Raging hormones: gender and renal disease.

Gender affects the progression of renal disease. In a variety of animal models and in certain human renal diseases, females exhibit a more modest course of kidney disease. Estrogens and testosterone have been implicated in this gender disparity. Doublier and colleagues explore the direct effects of sex hormones on podocyte viability in the α-estrogen receptor knockout (αERKO) mouse. They report that testosterone induces, and estradiol inhibits, podocyte damage in this model.

Raloxifene, a selective estrogen receptor modulator, is renoprotective: a post-hoc analysis.

Estrogens have a protective effect on kidney fibrosis in several animal models. Here, we tested the effect of raloxifene, an estrogen receptor modulator, on the change in serum creatinine or estimated glomerular filtration rate (eGFR) and incident kidney-related adverse events. We performed a post-hoc analysis of the multiple outcomes of raloxifene evaluation trial, a double-masked, placebo-controlled randomized clinical trial encompassing 7705 post-menopausal women (aged 31-80 years) with osteoporosis. Participants were randomized to either of two doses of raloxifene, 60 or 120 mg/day, or placebo. Serum creatinine was measured at a central laboratory at baseline and annually. Adverse events were assessed every 6 months and uniformly categorized. Compared with those in the placebo group, participants on raloxifene had a slower yearly rate of increase in creatinine (significant at the low dose) and a significantly slower yearly rate of decrease in eGFR for both doses over 3 years of follow-up. Raloxifene was associated with significantly fewer kidney-related adverse events compared with placebo. Thus, treatment with raloxifene was safe and renoprotective. Clinical trials of raloxifene in post-menopausal women with kidney disease designed to look at kidney outcomes are needed to confirm these findings.

The role of gender in the progression of renal disease.

The rate of progression of certain renal diseases in animals is greater in men than in women. In various animal models of renal disease, investigators have concluded that the presence of testosterone explains the worse course in men compared with women, whereas in other diseases, estrogen seems to confer protection for women. The gender disparity in renal disease progression found in animals is seen in certain human renal diseases, including chronic renal disease, membranous nephropathy, immunoglobin A nephropathy, and polycystic kidney disease. In humans, the differences between the genders in renal disease progression cannot be fully explained by differences in blood pressure or serum cholesterol levels. The underlying mechanisms for this gender disparity are potentially related to differences between the sexes in glomerular structure, glomerular hemodynamics, diet, variations in the production and activity of local cytokines and hormones, and/or the direct effect of sex hormones on kidney cells. Further investigation into the contribution of gender to renal disease progression may aid us in developing strategies for slowing this pathological process.

Effect of gender on the progression of nondiabetic renal disease: a meta-analysis.

There is previously published evidence that male gender is associated with a more rapid rate of progression of nondiabetic chronic renal disease. However, some investigators have concluded that no such association exists. To help resolve this issue, a meta-analysis was performed using 68 studies that met defined criteria and contained a total of 11,345 patients to evaluate the effect of gender on the progression of nondiabetic chronic renal disease. The results indicate that men with chronic renal disease of various etiologies show a more rapid decline in renal function with time than do women.

Effects of sex on renal structure.

AIMS: There are few data examining differences in renal structure between the sexes. Elucidation of the mechanisms responsible for the observed effects of sex on the progression of chronic renal disease requires knowledge of the effects of sex on renal structure. RESULTS: Although we found that male kidneys weigh more than female kidneys, sex is not an independent determinant of kidney weight. The increased kidney weight seen in men is solely dependent on their greater body surface area. We found no difference in glomerular number between men and women. Although men had larger glomeruli than women, sex is not an independent determinant of glomerular volume. The occurrence of larger glomeruli in men is solely dependent on their greater body surface area. Similarly, the greater total glomerular volume seen in men as compared to women reflects increased kidney weight in men. Sex is not an independent determinant of total glomerular volume. CONCLUSIONS: These findings do not support the hypothesis that renal structural differences contribute to sex-related differences in the rate of progression of chronic renal disease.