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.
Key Points
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Direct renin inhibitors (DRIs) competitively bind to renin to prevent interaction between renin and angiotensinogen
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Renin-catalyzed conversion of angiotensinogen to angiotensin I is the rate-limiting step in the event cascade that activates the renin–angiotensin system (RAS)
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The DRI aliskiren is safe and as effective in reducing blood pressure as agents such as angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers
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Preliminary evidence indicates that DRIs improve renovascular function to a greater extent than other RAS blockade agents
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Although prorenin is an ostensibly inactive precursor of renin, growing evidence suggests that this protein might be involved in precipitating pathological processes in patients with diabetic nephropathy
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The potential renoprotective effects of DRIs might be explained by their targeting of renin, the effect they might have on prorenin and by the lack of treatment-associated increase in plasma renin activity
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Hollenberg, N. Direct renin inhibition and the kidney. Nat Rev Nephrol 6, 49–55 (2010). https://doi.org/10.1038/nrneph.2009.201
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DOI: https://doi.org/10.1038/nrneph.2009.201
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