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REVIEW

Sex, diabetes and the kidney

Department of Physiology and Biophysics and the Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi

Submitted 22 August 2008 ; accepted in final form 7 January 2009

ABSTRACT

The incidence and the rate of progression of nondiabetic renal disease is generally greater in men compared with age-matched women, suggesting that the female sex is protective and/or that the male sex is a risk factor for the development and progression of nondiabetic renal disease. In diabetes, even though the male sex still appears to be a risk factor, this relationship is not as strong as it is in nondiabetic renal disease. Experimental evidence suggests that both estrogens and androgens play an important role in the pathophysiology of renal disease. Thus one of the potential mechanisms for the absence of a clear sex difference in the setting of diabetes may be alterations in sex hormone levels. Indeed, studies suggest that diabetes is a state of an imbalance in sex hormone levels; however, whether these changes correlate with the decline in renal function associated with diabetes is unclear. Furthermore, diabetic renal disease rarely develops before puberty, and the onset of puberty accelerates microalbuminuria, supporting the idea of the involvement of sex hormones in the development and progression of the disease. However, other than a handful of experimental studies indicating that treatment with or removal of sex hormones alters the course of diabetic renal disease, very few studies have actually directly examined the correlation between sex hormones and the disease development and progression. Further studies are necessary to determine the precise contribution of sex hormones in the pathophysiology of diabetic renal disease to develop novel and potentially sex-specific therapeutic treatments.

estrogen; testosterone; diabetes; kidney; diabetic nephropathy