-3Lapeyraque A. L., Bitzan M., Al-Dakkak I. et al. Clinical characteristics and outcome of canadian patients diagnosed with atypical hemolytic uremic syndrome. Can J Kidney Health Dis 2020; 7: 2054358119897229. doi: 10.1177/2054358119897229Lapeyraque A. L., Bitzan M., Al-Dakkak I. et al. Clinical characteristics and outcome of canadian patients diagnosed with atypical hemolytic uremic syndrome. Can J Kidney Health Dis 2020; 7: 2054358119897229. doi: 10.1177/2054358119897229Gupta M., Govindappagari S., Burwick R. M. Pregnancy-associated atypical hemolytic uremic syndrome: a systematic review. Obstet Gynecol 2020; 135 (1): 46–58. doi: 10.1097/AOG.0000000000003554Gupta M., Govindappagari S., Burwick R. M. Pregnancy-associated atypical hemolytic uremic syndrome: a systematic review. Obstet Gynecol 2020; 135 (1): 46–58. doi: 10.1097/AOG.0000000000003554Коротчаева Ю. В. Анализ течения и исходов острого повреждения почек при акушерском атипичном гемолитико-уремическом синдроме / Ю. В. Коротчаева, Н. Л. Козловская, К. А. Демьянова // Нефрология. – 2019. – 23 (приложение 1): 49 . doi: 10.36485/1561-6274-2019-23-5-44-54 / Korotchaevа Y. V., Kozlovskaya N. L., Demyanova K. A. Analysis of the course and outcomes of acute kidney injury in obstetric atypical hemolytic-uremic syndrome. Nephrology (Saint-Petersburg) 2019; 23 (supplement 1): 49 (In Russ.). doi: 10.36485/1561-6274-2019-23-5-44-54Коротчаева Ю. В. Анализ течения и исходов острого повреждения почек при акушерском атипичном гемолитико-уремическом синдроме / Ю. В. Коротчаева, Н. Л. Козловская, К. А. Демьянова // Нефрология. – 2019. – 23 (приложение 1): 49 . doi: 10.36485/1561-6274-2019-23-5-44-54 / Korotchaevа Y. V., Kozlovskaya N. L., Demyanova K. A. Analysis of the course and outcomes of acute kidney injury in obstetric atypical hemolytic-uremic syndrome. Nephrology (Saint-Petersburg) 2019; 23 (supplement 1): 49 (In Russ.). doi: 10.36485/1561-6274-2019-23-5-44-54Yüksel S., Gönül İ. I., Canpolat N. et al. Renal biopsy prognostic findings in children with atypical hemolytic uremic syndrome. Pediatr Dev Pathol 2020; 23 (5): 362–371. doi: 10.1177/1093526620925947Yüksel S., Gönül İ. I., Canpolat N. et al. Renal biopsy prognostic findings in children with atypical hemolytic uremic syndrome. Pediatr Dev Pathol 2020; 23 (5): 362–371. doi: 10.1177/1093526620925947Hofer J., Rosales A., Fischer C., Giner T. Extra-renal manifestations of complement-mediated thrombotic microangiopathies. Front Pediatr 2014 8; 2: 97. doi: 10.3389/fped.2014.00097Hofer J., Rosales A., Fischer C., Giner T. Extra-renal manifestations of complement-mediated thrombotic microangiopathies. Front Pediatr 2014 8; 2: 97. doi: 10.3389/fped.2014.00097Formeck C., Swiatecka-Urban A. Extra-renal manifestations of atypical hemolytic uremic syndrome. Pediatr Nephrol 2019; 34 (8): 1337–1348. doi: 10.1007/s00467-018-4039-7Formeck C., Swiatecka-Urban A. Extra-renal manifestations of atypical hemolytic uremic syndrome. Pediatr Nephrol 2019; 34 (8): 1337–1348. doi: 10.1007/s00467-018-4039-7Chan S., Weinstein A. R. Seizure as the Presenting Symptom for Atypical Hemolytic Uremic Syndrome. J Emerg Med 2019; 56 (4): 441–443. doi: 10.1016/j.jemermed.2018.12.034Chan S., Weinstein A. R. Seizure as the Presenting Symptom for Atypical Hemolytic Uremic Syndrome. J Emerg Med 2019; 56 (4): 441–443. doi: 10.1016/j.jemermed.2018.12.034González D. P., Iglicki M., Svetitsky S. et al. Occlusive retinal vasculopathy with macular branch retinal artery occlusion as a leading sign of atypical hemolytic uremic syndrome – a case report. BMC Ophthalmol 2021; 21 (1): 65. doi: 10.1186/s12886-021-01820-xGonzález D. P., Iglicki M., Svetitsky S. et al. Occlusive retinal vasculopathy with macular