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Aldosterone (Aldo) can be a profibrotic factor in cardiovascular and renal tissues. This study tests the hypothesis that prolonged Aldo exposure is able to directly induce fibrotic changes in the kidney of a normal nonhypertensive animal. Immortalized rat proximal tubule cells (IRPTC) containing ll[beta]-hydroxysteroid dehydrogenase (11[beta]-HSD1) but no mineralocorticoid receptors (MR) and mouse inner medullary collecting duct cells (IMCD) containing ll[beta]-HSD2 and MR were examined. IRPTC exposed to Aldo or corticosterone (10 nM) for 48 h demonstrated no change in collagen production as assessed by Sirius red staining. In contrast, IMCD treated with Aldo exhibited a marked increase in the expression of collagen, fibronectin, and connective tissue growth factor (CTGF), whereas corticosterone alone had no effect. The Aldo-induced overexperession of collagen, fibronectin, and CTGF was substantially attenuated by the MR antagonist RU-318 and by the 11[beta]-HSD end product 11-dehydrocorticosterone, but not by the glucocorticoid receptor antagonist RU-486. In vivo, early fibrotic changes with elevated collagen, fibronectin, and CTGF expression were observed in kidneys isolated from normotensive adrenalectomized mice receiving a continuous infusion of Aldo (8 [micro]g x [kg.sup.-1] x [day.sup.-1]) for l wk. These changes were not present in corticosterone-treated mice. Aldo-induced changes were attenuated in adrenally intact mice and in mice treated with RU-318 or 11-dehydrocorticosterone. Thus, extended Aldo exposure produces fibrotic changes in cells containing MR and in normal kidneys. MR antagonists and the end products of 11[beta]-HSD attenuate these fibrogenic effects. fibrosis; renal epithelia; kidney; mineralocorticoids; 11[beta]-hydroxysteroid dehydrogenase; glucocorticoids doi: 10.1152/ajprenal.00532.2009.

Abstract The Centers for Medicare & Medicaid Services' (CMS) end-stage renal disease (ESRD) Clinical Performance Measures (CPM) Project has collected data on all adolescent hemodialysis patients since 2000. Thus, by [...]

The kinetic properties of the enzyme 11beta-hydroxysteroid dehydrogenase as it exists in the urinary bladder of a toad were examined. Cell homogenates were prepared from isolated toad bladder epithelial cells and subjected to a high-performance liquid chromatography protocol and a short circuit current technique. The importance of 11beta-OHSD and its end products in the regulation of electrolyte transport responses was established.

Nephrotic syndrome is a condition that results from various diseases that injure the glomeruli, tiny coils of blood vessels in the kidneys. Characteristic features of nephrotic syndrome include spillage of protein into the urine, low levels of the blood protein albumin, and water retention (edema). For over 30 years, nephrotic syndrome has been treated with steroid drugs such as prednisone. About forty percent of the children who have this condition must take high doses of steroids for long periods of time to prevent illness relapse. Steroids can have some serious side effects, such as growth failure, cataracts, and high blood pressure. Little research has been done on the growth of children with nephrotic syndrome who are being treated with steroids. Because growth failure has been linked to steroids, another class of drugs has been recommended for treating children with nephrotic syndrome; these are the alkylating agents, such as cyclophosphamide and chlorambucil. The growth of twelve children was assessed before and after a period of treatment with cyclophosphamide or chlorambucil, supplemented by prednisone on alternate days. The combination of drugs constituted a break from continuous high-dose steroids, and it was expected that growth might improve during this time. The average age of the group was six years. Growth in height was about 4.3 centimeters (cm) per year before the combined drug regimen, and 8.7 cm per year after treatment. Thus, reduction of steroid use and substitution of alkylating agents improved growth significantly in children with nephrotic syndrome. The side effects of the short-term use of alkylating agents were minimal, but long-term adverse effects may be a concern. Children with nephrotic syndrome who show signs of reduced growth rate should be considered for this regimen. (Consumer Summary produced by Reliance Medical Information, Inc.)