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个性化免疫抑制治疗:马来西亚肾移植受者药物转换的预测因素

Personalizing immunosuppressive therapy: predictors of drug switches in Malaysian kidney transplant recipients.

作者信息

Choong Chiau Ling, Islahudin Farida, Makmor-Bakry Mohd, Mohd Tahir Nor Asyikin, Wong Hin-Seng, Yahya Rosnawati

机构信息

Center of Quality Medicine Management, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia.

出版信息

J Pharm Pharm Sci. 2025 Sep 8;28:14632. doi: 10.3389/jpps.2025.14632. eCollection 2025.

Abstract

OBJECTIVE

Tacrolimus-mycophenolic acid (MPA)-prednisolone immunosuppression remains the first-line management of kidney transplantation. Despite this, a switch to low-dose tacrolimus in combination with an mTOR inhibitor may be inevitable in some patients due to various factors. This study aims to identify the reasons and factors influencing the switch of tacrolimus-MPA to other combination immunosuppressive agents among kidney transplant recipients (KTRs).

METHODS

This retrospective observational cohort study included adult KTRs between year 2011-2019 at the two main kidney transplant centers in Malaysia. Demographic data, clinical, laboratory and medication information were collected. Multiple logistic regression was used to determine factors associated with the initial switch of tacrolimus-MPA immunosuppressive therapy.

RESULTS

From the 257 KTRs studied, 81 KTRs had their immunosuppressive agents switched from tacrolimus-MPA-prednisolone immunosuppressive regimen, with majority (96.3%, n = 78) switching to everolimus, an mTOR inhibitor in combination with low-dose tacrolimus. The average time switch was 125.8 ± 100.9 days. The main reasons for the initial switch include unresolved transaminitis (n = 15, 18.5%), cytomegalovirus (CMV) infection (n = 13, 16.0%) and BK virus (BKV) infection (n = 10, 12.3%). In the multiple logistic analysis, Malay ethnicity (P < 0.001), KTRs without post-transplant hypertension (P = 0.004) and KTRs with BKV infection (P < 0.001) were predictors for the initial switch of tacrolimus-MPA-prednisolone immunosuppressive therapy.

CONCLUSION

Early identification of factors associated with the switch may prepare healthcare professionals for KTRs risk stratification, allowing ample time for appropriate optimization of tacrolimus-MPA-prednisolone immunosuppressive therapy based on individual patient's needs. This can possibly be a cost-effective alternative to switching to mTOR inhibitors for improved transplant outcomes.

摘要

目的

他克莫司-霉酚酸(MPA)-泼尼松龙免疫抑制仍是肾移植的一线治疗方案。尽管如此,由于各种因素,部分患者可能不可避免地要改用低剂量他克莫司联合mTOR抑制剂。本研究旨在确定肾移植受者(KTR)中他克莫司-MPA转换为其他联合免疫抑制剂的原因和影响因素。

方法

这项回顾性观察队列研究纳入了2011年至2019年间马来西亚两个主要肾移植中心的成年KTR。收集了人口统计学数据、临床、实验室和用药信息。采用多因素logistic回归分析确定与他克莫司-MPA免疫抑制治疗初始转换相关的因素。

结果

在研究的257例KTR中,81例KTR的免疫抑制剂从他克莫司-MPA-泼尼松龙免疫抑制方案转换,其中大多数(96.3%,n = 78)转换为依维莫司,一种mTOR抑制剂联合低剂量他克莫司。平均转换时间为125.8±100.9天。初始转换的主要原因包括未解决的转氨酶升高(n = 15,18.5%)、巨细胞病毒(CMV)感染(n = 13,16.0%)和BK病毒(BKV)感染(n = 10,12.3%)。在多因素logistic分析中,马来族裔(P < 0.001)、移植后无高血压的KTR(P = 0.004)和有BKV感染的KTR(P < 0.001)是他克莫司-MPA-泼尼松龙免疫抑制治疗初始转换的预测因素。

结论

早期识别与转换相关的因素可为医护人员对KTR进行风险分层做准备,从而有足够时间根据个体患者需求对他克莫司-MPA-泼尼松龙免疫抑制治疗进行适当优化。这可能是一种具有成本效益的替代方案,可避免改用mTOR抑制剂以改善移植结局。

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