Involvement of glomerular renin−angiotensin system (RAS) activation in the development and progression of glomerular injury

Abstract

Recently, there has been a paradigm shift away from an emphasis on the role of the endocrine (circulating) renin−angiotensin system (RAS) in the regulation of the sodium and extracellular fluid balance, blood pressure, and the pathophysiology of hypertensive organ damage toward a focus on the role of tissue RAS found in many organs, including kidney. A tissue RAS implies that RAS components necessary for the production of angiotensin II (Ang II) reside within the tissue and its production is regulated within the tissue, independent of the circulating RAS. Locally produced Ang II plays a role in many physiological and pathophysiological processes such as hypertension, inflammation, oxidative stress, and tissue fibrosis. Both glomerular and tubular compartments of the kidney have the characteristics of a tissue RAS. The purpose of this article is to review the recent advances in tissue RAS research with a particular focus on the role of the glomerular RAS in the progression of renal disease.

Urinary Biomarkers for Screening for Renal Scarring in Children with Febrile Urinary Tract Infection: Pilot Study

“…Although the precise mechanism of action of RAS is currently unknown, we hypothesize that increased renal renin production caused by severe inflammation has an important role in scar formation because the renin content is reportedly increased depending on the severity of interstitial fibrosis in scarred kidneys. 26,27 As AGT is the only renin substrate in the renal RAS, 18 increased renin produces Ang I from AGT. Ang II converted from increased Ang I induces the expression of transforming growth factor-b1 and causes renal fibrosis through multiple mechanisms, including G1 cell cycle arrest, cellular hypertrophy, promotion of protein synthesis, inhibition of protease activity and increased extracellular matrix.…”

N-acetylcysteine alleviates angiotensin II-mediated renal fibrosis in mouse obstructed kidneys

“…Overactivation of RAS stimulates the proliferation of renal mesangial cells and interstitial fibroblasts, increases the synthesis and secretion of inflammatory factors by renal inherent cells, and promotes the morphological and functional remodeling of cells [6][7][8][9][10][11] . Because angiotensin II (Ang II) is the major effector in RAS, angiotensin-converting enzyme inhibitors (ACEI) and Ang II type I receptor blockers (ARB) are currently recommended as the first-line medications for the treatment of CKD.…”

Indoxyl sulfate induces renin release and apoptosis of kidney mesangial cells

“…It is evident that RAS plays a role in pathophysiology of hypertension and organ injury by regulating arterial pressure and sodium homeostasis. Recent studies have shown that aberrant activation of intrarenal RAS contributes to the development and progression of CKD and hypertension (Kagami, 2012;Wen et al, 2010). All components of RAS have been reported to be expressed in various cell types of kidney (Kobori et al, 2007).…”