title: 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.
authors.affiliation: Department of Surgery, University of Texas Medical School, Houston 77030, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: Senel
authors.forename: C T
authors.initials: CT
authors.lastname: Van Buren
authors.forename: M
authors.initials: M
authors.lastname: Welsh
authors.forename: B D
authors.initials: BD
authors.lastname: Kahan
mesh_terms: D000328:Adult; D015331:Cohort Studies; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D016231:Fluorescence Polarization Immunoassay; D006084:Graft Rejection / Q000097:blood*; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D012189:Retrospective Studies
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine