The reduced function allele SLCO1B1 c.521T>C is of no practical relevance for the renal graft function over the first post-transplant year in patients treated with mycophenolic acid.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-09-01 Epub Date: 2024-05-20 DOI:10.1097/FPC.0000000000000539

Sandra Nađ Škegro, Luka Penezić, Livija Šimičević, Tvrtko Hudolin, Željko Kaštelan, Nada Božina, Vladimir Trkulja

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引用次数: 0

Abstract

Objective: It is unclear whether renal transplant recipients treated with mycophenolic acid (MPA) who carry the reduced-function allele at polymorphism SLCO1B1 c.521T>C differ from their wild-type peers regarding renal outcomes and tolerability. We aimed to estimate the effect of this polymorphism on the graft function (estimated glomerular filtration rate, eGFR) over the first 12 post-transplant months in patients on MPA-based maintenance immunosuppression.

Methods: In a 12-month observational cohort study, consecutive adult patients were repeatedly assessed for eGFR. The SLCO1B1 c.521C>T variant allele carriers (exposed) and wild-type subjects (controls) were balanced on a range of demographic, medical, and genetic variables at baseline, and eGFR trajectory was estimated with further adjustment for time-varying covariates. A subset of patients were assessed for exposure to MPA 5-7 days after the transplantation.

Results: The adjusted eGFR slopes from day 1 to day 28 (daily), and from day 28 to day 365 (monthly) were practically identical in exposed (n = 86) and control (n = 168) patients [geometric means ratios (GMR) = 0.99, 95% confidence interval (CI) = 0.92-1.06 and GMR = 0.98, 0.94-1.01, respectively]. The rates of adverse renal outcomes and possible MPA-related adverse effects were low, and similar in exposed and controls [rate ratios (RR) = 0.94, 0.49-1.84 and RR = 1.08, 0.74-1.58, respectively]. The pharmacokinetic analysis did not signal meaningful differences regarding exposure to MPA, overall (exposed n = 23, control n = 45), if cotreated with cyclosporine (n = 17 vs. n = 26) or with tacrolimus (n = 8 vs. n = 17).

Conclusions: In patients treated with MPA, variant allele SLCO1B1 c.521T>C appears of no practical relevance regarding the 12-month renal graft function, MPA safety and exposure to MPA at early steady-state.

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功能减弱等位基因 SLCO1B1 c.521T>C 与霉酚酸治疗患者移植后第一年的肾移植功能没有实际意义。

目的：目前尚不清楚携带多态性 SLCO1B1 c.521T>C 的功能减低等位基因的霉酚酸（MPA）肾移植受者与野生型肾移植受者在肾脏预后和耐受性方面是否存在差异。我们的目的是估计这一多态性对接受基于 MPA 的维持性免疫抑制的患者移植后前 12 个月的移植物功能（估计肾小球滤过率，eGFR）的影响：在一项为期 12 个月的观察性队列研究中，连续对成年患者的 eGFR 进行了反复评估。基线时，SLCO1B1 c.521C>T变异等位基因携带者（暴露者）和野生型受试者（对照组）在一系列人口统计学、医学和遗传学变量上保持平衡，并在进一步调整随时间变化的协变量后估计eGFR轨迹。一部分患者在移植后5-7天接受了MPA暴露评估：暴露患者（n = 86）和对照患者（n = 168）从第1天到第28天（每天）以及从第28天到第365天（每月）的调整后eGFR斜率几乎相同[几何平均比（GMR）= 0.99，95%置信区间（CI）= 0.92-1.06，GMR= 0.98，0.94-1.01]。肾脏不良后果和可能与 MPA 相关的不良反应发生率较低，暴露组和对照组的发生率相似[比率比 (RR) = 0.94，分别为 0.49-1.84 和 RR = 1.08，0.74-1.58]。药代动力学分析显示，在与环孢素（n = 17 vs. n = 26）或他克莫司（n = 8 vs. n = 17）共同治疗的情况下，MPA的总体暴露量（暴露量 n = 23，对照量 n = 45）没有明显差异：结论：在接受 MPA 治疗的患者中，变异等位基因 SLCO1B1 c.521T>C 与 12 个月的肾移植功能、MPA 安全性和早期稳态时的 MPA 暴露似乎没有实际意义。

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

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.