branch retinal artery occlusion as a leading sign of atypical hemolytic uremic syndrome – a case report. BMC Ophthalmol 2021; 21 (1): 65. doi: 10.1186/s12886-021-01820-xKichloo A., Chugh S. S., Gupta S. et al. Atypical hemolytic uremic syndrome presenting as acute heart failure-a rare presentation: diagnosis supported by skin biopsy. J Investig Med High Impact Case Rep 2019; 7: 2324709619842905. doi: 10.1177/2324709619842905Kichloo A., Chugh S. S., Gupta S. et al. Atypical hemolytic uremic syndrome presenting as acute heart failure-a rare presentation: diagnosis supported by skin biopsy. J Investig Med High Impact Case Rep 2019; 7: 2324709619842905. doi: 10.1177/2324709619842905Al-Ahmad M., Kharita L., Wannous H. Atypical hemolytic uremic syndrome with peripheral gangrene and homocysteinemia in a child. Oxf Med Case Reports 2020; 2020 (7): omaa048. doi: 10.1093/omcr/omaa048Al-Ahmad M., Kharita L., Wannous H. Atypical hemolytic uremic syndrome with peripheral gangrene and homocysteinemia in a child. Oxf Med Case Reports 2020; 2020 (7): omaa048. doi: 10.1093/omcr/omaa048Al-Shyoukh A., Younis M., Abughanimeh O. et al. An unusual case of diffuse alveolar hemorrhage as a clinical manifestation of atypical hemolytic uremic syndrome: a case report. Cureus 2019; 11 (7): e5059. doi: 10.7759/cureus.5059Al-Shyoukh A., Younis M., Abughanimeh O. et al. An unusual case of diffuse alveolar hemorrhage as a clinical manifestation of atypical hemolytic uremic syndrome: a case report. Cureus 2019; 11 (7): e5059. doi: 10.7759/cureus.5059Fidan K., Göknar N., Gülhan B. et al. Extra-renal manifestations of atypical hemolytic uremic syndrome in children. Pediatr Nephrol 2018; 33 (8): 1395–1403. doi: 10.1007/s00467-018-3933-3Fidan K., Göknar N., Gülhan B. et al. Extra-renal manifestations of atypical hemolytic uremic syndrome in children. Pediatr Nephrol 2018; 33 (8): 1395–1403. doi: 10.1007/s00467-018-3933-3Noris M., Remuzzi G. Hemolytic uremic syndrome. J Am Soc Nephrol 2005; 16 (4): 1035–1050. doi: 10.1681/ASN.2004100861Noris M., Remuzzi G. Hemolytic uremic syndrome. J Am Soc Nephrol 2005; 16 (4): 1035–1050. doi: 10.1681/ASN.2004100861Nürnberger J., Philipp T., Witzke O. et al. Eculizumab for atypical hemolytic-uremic syndrome. N Engl J Med 2009; 360 (5): 542–544. doi: 10.1056/NEJMc0808527Nürnberger J., Philipp T., Witzke O. et al. Eculizumab for atypical hemolytic-uremic syndrome. N Engl J Med 2009; 360 (5): 542–544. doi: 10.1056/NEJMc0808527Gruppo R. A., Rother R. P. Eculizumab for congenital atypical hemolytic-uremic syndrome. N Engl J Med 2009; 360 (5): 544–546. doi: 10.1056/NEJMc0809959Gruppo R. A., Rother R. P. Eculizumab for congenital atypical hemolytic-uremic syndrome. N Engl J Med 2009; 360 (5): 544–546. doi: 10.1056/NEJMc0809959Legendre C. M., Licht C., Muus P. et al. Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic–Uremic Syndrome. N Engl J Med 2013; 368: 2169–2181. doi: 10.1056/NEJMoa1208981Legendre C. M., Licht C., Muus P. et al. Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic–Uremic Syndrome. N Engl J Med 2013; 368: 2169–2181. doi: 10.1056/NEJMoa1208981Emirova Kh., Volokhina E., Tolstova E., van den Heuvel B. Recovery of renal function after long-term dialysis and resolution of cardiomyopathy in a patient with aHUS receiving eculizumab. BMJ Case Rep 2016; 2016: bcr2015213928. doi: 10.1136/bcr-2015-213928Emirova Kh., Volokhina E., Tolstova E., van den Heuvel B. Recovery of renal function after long-term dialysis and resolution of cardiomyopathy in a patient with aHUS receiving eculizumab. BMJ Case Rep 2016; 2016: bcr2015213928. doi: 10.1136/bcr-2015-213928Kulagin A., Ptushkin V., Lukina E. et al. Phase III clinical trial of Elizaria® and Soliris® in adult patients