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|標題:||Impact of variability of sirolimus trough level on chronic allograft nephropathy||作者:||Wu, M.J.
|關鍵字:||chronic-renal-failure;recipients||Project:||Transplantation Proceedings||期刊/報告no：:||Transplantation Proceedings, Volume 40, Issue 7, Page(s) 2202-2205.||摘要:||
The efficacy of sirolimus is strictly dose-dependent; an inappropriate exposure may cause either rejection episodes or drug toxicity. The variability of sirolimus trough levels (CO) may also have an impact on renal allograft function. We prospectively evaluated the impact of the dose-normalized CO of sirolimus and the intrapatient coefficient of variation (% CV) on renal allograft function at 6 months after the administration of sirolimus to kidney transplant recipients with chronic allograft nephropathy (CAN). We enrolled 51 recipients with CAN who were treated with sirolimus. The dose-normalized CO of sirolimus was 3.8 +/- 1.9 ng/mL/mg. The intra- and interpatient variabilities of sirolimus C-0 were 26.1% and 51.9%, respectively. Based on receiver operating characteristic analysis, patients were divided into 2 groups: group 1, sirolimus % CV < 22.9% (n = 36) versus group II, sirolimus % CV > 22.9% (n = 15). Patients in group II experienced significantly greater risk for progressive deterioration of allograft function (group I vs group II: 11.1% vs 73.3%; P < .05). Multiple logistic regression analysis revealed that higher baseline serum creatinine, but not age, gender, or concomitant immunosuppressants, positively correlated with the sirolimus % CV. In conclusion, both higher baseline serum creatinine and higher intraindividual variability of sirolimus CO impact the outcome of renal allograft function in CAN. Thus, we suggest that close monitoring of sirolimus CO is necessary for recipients treated with sirolimus, especially for patients with CAN.
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