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肾移植受者肾功能与他克莫司C/D比值:来自MeltDose他克莫司前瞻性研究的见解

Renal Allograft Function and the Tacrolimus C/D Ratio: Insights from a Prospective Study on MeltDose Tacrolimus.

作者信息

Dębska-Ślizień Alicja, Kuźmiuk-Glembin Izabella, Hożejowski Roman, Kamińska Dorota, Krajewska Magdalena, Zawiasa-Bryszewska Anna, Kurnatowska Ilona, Smykał-Jankowiak Katarzyna, Głyda Maciej, Kozioł Lidia, Karczewski Marek, Ciechanowski Kazimierz, Kwiatkowska Ewa

机构信息

Department of Nephrology, Transplantology and Internal Diseases, Medical University of Gdansk, 80-952 Gdansk, Poland.

Medical Department, Chiesi Poland Sp. z o.o., 02-305 Warsaw, Poland.

出版信息

J Clin Med. 2024 Oct 19;13(20):6241. doi: 10.3390/jcm13206241.

Abstract

: The tacrolimus concentration-to-dose (C/D) ratio is valuable for optimizing nephrotoxicity-related renal outcomes. Prospective data on the C/D ratio in kidney transplant recipients newly treated with MeltDose tacrolimus are limited. We analyzed the C/D ratio pattern of MeltDose tacrolimus and its effect on posttransplant renal function, comparing it with the literature data on immediate-release tacrolimus (IR-Tac). : In total, 101 adult kidney transplant recipients on a standard immunosuppressive regimen including MeltDose tacrolimus were enrolled in this prospective, multicenter cohort study and followed for 12 months. The C/D ratio classified patients as fast, intermediate, or slow metabolizers. Renal function was assessed via the estimated glomerular filtration rate (eGFR). MeltDose tacrolimus data were compared with previous IR-Tac data by bootstrapping. : The cohort exhibited a right-skewed C/D ratio distribution with a mean of 2.12 ng/mL × 1/mg, which was significantly greater than the 1.29 mean for IR-Tac ( < 0.001). Compared with fast metabolizers, slow metabolizers of MeltDose tacrolimus experienced greater eGFR gains at 6 months post-transplantation (median +7.9 vs. -3.6 mL/min; = 0.005). A Bayesian linear mixed-effects model predicting the eGFR at month 12 identified the baseline eGFR, time from transplant, body mass index, and log-transformed C/D ratio as significant variables. A one-unit increase in the log-transformed C/D ratio corresponded to an approximate increase of 4.5 mL/min in the eGFR at month 12. : Slow metabolizers of MeltDose tacrolimus had significantly better renal function outcomes than fast metabolizers. MeltDose tacrolimus is associated with slower metabolism than is IR-Tac, as evidenced by its higher C/D ratios.

摘要

他克莫司浓度与剂量(C/D)比值对于优化与肾毒性相关的肾脏结局具有重要价值。关于新接受MeltDose他克莫司治疗的肾移植受者C/D比值的前瞻性数据有限。我们分析了MeltDose他克莫司的C/D比值模式及其对移植后肾功能的影响,并将其与速释他克莫司(IR-Tac)的文献数据进行比较。:总共101名接受包括MeltDose他克莫司在内的标准免疫抑制方案的成年肾移植受者被纳入这项前瞻性多中心队列研究,并随访12个月。C/D比值将患者分为快速、中等或缓慢代谢者。通过估算肾小球滤过率(eGFR)评估肾功能。通过自抽样法将MeltDose他克莫司的数据与先前的IR-Tac数据进行比较。:该队列的C/D比值分布呈右偏态,平均值为2.12 ng/mL×1/mg,显著高于IR-Tac的平均值1.29(<0.001)。与快速代谢者相比,MeltDose他克莫司的缓慢代谢者在移植后6个月时eGFR升高幅度更大(中位数+7.9 vs. -3.6 mL/min;P = 0.005)。预测第12个月eGFR的贝叶斯线性混合效应模型确定基线eGFR、移植时间、体重指数和对数转换后的C/D比值为显著变量。对数转换后的C/D比值每增加一个单位,对应第12个月时eGFR大约增加4.5 mL/min。:MeltDose他克莫司的缓慢代谢者的肾功能结局明显优于快速代谢者。MeltDose他克莫司的代谢速度比IR-Tac慢,其较高的C/D比值证明了这一点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1935/11508752/1e8507214fe0/jcm-13-06241-g001.jpg

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