with paroxysmal nocturnal hemoglobinuria: results of comparative analysis of efficacy, safety, and pharmacological data. Blood 2019; 134 (Suppl 1): 3748. doi:10.1182/blood-2019-125693Kulagin A., Ptushkin V., Lukina E. et al. Phase III clinical trial of Elizaria® and Soliris® in adult patients with paroxysmal nocturnal hemoglobinuria: results of comparative analysis of efficacy, safety, and pharmacological data. Blood 2019; 134 (Suppl 1): 3748. doi:10.1182/blood-2019-125693Птушкин В. В. Результаты открытого многоцентрового клинического исследования Ib фазы по оценке безопасности, фармакокинетики и фармакодинамики первого биоаналога экулизумаба у нелеченых пациентов с пароксизмальной ночной гемоглобинурией в фазе индукции терапии / В. В. Птушкин [и др.] // Тер Арх. – 2020. – 92 (7): 77–84. doi: 10.26442/00403660.2020.07.000818 / Ptushkin V. V., Kulagin A. D., Lukina E. A. et al. Results of phase Ib open multicenter clinical trial of the safety, pharmacokinetics and pharmacodynamics of first biosimilar of eculizumab in untreated patients with paroxysmal nocturnal hemoglobinuria during induction of therapy. Ter Arkh 2020; 92 (7): 77–84 (In Russ.). doi: 10.26442/00403660.2020.07.000818Птушкин В. В. Результаты открытого многоцентрового клинического исследования Ib фазы по оценке безопасности, фармакокинетики и фармакодинамики первого биоаналога экулизумаба у нелеченых пациентов с пароксизмальной ночной гемоглобинурией в фазе индукции терапии / В. В. Птушкин [и др.] // Тер Арх. – 2020. – 92 (7): 77–84. doi: 10.26442/00403660.2020.07.000818 / Ptushkin V. V., Kulagin A. D., Lukina E. A. et al. Results of phase Ib open multicenter clinical trial of the safety, pharmacokinetics and pharmacodynamics of first biosimilar of eculizumab in untreated patients with paroxysmal nocturnal hemoglobinuria during induction of therapy. Ter Arkh 2020; 92 (7): 77–84 (In Russ.). doi: 10.26442/00403660.2020.07.000818Эмирова Х. М. Опыт применения Элизарии® при атипичном гемолитико-уремическом синдроме / Х. М. Эмирова [и др.] // Педиатрия. Журнал им. Г. Н. Сперанского. – 2019. – 98 (5): 225–229. doi: 10.24110/0031-403X-2019-98-5-225-229 / Emirova Kh. M., Orlova O. M., Muzurov A. L. et al. The experience of using Elizaria® for atypical hemolytic uremic syndrome. Pediatriya – Zhurnal im G. N. Speranskogo 2019; 98 (5): 225–229 (In Russ.). doi: 10.24110/0031-403X-2019-98-5-225-229Эмирова Х. М. Опыт применения Элизарии® при атипичном гемолитико-уремическом синдроме / Х. М. Эмирова [и др.] // Педиатрия. Журнал им. Г. Н. Сперанского. – 2019. – 98 (5): 225–229. doi: 10.24110/0031-403X-2019-98-5-225-229 / Emirova Kh. M., Orlova O. M., Muzurov A. L. et al. The experience of using Elizaria® for atypical hemolytic uremic syndrome. Pediatriya – Zhurnal im G. N. Speranskogo 2019; 98 (5): 225–229 (In Russ.). doi: 10.24110/0031-403X-2019-98-5-225-229Lavrishcheva I. V., Jakovenko A. A., Kudlay D. A. A case report of atypical hemolytic-uremic syndrome treatment with the first Russian eculizumab in adult patient. Urol Nephrol Open Access J 2020; 8 (2): 37–40. URL: https://www.generium.ru/upload/preparations/elizariya/Lavrishcheva-IV-et-al.-aHUS-case-report_UNOAJ-08-00272.pdf?ysclid=l7u871m2pf677526603Lavrishcheva I. V., Jakovenko A. A., Kudlay D. A. A case report of atypical hemolytic-uremic syndrome treatment with the first Russian eculizumab in adult patient. Urol Nephrol Open Access J 2020; 8 (2): 37–40. URL: https://www.generium.ru/upload/preparations/elizariya/Lavrishcheva-IV-et-al.