nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical Universitynefr-169Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯORIGINAL ARTICLES CLINICAL STUDIESАкушерский атипичный гемолитико-уремический СИНДРОМ: ПЕРВЫЙ РОССИЙСКИЙ ОПЫТ ДИАГНОСТИКИ И ЛЕЧЕНИЯObstetric atypical hemolytic uremic syndrome: THE FIRST RUSSIAN EXPERIENCE OF DIAGNOSIS AND TREATMENTКозловскаяНаталья ЛьвовнаKozlovskayaNatalia L.nkozlovskaya@yandex.ruКоротчаеваЮлия ВячеславовнаKorotchaevaYulia V.Lumis-j@bk.ruБоброваЛариса АлександровнаBobrovaLarysa A.mrlee2005@yandex.ruШиловЕвгений МихайловичShilovEugeny M.emshilov@mma.ruГосударственное бюджетное образовательное учреждение высшего профессионального образования Первый Московский государственный медицинский университет им. И.М. Сеченова Министерства здравоохранения Российской ФедерацииРоссияState Federal-Funded Educational Institution of Higher Professional Training I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian FederationRussian Federation2016010320162026880Copyright © Козловская Н.Л., Коротчаева Ю.В., Боброва Л.А., Шилов Е.М., 20162016Козловская Н.Л., Коротчаева Ю.В., Боброва Л.А., Шилов Е.М.Kozlovskaya N.L., Korotchaeva Y.V., Bobrova L.A., Shilov E.M.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/169

Атипичный гемолитико-уремический синдром (аГУС) в 12-31% случаев связан с беременностью или родами и может определять прогноз как матери, так и ребенка. ЦЕЛЬ. Анализ клинических проявлений, особенностей течения и исходов акушерского аГУС. ПАЦИЕНТЫ И МЕТОДЫ. С 2012 по 2015 г. наблюдались 17 пациенток в возрасте от 19 до 38 лет, у которых аГУС развился во время беременности или непосредственно после родов. РЕЗУЛЬТАТЫ. Развитию аГУС предшествовали, преимущественно, преэклампсия и/или HELLP-синдром и другие акушерские осложнения, диарея. Все пациентки имели полный симптомокомплекс тромботической микроангиопатии (ТМА): резкое снижение уровня гемоглобина (67,7 ± 15,9 г/л) с признаками микроангиопатического гемолиза (повышение уровня ЛДГ 2737,3 ± 3276,7 ЕД/л, шизоцитоз), тромбоцитопению (55,9±30,9 тыс. в 1 мкл), острое повреждение почек (гиперкреатининемия 447.6 ±226,7 мг/дл, олигурия или анурия). У большинства пациенток (82%, 14 из 17) впервые отмечена артериальная гипертензия. У всех пациенток ТМА носила системный характер: признаки поражения печени, ЦНС, легких имели 73% женщин (13 из 17), сердца - 41% (7 из 17). При анализе течения аГУС в зависимости от сроков беременности на момент развития заболевания клинико-лабораторные показатели были более тяжелыми у женщин с манифестацией аГУС в III триместре и после родов. Лечение состояло, преимущественно, из плазмотерапии в режимах инфузий свежезамороженной плазмы и плазмообмена (14 из 17, 82%), семи пациенткам было начато лечение экулизумабом. Материнская смертность составила 29%. ЗАКЛЮЧЕНИЕ. Акушерский аГУС характеризуется развитием полиорганной недостаточности у большинства пациенток. Развитию аГУС предшествуют различные комплемент-активирующие состояния. По-видимому, что именно осложнения беременности, а не сама беременность per se, являются триггерами аГУС у женщин с генетической предрасположенностью к его развитию.

