Impact of early cyclosporin average blood concentration on early kidney transplant failure.

Abstract

This retrospective study served to examine the correlation between the degree of cyclosporin (CyA) exposure, as estimated by a single pharmacokinetic (PK) profile performed at 1 week post-transplant, and the outcome of 290 consecutive renal transplants performed over a 6-year period. For this retrospective analysis patients were stratified into four historical groups based on 12-versus 24-h PK studies and on the use of radioimmunoassay versus fluorescence polarization immunoassay methods for estimates of CyA concentrations. Four PK measures-trough concentration (C0), average concentration values (Cav; i.e., the dosing interval-corrected area under the concentration-time curve), maximum concentration (Cmax), and time to maximum concentration (tmax)-were examined as predictors of patient, graft, and rejection-free survival rates for each of the four groups individually and for all groups combined. Patients with an initial Cav > or = 550 ng/ml had higher 1-year (88%) and 6-year (66%) graft survival rates than patients with Cav < 550 ng/ml, who had 1- and 6-year graft survival rates of 80% and 59%, respectively (P = NS). Statistically significant differences were observed in graft survival rates between patients with Cav < 550 versus Cav > or = 550 ng/ml at 30 (88% vs 96%; P < 0.02), 60 (85% vs 94%; P < 0.007), 90 (85% vs 94%; P < 0.02), and 180 (83% vs 92%; P < 0.05) days. Moreover, patients with Cav < 550 ng/ml displayed more severe rejection episodes, as judged by Banff classification, than patients who displayed Cav > or = 550 ng/ml (grades II and III; 71% vs 50%; P = 0.036). In contrast, the C0, Cmax and tmax values did not correlate with patient, graft, or rejection-free survival rates. The pharmacokinetic parameter of Cav correlated strongly with early graft survival and may therefore, be a useful predictor of those renal transplant patients who may require more intensive post-transplant monitoring of CyA concentrations by serial PK studies to improve graft survival.