-aHUS-case-report_UNOAJ-08-00272.pdf?ysclid=l7u871m2pf677526603Fakhouri F., Hourmant M., Campistol J. M. et al. Terminal complement inhibitor eculizumab in adult patients with atypical hemolytic uremic syndrome: a single-arm, open-label trial. Am J Kidney Dis 2016; 68 (1): 84–93. doi: 10.1053/j.ajkd.2015.12.034Fakhouri F., Hourmant M., Campistol J. M. et al. Terminal complement inhibitor eculizumab in adult patients with atypical hemolytic uremic syndrome: a single-arm, open-label trial. Am J Kidney Dis 2016; 68 (1): 84–93. doi: 10.1053/j.ajkd.2015.12.034Greenbaum L. A., Fila M., Ardissino G. et al. Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome. Kidney Int 2016 Mar; 89 (3): 701–711. doi: 10.1016/j.kint.2015.11.026Greenbaum L. A., Fila M., Ardissino G. et al. Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome. Kidney Int 2016 Mar; 89 (3): 701–711. doi: 10.1016/j.kint.2015.11.026Licht C., Greenbaum L. A., Muus P. et al. Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies. Kidney Int 2015; 87 (5): 1061–1073. doi: 10.1038/ki.2014.423Licht C., Greenbaum L. A., Muus P. et al. Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies. Kidney Int 2015; 87 (5): 1061–1073. doi: 10.1038/ki.2014.423Valente R. A., Rodríguez G. E., Marcote Y. G. et al. Discontinuation of peritoneal dialysis after late initiation of eculizumab in a case of familial atypical hemolytic-uremic syndrome: a case report. Case Rep Nephrol Dial 2017; 7 (1): 18–25. doi: 10.1159/000457950Valente R. A., Rodríguez G. E., Marcote Y. G. et al. Discontinuation of peritoneal dialysis after late initiation of eculizumab in a case of familial atypical hemolytic-uremic syndrome: a case report. Case Rep Nephrol Dial 2017; 7 (1): 18–25. doi: 10.1159/000457950Popova V. O., Galkina E. V., Telegina T. A. et al. partial recovery of kidney function in a case of delayed use of eculizumab in a patient with atypical hemolytic-uremic syndrome. Nephrology and Dialysis 2021; 23 (3): 425–433. doi: 10.28996/2618-9801-2021-3-425-433Popova V. O., Galkina E. V., Telegina T. A. et al. partial recovery of kidney function in a case of delayed use of eculizumab in a patient with atypical hemolytic-uremic syndrome. Nephrology and Dialysis 2021; 23 (3): 425–433. doi: 10.28996/2618-9801-2021-3-425-433Alexion Pharmaceuticals Inc. Soliris (eculizumab) summary of product characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000791/WC500054208.pdfAlexion Pharmaceuticals Inc. Soliris (eculizumab) summary of product characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000791/WC500054208.pdfGarcía Monteavaro C., Peralta Roselló C., Quiroga B. et al. Adjustment of eculizumab dosage pattern in patients with atypical hemolytic uremic syndrome with suboptimal response to standard treatment pattern. Case Rep Nephrol 2016; 2016: 7471082. doi: 10.1155/2016/7471082García Monteavaro C., Peralta Roselló C., Quiroga B. et al. Adjustment of eculizumab dosage pattern in patients with atypical hemolytic uremic syndrome with suboptimal response to standard treatment pattern. Case Rep Nephrol 2016; 2016: 7471082. doi: 10.1155/2016/7471082Teoh C. W., Gorman K. M., Lynch B. et al. Сinical relapses of atypical HUS on eculizumab: clinical gap for monitoring and individualized therapy. Case Rep Nephrol 2018; 2018: 2781789. doi: 10.1155/2018/2781789Teoh C. W., Gorman K. M., Lynch B. et al. Сinical relapses of atypical HUS on eculizumab: clinical gap for monitoring and individualized therapy. Case Rep Nephrol 2018; 2018: 2781789. doi: 10.1155/2018/2781789Deville C., Garrouste C., Coppo P. et al. Efficacy of rituximab and plasmapharesis in an adult patient with antifactor H autoantibody-associated hemolytic uremic syndrome: A case report and literature review. Medicine (Baltimore) 2016; 95 (39): e5007. doi: 10.1097/MD.0000000000005007Deville C., Garrouste C., Coppo P. et al. Efficacy of rituximab and plasmapharesis in an adult patient with antifactor H autoantibody-associated hemolytic uremic syndrome: A case report and literature review. Medicine (Baltimore) 2016; 95 (39): e5007. doi: 10.1097/MD.0000000000005007Loirat C., Fakhouri F., Ariceta G. et al. