Evaluation of cyclosporine C2 levels in long-term stable renal allograft recipients

BACKGROUND: The use of cyclosporine was traditionally monitored by the trough level (C(0)). However, the immunosuppressive effects of cyclosporine correlate with its drug exposure, represented by the area under curve (AUC). It was also noted that cyclosporine C(0) level correlated with AUC poorly, while C(2) level (concentration at 2 hours after drug administration) satisfactorily correlated with AUC. Most recent studies concern the use of C(2) levels in de novo renal transplant patients; target levels of C(2) have been suggested. There is rare discussion about the C(2) target level for long-term cyclosporine-maintenance patients. Our objectives were to analyze the cyclosporine C(2) levels of patients more than 12 months after transplantation as well as changes in C(2) with time and the correlation between C(2) level and renal function. METHODS AND PATIENTS: This was a cross-sectional case-controlled study of 101 kidney recipients immunosuppressed with a cyclosporine-based regimen for at least 12 months. Both C(0) and C(2) levels were examined at various time points during outpatient clinic follow-up. The patients were stratified according to the time after transplant surgery, or to their renal function. RESULTS: The 101 patients were divided into three groups based on the time after renal transplant surgery. Groups 1, 2, and 3 represented patients transplanted for 1 to 3 years (n = 16), 4 to 6 years (n = 35), and more than 6 years (n = 50), respectively. The C(2) levels for each group were 657 +/- 232, 561 +/- 186, and 580 +/- 243 ng/mL, respectively, (P = NS). When stratified into low versus high C(2) groups, there were no significant differences in renal function both at the beginning and at the end of 1 year follow-up. Seven of 67 patients shifted to stronger immunosuppression in the low C(2) group, but only 2/34 in the high C(2) group, a difference that was not significant (P = .234 by Fisher Exact Test). Patients with creatinine levels greater than 1.5 mg/dL or lower than 1.5 mg/dL showed no difference in C(2) on C(0) levels. Patients with deterioration of renal function during this period had no different C(2) levels as those with no deterioration of renal function. CONCLUSION: The average C(2) levels among long-term cyclosporine-maintained patients were significantly lower than those previously suggested. C(2) levels did not correlate with the long-term outcome of renal function in patients at least 1 year after renal transplantation.