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

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 (C-0), average concentration values (C-av; i.e.. the dosing interval-corrected area under the concentration-time curve), maximum concentration (C-max), and time to maximum concentration (t(max))- 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 C-av greater than or equal to 550 ng/ml had higher 1-year (88 %) and 6-year (66 %) graft survival rates than patients with C-av < 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 C-av < 550 versus C-av greater than or equal to 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 C-av < 550 ng/ml displayed more severe rejection episodes, as judged by Banff classification, than patients who displayed C-av greater than or equal to 550 ng/ml (grades II and III; 71 % vs 50 %; P = 0.036). In contrast, the C-0, C-max, and t(max) values did not correlate with patient, graft, or rejection-free survival rates. The pharmacokinetic parameter of C-av correlated strongly with early graft survival and may, therefore, be a useful predictor of those renal transplant patients who may require more intensive posttransplant monitoring of CyA concentrations by serial PK studies to improve graft survival.