The aim of our retrospective, observational, single center study was to analyze renal function changes among stable kidney transplant patients treated with a calcineurin inhibitor (CNI) + azathioprine (AZA), in whom immunosuppression was optimized by a switch from AZA to enteric-coated mycophenolate sodium (EC-MPS) with a view to protecting long-term renal function. Between April 2005 and June 2008, 36 renal transplant patients on previous treatment with a CNI and AZA for a period of 86.94 +/- 66.9 months were switched to EC-MPS. After the change, there were no cases of acute rejection episodes. Six patients (16.6%) developed gastrointestinal secondary effects and 5 had to discontinue EC-MPS treatment: 4 due to severe diarrhea 1 due to thrombocytopenia. Among the remaining patients, it was possible to gradually increase the EC-MPS dose (starting at 376 +/- 122 mg/d vs current at 533.5 +/- 210 mg/d; P < .002), maintaining through levels at 2.1 +/- 1.9 ng/mL. Although 11 patients (30.5%) displayed chronic allograft nephropathy upon the preconversion biopsy, at a follow-up of 29.2 +/- 9.4 months they showed significantly improved renal function (Modification of Diet in Renal Disease [MDRD4] at change 49.5 +/- 19.8 mL/min/1.73 m(2) vs current MDRD4 55.6 +/- 23.4 mL/min/1.73 m(2); P = .02), with no increase in proteinuria (proteinuria at change 0.4 +/- 0.4 g/d vs current proteinuria 0.4 +/- 0.5 g/d; P = NS). This improvement was evident without changes in CNI levels: cyclosporine at change 133.1 +/- 30.2 ng/mL vs current 122 +/- 28 ng/mL (P = NS) and tacrolimus at change 7.7 +/- 2.2 ng/mL vs current 8.2 +/- 2.4 ng/mL (P = NS). In conclusion, conversion from AZA to EC-MPA to optimize immunosuppression seemed to be safe, with no complications in 85% of cases, as well as effective, achieving improved long-term renal function protection. These results suggested a greater protective immunological effect by switching from AZA to EC-MPA.