Sex differences and the role of sex steroids in renal injury.
OBJECTIVE
There 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.


METHODS
The current clinical evidence of increased male susceptibility to acute and chronic renal injury, and experimental data elucidating potential mechanisms of this phenomenon were reviewed.


RESULTS
Renal 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-beta1, tumor necrosis factor-alpha 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.


CONCLUSIONS
Greater 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.
Metcalfe
Peter D
PD
Riley Hospital for Children, Indiana University School of Medicine, 702 Barnhill Drive, Indianapolis, IN 46202, USA.
Meldrum
Kirstan K
KK
D000818:Animals; D017209:Apoptosis; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D007668:Kidney / Q000098:blood supply; D008297:Male; D051437:Renal Insufficiency / Q000503:physiopathology*; D012727:Sex Characteristics; D015398:Signal Transduction
D012739:Gonadal Steroid Hormones; D018836:Inflammation Mediators