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

Fadi Fakhouri,Imad Al-Dakkak,Marie Scully,Benjamin Miller,Eric Rondeau,Gianluigi Ardissino

doi:10.1007/s40620-021-01025-x

Abstract

BackgroundAtypical 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.MethodsThe 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.ResultsBaseline 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.ConclusionFindings from this study support the characterization of p-aHUS as a complement-mediated TMA.Graphic abstract

Highlights

Atypical hemolytic uremic syndrome is a rare disease caused by dysregulation of the alternative pathway of complement
The mean time from initial thrombotic microangiopathy (TMA) manifestation to Atypical hemolytic uremic syndrome (aHUS) diagnosis was shorter in the pregnancy-triggered aHUS (p-aHUS) group compared with the non-p-aHUS group
Our results showed that both groups were similar in several demographic and clinical characteristics, as well as in their response to eculizumab

Summary

Introduction

Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by dysregulation of the alternative pathway of complement. Patients with aHUS are at risk of unpredictable and/or progressive TMA-mediated damage to renal and other organ systems, leading to severe morbidity and premature death [4,5,6]. 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. 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. 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

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