title: Aldosterone blockade in CKD: emphasis on pharmacology.
abstract: Besides its epithelial effect on sodium retention and potassium excretion in the distal tubule, aldosterone promotes inflammation and fibrosis in the heart, kidneys, and blood vessels. As glomerular filtration rate falls, aldosterone is inappropriately elevated relative to extracellular fluid expansion. In addition, studies in CKD patients on angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and/or direct renin inhibitors have shown that aldosterone levels paradoxically rise in approximately 30% to 40% of patients on these renin-angiotensin system-blocking drugs. Hence, there is interest in using mineralocorticoid receptor blockers that directly target the inflammatory and fibrotic effects of aldosterone in CKD patients. This interest, however, is tempered by a number of unresolved issues, including the safety of using such drugs in advanced CKD and ESRD populations, and the potential for differences in drug efficacy according to race and ethnicity of patient populations. A better understanding of mineralocorticoid receptor blocker pharmacology should help inform future research directions and clinical practice decisions as to how best to use these agents in CKD.
authors.affiliation: Clinical Trials Office, Research Pharmacy, Columbia University Medical Center, New York, NY; and Division of Nephrology, Department of Medicine, Columbia University Medical Center, New York, NY.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Schwenk
authors.affiliation: Clinical Trials Office, Research Pharmacy, Columbia University Medical Center, New York, NY; and Division of Nephrology, Department of Medicine, Columbia University Medical Center, New York, NY.
authors.forename: Jamie S
authors.initials: JS
authors.lastname: Hirsch
authors.affiliation: Clinical Trials Office, Research Pharmacy, Columbia University Medical Center, New York, NY; and Division of Nephrology, Department of Medicine, Columbia University Medical Center, New York, NY. Electronic address: asb68@columbia.edu.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Bomback
mesh_terms: D000450:Aldosterone / Q000097:blood*; D057911:Angiotensin Receptor Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D001682:Biological Availability; D005355:Fibrosis / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006177:Gynecomastia / Q000209:etiology; D006801:Humans; D006947:Hyperkalemia / Q000209:etiology*; D007249:Inflammation / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D000451:Mineralocorticoid Receptor Antagonists / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012084:Renin-Angiotensin System / Q000187:drug effects*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D000450:Aldosterone
keywords: Chronic kidney failure; Hyperkalemia; Mineralocorticoid receptor antagonists; Pharmacokinetics; Proteinuria