Conversion from calcineurin inhibitors to sirolimus in chronic allograft nephropathy: a 4-year prospective study

Abstract

To evaluate the safety and effect of sirolimus (SIR) substitution for calcineurin inhibitors (CNI) in chronic allograft nephropathy (CAN). A prospective, open-label and non-randomized comparative study was performed in 74 kidney recipients from January 2004 to June 2006 with a diagnosis of CAN at a baseline estimated glomerular filtration rate (eGFR) of 30 - 60 ml×min(-1)·(1.73 m(2))(-1). Patients in the SIR group (n = 36) received SIR at 12 hours after a cessation of CNI. For those in the CNI group (n = 38), a cyclosporine (CsA)-based immunosuppressive regimen was prescribed in 30 patients and a tacrolimus (FK506)-based regimen in another 8 patients. All patients were maintained under a high level of mycophenolate mofetil and followed up for 4 years to evaluate the renal function, eGFR, blood routines, blood lipids and liver function, etc. The renal function and eGFR profiles of the SIR group improved significantly after substitution. The baseline eGFR was (40 ± 7) ml×min(-1)·(1.73 m(2))(-1) in the SIR group versus (38 ± 6) ml×min(-1)·(1.73 m(2))(-1) in the CNI group (P > 0.05). In SIR group, the levels of eGFR were higher than those in the CNI group at months 3, 12, 24, 36 and 48 (all P < 0.05). For the endpoint of serum creatinine doubling, the 4-year survival was 75.0% in the SIR group versus 50.0% in the CNI group (P = 0.03). There were 2 cases of acute rejections, 1 proteinuria, 1 pneumonia in the SIR group while 2 patients in the CNI group dropped out as a result of acute rejections (P > 0.05). The total bilirubin value of all the patients decreased significantly but serum cholesterol and triglyceride levels increase significantly after conversion (all P < 0.05). The substitution of SIR for CNI is both safe and effective in renal transplant recipients with CAN. And a conversion from CNI to SIR may improve the graft survival.