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Diagnosis: Active Antibody Mediated Rejection with Thrombotic Microangiopathy, and Acute T Cell Mediated Rejection

Thrombotic microangiopathy (TMA) is characterized by microvascular thrombosis that results from activation of glomerular endothelial cells. Glomerular endothelium exhibits distinct characteristics that increase its susceptibility to oxidative stress; glomerular endothelial cells produce fibrinolytic factors and glycocalyx avidly binding complement factor H. In response to HLA-antibody binding these functions are lost, and local inflammation is enhanced to a higher extent than other endothelial cells exposed to similar conditions. Glomerular endothelium injury is therefore associated with poorly controlled alternative complement pathway activation. Loss of fibrinolytic phenotype enhances microvascular thrombosis, and ischemic insult further worsens dysfunction of glomerular endothelium; thus, TMA develops.

The presence of de novo TMA decreases graft survival regardless of cause. About one-third of TMA cases are associated with rejection, either active AMR, or vascular rejection. The rejection phenotype of de novo TMA is associated with worse graft survival. Endothelial injury caused by donor-specific antibodies is a cornerstone of AMR pathogenesis, as evidenced by transcriptomic analyses, and TMA is thus a consequence of severe antibody-mediated endothelial injury as reflected by Banff classification.

See the chapter: Kidney Transplantation Pathology of our Tutorial.

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