Atypical hemolytic uremic syndrome (AHUs) in 12-31% of cases is associated with pregnancy or delivery, and may determine the prognosis of both mother and child. AIM: Analysis of clinical manifestations, features of course and outcomes of obstetric aHUS. PATIENTS AND METHODS: From 2012 to 2015 were observed 17 patients aged 19 to 38 years, in whom aHUS developed during pregnancy or directly after delivery. RESULTS: The development of aHUS was preceded by a mainly preeclampsia and/or HELLP syndrome and other pregnancy complications, diarrhea. All patients had complete symptom complex of thrombotic microangiopathy (TMA): sharp decrease of hemoglobin level (67,7 ± 15,9 g/l) with signs of microangiopathic hemolysis (increased LDH levels 2737,3 ± 3276,7 U/l, schistocytosis), thrombocytopenia (55,9±30.9 thousand in mcl.), acute kidney injury (hypercreatininemia 447.6 ±of 226.7 mg/DL, oliguria or anuria). Most patients (82%, 14 of 17) had first time mentioned arterial hypertension. In all patients the TMA was of a systemic nature: the signs of damage of liver, central nervous system, lungs had 73% of women (13 of 17), heart - 41% (7 of 17). In the analysis of flow aHUS depending on the stages of pregnancy at the time of the disease development clinical and laboratory parameters were more severe in women with manifestations of AHUs in the third trimester and after delivery. Treatment included plasma exchange and/or plasma infusions (14 of 17, 82%) with following Eculizumab treatment in 7 patients. Maternal mortality was 29%. CONCLUSION. Obstetric aHUS is characterized by the development of multiple organ failure in most patients. Development aHUS preceded by various complement-activating state. It seems that complications of pregnancy, not the pregnancy per se, are triggers of aHUS in women with a genetic predisposition to its development.

тромботическая микроангиопатияатипичный гемолитико-уремический синдромбеременностьпреэклампсияHELLP-синдромthrombotic microangiopathyatypical hemolytic uremic syndromepregnancypreeclampsiaHELLP-syndromeReferencesFakhouri F1, Vercel C, Frémeaux-Bacchi V. Obstetric nephrology: AKI and thrombotic microangiopathies in pregnancy. Clin J Am Soc Nephrol 2012 Dec;7(12):2100-2106Fakhouri F1, Vercel C, Frémeaux-Bacchi V. Obstetric nephrology: AKI and thrombotic microangiopathies in pregnancy. Clin J Am Soc Nephrol 2012 Dec;7(12):2100-2106Machado S, Figueiredo N, Borges A et al. Acute kidney injury in pregnancy: a clinical challenge. J Nephrol 2012;25(01):19-30Machado S, Figueiredo N, Borges A et al. Acute kidney injury in pregnancy: a clinical challenge. J Nephrol 2012;25(01):19-30Tsai HM. A Mechanistic Approach to the Diagnosis and Management of Atypical Hemolytic Uremic Syndrome. Transfus Med Rev 2014; Oct;28(4):187-197Tsai HM. A Mechanistic Approach to the Diagnosis and Management of Atypical Hemolytic Uremic Syndrome. Transfus Med Rev 2014; Oct;28(4):187-197Fakhouri F, Fremeaux-Bacchi V. Does hemolytic uremic syndrome differ from thrombotic thrombocytopenic purpura. Nat Clin Pract Nephrol 2007; 3: 679-687Fakhouri F, Fremeaux-Bacchi V. Does hemolytic uremic syndrome differ from thrombotic thrombocytopenic purpura. Nat Clin Pract Nephrol 2007; 3: 679-687Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med 2009; 361:1676-1687Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med 2009; 361:1676-1687Meri S. Complement activation in diseases presenting with thrombotic microangiopathy. Eur J Intern Med2013 Sep;24(6):496-502.Meri S. Complement activation in diseases presenting with thrombotic microangiopathy. Eur J Intern Med2013 Sep;24(6):496-502.Fakhouri F, Roumenina L, Provot F et al. Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J Am Soc Nephrol 2010;21:859-867Fakhouri F, Roumenina L, Provot F et al. Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J Am Soc Nephrol 2010;21:859-867Ganesan C, Maynard SE. Acute kidney injuryin pregnancy: the thrombotic microangiopathies. J Nephrol 2011;24(05)554-563Ganesan C, Maynard SE. Acute kidney injuryin pregnancy: the thrombotic microangiopathies. J Nephrol 2011;24(05)554-563McMinn JR, George JN. Evaluation of women with clinically suspected thrombotic thrombocytopenic purpura-hemolytic uremic syndrome during pregnancy. J Clin lApheresis 2001;16:202-209McMinn JR, George JN. Evaluation of women with clinically suspected thrombotic thrombocytopenic purpura-hemolytic uremic syndrome during pregnancy. J Clin lApheresis 2001;16:202-209Girardi G, Bulla R, Salmon JE, Tedesco F The complement system in the pathophysiology of pregnancy. Mol Immunol 2006;43:68-77Girardi G, Bulla R, Salmon JE, Tedesco F The complement system in the pathophysiology of pregnancy. Mol Immunol 2006;43:68-77Noris 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: 1844-1859Noris 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: 1844-1859Buurma A, Cohen D, Veraar K. Preeclamsia is characterized by placental complement dysregulation. Hypertension 2012;60(5):1332-1337Buurma A, Cohen D, Veraar K. Preeclamsia is characterized by placental complement dysregulation. Hypertension 2012;60(5):1332-1337Rampressad R, Barton A, Sadovsky Y Nelson DM. The 5b-9 membrane attack complex of complement activation localizes to villous trophoblast injuri in vivo and modulates human trophoblast function in vitro. Placenta 2008;29(10):855-886Rampressad R, Barton A, Sadovsky Y Nelson DM. The 5b-9 membrane attack complex of complement activation localizes to villous trophoblast injuri in vivo and modulates human trophoblast function in vitro. Placenta 2008;29(10):855-886Lynch AM, Murphy JR, Byers T. Alternative complement pathway activation fragment Bb in early pregnancy as a predictor of preeclampsia. Am J Obstet Gynecol 2008;198(4):385-389Lynch AM, Murphy JR, Byers T. Alternative complement pathway activation fragment Bb in early pregnancy as a predictor of preeclampsia. Am J Obstet Gynecol 2008;198(4):385-389Dennya KJ, Coultharda LG, Finnellc RH. Elevated complement factor C5a in maternal and umbilical cord plasma in preeclampsia. J Reprod Immunol 2013;97:211-216Dennya KJ, Coultharda LG, Finnellc RH. Elevated complement factor C5a in maternal and umbilical cord plasma in preeclampsia. J Reprod Immunol 2013;97:211-216Hoffman MC, Rumer KK, Kramer A et al. Maternal and fetal alternative complement pathway activation in early severe preeclamsia. Am J Reproduct Immunol 2014;71:55-60Hoffman MC, Rumer KK, Kramer A et al. Maternal and fetal alternative complement pathway activation in early severe preeclamsia. Am J Reproduct Immunol 2014;71:55-60Girardi G, Yarilin D, Thurman JM et al. Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction. J Experiment Med 2006;203:2165-2175Girardi G, Yarilin D, Thurman JM et al. Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction. J Experiment Med 2006;203:2165-2175Maynard SE, Min JY Lim KH et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt-1) may contribute to endothelian dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 2003; 111: 649-658Maynard SE, Min JY Lim KH et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt-1) may contribute to endothelian dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 2003; 111: 649-658Eremina V, Jefferson A, Kowalewska J et al. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 2008; 358:1129-1139Eremina V, Jefferson A, Kowalewska J et al. