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Application of direct renin inhibition to chronic kidney disease

Christian W Mende1

  • 1Department of Medicine, University of California at San Diego, 6950 Fairway Road, La Jolla, CA 92037, USA. cmende4730@aol.com

Cardiovascular Drugs and Therapy
|May 22, 2010
PubMed

Insights

Renin-angiotensin-aldosterone system (RAAS) inhibitors like ACE inhibitors and ARBs are key for chronic kidney disease (CKD). However, complete RAAS suppression is not achieved, and novel direct renin inhibitors like aliskiren show promise for improved CKD management.

Area of Science:

  • Nephrology
  • Cardiovascular Medicine
  • Pharmacology

Background:

  • Chronic kidney disease (CKD) presents significant risks for renal function decline, cardiovascular events, and financial burden.
  • The renin-angiotensin-aldosterone system (RAAS) is often overactive in CKD, particularly in diabetic and hypertensive patients, the primary drivers of the disease.
  • Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are standard therapies shown to slow nephropathy progression.

Purpose of the Study:

  • To review key clinical trials on ACE inhibitors and ARBs in CKD management.
  • To discuss advancements in RAAS biology and the role of direct renin inhibition for CKD prevention and treatment.

Main Methods:

  • Discussion of pivotal clinical trials evaluating ACE inhibitors and ARBs in chronic kidney disease.
  • Review of recent findings in RAAS biology and direct renin inhibition strategies.
  • Analysis of the potential impact of these interventions on CKD outcomes.

Main Results:

  • Despite current therapies, high rates of mortality and progression to renal failure persist in CKD patients.
  • Standard doses of ACE inhibitors or ARBs do not fully suppress the RAAS.
  • Aliskiren, a direct renin inhibitor, presents a new therapeutic avenue for RAAS inhibition in CKD.

Conclusions:

  • High-dose ARBs or combination therapy with ACE inhibitors and ARBs improve surrogate markers in CKD.
  • Preliminary data suggest aliskiren, alone or with ARBs, may play a novel role in managing CKD, based on urinary protein excretion rates.
Abstract

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