A Retrospective Study of Pregnancy-Associated Atypical Hemolytic Uremic Syndrome

Kidney Int. 2018 Feb;93(2):450-459. doi: 10.1016/j.kint.2017.06.022. Epub 2017 Sep 12.

Abstract

Pregnancy-associated atypical hemolytic uremic syndrome (aHUS) refers to the thrombotic microangiopathy resulting from uncontrolled complement activation during pregnancy or the postpartum period. Pregnancy-associated aHUS is a devastating disease for which there is a limited clinical understanding and treatment experience. Here we report a retrospective study to analyze the clinical and prognostic data of 22 cases of pregnancy-associated aHUS from the Spanish aHUS Registry under different treatments. Sixteen patients presented during the first pregnancy and as many as nine patients required hemodialysis at diagnosis. Identification of inherited complement abnormalities explained nine of the 22 cases, with CFH mutations and CFH to CFHR1 gene conversion events being the most prevalent genetic alterations associated with this disorder (66%). In thirteen of the cases, pregnancy complications were sufficient to trigger a thrombotic microangiopathy in the absence of genetic or acquired complement alterations. The postpartum period was the time with highest risk to develop the disease and the group shows an association of cesarean section with pregnancy-associated aHUS. Seventeen patients underwent plasma treatments with a positive renal response in only three cases. In contrast, ten patients received eculizumab with an excellent renal response in all, independent of carrying or not inherited complement abnormalities. Although the cohort is relatively small, the data suggest that pregnancy-associated aHUS is not different from other types of aHUS and suggest the efficacy of eculizumab treatment over plasma therapies. This study may be useful to improve prognosis in this group of aHUS patients.

Keywords: cesarean section; complement; eculizumab; hemolytic uremic syndrome; postpartum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Atypical Hemolytic Uremic Syndrome* / epidemiology
  • Atypical Hemolytic Uremic Syndrome* / genetics
  • Atypical Hemolytic Uremic Syndrome* / immunology
  • Atypical Hemolytic Uremic Syndrome* / therapy
  • Cesarean Section
  • Complement Activation
  • Complement C3b Inactivator Proteins / genetics
  • Complement Factor H / genetics
  • Female
  • Gene Conversion
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Mutation
  • Parity
  • Plasma Exchange
  • Postpartum Period
  • Pregnancy
  • Pregnancy Complications* / epidemiology
  • Pregnancy Complications* / genetics
  • Pregnancy Complications* / immunology
  • Pregnancy Complications* / therapy
  • Registries
  • Renal Dialysis
  • Retrospective Studies
  • Risk Factors
  • Spain / epidemiology
  • Thrombotic Microangiopathies* / epidemiology
  • Thrombotic Microangiopathies* / genetics
  • Thrombotic Microangiopathies* / immunology
  • Thrombotic Microangiopathies* / therapy
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • CFHR1 protein, human
  • Complement C3b Inactivator Proteins
  • Immunosuppressive Agents
  • complement factor H, human
  • Complement Factor H
  • eculizumab