Evolving Landscape of Thrombotic Microangiopathy in Kidney Transplant Recipients in the post C5 inhibitor Era.

Abstract

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 factor associated with death-censored graft survival, in two French center. Pathological criteria were assessed according to the TMA Banff Working Group, followed by an unbiased analysis to identify distinct subgroups. 119 cases were identified, 8(6.7%) primary TMA, and 23(19.3%) antibody-mediated rejection. In 98 cases (82.4%), more than one potential trigger was involved. Latent class analysis identified two 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 presentation, were not indicative of specific causes but had different outcome. 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, while fibrin thrombi in glomerular capillaries were associated with a better outcome. KT-TMA is a severe condition in which the pathological pattern may reflect the disease stage, rather than the often intricate underlying mechanism.