CALCINEURIN INHIBITOR WITHDRAWAL IN RENAL TRANSPLANT RECIPIENTS: IMPROVEMENT IN RENAL FUNCTION AND REDUCTION OF CARDIOVASCULAR RISK

Abstract

P239 Aims: Immunosuppressive regimens with cyclosporine (CSA) reduced the occurrence of acute rejection episodes in renal transplants, with better graft survival. However, side effects such as nephrotoxicity, systemic hypertension and metabolic disorders have a negative impact on patient survival, increasing the cardiovascular mortality. Regimens with lower CSA doses has been proposed to reduce cardiovascular risk. The aim of the present study was to analyze the safety and efficacy of slow CSA withdrawal in renal transplant patients with chronic allograft nephropathy (CAN). Methods: renal transplant patients followed >12 months, with impaired renal function (serum creatinine >1.5mg%) and/or hyperlipidemia and hyperuricemia were included in the present protocol. Immunossupressive regimen included full dose of mofetil mycophenolate (MMF, 2 to 3 grams/day) and at least 5 mg/day of prednisone. CSA dose was reduced in a step by step basis (0.5mg/kg/day every month), with complete withdrawal after 6 months of study. Clinical and laboratory data were analyzed at each time point. Results: 63 renal transplant patients (56 male, 7 female), mean age 41 ± 9 years old, recipients from cadaveric (n=39) or living related (n=24), followed for 66 ± 30 months post transplant (12 to 122 months) were included in this study. Sixty one patients completed the CSA withdrawn and no acute rejection episodes were observed during the study period (mean follow up of 8 months after withdrawal). Two patients were drop out because of GI intolerance to MMF. A significant reduction in both serum creatinine (2.05 ± 0.7mg/dl CSA treatment vs. 1.69 ± 0.7 mg/dl CSA free p<0.05), and in systemic blood pressure (104 ± 8 mmHg CSA vs. 97.5 ± 7 mmHg CSA free, p<0.05) occurred with CSA withdrawal. Increase in glomerular filtration rate occurred after CSA withdrawal (Cockrofi Gault clearance 64.5 ± 10.1 ml/min with CSA vs. 74.4 ± 9.4 ml/min, CSA free, p<0.05). A improvement in metabolic profile was also observed after CSA withdrawal, with reduction in both total cholesterol levels (233 ± 52 mg/dl vs. 196 ± 57 mg/dl, p<0.05) and serum uric acid levels (8.2 ± 1.7 mg/dl vs. 7.5 ± 1.6 mg/dl, p<0.05). The number and dose of anti-hypertension drugs, allopurinol and statins was also observed after CSA withdrawal.. Conclusions: in renal transplant patients with CAN and metabolic disorders, CSA withdrawal in presence of full dose MMF was safe, leading to a better blood pressure control and glomerular filtration recovery. The slowly reduction in CSA dosage avoided acute rejection episodes in this series. A longer follow up is needed in order to evaluate the effect of CSA free regimen in the occurrence of cardiovascular events.