Exuberant Endothelial C5b-9 Formation in Recurrent and De Novo Posttransplant Thrombotic Microangiopathy

Thrombotic microangiopathy (TMA) is a severe complication of kidney transplantation. It may present as a recurrence of atypical hemolytic uremic syndrome (aHUS) or may occur de novo. 1 Kidney graft outcome in patients with recurrent aHUS is poor and strongly dependent on the early initiation of anti-C5 therapy.1 However, diagnosing aHUS recurrence, as well as de novo TMA, is challenging because patients may present without hematological signs.1 A biopsy may not be feasible, particularly in patients with thrombocytopenia. Here, we evaluated whether an ex vivo assay of serum-induced terminal complement complex (C5b-9) formation on human microvascular endothelial cells (HMEC-1), which efficiently detects complement dysregulation in nontransplanted patients with aHUS,2 could also help diagnose posttransplant recurrent aHUS. We also evaluated whether de novo posttransplant TMA is associated with endothelial complement activation, which remains a widely discussed issue,3,4 and whether the C5b-9 formation assay could support diagnosis. Due to the high risk of recurrence, the incidence of TMA in kidney grafts exceeds 36 times in patients with a pretransplant history of aHUS, compared to those with other causes of end-stage renal disease. This underscores the importance of accurately diagnosing native kidney disease.1 Unfortunately, 20% to 30% of patients on transplant waiting lists have no diagnosis.5 To address this additional issue, we investigated whether the C5b-9 assay could help to identify aHUS cases among patients with end-stage renal disease.