The established antiproliferative and non-nephrotoxic activity of sirolimus has been exploited in the treatment of patients with chronic allograft nephropathy (CAN); therefore conversion from calcineurin inhibitors (CNIs) to sirolimus has become an option in patients with CAN. The aim of the present retrospective study was to analyze the effects of sirolimus as rescue therapy whilst withdrawing CNIs in renal transplant recipients primarily presenting with CAN.
Methods. We assessed long term efficacy and safety parameters in 21 renal transplant recipients who were switched from a CNI (cyclosporin A, 67%; and tacrolimus, 37%) to sirolimus for either CNIs nephrotoxicity (n=18) or chronic rejection (n=2) or CNIinduced insulin-dependant diabetes mellitus (n=1). A kidney biopsy was done in 10 patients prior to conversion. Conversion was either abrupt or progressive, with CNI withdrawal over 4 weeks. All patients also received steroids with mycophenolate mofetil. Patient data were recorded at baseline (D0), at 1month (D30), and at 3 months (D90) post conversion and lastly at the time of conducting this study which comes after a mean period of 23 months post-conversion. GFR was calculated using Cockroft-Gault formula. Sirolimus therapy was started 10 months (1.5-38) after transplantation. After a mean post-conversion follow-up of 23 months(2-39), 17 patients (81%) were still on sirolimus. Patients and graft survival was 95% and 81%, respectively. Creatinine clearance increased from a mean baseline of 54(18-91) to 66ml/min/1.73m² at D30, and to 70ml/min/1.73m² at D90, and to 73ml/min/1.73m² after a mean post-conversion period of 23 months. Thus the mean improvement of renal function at the end of follow-up was equal to 19ml/min/1.73m² compared to the baseline GFR. We divided our patients into two groups: responders (n=17), those with an increase in creatinine clearance at 3 months post-conversion compared with D0, and non-responders (n=4), those with a decrease in creatinine clearance at 3 months post-conversion compared with D0. Factors predicting of response included serum creatinine of less than 3mg/dl prior to conversion. The conversion was associated with (i) decreasing serum creatinine in 81% of the entire patients, (ii) the appearance of de novo proteinuria of >0.5g/day in 43% of patients, (iii) decreased hemoglobin level in 57% of patients at 3 months post-conversion. Conversion from CNIs to sirolimus in renal transplant patients with chronic allograft nephropathy was associated with improved renal function; however, 43% of patients developed overt proteinuria, calcineurin inhibitor, sirolimus, chronic allograft nephropathy, anemia, proteinuria.