IS THE IMPROVEMENT OF RENAL FUNCTION IN CHRONIC ALLOGRAFT NEPHROPATHY, AFTER MMF INTRODUCTION, RELATED TO CYCLOSPORINE REDUCTION?

Abstract

320 Chronic allograft nephropathy (CAN) is the leading cause of late graft failure. Both chronic rejection (CR) and CYA chronic nephrotoxicity (CYA-Nx) may play a role in the progressive deterioration of renal function. Introduction of mycophenolate mofetil (MMF) and reduction of CYA doses is therapeutic approach in this situation. We evaluated the impact of such approach on graft function. A total of 54 pts entered the study. Of these, 2 pts were excluded because of MMF discontinuation. Mean age was 33±19 y and time after Tx was 62±4 months. 28 pts had the diagnosis of CR and 11 CYA-Nx. Biopsy confirmation was obtained in 20 pts (85%) and 8 pts (83%), respectively. In the remaining 13 pts (AZA), with no evidence of CAN, MMF was introduced due to AZA intolerance only. Mean follow-up period after MMF introduction was 9±6 months. No acute rejection episodes were observed. Average MMF dosage was 1588±442 mg/d, with no difference among the groups. 13 pts had CYA withdrawn, 7 in CR, 3 in CYA-Nx, and 3 in AZA groups. In those who remained on CYA, mean doses were reduced in all groups (CR: 4.3±1.9 vs 3.0±1.6 mg/kg/d; p=0,003), (CYA-Nx: 3.5±1.7 vs 2.4±0.8, p=0.09), (AZA: 3.2±1 vs 2.6±0.6, NS). 6 pts lost their graft or died during the follow-up period, 4 in CR, 1 in CYA-Nx and 1 in AZA (NS). In the remaining 46 pts, SCr decreased in CR (2.7±1.5 vs 1.8±0.8 mg/dl, p<0.001) and CYA-Nx (2.3±0.8 vs 1.7±0.5 mg/dl, p=0.008). In the AZA group, no reduction of SCr was observed (1.7±0.6 vs 1.5±0.6mg/dl). There was a significant relationship between improvement in SCr (≥20%) and CYA dose reduction. Improvement in SCr, either in CR or in CYA-Nx, was more frequent in pts with decrease in CYA dose (19/27 −70%) when compared to patients who did not have CYA reduced (1/6 −16%, p=0.02). Complete CYA discontinuation did not add further benefit to the graft function improvement when compared to dose reduction only. In conclusion, introduction of MMF as a therapeutic approach to CAN is a safe procedure, ensures no acute rejection to develop, even after CYA withdrawn, and is associated with a significant augment in renal function. This increment in graft function is probably related to CYA dose reduction which has been made possible by the MMF introduction.