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依维莫司作为肾移植中的一线免疫抑制剂:从钙调磷酸酶抑制剂转换的经验。

Everolimus as primary immunosuppression in kidney transplantation: experience in conversion from calcineurin inhibitors.

机构信息

Nephrology Department, Hospital Clínico Universitario San Carlos, Madrid, Spain.

出版信息

Transplantation. 2012 Feb 27;93(4):398-405. doi: 10.1097/TP.0b013e31823ffd0e.

Abstract

BACKGROUND

We analyzed our clinical experience with everolimus (EVL) and identified prognostic factors for a successful conversion.

METHODS

Retrospective study of 220 kidney recipients consecutively converted to EVL with calcineurin inhibitor elimination. We studied risk factors for proteinuria at 1 year after conversion, decline in renal function, and graft survival.

RESULTS

Baseline creatinine clearance was 52.4±17.8 mL/min vs. 53.4±20.1 mL/min 1 year after conversion (P=0.150). Median proteinuria increased from 304 mg/day (interquartile range 160-507) to 458 mg/day (interquartile range 238-892; P<0.001). Risk factors for development of proteinuria ≥900 mg/day (P75) at 1-year postconversion were creatinine clearance less than 60 mL/min (odds ratio [OR] 3.37; 95% confidence interval [CI]: 1.15-9.89), serum triglycerides ≥150 mg/day (OR 4.35; 95% CI: 1.70-11.17), no treatment with prednisone (OR 3.04; 95% CI: 1.22-7.59), baseline proteinuria ≥550 mg/day (OR 10.37; 95% CI: 3.99-26.99), and conversion ≥3 years after transplant (OR 5.77; 95% CI: 1.89-17.59). An interaction was observed between baseline proteinuria and time to conversion: in patients with baseline proteinuria ≥550 mg/day, the risk of developing proteinuria ≥900 mg/day was 77.1% if they were converted after ≥3 years posttransplant. However, this risk was 29.8% in the subgroup converted before (P=0.02). Actuarial graft survival at 1 and 4 years postconversion was 98.2% and 86.5%, respectively. Baseline proteinuria ≥550 mg/day was a risk factor for graft loss in patients converted after the third year but not in patients converted before this time. EVL discontinuation rate was 24% in the first year postconversion.

CONCLUSIONS

Conversion to EVL and elimination of calcineurin inhibitors is safe. Success depends on not making late conversions and not converting patients with high baseline proteinuria.

摘要

背景

我们分析了使用依维莫司(EVL)的临床经验,并确定了成功转换的预测因素。

方法

回顾性研究了 220 例连续接受钙调神经磷酸酶抑制剂消除的肾移植患者。我们研究了转换后 1 年蛋白尿、肾功能下降和移植物存活率的危险因素。

结果

基线肌酐清除率为 52.4±17.8mL/min 与转换后 1 年的 53.4±20.1mL/min(P=0.150)。中位蛋白尿从 304mg/天(四分位间距 160-507)增加到 458mg/天(四分位间距 238-892;P<0.001)。转换后 1 年蛋白尿≥900mg/天(P75)的发展风险因素是肌酐清除率<60mL/min(优势比[OR]3.37;95%置信区间[CI]1.15-9.89)、血清甘油三酯≥150mg/dL(OR 4.35;95% CI 1.70-11.17)、未使用泼尼松治疗(OR 3.04;95% CI 1.22-7.59)、基线蛋白尿≥550mg/dL(OR 10.37;95% CI 3.99-26.99)和转换后≥3 年(OR 5.77;95% CI 1.89-17.59)。在基线蛋白尿和转换时间之间观察到相互作用:在基线蛋白尿≥550mg/天的患者中,如果在移植后≥3 年内进行转换,发生蛋白尿≥900mg/天的风险为 77.1%。然而,在转换前亚组中,这一风险为 29.8%(P=0.02)。转换后 1 年和 4 年的移植物存活率分别为 98.2%和 86.5%。基线蛋白尿≥550mg/dL 是移植后第 3 年发生移植物丢失的危险因素,但不是移植前发生移植物丢失的危险因素。转换后第一年依维莫司停药率为 24%。

结论

转换为依维莫司并消除钙调神经磷酸酶抑制剂是安全的。成功取决于不进行晚期转换和不转换基线蛋白尿高的患者。

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