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol 2016; 31 (1): 15–39. doi: 10.1007/s00467-015-3076-8Loirat C., Fakhouri F., Ariceta G. et al. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol 2016; 31 (1): 15–39. doi: 10.1007/s00467-015-3076-8Saida K., Ito S. Successful therapy switch from eculizumab to mycophenolate mofetil in a girl with DEAP-HUS. Pediatr Nephrol 2017; 32 (10): 1997–1998. doi: 10.1007/s00467-017-3738-9Saida K., Ito S. Successful therapy switch from eculizumab to mycophenolate mofetil in a girl with DEAP-HUS. Pediatr Nephrol 2017; 32 (10): 1997–1998. doi: 10.1007/s00467-017-3738-9Ulitkina O. N., Filippovskaya Zh. S., Prokopenko E. I. et al. Successful treatment for atypical hemolytic-uremic syndrome in a puerpera. General Reanimatology 2015; 11 (6): 61–68. doi: 10.15360/1813-9779-2015-6-61-68Ulitkina O. N., Filippovskaya Zh. S., Prokopenko E. I. et al. Successful treatment for atypical hemolytic-uremic syndrome in a puerpera. General Reanimatology 2015; 11 (6): 61–68. doi: 10.15360/1813-9779-2015-6-61-68Stefanovic V. The extended use of eculizumab in pregnancy and complement activation-associated diseases affecting maternal, fetal and neonatal kidneys-the future is now? J Clin Med 2019; 8 (3): 407. doi: 10.3390/jcm8030407Stefanovic V. The extended use of eculizumab in pregnancy and complement activation-associated diseases affecting maternal, fetal and neonatal kidneys-the future is now? J Clin Med 2019; 8 (3): 407. doi: 10.3390/jcm8030407Fakhouri F., Scully M., Ardissino G. et al. Pregnancy-triggered atypical hemolytic uremic syndrome (aHUS): a Global aHUS Registry analysis. J Nephrol 2021; 34 (5): 1581–1590. doi: 10.1007/s40620-021-01025-xFakhouri F., Scully M., Ardissino G. et al. Pregnancy-triggered atypical hemolytic uremic syndrome (aHUS): a Global aHUS Registry analysis. J Nephrol 2021; 34 (5): 1581–1590. doi: 10.1007/s40620-021-01025-xAndries G., Karass M., Yandrapalli S. et al. Atypical hemolytic uremic syndrome in first trimester pregnancy successfully treated with eculizumab. Exp Hematol Oncol 2017; 6: 4. doi: 10.1186/s40164-017-0064-7Andries G., Karass M., Yandrapalli S. et al. Atypical hemolytic uremic syndrome in first trimester pregnancy successfully treated with eculizumab. Exp Hematol Oncol 2017; 6: 4. doi: 10.1186/s40164-017-0064-7Huerta A., Arjona E., Portoles J. et al. A retrospective study of pregnancy-associated atypical hemolytic uremic syndrome. Kidney Int 2018; 93 (2): 450–459. doi: 10.1016/j.kint.2017.06.022Huerta A., Arjona E., Portoles J. et al. A retrospective study of pregnancy-associated atypical hemolytic uremic syndrome. Kidney Int 2018; 93 (2): 450–459. doi: 10.1016/j.kint.2017.06.022Shanmugalingam R., Hsu D., Makris A. Pregnancy-induced atypical haemolytic uremic syndrome: A new era with eculizumab. Obstet Med 2018; 11 (1): 28–31. doi: 10.1177/1753495X17704563Shanmugalingam R., Hsu D., Makris A. Pregnancy-induced atypical haemolytic uremic syndrome: A new era with eculizumab. Obstet Med 2018; 11 (1): 28–31. doi: 10.1177/1753495X17704563Le Quintrec M., Zuber J., Moulin B. et al. Complement genes strongly predict recurrence and graft outcome in adult renal transplant recipients with atypical hemolytic and uremic syndrome. Am J Transplant 2013; 13 (3): 663–675. doi: 10.1111/ajt.12077Le Quintrec M., Zuber J., Moulin B. et al. Complement genes strongly predict recurrence and graft outcome in adult renal transplant recipients with atypical hemolytic and uremic syndrome. Am J Transplant 2013; 13 (3): 663–675. doi: 10.1111/ajt.12077Goodship T. H., Cook H. T., Fakhouri F. et al. