Delaying progression of chronic allograft nephropathy by conversion from cyclosporine to tacrolimus

Objective To investigate the effects of substituting tacrolimus(FK506) for cyclosporine(CsA) on delaying the pace of renal dysfunction in patients with biopsy-proven chronic allograft nephropathy(CAN) and the molecular mechanism of the therapy.Methods From January 1,1999 to April 30,2003,124 renal transplant recipients with declining graft function and biopsy-proven CAN(GradeⅠ),who had been taking cyclosporine(CsA) as immunosuppressive agent,were studied.The patients were randomly divided into Group A and Group B.CsA was replaced with FK506 in Group A that included 68 patients.Group B including the other 56 patients was studied as control.Substituting CsA by FK506 in a dose of about 1∶75.All patients were followed up at least three years.Renal functions,losses of creatinine clearance rates within 3 years,incidences of acute renal graft rejection and plasma TGF-β_1 concentrations were compared between the two groups.Results Three year later,there were 42 patients((61.8)%) with stabilized or improved graft function in Group A, and 6 patients(10.7%%) in Group B.The difference was significant(P0.01).During the 3-year study period,loss of creatinine clearance in Group A was(10.1±9.9)ml/min which is significantly more than(22.3±16.7)ml/min in Group B (P0.01).At the end of the study,plasma TGF-β_1 concentration in Group A was(16.7±8.7)ng/ml which is significantly lower than(39.7±10.8)ng/ml in Group B(P0.01).The incidences of acute rejection in both groups were not significantly different.Conclusion This study suggests that in renal recipients with biopsy-proven CAN,substituting FK506 for CsA have an effect to slow progression of CAN.Reducing production of TGF-beta1 may play a decisive role in the efficacy of the therapy.