Aldosterone Blockade in CKD: Emphasis on Pharmacology

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 expans...

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Published inAdvances 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
LanguageEnglish
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
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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.
AbstractList 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.
Author Schwenk, Michael H
Bomback, Andrew S
Hirsch, Jamie S
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  fullname: Bomback, Andrew S
BackLink https://www.ncbi.nlm.nih.gov/pubmed/25704349$$D View this record in MEDLINE/PubMed
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Keywords Hyperkalemia
Chronic kidney failure
Pharmacokinetics
Mineralocorticoid receptor antagonists
Proteinuria
Language English
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Snippet Besides its epithelial effect on sodium retention and potassium excretion in the distal tubule, aldosterone promotes inflammation and fibrosis in the heart,...
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SubjectTerms 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
Title Aldosterone Blockade in CKD: Emphasis on Pharmacology
URI https://www.clinicalkey.es/playcontent/1-s2.0-S1548559514001232
https://dx.doi.org/10.1053/j.ackd.2014.08.003
https://www.ncbi.nlm.nih.gov/pubmed/25704349
https://search.proquest.com/docview/1672093225
Volume 22
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