Abstract
Hypertension (HTN) is an important factor in progressive loss of renal function. The kidney can be both a contributor to and a target of HTN. The functional integrity of the kidney is vital for the maintenance of cardiovascular homeostasis. Chronic activation of the renin system causes HTN and, ultimately, end-organ damage. Direct renin inhibitors (DRIs) inhibit plasma renin activity (PRA), thereby preventing the conversion of angiotensinogen to angiotensin I; consequently, the levels of both Ang I and Ang II are reduced. There is no compensatory increase in PRA activity with DRIs as seen with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). There are reasons to speculate that renin inhibition might prove to be a superior strategy for blocking the renin-angiotensin-aldosterone system compared with ACEIs or ARBs. Evidence for the efficacy of aliskiren (a DRI) is considered to be relatively strong, based on published, short-term, double-blind, randomized, controlled trials showing that aliskiren is as effective as other antihypertensive agents in reducing blood pressure (BP), with no rebound effects on BP after treatment withdrawal. When combined with diuretics, fully additive BP reduction is seen. When given with an ACEI or ARB, aliskiren produces significant additional BP reduction indicative of complimentary pharmacology and more complete renin-angiotensin system blockade.