CONVERSION OF AZATHIOPRINE TO MYCOPHENOLATE MOFETIL AND CHRONIC GRAFT FAILURE PROGRESSION

Abstract

P217 Aims: Progressive deterioration of renal function in kidney transplant recipients is the leading cause of graft lost. Mycophenolate mofetil (MMF) has been shown to reduce risk of acute rejection and protect graft against renal function deterioration compared to azathioprine (AZA). The purpose of this study was to evaluate the impact of conversion of AZA to MMF on the rate of graft function change. Methods: Thirty-five renal transplant recipients (5 cadaveric, 30 living donor) with different stages of chronic allograft failure and proteinuria were enrolled in a clinical trial. Their immunosuppressive regimen consisted of AZA, cyclosporine A (CsA) and prednisone. At the onset of the study (mean period 39 months), graft biopsy was performed in all pts. Biopsy specimens were reviewed with grading according to the Banff criteria. Thereafter, pts were randomly divided in two groups. In group 1 (17 pts) AZA was discontinued, and MMF was added to the medical regimen. The remaining 18 pts (group 2) were maintained on triple therapy of AZA, CsA and prednisone. During the first two weeks after conversion, prednisone was temporarily doubled and than tapered to the previous dose, and CsA dose was adjusted to keep through blood level between 80 and 100 ng/ml. In order to find out the influence of therapy change on graft function and proteinuria, two periods were analyzed: period I- 12 months before (retrospective analysis) and period II-12 months after biopsy (prospective analysis). Graft function was assessed by 24 hours clearance of creatinine (CCr) determined monthly. ANOVA was used to compare the differences in repeated measures of CCr and proteinuria, as well as the rate of graft function changes between the groups. Results: No difference in the baseline data was found between groups (recipient age, gender, underlying kidney disease, duration of hemodialysis, donor age, sex, age and sex difference between donor and recipient). Similar incidence of delayed graft function and acute rejection in both groups was found. No significant difference in the mean of all CCr measured in the period I was found between groups i.e. 41±4.3 ml/min for group 1, and 51±3.6 ml/min for group 2. Morphological changes in both groups were typical for chronic allograft nephropathy in all biopsy specimens. The degree of glomerulosclerosis, interstitial fibrosis, tubular atrophy and vascular changes correlated with graft function. The similar CCr changes were seen in both groups during the period I, although CCr was slightly better for patients from group 2. MMF is well tolerated and there were no acute rejections after the immunosuppression change in group 1, as well as in group 2. The CCr continued to decrease in the period II for all studied pts, and the mean CCr was 32.3±4.7 ml/min for group 1 and 43.4±3.6 ml/min for group 2. The CCr change was equal in both groups during the period II. No significant CCr difference was found between groups, either. Proteinuria was similar for both groups throughout of the study. No significant difference in the mean CsA dose/kg b.w. was found between the groups, although CsA doses were lower for group 1 after conversion to MMF. Conclusions: Conversion of AZA to MMF in pts with chronic allograft nephropathy was safe but without significant influence on chronic graft failure progression during a year period.