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference. Kidney Int 2017; 91 (3): 539–551. doi: 10.1016/j.kint.2016.10.005Goodship T. H., Cook H. T., Fakhouri F. et al. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference. Kidney Int 2017; 91 (3): 539–551. doi: 10.1016/j.kint.2016.10.005Kant S., Bhalla A., Alasfar S., Alachkar N. Ten-year outcome of Eculizumab in kidney transplant recipients with atypical hemolytic uremic syndrome – a single center experience. BMC Nephrol 2020; 21 (1): 189. doi: 10.1186/s12882-020-01847-0Kant S., Bhalla A., Alasfar S., Alachkar N. Ten-year outcome of Eculizumab in kidney transplant recipients with atypical hemolytic uremic syndrome – a single center experience. BMC Nephrol 2020; 21 (1): 189. doi: 10.1186/s12882-020-01847-0Siedlecki A. M., Isbel N., Walle J. V. et al. Eculizumab use for kidney transplantation in patients with a diagnosis of atypical hemolytic uremic syndrome. Kidney Int Rep 2018; 4 (3): 434–446. doi: 10.1016/j.ekir.2018.11.010Siedlecki A. M., Isbel N., Walle J. V. et al. Eculizumab use for kidney transplantation in patients with a diagnosis of atypical hemolytic uremic syndrome. Kidney Int Rep 2018; 4 (3): 434–446. doi: 10.1016/j.ekir.2018.11.010Plasse R. A., Olson S. W., Yuan C. M. et al. Prophylactic or early use of eculizumab and graft survival in kidney transplant recipients with atypical hemolytic uremic syndrome in the United States: research letter. Can J Kidney Health Dis 2021 Mar 31; 8: 20543581211003763. doi: 10.1177/20543581211003763. eCollection 2021Plasse R. A., Olson S. W., Yuan C. M. et al. Prophylactic or early use of eculizumab and graft survival in kidney transplant recipients with atypical hemolytic uremic syndrome in the United States: research letter. Can J Kidney Health Dis 2021 Mar 31; 8: 20543581211003763. doi: 10.1177/20543581211003763. eCollection 2021Zuber J., Frimat M., Caillard S. et al. Use of highly individualized complement blockade has revolutionized clinical outcomes after kidney transplantation and renal epidemiology of atypical hemolytic uremic syndrome. J Am Soc Nephrol 2019; 30 (12): 2449–2463. doi: 10.1681/ASN.2019040331Zuber J., Frimat M., Caillard S. et al. Use of highly individualized complement blockade has revolutionized clinical outcomes after kidney transplantation and renal epidemiology of atypical hemolytic uremic syndrome. J Am Soc Nephrol 2019; 30 (12): 2449–2463. doi: 10.1681/ASN.2019040331Gonzalez Suarez M. L., Thongprayoon C., Mao M. A. et al. Outcomes of kidney transplant patients with atypical hemolytic uremic syndrome treated with eculizumab: a systematic review and meta-analysis. J Clin Med 2019; 8 (7): 919. doi: 10.3390/jcm8070919Gonzalez Suarez M. L., Thongprayoon C., Mao M. A. et al. Outcomes of kidney transplant patients with atypical hemolytic uremic syndrome treated with eculizumab: a systematic review and meta-analysis. J Clin Med 2019; 8 (7): 919. doi: 10.3390/jcm8070919Каабак М. М. Резолюция междисциплинарного совета экспертов. Трансплантация почки у пациентов с атипичным гемолитико-уремическим синдромом: клинические и организационно-методические аспекты ведения пациентов / М. М. Каабак [и др.] // Клиническая нефрология. – 2018. – 3: 8–14. URL: https://nephrologyjournal.ru/archive/article/36665?ysclid=l7u8chus6584513993 Kaabak M. M., Molchanova E. A., Nesterenko I. V. et al. Interdisciplinary expert council resolution. Kidney transplantation in patients with atypical hemolytic-uremic syndrome: clinical and organizational-methodical aspects of patient management. Clinical Nephrology 2018; 3: 8–14 (In Russ.). URL: https://nephrologyjournal.ru/archive/article/36665?