Protocol renal allograft biopsies and the design of clinical trials aimed to prevent or treat chronic allograft nephropathy

Background The minimum sample size to perform a clinical trial aimed to mod ify the natural history of chronic allograft nephropathy (CAN) is very larg e. Since the presence of chronic tubulointerstitial damage in renal protoco l biopsy specimens is an independent predictor of late outcome, we evaluate d whether protocol biopsies could facilitate the design of trials aimed to prevent or treat CAN, Methods. Two hundred eighty-two protocol biopsy specimens were obtained 3 m onths after transplantation in 280 patients with serum creatinine levels <3 00 mu mol/L, proteinuria <1000 mg/day, and stable function, The specimens w ere evaluated according to the Banff criteria. Results, Graft survival depended on the presence of CAN and renal transplan t vasculopathy (RTV). Thus, biopsy specimens were classified as: (a) no CAN (n = 174); (b) CAN without RTV (n = 87); and (c) CAN with RTV (n = 21), Gr aft survival at 10 years was 95%, 82%, and 41%, respectively (P = 0.001), T otal serum cholesterol before transplantation was 4.5 +/- 11.1, 4.6 +/- 1.1 , and 5.3 +/- 1.6 mmol/L, respectively (P = 0,009) and it was the only pred ictor of RTV, Power analysis (beta = 20%, alpha = 5%) was done to evaluate whether protoc ol biopsies can facilitate the design of clinical trials aimed either to pr event or treat CAN. We showed that the most feasible approach would be to u se the presence of CAN as the primary efficacy end point in a prevention tr ial. To demonstrate a 50% reduction in the incidence of CAN at 3 months, 57 0 patients would be required. Conclusions. Protocol biopsies may allow a reduction of sample size and esp ecially the time of follow-up in a trial aimed to prevent CAN.