Abstract
Optimizing immunosuppressant dosing presents significant challenges in kidney transplantation due to narrow therapeutic ranges and considerable inter-patient pharmacokinetic differences. Emerging strategies for precision dosing, encompassing Bayesian population pharmacokinetic models, pharmacogenomic integration, and artificial intelligence algorithms, aim to enhance drug monitoring by moving beyond traditional trough-based approaches. This review critically assesses available evidence for predictive dosing models targeting immunosuppressants, including calcineurin inhibitors, antimetabolites, and mTOR inhibitors in kidney transplant patients. Available observational and simulation studies demonstrate substantial methodological diversity, with Bayesian PopPK-guided strategies showing 15-35% better target exposure achievement compared to trough-based monitoring. The absence of pooled estimates precludes a precise summary effect size, and evidence from randomized controlled trials remains limited. Machine learning models, particularly for tacrolimus, frequently reduced prediction error relative to traditional regression approaches, but substantial heterogeneity in study design, outcome definitions, and external validation limits quantitative synthesis. Hybrid Bayesian-AI frameworks and explainable AI tools show conceptual promise but are largely supported by proof-of-concept studies rather than reproducible clinical implementations. Overall, Bayesian pharmacokinetic modelling represents the most mature and clinically interpretable approach for precision dosing in transplantation, whereas AI-driven and hybrid systems remain investigational. Key gaps include the need for standardized reporting, rigorous risk-of-bias assessment, prospective validation, and clearer regulatory and implementation pathways to support safe and equitable clinical adoption.