Urinary angiotensin-converting enzyme 2 increases in diabetic nephropathy by angiotensin II type 1 receptor blocker olmesartan

Abstract

Introduction: Angiotensin-converting enzyme 2 (ACE2) is a member of the renin–angiotensin system that degrades angiotensin (Ang) II to the seven-amino acid peptide fragment Ang-(1-7). We evaluated the changes in urinary ACE2 levels in response to treatment with the angiotensin II type 1 receptor blocker olmesartan in diabetes patients with nephropathy. Materials and methods: This prospective, open-label, interventional study was conducted with 31 type 2 diabetes patients with nephropathy. After initial evaluation, patients received 20 mg/day olmesartan, which was increased to 40 mg/day over a 24-week period. Results: In diabetes patients with chronic kidney disease, olmesartan significantly increased urinary ACE2 levels independently of blood pressure and plasma aldosterone levels and reduced albuminuria, urinary liver-type fatty acid binding protein (L-FABP), and plasma aldosterone levels. Multivariable regression analysis revealed that the change in urinary L-FABP levels was an independent predictor of increased urinary ACE2 levels. Conclusion: Olmesartan may have the unique effect of increasing urinary ACE2 levels. However, whether this contributes to olmesartan’s renoprotective effect must be examined further.

Urinary ACE2 is associated with urinary L-FABP and albuminuria in patients with chronic kidney disease

“…Increased urinary L-FAbP levels may occur in response to oxidative stress induced by hypoxia, which is a pathogenetic factor underlying diabetic complications such as nephropathy [31][32][33][34]. Urinary L-FAbP is an important marker of tubulointerstitial changes in diabetic nephropathy, while oxidative stress is a pathogenetic factor underlying diabetic complications such as nephropathy [32][33][34][35]. Therefore, the present data suggest that ACE2 is an endogenous protector against the progression of tubulointerstitial damage since multivariate regression analysis showed that urinary L-FAbP is an independent variable significantly associated with urinary ACE2 levels.…”

Current Metabolic Status Affects Urinary Liver-Type Fatty-Acid Binding Protein in Normoalbuminuric Patients With Type 2 Diabetes

“…The authors also reported that the administration of telmisartan, an angiotensin II receptor antagonist (ARB), led to a reduction of the urinary L-FABP level in the patients with diabetic nephropathy [ 35 , 36 ]. It was also demonstrated that the administration of olmesartan [ 37 ], another ARB, lisinopri [ 38 ], an angiotensin-converting enzyme inhibitor, and azelnidipine [ 39 ], a calcium channel blocker, reduced the level of urinary L-FABP in patients with type 2 diabetes. Thus, although the changes in systolic blood pressure were not found to be associated with the changes in urinary L-FABP in the present study, the reduction in urinary L-FABP may be caused by the control of hypertension.…”

Disequilibrium between the classic renin-angiotensin system and its opposing arm in SARS-CoV-2-related lung injury

“…DISEQUILIBRIUM OF RAS IN SARS-CoV-2-RELATED LUNG INJURY ACE, abundant in lung tissue, consisting of an extracellular NH 2 -terminal domain containing a catalytic site and intracellular COOH-terminal tail. ACE2 has many peptides as substrates, but mainly cleaves Ang I into a nonapeptide [Ang (1)(2)(3)(4)(5)(6)(7)(8)(9)] that binds AT 2 R and Ang II into a heptapeptide [Ang(1-7)] that binds an endogenous orphan receptor (Mas receptor, MasR) ( Fig. 2A, top) (73).…”