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

Objective: To evaluate the safety and effect of sirolimus (SIR) substitution for calcineurin inhibitors (CNI) in chronic allograft nephropathy (CAN).
Methods: 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.
Results: 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).
Conclusion: 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.