Utility of C-2 (Cyclosporine) monitoring in postrenal transplant patients: A study in the Indian population.

The study was planned and conducted to assess the benefit of C-2 levels (blood cyclosporine levels two hours postdosing) monitoring over trough (C0) levels (predosing) in postrenal transplant patients. The patient population included 34 postrenal transplant individuals (28 males and six females, mean age of 39.9 +/- 12.3 years). The patients were first-transplant patients and were receiving a microemulsion form of cyclosporine A (CsA) as an immunosuppressant along with azathioprine and prednisolone. In addition, they were not on any enzyme inducer/inhibitor drugs, except for diltiazem. Timed collection of C0 and C-2 samples was done and the samples were immediately processed using the cedia cyclosporine plus assay kit. Estimation was done on a Beckman synchron CX5CE fully automated chemistry analyzer. Serum urea nitrogen and creatinine levels were checked. Poor graft survival was found in this population with 29.3% patients showing graft rejection. The graft rejection patients were assigned to two groups: group I with chronic graft rejection patients (17.6%) and group II with acute graft rejection patients (11.7%). Group III consisted of graft survival patients (70.7%). Mean +/- SD was calculated for C0 and C2 levels. Individual values for C0 and C-2 were plotted on a scatter chart. C0 and C-2 levels were normalized by calculating them as the percentage of their targets (data not shown) and compared using the Kruskal Wallis one-way analysis of variance. C0 levels in all the three groups were within the recommended therapeutic range (150-300 ng/mL) (P < 0.182). Blood C-2 concentrations did not achieve the recommended target levels in these patients. One-way analysis of variance for C-2 values when expressed as the percentage of the target values did not show any significant difference between these groups (P < 0.84). No significant difference was found in C0 levels between groups I, II, and group III patients when expressed as the percentage of the target values (P < 0.182). The mean serum urea nitrogen level was 26.4 +/- 8.1 mg/dL whereas the mean serum creatinine level was 1.79 +/- 0.8 mg/dL. As is evident in the present study, the target C2 levels of cyclosporine dosage were not achieved whereas the C0 levels in all the three groups were within the optimum therapeutic range. As the incidence of graft dysfunction was also proportionately high, the importance of C2 monitoring is further highlighted on the basis of this study The contributory factors for levels lower than the target levels, such as the use of low doses of cyclosporine and interacting drugs should be carefully monitored in clinical practice. The achievement of optimum levels of C-2 may help in reducing the higher incidence of graft rejection in these patients. This practice is of equal importance in reducing cyclosporine-related renal toxicity, a rather irreversible process.