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.

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.

The effects of hormone replacement therapy on renal function.

This Practice Point commentary discusses a study by Ahmed et al. that evaluated the effects of hormone replacement therapy (conjugated estrogen alone, progestin alone or a combination of progestin and conjugated estrogen) on renal function in elderly community-dwelling postmenopausal women. The authors found that oral estrogen therapy in this population was associated with accelerated decline in kidney function over a 2-year period.

Gender and human chronic renal disease.

Background: Gender affects the incidence, prevalence, and progression of renal disease. In animal models of the disease, female sex appears to modify the course of progression. Hormonal manipulation by male or female castration also changes the course of renal disease progression, suggesting direct effects of sex hormones in influencing the course of these maladies.

Estradiol reverses renal injury in Alb/TGF-beta1 transgenic mice.

Background: Men with chronic renal disease progress more rapidly to renal failure than do women. Tranforming growth factor-beta (TGF-beta) plays a central role in promoting progressive renal injury, in part due to transcriptional effects mediated by cooperation between Smad proteins and the transcription factor Sp1. Estrogen negatively regulates Sp1 activity and reverses the stimulatory effects of TGF-beta on type IV collagen synthesis and cellular apoptosis in cultured mesangial cells.

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.

Estradiol reverses TGF-beta1-induced mesangial cell apoptosis by a casein kinase 2-dependent mechanism.

Background: The slower rate of progression of chronic renal disease in women than in men is explained in part by the ability of estradiol to reverse the stimulatory effect of transforming growth factor-beta1 (TGF-beta1) on collagen IV synthesis at the level of casein kinase 2 activation. Casein kinase 2 also phosphorylates and activates the pro-apoptotic protein, p53. We hypothesized that estradiol would reverse TGF-beta1-induced mesangial cell apoptosis by antagonizing the stimulatory effects of TGF-beta1 on casein kinase 2 activity, thereby preventing p53 activation.

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.

Estradiol upregulates mesangial cell MMP-2 activity via the transcription factor AP-2.

The accumulation of extracellular matrix in the glomerular mesangium reflects the net balance between the synthesis and degradation of matrix components. We have shown that estradiol suppresses the synthesis of types I and IV collagen by cultured mesangial cells (Kwan G, Neugarten J, Sherman M, Ding Q, Fotadar U, Lei J, and Silbiger S. Kidney Int 50: 1173-1179, 1996; Neugarten J, Acharya A, Lei J, and Silbiger S.

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.