Pregnancy-triggered atypical hemolytic uremic syndrome (aHUS): a Global aHUS Registry analysis

J Nephrol. 2021 Oct;34(5):1581-1590. doi: 10.1007/s40620-021-01025-x. Epub 2021 Apr 7.

Abstract

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare disease in which uncontrolled terminal complement activation leads to systemic thrombotic microangiopathy (TMA). Pregnancy can trigger aHUS and, without complement inhibition, many women with pregnancy-triggered aHUS (p-aHUS) progress to end-stage renal disease (ESRD) with a high risk of morbidity. Owing to relatively small patient numbers, published characterizations of p-aHUS have been limited, thus the Global aHUS Registry (NCT01522183, April 2012) provides a unique opportunity to analyze data from a large single cohort of women with p-aHUS.

Methods: The demographics and clinical characteristics of women with p-aHUS (n = 51) were compared with those of women of childbearing age with aHUS and no identified trigger (non-p-aHUS, n = 397). Outcome evaluations, including renal survival according to time to ESRD, were compared for patients with and without eculizumab treatment (a complement C5 inhibitor) in both aHUS groups.

Results: Baseline demographics and clinical characteristics were broadly similar in both groups. The proportion of women with p-aHUS and non-p-aHUS with pathogenic variant(s) in complement genes and/or anti-complement factor H antibodies was similar (45% and 43%, respectively), as was the proportion with a family history of aHUS (12% and 13%, respectively). Eculizumab treatment led to significantly improved renal outcomes in women with aHUS, regardless of whether aHUS was triggered by pregnancy or not: adjusted hazard ratio for time to ESRD was 0.06 (p = 0.006) in the p-aHUS group and 0.20 (p < 0.0001) in the non-p-aHUS group.

Conclusion: Findings from this study support the characterization of p-aHUS as a complement-mediated TMA.

Keywords: Atypical hemolytic uremic syndrome (aHUS); Complement C5 inhibitor; Complement-mediated TMA; End-stage renal disease (ESRD); Pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atypical Hemolytic Uremic Syndrome* / diagnosis
  • Atypical Hemolytic Uremic Syndrome* / epidemiology
  • Atypical Hemolytic Uremic Syndrome* / genetics
  • Complement Inactivating Agents / therapeutic use
  • Complement System Proteins
  • Female
  • Humans
  • Pregnancy
  • Registries
  • Thrombotic Microangiopathies* / diagnosis
  • Thrombotic Microangiopathies* / epidemiology

Substances

  • Complement Inactivating Agents
  • Complement System Proteins