Gender and the prevalence and progression of renal disease.

In most experimental models of CKD, male animals progress more rapidly than females. Modulation of the hormonal milieu can replicate the effects of gender on the course of kidney disease. These observations suggest that sex hormones per se may be important determinants of the greater susceptibility of males to progressive kidney injury. The predominance of data in humans suggests that the course of nondiabetic kidney disease is more aggressive in men than women. Male gender is arguably also a risk factor for progression of diabetic nephropathy. Sex hormones directly or indirectly affect many cellular processes by modulating the synthesis of various cytokines, growth factors, and vasoactive agents. In particular, estrogen acts in a receptor-dependent mechanism to regulate genes involved in extracellular matrix metabolism. Estrogen has profound effects on transforming growth factor-β signal transduction and on the renin-angiotensin system. These effects may contribute to alterations in kidney hemodynamics and affect kidney disease progression. Selective estrogen receptor modulators, agents that mimic many of the beneficial effects of estrogen without reproducing estrogen's deleterious effects on reproductive tissue, ameliorate the course of kidney disease in animal models and in postmenopausal women.