Drug discovery for overcoming chronic kidney disease (CKD): pharmacological effects of mineralocorticoid-receptor blockers.
There is increasing evidence demonstrating that the renoprotective effects of mineralocorticoid receptor (MR) blockade are independent of the effects exerted by renin-angiotensin 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 an effective therapeutic strategy for patients with CKD.
Nishiyama
Akira
A
Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan. akira@kms.ac.jp
Hitomi
Hirofumi
H
Rahman
Asadur
A
Kiyomoto
Hideyasu
H
D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D000451:Mineralocorticoid Receptor Antagonists; D008954:Models, Biological; D018161:Receptors, Mineralocorticoid / Q000502:physiology
D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid