Direct renin inhibition and the kidney

Abstract

Direct renin inhibition is a new means for blocking the renin-angiotensin system at the rate-limiting step of the cascade of events triggered by renin release--the interaction of renin with its physiological substrate angiotensinogen. The remarkable success of angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers in the management of cardiovascular and renal disease has led to great interest in the potential of direct renin inhibitors. This Review focuses on the evidence that suggests that direct renin inhibitors might block the renin-angiotensin system in the kidney more completely than either angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers. The therapeutic implications of this evidence are also reviewed, as well as the possible mechanistic routes by which direct renin inhibition might exert its influence on the kidney.

Aliskiren reduced renal fibrosis in mice with chronic ischemic kidney injury—beyond the direct renin inhibition

“…However, the effectiveness of these treatments is limited due to compensatory increases in plasma renin levels that lead to adjustments in angiotensin production and conversion. 16 A direct renin inhibitor, aliskiren, is now available to inhibit angiotensin production directly at its rate-limiting step. 17 The goal of the present study was to understand the effect of aliskiren-a direct renin inhibitor-on renal fibrosis and possible mechanisms other than RAAS activation.…”

Aliskiren affects fatty-acid uptake and lipid-related genes in rodent and human cardiomyocytes

“…Aliskiren is the first clinically effective anti-hypertensive agent to have been developed by molecular modelling and to work by direct renin inhibition (DRI) in the renin-angiotensinaldosterone system (RAAS) [1][2][3][4]. Approved by the US FDA in 2007, aliskiren produces sustained suppression of plasma renin activity when used in monotherapy in hypertensive patients [5,6], of cardiac angiotensin in spontaneously hypertensive rats [7], and of renal angiotensin in human renal podocytes [8].…”

Chronic blockade of the (pro)renin receptor ameliorates the kidney damage in the non-clipped kidney of Goldblatt hypertension

“…Surprisingly, the concentration of ATG is approximately 5000-fold higher than that of AngI. 3 This phenomenon indicates that a conversion of ATG to AngI seems to be the bottleneck in the process; in other words, this reaction is the rate-limiting step of the RAS cascade. Therefore, utilizing the concept of renin inhibition is a logical approach to the management of hypertension; the first direct renin inhibitor, aliskiren, has recently been marketed as a treatment for hypertension.…”

“…Therefore, utilizing the concept of renin inhibition is a logical approach to the management of hypertension; the first direct renin inhibitor, aliskiren, has recently been marketed as a treatment for hypertension. 3 Although more than 100 years have passed, since the discovery of renin, prorenin had long been believed to be an inactive precursor of renin in the RAS. Recently, the (pro)renin receptor, which binds to both renin and prorenin, was identified.…”