International variation in the interpretation of renal transplant biopsies: Report of the CERTPAP Project

Background. The Banff working formulation of renal transplant pathology is intended to have international application. There remains a need to develop methods to harmonize the application of such grading systems between laboratories. Banff grades do not always permit precise management decisions to be made. Alternative schemes have been devised for the diagnosis of acute rejection, but there have been no independent tests of the different approaches. Methods. Sections from 55 renal transplant biopsies were circulated around the laboratories of 22 major transplant units for the Convergence of European Renal Transplant Pathology Assessment Procedures (CERTPAP) Project. Participating pathologists were asked to grade 32 different histological features, without any clinical information. After each circulation of five cases, feedback was provided to participants. Statistical evidence of improvement in interobserver variation was sought. At the end of the study, correlations with the original clinicopathological diagnosis were sought. Results. Interobserver variation was greater than has previously been reported. For every feature studied, some pathologists consistently under-grade or over-grade. There was relatively little evidence of improvement in interobserver variation as a result of the feedback system. No single feature permitted a reliable diagnosis of acute rejection. Applying the Banff and CCTT schemas to the histological grades showed no clear diagnostic advantage for either system, but a simple computer-based inference network, which combined data from 12 histological features, out performed either approach. Within the protocol biopsies studied, long-term survival correlated better with acute than with chronic histological features. Conclusions. These results do not undermine the value of the Banff classification, but they demonstrate a need for caution when translating biopsy results between institutions. It is obvious that evaluation of biopsies in multicenter trials must be done in one center. In the management of individual patients, the need to interpret Banff grades in the light of local experience and clinical information is stressed.