간이식 후 Tacrolimus 신독성을 최소화하기 위한 적정 농도에 관한 연구 = Optimal Level of Tacrolimus to Minimize Nephrotoxicity in Liver Transplantation

다국어 초록 (Multilingual Abstract)

Purpose: Calcineurin inhibitor (CNI)?induced nephrotoxicity is the main cause of renal dysfunction after liver transplantation (LT). The aims of this study were to investigate the temporal changes in kidney function after LT and to set the optimal tacrolimus level to minimize nephrotoxicity at various time points after LT.
Methods: 37 patients who underwent LT at Ulsan University Hospital with preoperative estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73m2, immunosuppression including tacrolimus and follow-up of a minimum of 6 months were eligible. All these patients received tacrolimus, steroid and mycophenolate mofetil. 16 patients received induction therapy with Simulect. Steroid was withdrawn within 3 to 6 months after LT in all patients. Renal function was assessed with eGFR 2 weeks, 1, 3, 6 and 12 months after LT. Tacrolimus trough level was also measured at the same time and its mean level was calculated. To set the tacrolimus level minimizing nephrotoxicity, multivariate regression analysis was applied to identify mean tacrolimus level minimizing decrease in eGFR at those time periods. Age, sex, presence of diabetes or hypertension and use of Simulect were the covariates. Incidence of acute rejection and infection were compared between the tac-high and tac-low groups at 1 month using Fisher’s exact test.
Results: The mean age was 51.6 years and 32 patients were male. Mean eGFR declined from 88.96 ± 27.11 ml/min/1.73m2 to 57 ml/min/1.73m2 by 3 months after LT. Renal function was kept stationary thereafter until 1 year after LT. On multivariate regression analysis, mean tacrolimus level minimizing decline in eGFR most significantly could be obtained. In 12 patients whose mean tacrolimus level was kept below 7.96 ng/ml, changes in eGFR (?eGFR) was only -0.29 ml/min/1.73m2, compared to -23.38 ml/min/1.73m2 in 25 patients whose level were kept above 7.96 ng/ml (p=0.0156). There was no significant difference in the incidence of acute rejection and infection between the two groups. Likewise, tacrolimus level minimizing decline in eGFR obtained through regression analysis were 8.17 ng/ml at 3 months, 7.74 ng/ml at 6 months, and 7.43 ng/ml at 1 year after LT (0.0385, 0.0195 and 0.0296, respectively).
Conclusions: Kidney function declined until 3 months after LT but stationary thereafter until 1 year. Progression of renal dysfunction could be decelerated by optimizing tacrolimus level at various time points.

목차 (Table of Contents)

• 차 례
• 국문요약
• 그림 차례
• 표 차례
• 서론
• 재료 및 연구방법
• 결과
• 고찰
• 결론
• 참고문헌
• 영문요약