Каабак М. М. Резолюция междисциплинарного совета экспертов. Трансплантация почки у пациентов с атипичным гемолитико-уремическим синдромом: клинические и организационно-методические аспекты ведения пациентов / М. М. Каабак [и др.] // Клиническая нефрология. – 2018. – 3: 8–14. URL: https://nephrologyjournal.ru/archive/article/36665?ysclid=l7u8chus6584513993 Kaabak M. M., Molchanova E. A., Nesterenko I. V. et al. Interdisciplinary expert council resolution. Kidney transplantation in patients with atypical hemolytic-uremic syndrome: clinical and organizational-methodical aspects of patient management. Clinical Nephrology 2018; 3: 8–14 (In Russ.). URL: https://nephrologyjournal.ru/archive/article/36665?Pugh D., O'Sullivan E. D., Duthie F. A. I. et al. Interventions for atypical haemolytic uraemic syndrome. Cochrane Data-base of Systematic Reviews 2021, Issue 3. Art. No.: CD012862. doi: 10.1002/14651858.CD012862.pub2Pugh D., O'Sullivan E. D., Duthie F. A. I. et al. Interventions for atypical haemolytic uraemic syndrome. Cochrane Data-base of Systematic Reviews 2021, Issue 3. Art. No.: CD012862. doi: 10.1002/14651858.CD012862.pub2Davin J. C., van de Kar N. C. Advances and challenges in the management of complement-mediated thrombotic microangiopathies. Ther Adv Hematol 2015; 6: 171–185. doi: 10.1177/2040620715577613Davin J. C., van de Kar N. C. Advances and challenges in the management of complement-mediated thrombotic microangiopathies. Ther Adv Hematol 2015; 6: 171–185. doi: 10.1177/2040620715577613Struijk G. H., Bouts A. H., Rijkers G. T. et al. Meningococcal sepsis complicating eculizumab treatment despite prior vaccination. Am J Transplant 2013; 13 (3): 819–820. doi: 10.1111/ajt.12032Struijk G. H., Bouts A. H., Rijkers G. T. et al. Meningococcal sepsis complicating eculizumab treatment despite prior vaccination. Am J Transplant 2013; 13 (3): 819–820. doi: 10.1111/ajt.12032Jentzsch M., Schwind S., Vucinic V. et al. Meningococcal sepsis without cerebrospinal fluid abnormalities under treatment with eculizumab. Med Klin Intensivmed Notfmed 2020; 115 (4): 340–342. doi: 10.1007/s00063-019-0552-0Jentzsch M., Schwind S., Vucinic V. et al. Meningococcal sepsis without cerebrospinal fluid abnormalities under treatment with eculizumab. Med Klin Intensivmed Notfmed 2020; 115 (4): 340–342. doi: 10.1007/s00063-019-0552-0Macia M., de Alvaro Moreno F., Dutt T. et al. Current evidence on the discontinuation of eculizumab in patients with atypical haemolytic uraemic syndrome. Clin Kidney J 2017; 10 (3): 310–319. doi: 10.1093/ckj/sfw115Macia M., de Alvaro Moreno F., Dutt T. et al. Current evidence on the discontinuation of eculizumab in patients with atypical haemolytic uraemic syndrome. Clin Kidney J 2017; 10 (3): 310–319. doi: 10.1093/ckj/sfw115Ardissino G., Testa S., Possenti I. et al. Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome: a report of 10 cases. Am J Kidney Dis 2014; 64: 633–637. doi: 10.1053/j.ajkd.2014.01.434Ardissino G., Testa S., Possenti I. et al. Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome: a report of 10 cases. Am J Kidney Dis 2014; 64: 633–637. doi: 10.1053/j.ajkd.2014.01.434Ardissino G., Possenti I., Tel F. et al. Discontinuation of eculizumab treatment in atypical hemolytic uremic syndrome: an update. Am J Kidney Dis 2015; 66: 172–173. doi: 10.1053/j.ajkd.2015.04.010Ardissino G., Possenti I., Tel F. et al. Discontinuation of eculizumab treatment in atypical hemolytic uremic syndrome: an update. Am J Kidney Dis 2015; 66: 172–173. doi: 10.1053/j.ajkd.2015.04.010Sheerin N. S., Kavanagh D., Goodship T. H. J. et al. A national specialized service in England for atypical haemolytic uraemic syndrome—the first year’s experience. QJM 2016; 109 (1): 27–33. doi: 