Evolving landscape of thrombotic microangiopathy in kidney transplant recipients in the post-C5 inhibitor era.

A comprehensive analysis was performed on all consecutive biopsy-proven thrombotic microangiopathy (TMA) complicating kidney transplantation in the post-C5 inhibitor era (from 2009) to identify pathological profiles, determine causes, and establish risk factors associated with death-censored graft survival, in 2 French centers. Pathological criteria were assessed according to the TMA Banff Working Group, followed by an unbiased analysis to identify distinct subgroups. One hundred nineteen cases were identified, 8 (6.7%) primary TMA, and 23 (19.3%) antibody-mediated rejection. In 98 cases (82.4%), more than 1 potential trigger was involved. Latent class analysis identified 2 groups: acute TMA pattern (n = 79 [66.4%]), enriched for fibrin thrombi in glomerular capillaries and arterioles and mesangiolysis, and chronic active TMA pattern (n = 40 [33.6%]), enriched for collapsed capillaries. Both had similar presentations, were not indicative of specific causes, but had different outcomes. In multivariate analysis, grade 3 hypertension, low hemoglobin levels, proteinuria, baseline serum creatinine, and the value of a Banff-based chronicity index (ct + ci + 2xcg + cv) were associated with poorer death-censored graft survival, whereas fibrin thrombi in glomerular capillaries were associated with a better outcome. Kidney transplant-associated TMA is a severe condition in which the pathological pattern may reflect the disease stage, rather than the often intricate underlying mechanism.