Revisiting the changes in the Banff Classification for antibody‐mediated rejection after kidney transplantation

Key Takeaways

• In the search for potential treatments and personalized prognostication, a clear definition of antibody-mediated rejection (ABMR) is an indispensable prerequisite.
• The discriminative performance for allograft failure was lowest in Banff’17, and highest in Banff’13 (Banff ‘17 did not improve risk stratification compared to Banff ‘13).
• Banff ’17 oversimplifies the heterogeneous clinical and histological picture of ABMR.
• The Molecular Microscope^® Diagnostic System (MMDx^®) may resolve these issues by providing a clear molecular interpretation of the phenotype of rejection and extent of the injury.

Summary Statement

With the 2017 classification for kidney allograft pathology Banff may have taken a retrograde step in the identification and prognostication of antibody mediated rejection. This study highlights the over simplification of the diagnosis of ABMR leading to a group of patients with less good outcomes being reclassified as ‘no ABMR’. The authors propose new intermediate categories of ABMR to replace ‘suspicious for ABMR’ and to improve personalization of diagnosis, tailoring of therapy and superior prognostication.

Summary

The Banff process of revising the diagnostic criteria for allograft pathology every two years is assumed to be an incremental, step-wise process of improvement however it is unclear to what extent new iterations have numerically influenced the categorization of kidney transplant biopsies, and whether these changes have contributed to better risk stratification.

In this study Callemeyn and Ameye et al. studied 3662 biopsies (2775 protocol 847 indication) in 949 kidney transplant recipients followed at a single centre for a median of 7.5 years. Retrospective review of all biopsies was performed by a single pathologist and the biopsies graded by Banff ’01,’13 and ’17. Importantly sera for determination of HLA-DSA were available for 97% of biopsies. Across all protocol biopsies Banff ’17 had the lowes discriminatory performance for allograft failure and Banff ’13 the best.

Banff ’13 contained the largest number of biopsies with suspicious for ABMR (sABMR, 292) and ABMR (199). Banff ’17 reclassified 248/292 sABMR as no ABMR.

However, graft survival analysis shows that patients classified as sABMR in Banff ’13 but no ABMR in Banff’17 have worse outcome than patients classified with no ABMR in Banff ’13. The sABMR classification excluded by Banff ’17 would appear to have clinical significance. The main differences were due to HLA-DSA and extent of microvascular injury leading the investigators to propose two new intermediate categories:

• DSA negative with microvascular injury and
• DSA positive with suspicious changes for ABMR

A cohort of patients transplanted at another transplant center formed a validation cohort and confirmed the group’s findings.

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