Prospective randomized study of azathioprine vs cyclosporine based therapy in primary haplo-identical living-donor kidney transplantation: 20-year experience

Background The achievements in short-term graft survival since the introduction of cyclosporine (CsA) have not been matched by improvements in long-term graft function. Chronic allograft nephropathy (CAN) remains the second most common cause of graft attrition over time, after patient mortality. We aimed to evaluate the long-term results of azathioprine vs CsA in live-donor kidney transplantation in a prospective randomized study. Methods We studied 475 renal transplant recipients who had had transplantations performed at the Urology and Nephrology Center, Mansoura University, before 1988 and who had received a primary immunosuppressive protocol consisting of either steroid and azathioprine (steroid/Aza; group 1, 300 patients) or steroid and CsA (steroid/CsA; group 2, 175 patients). Only adult primary renal transplant recipients aged between 18 and 60 years and with one haplotype HLA mismatch were included. All patients received kidneys from living-related donors, with previous donor nonspecific blood transfusions. The study was based on the long-term follow-up data of these renal transplant recipients. Comparative analyses included patient and graft survival rates, condition at last follow up, rejection (acute and chronic), and graft function (serum creatinine and creatinine clearance). Results The overall frequency of acute rejection episodes was not significantly different between the two groups. Graft survival rates were: group 1 vs group 2, 69% vs 58% at 5 years, and 52% vs 36% at 10 years, but at 20 years, graft survival rates had declined to 26% and 24%. No significant differences were encountered between the two groups regarding post-transplant malignancies, diabetes mellitus, hepatic impairment, or serious bacterial infections. Conclusions From this study we can conclude that the long-term result of historical conventional therapy (steroid/Aza) without induction therapy is effective for living-donor kidney transplants. In spite of the comparable graft function for the two groups, the steroid/CsA group experienced more hypertension, as well as many adverse reactions to CsA. Nowadays, since the introduction of induction therapy and the utilization of newer maintenance immunosuppressive agents – such as mycophenolate mofetil (MMF) and rapamycin – it is possible to achieve an excellent calcineurin inhibitors (CNI)-free regimen.