Estradiol is nephroprotective in the rat remnant kidney

Background. Female sex hormones may influence the progression of renal diseases. We therefore evaluated the effects of estradiol on the development of glomerulosclerosis in a remnant kidney model. Methods. Ovariectomized or intact female Wistar rats underwent 5/6 nephrectomy. Ovariectomized animals were treated with vehicle, 17beta-estradiol alone or in combination with progesterone, intact rats received vehicle only. Twenty-four weeks after renal ablation, histological as well as molecular analysis were performed. Results. Vehicle-treated ovariectomized animals developed severe proteinuria and glomerulosclerosis as compared with vehicle-treated intact rats. In addition, renal mRNA levels of platelet-derived growth factor-A chain (PDGF-A) were increased. Estradiol replacement reduced proteinuria, which was paralleled by a diminished glomerular injury and reduced transforming growth factor-beta1 (TGF-beta1) and PDGF-A mRNA expression. In animals that received combined hormone treatment there were no significant differences in proteinuria, creatinine clearance, renal histopathology and growth factor mRNA levels compared with those measured in vehicle-treated ovariectomized rats. Serum cholesterol and triglyceride levels were comparable between all groups during the whole follow-up period. Conclusions. The data suggest that estrogens protect against the development of glomerulosclerosis in the rat remnant kidney model.