Thrombotic Microangiopathy in the Renal Allograft: Results of the TMA Banff Working Group Consensus on Pathologic Diagnostic Criteria

Abstract

The Banff community summoned the TMA Banff Working Group to develop minimum diagnostic criteria (MDC) and recommendations for renal transplant TMA (Tx-TMA) diagnosis, which currently lacks standardized criteria. Using the Delphi method for consensus generation, 23 nephropathologists (panelists) with >3 years of diagnostic experience with Tx-TMA were asked to list light, immunofluorescence, and electron microscopic, clinical and laboratory criteria and differential diagnoses for Tx-TMA. Delphi was modified to include 2 validations rounds with histological evaluation of whole slide images of 37 transplant biopsies (28 TMA and 9 non-TMA). Starting with 338 criteria in R1, MDC were narrowed down to 24 in R8 generating 18 pathological, 2 clinical, 4 laboratory criteria, and 8 differential diagnoses. The panelists reached a good level of agreement (70%) on 76% of the validated cases. For the first time in Banff classification, Delphi was used to reach consensus on MDC for Tx-TMA. Phase I of the study (pathology phase) will be used as a model for Phase II (nephrology phase) for consensus regarding clinical and laboratory criteria. Eventually in Phase III (consensus of the consensus groups) and the final MDC for Tx-TMA will be reported to the transplantation community.

Keywords: Banff; Delphi; kidney; pathology criteria; thrombotic microangiopathy; transplant.

FIGURE 1

Criteria evolution during eight rounds of Delphi. The X-axis represents each R and the Y-axis the cumulative number of data entries. R1 started with 338 criteria (arrow) which were narrowed down to 66 in R5 and remained 66 in R6. The criteria were further narrowed down to 35 (comprising eight differential diagnosis) in R7. R6 and R7 were two validation rounds and R9 was the control round also called the definition round. Abbreviations: Clin-, clinical data negative; Clin+, clinical data positive; #D, differential diagnosis; EM-, electron microscopy negative; EM+, electron microscopy positive; IF-, immunofluorescence microscopy negative; IF+, immunofluorescence microscopy positive; Lab-, laboratory negative; Lab+, laboratory positive; LM-, light microscopy negative; LM+, light microscopy positive.