Safety and efficacy of everolimus in chronic allograft nephropathy

Abstract

Chronic allograft nephropathy (CAN) is a major cause of late kidney allograft loss. Everolimus, a novel proliferation signal inhibitor, ameliorates CAN by its antiproliferative or apoptosis-enhancing effects. This study aims to evaluate the safety and efficacy of everolimus in renal transplant recipients with calcineurin inhibitor (CNI) withdrawal either due to CAN or cal-cineurin inhibitor toxicity (CNIT). A total 21 patients with CAN or CNIT converted from CNI to everolimus were prospectively studied from 2006 to 2009. There were 19 males and two females, with a mean age of 32.9 ± 10.7 years. Eight patients had chronic interstitial nephritis, three had diabetes mellitus, nine had end-stage renal disease and one had focal segmental glomerulosclerosis as native kidney disease. The mean duration of dialysis was 10.7 ± 7 months. 57.2% of the patients had CAN and 42.8% had CNIT. Everolimus was started within six months of post-transplantation in six patients, within 6-12 months in two patients, within 1-2 years in four patients and after more than 2 years in nine patients. The mean dose at first month was 1.25 mg/day, at six month was 1.028 ± 0.3 mg/day and at 12 th month was 0.97 ± 0.2 mg/day, with a mean trough level of 6.35 ± 3 ng/dL, 5.18 ± 3 ng/dL and 6.43 ± 1.7 ng/dL, respectively. At the 12 th month, serum creatinine declined from 2.07 ± 0.58 mg/dL to 1.65 ± 0.81 mg/dL. The mean calculated glomerular filtration rate improved from 40.85 ± 8.8 mL/min to 56.84 ± 11.4 mL/min. No major side-effects were observed. Everolimus along with mycophenolate mofetil or azathioprine and prednisolone as a maintenance immunosuppressive therapy was found to be effective and safe in patients with CNIs withdrawal either due to CAN or CNIT.