Sex and gender differences in the effects of immunosuppressive drugs in patients with kidney transplantation

Abstract

INTRODUCTION Kidney transplantation requires lifelong immunosuppressive therapy, yet substantial interindividual variability in drug exposure and toxicity remains a major clinical challenge. Emerging evidence indicates that sex (biological attributes) and gender (socio- cultural and behavioral factors) significantly influence pharmacokinetics, pharmacodynamics, and safety profiles of immunosuppressive agents highlighting the need for dosing strategies to optimize efficacy and minimize adverse events. In addition to biological sex differences, gender-related factors such as treatment adherence, healthcare access, and reporting of adverse events may also influence therapeutic response in transplant recipients, although available evidence remains limited.AREAS COVERED This review summarizes current evidence on sex- and gender-specific differences in the pharmacology of major immunosuppressants used in kidney transplantation and discusses their implications for therapeutic drug monitoring and personalized medicine. A comprehensive literature search was conducted in PubMed, Scopus and Web of Science form database through July 2025, focusing on clinical studies evaluating pharmacokinetics, toxicity profiles, and therapeutic drug monitoring strategies. Available data indicate that women often have different systemic exposure to immunosuppressive agents compared to men.EXPERT OPINION Integration of sex-informed therapeutic strategies and individualized drug monitoring may improve safety and long-term graft outcomes. Prospective sex-stratified studies are essential to define optimized dosing algorithms and facilitate implementation in clinical practice.