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 2008; 358:1129-1139Fang C, Richards A, Liszewski MK et al. Advances in understanding of pathogens is of aHUS and HELLP. Brit J Haematol 2008;143:336-348Fang C, Richards A, Liszewski MK et al. Advances in understanding of pathogens is of aHUS and HELLP. Brit J Haematol 2008;143:336-348Bucciarelli S, Espinosa G, Cervera R. The CAPS Registry: morbidity and mortality of the catastrophic antiphospholipid syndrome. Lupus 2009; 18(10):905-912Bucciarelli S, Espinosa G, Cervera R. The CAPS Registry: morbidity and mortality of the catastrophic antiphospholipid syndrome. Lupus 2009; 18(10):905-912Hofer J, Rosales A, Fisher C, Giner T. Extra-renal manifestation of complement-mediates thrombotic microangiopathies. Pediatric Nephrology 2014; 2: doi:10.3389/fped.2014.00097Hofer J, Rosales A, Fisher C, Giner T. Extra-renal manifestation of complement-mediates thrombotic microangiopathies. Pediatric Nephrology 2014; 2: doi:10.3389/fped.2014.00097Лора Ш, Фремю-Бачи В. Атипичный гемолитико-уремический синдром. Нефрология 2012;16(2):16-48Лора Ш, Фремю-Бачи В. Атипичный гемолитико-уремический синдром. Нефрология 2012;16(2):16-48Owens MY, Martin JN, Wallace K et al. Postpartum thrombotic microangiopathic syndrome. Transfusion Apheresis Sci 2013;48:51-57Owens MY, Martin JN, Wallace K et al. Postpartum thrombotic microangiopathic syndrome. Transfusion Apheresis Sci 2013;48:51-57Iannuzzi M, Siconolfi P, D'Angelillo A et al. A postpartum hemolytic uremic syndrome-like syndrome in a patient with preeclampsia: description of a clinical case. Transfus Apher Sci 2006;34:11-140Iannuzzi M, Siconolfi P, D'Angelillo A et al. A postpartum hemolytic uremic syndrome-like syndrome in a patient with preeclampsia: description of a clinical case. Transfus Apher Sci 2006;34:11-140Obeidat B, MacDougall J, Harding K. Plasma exchange in a woman with thrombotic thrombocytopenic purpura or severe preeclampsia. Br J Obstet Gynecol 2002;109:961-962Obeidat B, MacDougall J, Harding K. Plasma exchange in a woman with thrombotic thrombocytopenic purpura or severe preeclampsia. Br J Obstet Gynecol 2002;109:961-962Roberts G, Gordon MM, Porter D et al. Acute renal failure complicated HELLP syndrome, SLE and antiphospholipid syndrome: successful outcome using plasma exchange therapy. Lupus 2003;12:251-257Roberts G, Gordon MM, Porter D et al. Acute renal failure complicated HELLP syndrome, SLE and antiphospholipid syndrome: successful outcome using plasma exchange therapy. Lupus 2003;12:251-257Козловская НЛ, Меркушева ЛИ, Кирсанова ТВ, Рунихина НК. Особенности течения и исхода атипичного гемолитико-уремического синдрома при беременности. Клин нефрол 2012; (3):44-49Козловская НЛ, Меркушева ЛИ, Кирсанова ТВ, Рунихина НК. Особенности течения и исхода атипичного гемолитико-уремического синдрома при беременности. Клин нефрол 2012; (3):44-49Коротчаева ЮВ, Козловская НЛ, Бондаренко ТВ, Веселов ГА. Особенности течения и лечения «акушерского» гемолитико-уремического синдрома Нефрология 2015; 19 (2):76-81Коротчаева ЮВ, Козловская НЛ, Бондаренко ТВ, Веселов ГА. Особенности течения и лечения «акушерского» гемолитико-уремического синдрома Нефрология 2015; 19 (2):76-81Burwick RM, Feinberg BB. Eculizumab for the treatment of preeclampsia/HELLP syndrome. Placenta 2013; 34: 201-203Burwick RM, Feinberg BB. Eculizumab for the treatment of preeclampsia/HELLP syndrome. Placenta 2013; 34: 201-203Mackaness DO, Craig A. Eculizumab in the Successful Treatment of Postpartum Hemolytic Uremic Syndrome - A Case Report. NKF 2014 Spring Clinical Meetings Abstracts. Am J Kidney Dis 2014; 63(5):75Mackaness DO, Craig A. Eculizumab in the Successful Treatment of Postpartum Hemolytic Uremic Syndrome - A Case Report. NKF 2014 Spring Clinical Meetings Abstracts. Am J Kidney Dis 2014; 63(5):75Kourouklaris A, Ioannou K, Athanasiou L et al. Postpartum thrombotic microangiopathy revealed as atypical hemolytic uremic syndrome successfully treated with eculizumab: a case report. J Med Case Rep 2014; 8:307Kourouklaris A, Ioannou K, Athanasiou L et al. Postpartum thrombotic microangiopathy revealed as atypical hemolytic uremic syndrome successfully treated with eculizumab: a case report. J Med Case Rep 2014; 8:307

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