Role of aldosterone in the progression of chronic kidney disease and potential use of aldosterone blockade in children.
Much focus has been placed on the role of the renin-angiotensin system as a mediator of the progression of chronic kidney disease. Novel therapeutic strategies to inhibit the negative impact of renin-angiotensin activation, including dual therapy with an angiotensin-converting enzyme inhibitor and an angiotensin-receptor blocker, have been suggested to achieve more complete disruption of the renin-angiotensin system. The role played by aldosterone, a target of angiotensin II, in the progression of chronic kidney disease has become a subject of significant interest over the past decade. Experimental studies in animals have shown that persistently elevated aldosterone levels lead to pathohistological changes in the kidney, along with renal and cardiac fibrosis. Incomplete suppression of aldosterone may, therefore, contribute to the deleterious effects of the renin-angiotensin system in the setting of chronic kidney disease. Clinical trials in adults have shown a potential role for mineralocorticoid receptor blockers to delay further the development of end-stage renal disease by completing renin-angiotensin blockade. In adults, mineralocorticoid receptor blockade produces a significant anti-proteinuric effect and has minimal risk of causing hyperkalemia if the condition of the patients is closely monitored. Further studies will need to be conducted to determine whether mineralocorticoid receptor blockers are equally effective and safe for the treatment of chronic kidney disease in children.
Ku
Elaine
E
Division of Nephrology, Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
Campese
Vito M
VM
D000450:Aldosterone / Q000627:therapeutic use*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D002648:Child; D018450:Disease Progression; D004359:Drug Therapy, Combination; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy*; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013148:Spironolactone / Q000627:therapeutic use
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone