Effects of sex hormones on fluid and solute transport in Madin-Darby canine kidney cells

Effects of sex hormones on fluid and solute transport in Madin-Darby canine kidney cells. Polycystic kidney disease progresses more rapidly in men than in women. To investigate the basis for this sexual dimorphism, we exposed Madin-Darby canine kidney (MDCK) cells grown on collagen-coated cell culture inserts to control media, or to estradiol or testosterone (1 nM-1 µM). Compared to control and estradiol-treated cells, testosterone stimulated fluid secretion in a dose-dependent manner, enhancing fluid secretion 4.8-fold at 1nM and 19.7-fold at 1 µM (0.59 ± 0.18 vs. 0.03 ± 0.01 µ1/cm2/hr, P < 0.001). Chloride transport paralleled fluid secretion. Testosterone increased cellular cyclic AMP levels 3.2-fold at 1 µM and 12.3-fold at 1 µM (81.3 ± 30.7 vs. 6.6 ± 3.3 pmol/mg protein, P < 0.001). GDPβS (500 µM), an inhibitor of Gs, and 2′,3′-dideoxyadenosine (10 µM), an inhibitor of the catalytic subunit of adenylate cyclase, suppressed testosterone-induced fluid and solute secretion. Neither testosterone nor estradiol had any effect on microsomal Na,K-ATPase activity, cellular proliferation or cellular total protein content. Our studies show that testosterone stimulates fluid secretion and solute transport by MDCK cells by increasing cAMP generation. In vivo, testosterone may contribute to cyst expansion by enhancing fluid secretion. This observation may help explain the worse prognosis of polycystic kidney disease observed in men

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