Fadi Fakhouri1, Marie Scully2, Gianluigi Ardissino3, Imad Al-Dakkak4, Benjamin Miller4, Eric Rondeau5. 1. Service of Nephrology and Hypertension, University of Lausanne, Lausanne, Switzerland. fadi.fakhouri@unil.ch. 2. University College London, London, UK. 3. Center for HUS Control, Prevention and Management, Milan, Italy. 4. Alexion Pharmaceuticals, Inc., Boston, MA, USA. 5. Hôpital Tenon, Paris, France.
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.
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.
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