title: Obstetric nephrology: AKI and thrombotic microangiopathies in pregnancy.
abstract: AKI in pregnancy remains a cause of significant fetomaternal mortality and morbidity, particularly in developing countries. Hypertensive complications of pregnancy (preeclampsia/eclampsia or hemolysis, elevated liver enzymes, and low platelets count syndrome) are the leading cause of AKI in pregnancy worldwide. Thrombotic microangiopathy is another peculiar and devastating cause of AKI in pregnancy. During the last decade, our understanding, and in some cases, our management, of these causes of AKI in pregnancy has dramatically improved. For instance, convincing data have linked pre-eclampsia/eclampsia to an increase in circulating antiangiogenic factors soluble Flt 1 and endoglin, which induce endothelial cell dysfunction, hypertension, and proteinuria. Several distinct pathogenic mechanisms underlying thrombotic microangiopathy, including thrombotic microangiopathy occurring during pregnancy, have been established. Thrombotic microangiopathy, which can present as hemolytic uremic syndrome or thrombotic thrombocytopenic purpura, can be reclassified in four potentially overlapping subtypes: disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 deficiency-related thrombotic microangiopathy, complement alternative pathway dysregulation-related thrombotic microangiopathy, secondary thrombotic microangiopathy (verotoxin and antiangiogenic drugs), and thrombotic microangiopathy of undetermined mechanism. In most cases, pregnancy is only a precipitating factor for thrombotic microangiopathy. Treatment of thrombotic microangiopathy occurring during pregnancy should be tailored to the underlying pathogenic mechanism: (1) restoration of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 serum activity in the setting of thrombotic thrombocytopenic purpura through plasma exchanges and in some cases, B cell-depleting therapy and (2) inhibition of complement alternative pathway activation in atypical hemolytic uremic syndrome using antiC5 blocking antibody (eculizumab).
authors.affiliation: Institut de Transplantation, Urologie et Néphrologie, Department of Nephrology and Immunology, Institut National de la Santé et de la Recherche Médicale UMR S-1064, Centre Hospitalo-Universitaire de Nantes, Nantes, France. fadi.fakhouri@univ-nantes.fr
authors.forename: Fadi
authors.initials: F
authors.lastname: Fakhouri
authors.forename: Caroline
authors.initials: C
authors.lastname: Vercel
authors.forename: Véronique
authors.initials: V
authors.lastname: Frémeaux-Bacchi
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D004461:Eclampsia / Q000378:metabolism*; D000071063:Endoglin; D005260:Female; D017359:HELLP Syndrome / Q000378:metabolism*; D006801:Humans; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000378:metabolism; D057049:Thrombotic Microangiopathies / Q000209:etiology / Q000378:metabolism / Q000628:therapy*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1