Correlation of cyclosporine A blood concentration with kidney injury for pediatric patients after hematopoietic stem cell transplantation: a retrospective cohort study.

IF 2.4 3区医学 Q3 PHARMACOLOGY & PHARMACY

European Journal of Clinical Pharmacology Pub Date : 2025-01-07 DOI:10.1007/s00228-024-03792-5

Wei Shi, Xin Qiu, Liang Huang, Linan Zeng, Runxin Lu, Hailong Li, Kun Zou, Zhijun Jia, Guo Cheng, Qin Yu, Limei Zhao, Lingli Zhang

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Abstract

Background: The potential nephrotoxicity of cyclosporine A (CsA) has been a problem for treating graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the relationship between CsA blood concentration and acute kidney injury (AKI) in pediatric patients after allo-HSCT remains unclear.

Methods: We performed a retrospective study including pediatric patients who received allo-HSCT in West China Second Hospital of Sichuan University from 2000 to 2022 and collected their clinical data. Included patients' CsA blood concentration were divided into three cohorts according to the guideline. Multivariate logistic regression was used to estimate the relationship between AKI and CsA blood concentration and other factors. And the maximum cut-off value for the safe blood concentration range of CsA was obtained by the receiver operating characteristic (ROC) curve.

Results: Seventy-nine patients (average age 6.75 ± 4.25) were included. The incidence of kidney injury for three CsA blood concentration cohorts (< 200 ng/ml, 200-300 ng/ml, > 300 ng/ml) were 21.30%, 23.50%, and 66.70%, respectively. A multivariate logistic regression identified CsA blood concentration (> 300 ng/ml) and infection were risk factors for AKI (OR _<200 ng/ml: 0.115, 95% CI: 0.029-0.458; OR _{200-300 ng/ml}: 0.184, 95% CI: 0.036-0.929; OR _infection: 5.006, 95% CI: 1.491-16.810). Meanwhile, the maximum cut-off value for the safe blood concentration range of CsA is 276.85 ng/ml with an AUC value of 0.684 (P = 0.010).

Conclusion: In conclusion, clinical treatment for the pediatric patients after allo-HSCT may be considered to control the blood concentration of CsA in 200-276.85 ng/ml and closely monitoring patients who have infections.

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环孢素A血药浓度与儿童造血干细胞移植后肾损伤的相关性：一项回顾性队列研究。

背景：环孢素A （CsA）的潜在肾毒性一直是治疗同种异体造血干细胞移植（alloo - hsct）后移植物抗宿主病（GVHD）的一个问题。然而，儿科患者同种异体造血干细胞移植后CsA血药浓度与急性肾损伤（AKI）之间的关系尚不清楚。方法：我们对2000 - 2022年在四川大学华西第二医院接受同种异体造血干细胞移植的儿童患者进行回顾性研究，收集他们的临床资料。纳入患者的CsA血药浓度根据指南分为三个队列。采用多因素logistic回归分析AKI与CsA血药浓度等因素的关系。通过受试者工作特征（ROC）曲线得出CsA安全血药浓度范围的最大临界值。结果：纳入79例患者，平均年龄（6.75±4.25）岁。3个CsA血药浓度组（300 ng/ml）肾损伤发生率分别为21.30%、23.50%和66.70%。多因素logistic回归发现CsA血药浓度（> 300 ng/ml）和感染是AKI的危险因素(OR: 0.115, 95% CI: 0.029-0.458；OR 200-300 ng/ml: 0.184, 95% CI: 0.036-0.929；OR感染：5.006,95% CI: 1.491-16.810)。同时，CsA安全血药浓度范围的最大临界值为276.85 ng/ml， AUC值为0.684 （P = 0.010）。结论：小儿同种异体造血干细胞移植后的临床治疗可考虑将CsA血药浓度控制在200-276.85 ng/ml，并密切监测感染患者。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Clinical Pharmacology 医学-药学

CiteScore

5.40

自引率

3.40%

发文量

170

审稿时长

3-8 weeks

期刊介绍： The European Journal of Clinical Pharmacology publishes original papers on all aspects of clinical pharmacology and drug therapy in humans. Manuscripts are welcomed on the following topics: therapeutic trials, pharmacokinetics/pharmacodynamics, pharmacogenetics, drug metabolism, adverse drug reactions, drug interactions, all aspects of drug development, development relating to teaching in clinical pharmacology, pharmacoepidemiology, and matters relating to the rational prescribing and safe use of drugs. Methodological contributions relevant to these topics are also welcomed. Data from animal experiments are accepted only in the context of original data in man reported in the same paper. EJCP will only consider manuscripts describing the frequency of allelic variants in different populations if this information is linked to functional data or new interesting variants. Highly relevant differences in frequency with a major impact in drug therapy for the respective population may be submitted as a letter to the editor. Straightforward phase I pharmacokinetic or pharmacodynamic studies as parts of new drug development will only be considered for publication if the paper involves -a compound that is interesting and new in some basic or fundamental way, or -methods that are original in some basic sense, or -a highly unexpected outcome, or -conclusions that are scientifically novel in some basic or fundamental sense.