Ben-Fredj Nadia, Dridi Issam, Dridi Ichrak, Ben-Yahya Noureddine, Aouam Karim
Service de Pharmacologie Clinique, CHU Fattouma Bourguiba de Monastir, Rue Avicenne, 5019, Monastir, Tunisia.
Faculté de Médecine de Monastir, Université de Monastir, Rue Avicenne, 5019, Monastir, Tunisia.
Eur J Drug Metab Pharmacokinet. 2025 May;50(3):243-250. doi: 10.1007/s13318-025-00942-7. Epub 2025 May 8.
Model-informed precision dosing (MIPD), based on a Bayesian approach and machine learning (ML) algorithms, is a suitable approach to personalize dosage recommendations and to improve the concentration target attainment for each patient. The objective of this study is to compare the predictive performance of two ML approaches, XGBoost and LSTM, with a previously developed Bayesian model of tacrolimus (Tac) in a cohort of Tunisian kidney transplant patients during the early post-transplant period (0-3 months) METHOD: This was a cross-sectional study conducted at the Pharmacology department in Fattouma Bourguiba's hospital in Monastir, Tunisia. We included patients who had undergone kidney transplantation in the Nephrology department of Monastir Hospital and received the Tac immunosuppressant protocol, for whom routine therapeutic drug monitoring (TDM) during the early post-transplant period (0-3 months) had been performed in our department.
A total of 187 Tac predose concentration (C) issued from 56 adult renal transplant patients were included in the present study. The whole population was divided into building (n = 39 patients, 119 C) and validation groups (n = 17 patients, 68 C). In the validation dataset, the RMSE was 0.76, 0.19, and 0.01, and the MAE was 0.55, 0.36, and 0.06, respectively, for the Bayesian approach, XGBoost, and LSTM.
Our study demonstrates that the LSTM approach outperforms XGBoost and Bayesian estimation in predicting tacrolimus concentration in Tunisian kidney transplant patients. Implementing TDM-based LSTM models during the first PT 3 months in clinical practice can significantly enhance patient outcomes and prevent acute kidney rejection in this population.
基于贝叶斯方法和机器学习(ML)算法的模型指导下的精准给药(MIPD)是一种适用于个性化剂量推荐并提高每位患者浓度目标达成率的方法。本研究的目的是比较两种ML方法(XGBoost和长短期记忆网络(LSTM))与先前开发的他克莫司(Tac)贝叶斯模型在一组突尼斯肾移植患者移植后早期(0 - 3个月)的预测性能。
这是一项在突尼斯莫纳斯提尔法图玛·布尔吉巴医院药理科进行的横断面研究。我们纳入了在莫纳斯提尔医院肾内科接受肾移植并接受Tac免疫抑制方案的患者,且我们科室在移植后早期(0 - 3个月)对其进行了常规治疗药物监测(TDM)。
本研究共纳入了56例成年肾移植患者的187个Tac给药前浓度(C)。总体人群分为构建组(n = 39例患者,119个C)和验证组(n = 17例患者,68个C)。在验证数据集中,对于贝叶斯方法、XGBoost和LSTM,均方根误差(RMSE)分别为0.76、0.19和0.01,平均绝对误差(MAE)分别为0.55、0.36和0.06。
我们的研究表明,在预测突尼斯肾移植患者的他克莫司浓度方面,LSTM方法优于XGBoost和贝叶斯估计。在临床实践中,在移植后前3个月实施基于TDM的LSTM模型可显著改善患者预后并预防该人群的急性肾排斥反应。