Aldosterone Blockade in CKD: Emphasis on Pharmacology

• Published in: Advances in chronic kidney disease Vol. 22; no. 2; pp. 123 - 132
• Main Authors: Schwenk, Michael H, Hirsch, Jamie S, Bomback, Andrew S
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2015
• Subjects: Aldosterone - blood; Angiotensin Receptor Antagonists - pharmacokinetics; Angiotensin Receptor Antagonists - therapeutic use; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Biological Availability; Chronic kidney failure; Fibrosis - metabolism; Glomerular Filtration Rate - drug effects; Gynecomastia - etiology; Humans; Hyperkalemia; Hyperkalemia - etiology; Inflammation - metabolism; Kidney Failure, Chronic - blood; Kidney Failure, Chronic - drug therapy; Kidney Failure, Chronic - physiopathology; Mineralocorticoid receptor antagonists; Mineralocorticoid Receptor Antagonists - pharmacokinetics; Mineralocorticoid Receptor Antagonists - therapeutic use; Nephrology; Pharmacokinetics; Proteinuria; Renin-Angiotensin System - drug effects; Hyperkalemia; Chronic kidney failure; Pharmacokinetics; Mineralocorticoid receptor antagonists; Proteinuria
• ISSN: 1548-5595; 1548-5609
• DOI: 10.1053/j.ackd.2014.08.003

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.