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.