The tacrolimus concentration-to-dose ratio is associated with kidney function in heart transplant recipients.

IF 3.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Maaike R Schagen, Teun B Petersen, Boris C A Seijkens, Jasper J Brugts, Kadir Caliskan, Alina A Constantinescu, Brenda C M de Winter, Isabella Kardys, Dennis A Hesselink, Olivier Manintveld
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Abstract

Aim: Heart transplantation (HT) is frequently complicated by chronic kidney disease, of which tacrolimus-related nephrotoxicity is an important cause. In kidney and liver transplant recipients, fast tacrolimus metabolism (defined as a low concentration-to-dose [C0/D] ratio), negatively affects kidney function. Here, the association between the C0/D ratio and kidney function in HT recipients was investigated.

Methods: This was a retrospective study including 209 HT recipients who received an immediate-release tacrolimus formulation. The C0/D ratio and kidney function (estimated glomerular filtration rate [eGFR]) were assessed at 3, 6, 12, 36 and 60 months post-HT. Patients were categorized as fast, intermediate and slow metabolisers, depending on their individual median C0/D ratio as calculated over the follow-up period. A linear mixed-effects model analysis was performed, in which the time-varying eGFR was the dependent variable.

Results: The distribution of the individual median C0/D ratios ranged from 0.41 to 8.9 ng/mL/mg. At baseline, patients' kidney function was comparable. In the multivariable linear mixed-effects model, fast metabolisers (C0/D ratio ≤1.53) had a significantly lower eGFR compared to slow metabolisers (C0/D ratio >2.27) (-6.8 mL/min/1.73 m2, 95% CI -11.2, -2.4, p = 0.002). This association was confirmed when utilizing the individual median C0/D ratio as a continuous variable: for each 1 unit increase in the C0/D ratio there was a 2.8 mL/min/1.73 m2 (95% CI 1.0, 4.5) increase in eGFR (P = 0.002).

Conclusion: Fast tacrolimus metabolism is significantly associated with worse kidney function in HT recipients in the first 5 years post-HT when compared to recipients with intermediate and slow tacrolimus metabolism.

他克莫司浓度剂量比与心脏移植受者肾功能相关。
目的:心脏移植常并发慢性肾脏疾病,他克莫司相关肾毒性是其重要原因。在肾和肝移植受者中,他克莫司快速代谢(定义为低浓度剂量比)会对肾功能产生负面影响。本研究探讨了羟色胺受体C0/D比值与肾功能之间的关系。方法:这是一项回顾性研究,包括209名接受他克莫司速释制剂治疗的HT受体。在ht后3、6、12、36和60个月评估C0/D比率和肾功能(估计肾小球滤过率[eGFR])。根据随访期间计算的个体中位C0/D比率,将患者分为快速、中等和缓慢代谢者。采用线性混合效应模型分析,时变eGFR为因变量。结果:个体中位C0/D比值分布范围为0.41 ~ 8.9 ng/mL/mg。在基线时,患者的肾功能具有可比性。在多变量线性混合效应模型中,快速代谢组(C0/D比值≤1.53)的eGFR显著低于慢代谢组(C0/D比值bbb2.27) (-6.8 mL/min/1.73 m2, 95% CI -11.2, -2.4, p = 0.002)。当使用个体中位C0/D比率作为连续变量时,这种关联得到了证实:C0/D比率每增加1个单位,eGFR增加2.8 mL/min/1.73 m2 (95% CI 1.0, 4.5) (P = 0.002)。结论:与他克莫司中度和缓慢代谢的受体相比,他克莫司快速代谢与HT受体术后前5年肾功能恶化有显著相关性。
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
CiteScore
6.30
自引率
8.80%
发文量
419
审稿时长
1 months
期刊介绍: Published on behalf of the British Pharmacological Society, the British Journal of Clinical Pharmacology features papers and reports on all aspects of drug action in humans: review articles, mini review articles, original papers, commentaries, editorials and letters. The Journal enjoys a wide readership, bridging the gap between the medical profession, clinical research and the pharmaceutical industry. It also publishes research on new methods, new drugs and new approaches to treatment. The Journal is recognised as one of the leading publications in its field. It is online only, publishes open access research through its OnlineOpen programme and is published monthly.
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