Factors That Affect Concentrations of Cyclosporine During the Induction Period of Kidney Transplantation: Multivariate Analysis
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Date
2011
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ELSEVIER SCIENCE INC
Abstract
Objective. The pharmacokinetics of cyclosporine (CsA) depend on numerous factors over the transplantation course. The aim of this study was to evaluate the impact of several clinical variables on CsA concentrations during the induction period after kidney transplantation.
Methods. Potential variables were contrasted with CsA concentrations at 2 hours postdose (C-2) and with the area under the concentration curve of CsA (AUC) at days 3 and 10 after transplantation. Evaluated variables were: recipient age, gender, body mass index (BMI), type/duration of previous dialysis, pretransplant serum creatinine (sCr), donor type, CsA dose, cold ischemia time, reduction of sCr, and use of other immunosuppressive drugs.
Results. This series included 112 patients who displayed an average age of 43 13 years, including 62 men and 31 recipients of living donor organs. The induction dose of CsA was 8.36 +/- 1.53 mg/kg. On day 3, the C-2 was related to the reduction of sCr (P = 0.034) and to the BMI (P = 0.033). There was an inverse correlation with pretransplant sCr (P = 0.012). The AUC correlated with BMI (P = 0.027) and living donor category (P = .002). Patients receiving rapamycin or a locally procured kidney showed a trend toward higher AUC values. On day 10, the CsA dose and use of rapamycin showed a trend to higher values of C-2; the AUC was related to the CsA dose (P = .034). None of the other variables showed significant effects. Analysis between variables showed that time on dialysis correlated with the pretransplant sCr (P = .002) and that the CsA dose was negatively associated with BMI (P = .009).
Conclusion. Pretransplant sCr, BMI, living donor kidney category, better functional recovery, and the dose of CsA were predictors of CsA concentrations of clinical interest during this induction period. The effect of BMI was not related to higher doses of CsA.
Methods. Potential variables were contrasted with CsA concentrations at 2 hours postdose (C-2) and with the area under the concentration curve of CsA (AUC) at days 3 and 10 after transplantation. Evaluated variables were: recipient age, gender, body mass index (BMI), type/duration of previous dialysis, pretransplant serum creatinine (sCr), donor type, CsA dose, cold ischemia time, reduction of sCr, and use of other immunosuppressive drugs.
Results. This series included 112 patients who displayed an average age of 43 13 years, including 62 men and 31 recipients of living donor organs. The induction dose of CsA was 8.36 +/- 1.53 mg/kg. On day 3, the C-2 was related to the reduction of sCr (P = 0.034) and to the BMI (P = 0.033). There was an inverse correlation with pretransplant sCr (P = 0.012). The AUC correlated with BMI (P = 0.027) and living donor category (P = .002). Patients receiving rapamycin or a locally procured kidney showed a trend toward higher AUC values. On day 10, the CsA dose and use of rapamycin showed a trend to higher values of C-2; the AUC was related to the CsA dose (P = .034). None of the other variables showed significant effects. Analysis between variables showed that time on dialysis correlated with the pretransplant sCr (P = .002) and that the CsA dose was negatively associated with BMI (P = .009).
Conclusion. Pretransplant sCr, BMI, living donor kidney category, better functional recovery, and the dose of CsA were predictors of CsA concentrations of clinical interest during this induction period. The effect of BMI was not related to higher doses of CsA.
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Keywords
CHRONIC-RENAL-FAILURE, MYCOPHENOLIC-ACID, BLOOD-LEVELS, PHARMACOKINETICS, ORGAN, ABSORPTION, EXPOSURE, GUT