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.

“Eculizumab First” in the Management of Posttransplant Thrombotic Microangiopathy

“…With electron microscopy, TMA signs were the subendothelial widening by flocculent material and the endothelial cell swelling. 1 , 15 …”

Thrombotic microangiopathy after kidney transplantation: Expanding etiologic and pathogenetic spectra

“…The endothelial injury may be caused by a myriad of injurious agents including but not limited to immunologic, genetic, and hematologic disorders and drugs either alone or in various combinations[ 28 - 30 ]. A kidney transplant biopsy is required for a definitive diagnosis[ 31 ]. The histopathologic diagnosis of PT-TMA is based on the subjective interpretation of a large number of histopathologic lesions, whose nature, prevalence, and extent vary from case to case depending on many factors including the duration of the pathologic process.…”

“…The histopathologic diagnosis of PT-TMA is based on the subjective interpretation of a large number of histopathologic lesions, whose nature, prevalence, and extent vary from case to case depending on many factors including the duration of the pathologic process. It also depends on the expertise and diagnostic insight of the pathologist[ 31 ]. Accurate diagnosis and classification are important for optimal treatment of the condition and favorable patient outcomes.…”

“…Moreover, the histopathologic diagnosis is a subjective task. The Banff Working Group (BWG) on TMA was formed in 2016 under the auspices of the Banff Foundation for Allograft Pathology, with the aim of standardizing the diagnostic criteria of TMA and formulating recommendations[ 31 ]. A survey conducted in January 2016 among the BWG participants, showed considerable heterogeneity among pathologists, using a variety of known TMA features with imprecise or subjective definitions.…”

“…Diagnosis of TMA in the renal allograft is not merely a morphologic task; clinical and laboratory information is also critical for diagnosis and needs to be standardized in phase II of the study. The Delphi approach was used by the BWG, for the first time in the Banff classification, to generate consensus, among an expert panel[ 31 ]. The group generated consensus on 24 criteria, provided a list of eight differential diagnoses, and identified areas of diagnostic difficulty.…”