Role of renal allograft biopsy in multicenter clinical trials in transplantation

There is current agreement that in the design of prospective clinical trials, patients should be assigned to various treatment groups based on histological diagnosis of acute renal allograft rejection. The Banff schema is satisfactory in reporting and grading histology for patient entry into clinical trials, particularly in multicenter studies because it standardizes the entry and randomization criteria and maintains reproducibility of the histological interpretation between the different centers. It should be emphasized that for biopsy specimens to be effective tools for either clinical practice or clinical trials, they need to be obtained before therapeutic intervention and handled by experienced histopathology laboratory technicians. Adequate tissue sampling is necessary for diagnosis and for proper grading of rejection. It is recommended that a minimum of two cores of renal tissue are needed to avoid underestimation of rejection grade. Banff classification considers a biopsy specimen to be adequate if it contains seven or more glomeruli and at least a single artery. Examination of serial step sections through the tissue samples is crucial to identify focal lesions of toxicity and to properly score intimal arteritis and tubulitis, in addition, fast interpretation of the biopsy by an experienced nephropathologist or a transplant pathologist within 24 hours optimizes the utilization of the biopsy-acquired information, At the present time, it is premature to decide on the role of graft histology as an endpoint in clinical trials, but posttreatment biopsies should be encouraged in large, multicenter, prospective trials because they may be our only tools to study postrejection changes. Semiquantitative biopsy reporting systems should be routinely included in clinical databases to allow for the prospective examination of structure-function relationships and long-term outcomes following acute rejection. (C) 1998 by the National Kidney Foundation, Inc.