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Drug Discovery for Overcoming Chronic Kidney Disease (CKD): Pharmacological Effects of Mineralocorticoid-Receptor Blockers

Journal

JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 109, Issue 1, Pages 1-6

Publisher

JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1254/jphs.08R12FM

Keywords

aldosterone; mineralocorticoid receptor (MR); eplerenone; kidney; chronic kidney disease (CKD)

Funding

  1. Ministry of Education, Culture, Sports, Science, and Technology of Japan [20590253]
  2. Uehara Memorial Fundation, Japan Research Foundation
  3. Kagawa University Project Research

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There is increasing evidence demonstrating that the renoprotective effects of mineralocorticoid receptor (MR) blockade are independent of the effects exerted by reninangiotensin inhibitors. MR is expressed not only in tubular cells but also in other renal cells including glomerular mesangial cells, podocytes, and renal interstitial Fibroblasts. Animal experiments have shown that MR blockers prevent aldosterone-induced proteinuria, glomerular injury, and tubulointerstitial fibrosis. In vitro studies have also demonstrated that MR blockers inhibit aldosterone-induced renal cell damage. Recent clinical Studies have shown that treatment with MR blockers attenuates the development of proteinuria in patients with chronic kidney disease (CKD) and hypertension, independent of changes in blood pressure. In some cases, MR blockers elicit potent renoprotective effects in conditions where aldosterone levels are not elevated. These data suggest that treatment with MR blockers may possibly present ail effective therapeutic strategy for patients with CKD.

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