Experience with cyclosporine: approaching the therapeutic window for C₂ levels in maintenance kidney transplant recipients

Abstract 

This study was aimed to evaluate the clinical benefit of C₂ monitoring in 191 stable renal transplant patients previously monitored by C₀. All patients had been transplanted for at least 1 year and received cyclosporine (CsA)-based immunosuppression since the start. At the inceptions C₀ levels were significantly correlated with C₂ values (P < .0001). Patients with starting C₂ levels >1000 ng/mL showed significantly higher levels of serum creatinine (sCr) both at inception (1.66 ± 0.50 vs 1.44 ± 0.41 mg/dL; P = .0021) and at the end of a 2-year follow-up (1.84 ± 0.80 vs 1.46 ± 0.51 mg/dL; P = .005). C₂ monitoring revealed that a high percentage of patients were overexposed to CsA, mainly in the subgroup with most recent renal engraftments (12 to 24 months). The switch to C₂ monitoring was associated with a slower deterioration of graft function (P = .02). Further, the mean values of C₂ over a 2-year follow-up were inversely correlated with sCr at the end of follow-up (P = .0005). Finally, patients with mean threshold C₂ levels above 720 ng/mL, roughly corresponding to the median value of C₂, showed significantly lower levels of sCr at the end of follow-up (P = .0004). In conclusion, C₂ monitoring of maintenance renal transplant patients allows one to identify a significant percentage of overexposed subjects, possibly limiting the rate of progression of chronic graft dysfunction. Target range values between 700 and 900 ng/mL appear to be associated with better long-term kidney graft function.