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

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.

• Authors: Fadi Fakhouri, Marie Scully, Gianluigi Ardissino, Imad Al-Dakkak, Benjamin Miller, Eric Rondeau
• Journal: Journal of nephrology (J Nephrol) Vol. 34 Issue 5 Pg. 1581-1590 (10 2021) ISSN: 1724-6059 [Electronic] Italy
• PMID: 33826112 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Complement Inactivating Agents
• Complement System Proteins

Topics

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