Gender Issues in Chronic Kidney Disease

Gender influences the incidence, prevalence, and progression of chronic kidney disease (CKD). In numerous experimental models of renal disease, progression is accelerated in male animals. Gender dimorphism in the course of renal disease is replicated by hormonal manipulation, suggesting that the actions of sex hormones, rather than structural differences between the sexes, are responsible for gender-related differences in renal disease progression. Sex hormones influence many of the processes known to mediate progressive renal injury including cell proliferation, mesangial matrix synthesis and degradation, generation of reactive oxygen species, and the expression of profibrotic proinflammatory cytokines, hormones, and vasoactive agents. In humans, the progression of CKD is arguably more rapid in men than in women, a finding which parallels observations in experimental animals. Translation of these observations into therapeutic interventions has not yet been realized, although selective estrogen receptor modulators, which lack the detrimental effects of estrogen on reproductive tissue, have shown renoprotective effects.