Aldosterone Escape vs Aldosterone Breakthrough

I recently came across the concept of aldosterone breakthrough in my readings and confused it with aldosterone escape, so I though it would be a good topic to clear up really quickly.

Aldosterone Escape

This concept explains why we don’t ever see edema in our primary hyperaldosteronism patients. Remember aldosterone typically causes an initial decrease in urinary sodium excretion (by way of increased ENaC and Na/K ATPase), which leads to renal sodium retention (which should cause edema). However, urinary sodium excretion subsequently increases to balance sodium intake before detectable edema develops. There are several mechanisms responsible, but I’ll only talk about two. First we get volume expansion from the sodium retention and get a decrease in proximal tubule reabsorption of sodium leading to increased sodium delivery to distal tubule. So much so, that we overwhelm the aldosterone-mediated reabsorption of distal tubule. Also, volume expansion increases levels of plasma natriuretic hormone and therefore its inhibitory effect on sodium reabsorption in the collecting duct. Of course these mechanisms can occur only in the setting of increased renal perfusion pressure, which differs from what we see in cardiac or liver failure where there is an activation of RAAS but decreased renal perfusion pressure. Thus preventing aldosterone escape due to increased proximal sodium reabsorption.

 

Aldosterone Breakthrough

This phenomenon is seen during RAAS blockade with ACE inhibitors and ARBs. ACE- inhibitors and ARBs block Ang II-dependent aldosterone production in patients. But there some patients that have an initial decrease in plama aldosterone followed later by a rise in aldosterone to greater than pre-treatment levels. This is thought to be due to increased renin, but the exact mechanism is not yet known. These patient (with CKD and aldo breakthrough) have a faster loss of GFR and worse prognosis, therefore treatment with low doses of a mineralocorticoid receptor agonist or direct renin inhibitor are though to offer some benefit.

-Adrian

Ref:
Nature Reviews Nephrology 6, 61 (February 2010) |
Schrier, R. W. Renal and Electrolyte Disorders 7th edn 45–85 [Lippincott Williams & Wilkins, Philadelphia, 2010]

 



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