A retrospective study of pregnancy-associated atypical hemolytic uremic syndrome

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.

Safety and effectiveness of eculizumab for adult patients with atypical hemolytic–uremic syndrome in Japan: interim analysis of post-marketing surveillance

“…Similarly, rare variants of complement genes were identified in 40-86% of pregnancy related aHUS, 46% of patients with HELLP syndrome [20][21][22][23] and 67% of hypertension associated TMA [24] in previous reports. Moreover, 65% of children and young adult patients with HSCT associated TMA had genetic variants in at least one complement related gene compared with 9% of patients without TMA [25].…”

Atypical Hemolytic‐Uremic Syndrome: An Update on Pathophysiology, Diagnosis, and Treatment

“…In patients with CFH, CFI, C3, or CFB mutations, eculizumab is the preferred intervention for therapy of current illness as well prevention of recurrences . It is also efficacious in patients with post‐transplant disease recurrence, transplantation‐associated aHUS , pregnancy‐associated aHUS , and HUS secondary to chemotherapy . By preventing MAC formation, eculizumab inhibits the mechanism by which aHUS causes pathology, making this novel drug the treatment of choice for aHUS patients.…”

“…Additionally, Fakhouri et al found that 85% of patients with pregnancy‐associated HUS had complement pathway abnormalities . Huerta et al retrospectively analyzed a cohort of patients with pregnancy‐associated aHUS and found that all of the 10 patients treated with eculizumab had normalization of all hematologic parameters and preservation of renal function . Moreover, none of the patients required dialysis or transplantation at the end of the follow‐up.…”

“…Moreover, none of the patients required dialysis or transplantation at the end of the follow‐up. Eculizumab was discontinued in 7 of the 10 cases after a median treatment time of 10 months .…”

Complement Biomarkers of Hemolytic Uremic Syndrome—If Not One Thing, Maybe Another

“…The drug is expensive and it increases patients' risk of infection, particularly with meningococcus. It is not yet clear whether eculizumab is effective in the other forms of "secondary" HUS, although reports suggest that it is beneficial in postpartum disease 4 and hematopoietic stem cell transplant recipients with HUS. 5 In other forms of secondary HUS, cost and infectious risks of eculizumab weigh against empirical use of the drug.…”