What is aldosterone escape?
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- The term aldosterone escape in primary hyperaldosteronism is escape from the salt and water retaining effects of aldosterone.
- In the treatment of heart failure with angiotensin converting enzyme inhibitors, it is the breakthrough occurrence of aldosterone effect.
Different types of aldosterone escape
The term ‘aldosterone escape’ has been used in two different settings:
- Aldosterone escape in primary hyperaldosteronism
- Aldosterone escape in the treatment of heart failure with angiotensin converting enzyme inhibitors
Aldosterone escape in primary hyperaldosteronism
Aldosterone escape in primary hyperaldosteronism is the escape from the salt and water retaining effect of excessive levels of aldosterone.1 This phenomenon is considered to be an important homeostatic mechanism and thought to be dependent on nitric oxide.2 Natriuresis produced by elevated levels of atrial natriuretic peptides is another proposed mechanism for escape from the salt retention in this situation.3 Pressure natriuresis is another proposed mechanism for aldosterone escape, with increased renal arterial pressure induced natriuresis.4 Aldosterone escape in the setting of primary hyperaldosteronism may have an important role in reducing the severity of hypertension in the condition. Aldosterone escape is the reason for edema not being a prominent manifestation of primary hyperaldosteronism.
This mechanism of aldosterone escape does not work in the aldosterone excess of edematous conditions like congestive heart failure and cirrhosis liver, possibly due to the renal hypoperfusion, which is not a feature of primary aldosteronism.
Aldosterone escape in the treatment of heart failure with angiotensin converting enzyme inhibitors
Aldosterone escape in chronic treatment of heart failure with angiotensin converting enzyme inhibitors is thought to be mediated by potassium dependent aldosterone secretion, which is unrelated to the renin-angiotensin-aldosterone system (RAAS). Potassium is one of the important stimuli for secretion of aldosterone from the zona glomerulosa of the adrenal cortex.5 This type of aldosterone escape in which plasma aldosterone levels return to pretreatment levels in over a third of patients treated with angiotensin converting enzyme inhibitors or angiotensin receptor blockers is better termed ‘aldosterone breakthrough’ according to some authors.6 This is one reason for the current practice of adding a mineralocorticoid antagonist to angiotensin converting enzyme inhibitor or angiotensin receptor blocker in the treatment of heart failure.
- Knox FG, Burnett JC Jr, Kohan DE, Spielman WS, Strand JC. Escape from the sodium-retaining effects of mineralocorticoids. Kidney Int. 1980 Mar;17(3):263-76.
- Turban S, Wang XY, Knepper MA. Regulation of NHE3, NKCC2, and NCC abundance in kidney during aldosterone escape phenomenon: role of NO. Am J Physiol Renal Physiol. 2003;285:F843-F851.
- Granger JP, Burnett JC, Jr, Romero JC, Opgenorth TJ, Salazar J, Joyce M. Elevated levels of atrial natriuretic peptide during aldosterone escape. Am J Physiol Regul Integr Comp Physiol. 1987;252:R878-R882.
- Hall JE, Granger JP, Smith MJ Jr, Premen AJ. Role of renal hemodynamics and arterial pressure in aldosterone “escape”. Hypertension. 1984 Mar-Apr;6(2 Pt 2):I183-92.
- Bravo EL. Regulation of aldosterone secretion: current concepts and newer aspects. Adv Nephrol Necker Hosp. 1977;7:105-20.
- Bomback AS, Klemmer PJ. The incidence and implications of aldosterone breakthrough. Nat Clin Pract Nephrol. 2007 Sep;3(9):486-92.