The obese transplant organ recipient: experimental and clinical evidence for tailored immunosuppression

Obesity has become a major determinant of outcomes across solid organ transplantation. Beyond its well-recognized metabolic and cardiovascular burden, obesity profoundly affects both immune regulation and the pharmacology of immunosuppressive therapy. Experimental evidence has established adipose tissue as an active immune organ that promotes low-grade inflammation through leptin, TNF-α, and IL-6, thereby altering alloimmune responses and impairing graft tolerance. Clinically, obesity is associated with increased surgical complications, delayed graft function, and reduced survival after kidney, liver, and thoracic organ transplantation. In parallel, obesity modifies drug disposition at every pharmacokinetic step, expanding the distribution volume for lipophilic agents such as calcineurin and mTOR inhibitors, altering CYP3A metabolism, and increasing interindividual variability in exposure. Consequently, both underexposure and toxicity remain frequent, underscoring the need for individualized therapeutic strategies. Current evidence supports the integration of therapeutic drug monitoring, pharmacogenomics, and biomarker-based approaches to refine immunosuppression intensity. This review summarizes experimental and clinical data linking obesity-induced inflammation with altered immunosuppressive pharmacology and proposes a framework for precision immunosuppression that balances efficacy, nephroprotection, and metabolic safety. Tailoring therapy to the specific immunometabolic profile of obese recipients may thus transform a major clinical challenge into an opportunity for precision transplant medicine.