Renal Protective Effects of the Renin-Angiotensin-Aldosterone System Blockade: From Evidence-Based Approach to Perspectives

Abstract

The renin-angiotensin-aldosterone system (RAAS) blockade is currently the best-documented treatment strategy to delay the progression of chronic nephropathies. Angiotensin-converting enzyme inhibitors (CEIs) or angiotensin II type 1 receptor antagonists (ARBs) should be used in every normotensive and hypertensive patient with chronic proteinuric nephropathy of both diabetic and non-diabetic origin. The therapy should be initiated as early as possible, bearing in mind that the renoprotection is more effective if used before overt proteinuria or a reduction in kidney function is present. The therapy should be offered to all patients, regardless of renal function, as well as to subjects with severely impaired glomerular filtration. CEIs and ARBs should be administered in therapeutic doses as high as possible to achieve maximal possible proteinuria reduction and systemic blood pressure target <130/80 mm Hg, and 125/75 mm Hg in those subjects with renal insufficiency who present with proteinuria above 1 g/24 h. The combined therapy with the concomitant use of CEIs and ARBs should be offered to all patients with proteinuric non-diabetic chronic nephropathies who do not achieve full and persistent remission of proteinuria with CEI or ARB alone. The article reviews an evidence-based approach on the use of RAAS-inhibiting agents in kidney diseases, considers treatment strategies in different clinical situations and discusses some perspectives related to the implementation of the RAAS blockade in renal protection.

Renin-Angiotensin System Blockade Is Renoprotective in Immune Complex–Mediated Glomerulonephritis

“…2,3 Most experimental studies of RAS blockade have used chronic nephropathy models resulting from diabetes, 4,5 hypertension, 6,7 nephrotoxicity, 8 reduction of renal…”

“…2,3 Most experimental studies of RAS blockade have used chronic nephropathy models resulting from diabetes, 4,5 hypertension, 6,7 nephrotoxicity, 8 reduction of renal mass, 6,9 or chronic renal injury subsequent to acute mesangiolysis induced in rats by anti-Thy-1 antibody 10,11 or subsequent to establishment of an immune complex-induced glomerulonephritis. 12,13 Similarly, the efficacy of RAS blockade in human kidney diseases has been best demonstrated in patients with diabetic nephropathy, 14,15 hypertension, 16,17 or chronic kidney disease (CKD) arising from multiple causes.…”

EJE Prize 2013: Regulation of aldosterone secretion: from physiology to disease

“…Chronic RAAS activation leads to persistent hypertension, setting off a cascade of inflammatory, thrombotic, and atherogenic effects eventually leading to end-organ damage (4,5). Accordingly, numerous studies have demonstrated that elevated aldosterone levels are predictors of adverse outcome in hypertension (6), heart failure (7,8), myocardial infarction (9), and renal insufficiency (10). Primary aldosteronism (PA) is the most common secondary form of hypertension with an estimated prevalence of around 4% in hypertensive patients in primary care and around 10% in those referred to specialized centers (11).…”

The Effect of N-Acetylcysteine on Proteinuria and Markers of Tubular Injury in Non-Diabetic Patients with Chronic Kidney Disease

“…Pharmacological inhibition of the renin-angiotensinaldosterone system constitutes a cornerstone strategy in the management of patients with chronic nephropathies with proteinuria and with chronic renal failure [1] . Angiotensin-converting enzyme inhibitors (ACEI) as well as angiotensin II subtype 1 receptor antagonists (ARB) have been shown to decrease proteinuria, reduce the local renal inflammatory processes and slow the progression of renal insufficiency [2][3][4][5][6] .…”