INTERSTITIAL FIBROSIS AND FIBROUS INTIMAL THICKENING IN DE NOVO RENAL ALLOGRAFTS UNDER SIROLIMUS OR CYCLOSPORINE: RESULTS OF A RANDOMISED, CONTROLLED TRIAL (FIBRASIC)

Calcineurin inhibitors are a major cause of chronic allograft nephropathy andlong-term graft failure. In a prospective, r andomised trial of sirolimus (SRL)-versus cyclosporine (CsA)-based immunosuppression inde novorenal allo-g rafts, we morphometrically determined the fractional interstitial vo lume (VvInt)and the arterial intima/media ratio (I/M) in implantation and protocol biop-sies at 6 months. The concomitant imm u nosuppression, including daclizumab,steroids and mycophenolate mof etil, was similar in 24 SRL and 21 CsAtreated patients. Graft function (eGFR) was evaluated at 6 and 12 months withthe MDRD form ula (Jeliffe). At implantation VvInt (SRL: 25±8.4% vs. CsA:27.2±11%) and I/M (SRL: 38.8±14.6% vs. CsA: 50.3±40.7%) were compa-r able in SRL and CsA treated grafts. In contr ast, at 6 months VvInt (SRL:20.9±7% vs. CsA: 27.5±9%; p = 0.055) and I/M (SRL: 27. 5±11.3% vs.CsA: 53.3±30%; p = 0.02) were lo wer in the SRL treated grafts. Graft func-tion (eGFR) was comparab le in the SRL and CsA treated patients at 6 months(SRL: 50±17 ml/min vs. CsA: 50±20 ml/min) and at 12 months (SRL: 49±13ml/min vs. CsA: 53±21 ml/min). Thus, Sirolim us appears to protect the re-nal allograft against the development of interstitial fibrosis and arterial vesselintimal hyperplasia in the early phase after transplantation. Ho wever, this ben-eficial effect was not associated with a superior graft function at 6 months and1 year. Longer f ollow-up may be needed to translate the histological improv e-ment into better gr a ft function.