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Renin-angiotensin-aldosterone system blockade in diabetes: role of direct renin inhibitors.
Postgrad Med. 2009 May; 121(3):33-44.PM

Abstract

Cardiovascular (CV) and renal complications associated with diabetes can be attenuated with antihypertensives that work on the renin-angiotensin-aldosterone system (RAAS),particularly angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and possibly direct renin inhibitors (DRIs). Cardioprotective and renoprotective benefits are independent of the blood pressure-lowering effect of the RAAS inhibitor. Given more complete RAAS blockade, evidence has suggested that the use of ACE inhibitor/ARB combination therapy may provide greater target organ protection. However, recent data have challenged this assumption. Although advances have been made in reducing diabetic nephropathy progression through use of ACE inhibitors and ARBs, improvement in organ protection is needed because diabetes remains the leading cause of end-stage renal disease. Despite the use of these agents in patients with CV disease and diabetes, CV adverse events remain high, suggesting the need for improved outcomes. Newer agents such as DRIs may have the potential to offer similar target organ protection. The first DRI, aliskiren, administered alone or in combination with other RAAS inhibitors, has been shown to confer renoprotective and cardioprotective benefits in human and animal studies that have measured surrogate endpoints. An ongoing outcomes study (Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints [ALTITUDE]), which is assessing renal and CV morbidity and mortality, will further define whether aliskiren provides additional benefits beyond RAAS inhibition and lowering of blood pressure.

Authors+Show Affiliations

School of Medicine, University of Colorado-Denver, CO, 80203, USA. ray.estacio@cpcmed.org

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

19491538

Citation

Estacio, Raymond O.. "Renin-angiotensin-aldosterone System Blockade in Diabetes: Role of Direct Renin Inhibitors." Postgraduate Medicine, vol. 121, no. 3, 2009, pp. 33-44.
Estacio RO. Renin-angiotensin-aldosterone system blockade in diabetes: role of direct renin inhibitors. Postgrad Med. 2009;121(3):33-44.
Estacio, R. O. (2009). Renin-angiotensin-aldosterone system blockade in diabetes: role of direct renin inhibitors. Postgraduate Medicine, 121(3), 33-44. https://doi.org/10.3810/pgm.2009.05.2000
Estacio RO. Renin-angiotensin-aldosterone System Blockade in Diabetes: Role of Direct Renin Inhibitors. Postgrad Med. 2009;121(3):33-44. PubMed PMID: 19491538.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Renin-angiotensin-aldosterone system blockade in diabetes: role of direct renin inhibitors. A1 - Estacio,Raymond O, PY - 2009/6/4/entrez PY - 2009/6/6/pubmed PY - 2009/6/24/medline SP - 33 EP - 44 JF - Postgraduate medicine JO - Postgrad Med VL - 121 IS - 3 N2 - Cardiovascular (CV) and renal complications associated with diabetes can be attenuated with antihypertensives that work on the renin-angiotensin-aldosterone system (RAAS),particularly angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and possibly direct renin inhibitors (DRIs). Cardioprotective and renoprotective benefits are independent of the blood pressure-lowering effect of the RAAS inhibitor. Given more complete RAAS blockade, evidence has suggested that the use of ACE inhibitor/ARB combination therapy may provide greater target organ protection. However, recent data have challenged this assumption. Although advances have been made in reducing diabetic nephropathy progression through use of ACE inhibitors and ARBs, improvement in organ protection is needed because diabetes remains the leading cause of end-stage renal disease. Despite the use of these agents in patients with CV disease and diabetes, CV adverse events remain high, suggesting the need for improved outcomes. Newer agents such as DRIs may have the potential to offer similar target organ protection. The first DRI, aliskiren, administered alone or in combination with other RAAS inhibitors, has been shown to confer renoprotective and cardioprotective benefits in human and animal studies that have measured surrogate endpoints. An ongoing outcomes study (Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints [ALTITUDE]), which is assessing renal and CV morbidity and mortality, will further define whether aliskiren provides additional benefits beyond RAAS inhibition and lowering of blood pressure. SN - 1941-9260 UR - https://www.unboundmedicine.com/medline/citation/19491538/Renin_angiotensin_aldosterone_system_blockade_in_diabetes:_role_of_direct_renin_inhibitors_ L2 - https://www.tandfonline.com/doi/full/10.3810/pgm.2009.05.2000 DB - PRIME DP - Unbound Medicine ER -