Embracing Sex-specific Differences in Engineered Kidney Models for Enhanced Biological Understanding

Abstract: In vitro models play a crucial role in advancing our understanding of biological processes, disease mechanisms, and developing screening platforms for drug discovery. Kidneys play an instrumental role in transport and elimination of drugs and toxins. However, despite the well-established patient-to-patient differences in kidney function and disease manifestation, progression and prognostic, few studies take this variability into consideration. In particular, the discrepancies between female and male biology warrants a better representation within kidney in vitro models. The omission of sex as a biological variable poses the significant risk of overlooking sex-specific mechanisms in health and disease and potential differences in drug efficacy and toxicity between males and females. This review aims to highlight the importance of incorporating sex dimorphism in kidney in vitro models by examining the sexual characteristics in the context of the current state-of-the-art. Furthermore, this review underscores opportunities for improving kidney models by incorporating sex-specific traits. Ultimately, this roadmap to incorporating sex-dimorphism in kidney in vitro models will facilitate the creation of better models for studying sex-specific mechanisms in the kidney and their impact on drug efficacy and safety.