Gender and Renal Insufficiency: Opportunities for Their Therapeutic Management?

Acute kidney injury (AKI) is a major clinical problem associated with increased morbidity and mortality. Despite intensive research, the clinical outcome remains poor, and apart from supportive therapy, no other specific therapy exists. Furthermore, acute kidney injury increases the risk of developing chronic kidney disease (CKD) and end-stage renal disease. Acute tubular injury accounts for the most common intrinsic cause of AKI. The main site of injury is the proximal tubule due to its high workload and energy demand. Upon injury, an intratubular subpopulation of proximal epithelial cells proliferates and restores the tubular integrity. Nevertheless, despite its strong regenerative capacity, the kidney does not always achieve its former integrity and function and incomplete recovery leads to persistent and progressive CKD. Clinical and experimental data demonstrate sexual differences in renal anatomy, physiology, and susceptibility to renal diseases including but not limited to ischemia-reperfusion injury. Some data suggest the protective role of female sex hormones, whereas others highlight the detrimental effect of male hormones in renal ischemia-reperfusion injury. Although the important role of sex hormones is evident, the exact underlying mechanisms remain to be elucidated. This review focuses on collecting the current knowledge about sexual dimorphism in renal injury and opportunities for therapeutic manipulation, with a focus on resident renal progenitor stem cells as potential novel therapeutic strategies.