Complement-Mediated Postpartum Atypical Hemolytic Uremic Syndrome With Collapsing Focal Segmental Glomerulosclerosis...

Thrombotic microangiopathies (TMAs) that occur during pregnancy or the postpartum period-including preeclampsia/HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), thrombotic thrombocytopenic purpura, and atypical hemolytic uremic syndrome (aHUS)-present a diagnostic challenge owing to their overlapping clinical features. We report a case of a 21-year-old primigravida of African origin who developed HELLP syndrome followed by postpartum aHUS. The clinical course was marked by thrombocytopenia, hemolytic anemia, acute kidney injury, and massive proteinuria. Kidney biopsy revealed TMA with collapsing focal segmental glomerulosclerosis (FSGS), suggesting concomitant podocyte injury. Genetic analysis identified a novel heterozygous deletion in CFHR5, resulting in a shorter-than-normal FHR5 protein, as revealed by Western blot, consistent with the predicted product of the deleted gene. Functional assays using endothelial cells demonstrated abnormal C5b-9 formation, indicating complement dysregulation. The patient achieved clinical recovery with mild residual proteinuria after plasma infusion and supportive therapy. This case highlights a potential pathogenic role of aberrant FHR5 proteins in postpartum aHUS and suggests a link between complement-mediated endothelial dysfunction and podocyte injury in TMA with collapsing FSGS. Complement genetic and functional testing should be considered in postpartum TMA, even in the absence of overt complement consumption, to guide diagnosis, prognosis, and treatment.