Role of the Intrarenal Renin-Angiotensin-Aldosterone System in Chronic Kidney Disease
- 18 May 2010
- journal article
- review article
- Published by S. Karger AG in American Journal of Nephrology
- Vol. 31 (6), 541-550
- https://doi.org/10.1159/000313363
Abstract
The existence of local or tissue-based renin-angiotensin-aldosterone systems (RAAS) is well documented and has been implicated as a key player in the pathogenesis of cardiovascular and renal diseases. The kidney contains all elements of the RAAS, and intrarenal formation of angiotensin II not only controls glomerular hemodynamics and tubule sodium transport, but also activates a number of inflammatory and fibrotic pathways. Experimental and clinical studies have shown that the intrarenal RAAS is activated early in diabetic nephropathy, the leading cause of chronic kidney disease (CKD). Although angiotensin-converting enzyme inhibitors and angiotensin receptor blockers decrease the rate of decline in kidney function in patients with diabetic and non-diabetic nephropathy, many patients still progress to end-stage renal disease or die from cardiovascular events. There is still a clear need for additional strategies to block the RAAS more effectively to reduce progression of CKD. The focus of this paper is to review the importance of the intrarenal RAAS in CKD and recent findings in renin-angiotensin biology pertinent to the kidney. We also discuss additional strategies to inhibit the RAAS more effectively and the potential impact of direct renin inhibition on the prevention and management of CKD.Keywords
This publication has 60 references indexed in Scilit:
- New insights into the renoprotective actions of the renin inhibitor aliskiren in experimental renal diseaseHypertension Research, 2010
- Aliskiren/valsartan combination for the treatment of cardiovascular and renal diseasesExpert Review of Cardiovascular Therapy, 2010
- Increased Urinary Angiotensinogen Is Precedent to Increased Urinary Albumin in Patients With Type 1 DiabetesThe American Journal of the Medical Sciences, 2009
- Aliskiren Combined with Losartan in Type 2 Diabetes and NephropathyNew England Journal of Medicine, 2008
- Slowly Progressive, Angiotensin II–Independent Glomerulosclerosis in Human (Pro)renin Receptor–Transgenic RatsJournal of the American Society of Nephrology, 2007
- A Novel Signal Transduction Cascade Involving Direct Physical Interaction of the Renin/Prorenin Receptor With the Transcription Factor Promyelocytic Zinc Finger ProteinCirculation Research, 2006
- Renin-Angiotensin-Aldosterone System and Progression of Renal DiseaseJournal of the American Society of Nephrology, 2006
- Glomerular Localization and Expression of Angiotensin-Converting Enzyme 2 and Angiotensin-Converting EnzymeJournal of the American Society of Nephrology, 2006
- Renin increases mesangial cell transforming growth factor-β1 and matrix proteins through receptor-mediated, angiotensin II-independent mechanismsKidney International, 2006
- Local Renal Aldosterone System and Its Regulation by Salt, Diabetes, and Angiotensin II Type 1 ReceptorHypertension, 2005