Pathological diagnostic criteria for thrombotic microangiopathy in the renal allograft: lessons learned during the Banff Working Group consensus process

Abstract

Rationale & Objective Given the challenges in diagnosing transplant thrombotic microangiopathy (Tx-TMA) highlighted in previous publications, the objectives were to: 1- summarize new diagnostic challenges of Tx-TMA; 2- explore reasons for discrepancies/disagreements between BWG members, particularly the relationship between Tx-TMA and antibody-mediated rejection (AMR), and; 3- provide illustrations of the criteria resulting from the Banff Working Group (BWG) consensus process. Study Design To uncover sources of disagreements, we provided new analyses from a different perspective, using the results of our prior publications, illustrating representative figures and a heatmap summarizing survey responses, and the contribution of each criterion to the diagnosis of Tx-TMA. Setting & Participants 23 experienced practicing nephropathologists from around the world, participated over 5 years (2016-2021) in a Delphi study to diagnose original kidney Tx biopsies, some carrying the diagnosis of TMA. Exposures Both men and women adults were included. Data were anonymized, digitized and stored at the University of Toronto. Outcomes This study was retrospective and did not have outcome data recorded. Analytical Approach Percentage agreement among participants was used. Results The heatmap revealed glomerular/arterial or arteriolar fibrin thrombi followed by glomerular endothelial swelling and bloodless glomerular capillaries and to a lesser extent, mesangiolysis and arterial/arteriolar intimal oedema were consistently recognized as hallmarks of Tx-TMA. Electron microscopy independently proved to be useful for diagnosis. Differentiating Tx-TMA due to antibody-mediated rejection (AMR) from Tx-TMA related to other causes, emerged as a diagnostic histopathological dilemma. Limitations No outcome data. Conclusions This paper provides clarifications on Tx-TMA diagnosis criteria, and addresses factors leading to over- or under-diagnosis. We recommend using the terms "clinical TMA" (cTMA) and "pathological TMA" (pTMA) as a two-step diagnostic practice, distinguishing between Tx-TMA suspected by clinical/laboratory findings and Tx-TMA confirmed by biopsy. We suggest the exploration of major and minor criteria, as well.