Aldosterone in clinical nephrology--old hormone, new questions

There has been a resurgence of interest in the use of aldosterone blockade with spironolactone and eplerenone in patients with hypertension and renal disease. This, combined with observations made in patients treated with angiotensinconverting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), has resulted in many questions regarding aldosterone, a hormone many of us previously thought we understood. It has long been known that the renin–angiotensin–aldosterone system (RAAS) has a pivotal role in regulating sodium, potassium and fluid balance. Accordingly, in this classical volume-related pathway (Figure 1), liver-derived angiotensinogen is cleaved by renin to angiotensin I, which ACE or kininase II then converts to the active principal angiotensin II. Angiotensin II then stimulates thirst, vasoconstriction and adrenal production of aldosterone that promote renal tubular sodium reabsorption and kaliuresis. We now know that this is a simplistic view of a much more complex system, with many redundancies in the pathways, and multiple non-volume-related effects demonstrated both experimentally and clinically, as outlined by Ritz and Tomaschitz [1]. In many respects, this has raised as many questions as it has answers.