title: Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations.
abstract: In contrast to pregnancy-associated thrombotic thrombocytopenic purpura, the pathogenesis and presentation of pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS) remain ill-defined. We conducted a retrospective study to assess the presentation and outcomes of patients presenting with P-aHUS and the prevalence of alternative C3 convertase dysregulation. P-aHUS occurred in 21 of the 100 adult female patients with atypical HUS, with 79% presenting postpartum. We detected complement abnormalities in 18 of the 21 patients. The outcomes were poor: 62% reached ESRD by 1 month and 76% by last follow-up. The risk for P-aHUS was highest during a second pregnancy. Thirty-five women, 26 (74%) of whom had complement abnormalities, had at least one pregnancy before the onset of a non-pregnancy-related aHUS. Outcomes did not differ between patients with pregnancy-related and non-pregnancy-related aHUS. Mutations in the SCR19-20 domains of factor H were less frequent in P-aHUS patients compared with non-pregnancy-related aHUS. Pregnancies in female patients with complement abnormalities (n = 44) were complicated by fetal loss and preeclampsia in 4.8% and 7.7%, respectively. Better understanding of complement dysregulation in pregnancy complications is essential, especially to guide development of pharmacologic agents to modulate this system.
authors.affiliation: Department of Nephrology and UMR 643, CHU de Nantes, Paris, France.
authors.forename: Fadi
authors.initials: F
authors.lastname: Fakhouri
authors.forename: Lubka
authors.initials: L
authors.lastname: Roumenina
authors.forename: François
authors.initials: F
authors.lastname: Provot
authors.forename: Marion
authors.initials: M
authors.lastname: Sallée
authors.forename: Sophie
authors.initials: S
authors.lastname: Caillard
authors.forename: Lionel
authors.initials: L
authors.lastname: Couzi
authors.forename: Marie
authors.initials: M
authors.lastname: Essig
authors.forename: David
authors.initials: D
authors.lastname: Ribes
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Dragon-Durey
authors.forename: Frank
authors.initials: F
authors.lastname: Bridoux
authors.forename: Eric
authors.initials: E
authors.lastname: Rondeau
authors.forename: Veronique
authors.initials: V
authors.lastname: Frémeaux-Bacchi
mesh_terms: D000328:Adult; D051561:Complement C3 Convertase, Alternative Pathway / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000201:enzymology* / Q000235:genetics; D011256:Pregnancy Outcome; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D051561:Complement C3 Convertase, Alternative Pathway