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长期暴露于他克莫司对肺移植后慢性肾脏病的影响:来自单一移植中心的回顾性分析。

The impact of long-term exposure to tacrolimus on chronic kidney disease after lung transplantation: A retrospective analysis from a single transplantation center.

作者信息

Xiong Dian, Yue Bingqing, Ye Shugao, Wang Hongmei, Ban Le, Chen Yuan, Lv Jian, Zhou Min, Yin Pan, Chen Jingyu

机构信息

Lung Transplantation Center, Department of Thoracic Surgery, Nanjing Medical University Affiliated Wuxi People's Hospital, Wuxi 214023, China.

Lung Transplantation Center, Department of Thoracic Surgery, Nanjing Medical University Affiliated Wuxi People's Hospital, Wuxi 214023, China; Department of Lung Transplant, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China.

出版信息

Transpl Immunol. 2023 Jun;78:101810. doi: 10.1016/j.trim.2023.101810. Epub 2023 Mar 12.

DOI:10.1016/j.trim.2023.101810
PMID:36918103
Abstract

BACKGROUND

Chronic kidney disease (CKD) is a progressive and irreversible complication in lung transplant patients who have received long-term treatment with tacrolimus. This study aimed to verify long-term tacrolimus exposure values in CKD progression.

METHODS

We retrospectively analyzed the clinical data of adult lung transplant recipients performed at our center between 2012 and October 2015. Patients who completed the 5-year follow-up period were enrolled in this study. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m.

RESULTS

Eighty patients were analyzed. Compared with baseline (109 ± 38.1 mL/min/1.73 m2), the average eGFR values of our patients gradually decreased during the fifth-year post transplantation (46.5%, 58.3 ± 28.3 mL/min/1.73 m2), and the decline in eGFR values was particularly pronounced in the first year (31.2%, 74.6 ± 28.91 mL/min/1.73 m2). Moreover, 10 (12.7%), 21 (26.9%), 24 (31.2%), 28 (41.2%), and 48 (60%) patients had eGFR <60 mL/min/1.73 m at 3, 6, 1, 3, and 5 years after lung transplantation (LT), respectively. A significant negative correlation was found between tacrolimus dose and eGFR 6 months after LT (P = 0.0414). We found no correlation between the serum tacrolimus concentration and CKD progression.

CONCLUSION

eGFR constantly decreased and the incidence of CKD increased during the 5-year follow-up period after LT. The tacrolimus dose had a significant negative correlation with eGFR at 6 months after LT. Meanwhile, whole-blood tacrolimus trough concentrations were not correlated with eGFR decline. When possible, lower dosing within 1 year after LT can reduce potential nephrotoxic side effects.

摘要

背景

慢性肾脏病(CKD)是接受他克莫司长期治疗的肺移植患者中一种进行性且不可逆的并发症。本研究旨在验证CKD进展过程中他克莫司的长期暴露值。

方法

我们回顾性分析了2012年至2015年10月在本中心进行的成年肺移植受者的临床资料。完成5年随访期的患者纳入本研究。CKD定义为估计肾小球滤过率(eGFR)<60 mL/min/1.73 m²。

结果

分析了80例患者。与基线(109±38.1 mL/min/1.73 m²)相比,患者的平均eGFR值在移植后第5年逐渐下降(下降46.5%,至58.3±28.3 mL/min/1.73 m²),且eGFR值在第1年下降尤为明显(下降31.2%,至74.6±28.91 mL/min/1.73 m²)。此外,分别有10例(12.7%)、21例(26.9%)、24例(31.2%)、28例(41.2%)和48例(60%)患者在肺移植(LT)后3年、6个月、1年、3年和5年时eGFR<60 mL/min/1.73 m²。LT后6个月时他克莫司剂量与eGFR之间存在显著负相关(P = 0.0414)。我们发现血清他克莫司浓度与CKD进展之间无相关性。

结论

LT后5年随访期间eGFR持续下降,CKD发病率增加。LT后6个月时他克莫司剂量与eGFR存在显著负相关。同时,全血他克莫司谷浓度与eGFR下降无关。在可能的情况下,LT后1年内降低剂量可减少潜在的肾毒性副作用。

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