Sex Differences and the Role of Sex Steroids in Renal Injury

PurposeThere is growing evidence that significant sex differences exist in the response of the kidney to injury. In this review we explored the cumulative clinical knowledge and experimental evidence of this phenomenon.Materials and MethodsThe current clinical evidence of increased male susceptibility to acute and chronic renal injury, and experimental data elucidating potential mechanisms of this phenomenon were reviewed.ResultsRenal damage induced by nephron reduction, patient age and renal ischemia is tolerated differently by the sexes. Sex differences in disease susceptibility have historically been attributed to the protective effects of estrogen but recent evidence suggests that male hormones also have an important role in these differences. Vascular mediators, such as endothelin, nitric oxide and angiotensin II, appear to be influenced by sex and sex steroids. Additionally, inflammatory mediators, such as transforming growth factor-β1, tumor necrosis factor-α and p38 mitogen activating protein kinase, similarly show differential expression and activity based on sex and the presence of sex steroids. These mediators have a significant impact on the kidney response to inflammation and injury.ConclusionsGreater understanding of the specific role of sex steroids in renal injury may provide new therapeutic strategies to protect against inflammatory injury and renal damage in the future.