10.1093/qjmed/hcv082Sheerin N. S., Kavanagh D., Goodship T. H. J. et al. A national specialized service in England for atypical haemolytic uraemic syndrome—the first year’s experience. QJM 2016; 109 (1): 27–33. doi: 10.1093/qjmed/hcv082Ariceta G. Optimal duration of treatment with eculizumab in atypical hemolytic uremic syndrome (aHUS)-a question to be addressed in a scientific way. Pediatr Nephrol 2019; 34 (5): 943–949. doi: 10.1007/s00467-019-4192-7Ariceta G. Optimal duration of treatment with eculizumab in atypical hemolytic uremic syndrome (aHUS)-a question to be addressed in a scientific way. Pediatr Nephrol 2019; 34 (5): 943–949. doi: 10.1007/s00467-019-4192-7Menne J., Delmas Y., Fakhouri F. et al. Outcomes in patients with atypical hemolytic uremic syndrome treated with eculizumab in a long-term observational study. BMC Nephrol 2019; 20 (1): 125. doi: 10.1186/s12882-019-1314-1Menne J., Delmas Y., Fakhouri F. et al. Outcomes in patients with atypical hemolytic uremic syndrome treated with eculizumab in a long-term observational study. BMC Nephrol 2019; 20 (1): 125. doi: 10.1186/s12882-019-1314-1Hackl A., Ehren R., Kirschfink M. et al. Successful discontinuation of eculizumab under immunosuppressive therapy in DEAP-HUS. Pediatr Nephrol 2017; 32 (6): 1081–1087. doi: 10.1007/s00467-017-3612-9Hackl A., Ehren R., Kirschfink M. et al. Successful discontinuation of eculizumab under immunosuppressive therapy in DEAP-HUS. Pediatr Nephrol 2017; 32 (6): 1081–1087. doi: 10.1007/s00467-017-3612-9Kise T., Fukuyama S., Uehara M. Successful treatment of antifactor H antibody-associated atypical hemolytic uremic syndrome. Indian J Nephrol 2020; 30 (1): 35–38. doi: 10.4103/ijn.IJN_336_18Kise T., Fukuyama S., Uehara M. Successful treatment of antifactor H antibody-associated atypical hemolytic uremic syndrome. Indian J Nephrol 2020; 30 (1): 35–38. doi: 10.4103/ijn.IJN_336_18Chaturvedi S., Dhaliwal N., Hussain S. et al. Outcomes of a clinician-directed protocol for discontinuation of complement inhibition therapy in atypical hemolytic uremic syndrome. Blood Adv 2021; 5 (5): 1504–1512. doi: 10.1182/bloodadvances.2020003175Chaturvedi S., Dhaliwal N., Hussain S. et al. Outcomes of a clinician-directed protocol for discontinuation of complement inhibition therapy in atypical hemolytic uremic syndrome. Blood Adv 2021; 5 (5): 1504–1512. doi: 10.1182/bloodadvances.2020003175Fakhouri F., Scully M., Provôt F. et al. Management of thrombotic microangiopathy in pregnancy and postpartum: report from an international working group. Blood 2020; 136 (19): 2103–2117. doi: 10.1182/blood.2020005221Fakhouri F., Scully M., Provôt F. et al. Management of thrombotic microangiopathy in pregnancy and postpartum: report from an international working group. Blood 2020; 136 (19): 2103–2117. doi: 10.1182/blood.2020005221Fakhouri F., Fila M., Provôt F. et al. Pathogenic variants in complement genes and risk of atypical hemolytic uremic syndrome relapse after eculizumab discontinuation. Clin J Am Soc Nephrol 2017; 12 (1): 50–59. doi: 10.2215/CJN.06440616Fakhouri F., Fila M., Provôt F. et al. Pathogenic variants in complement genes and risk of atypical hemolytic uremic syndrome relapse after eculizumab discontinuation. Clin J Am Soc Nephrol 2017; 12 (1): 50–59. doi: 10.2215/CJN.06440616Fakhouri F., Fila M., Hummel A. et al. Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: a prospective multicenter study. Blood 2021; 137 (18): 2438–2449. doi: 10.1182/blood.2020009280Fakhouri F., Fila M., Hummel A. et al. Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: a prospective multicenter study. Blood 2021; 137 (18): 2438–2449. doi: 10.1182/blood.2020009280

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