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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

A Novel Aldosterone Antagonist Limits Renal Injury in 5/6 Nephrectomy

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Fujihara, Clarice K. ; Kowala, M. C. ; Breyer, M. D. ; Sena, Claudia R. ; Rodrigues, Mariliza V. ; Arias, Simone C. A. ; Fanelli, Camilla ; Malheiros, Denise M. ; Jadhav, P. K. ; Montrose-Rafizadeh, Chahrzad ; Krieger, Jose E. ; Zatz, Roberto
Total Authors: 12
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 7, AUG 11 2017.
Web of Science Citations: 3
Abstract

Aldosterone antagonists slow the progression of chronic kidney disease (CKD), but their use is limited by hyperkalemia, especially when associated with RAS inhibitors. We examined the renoprotective effects of Ly, a novel non-steroidal mineralocorticoid receptor (MR) blocker, through two experimental protocols: In Protocol 1, male Munich-Wistar rats underwent 5/6 renal ablation (Nx), being divided into: Nx+V, receiving vehicle, Nx+Eple, given eplerenone, 150 mg/kg/day, and Nx+Ly, given Ly, 20 mg/kg/day. A group of untreated sham-operated rats was also studied. Ly markedly raised plasma renin activity (PRA) and aldosterone, and exerted more effective anti-albuminuric and renoprotective action than eplerenone. In Protocol 2, Nx rats remained untreated until Day 60, when they were divided into: Nx+V receiving vehicle; Nx+L treated with losartan, 50 mg/kg/day; Nx+L+Eple, given losartan and eplerenone, and Nx+L+Ly, given losartan and Ly. Treatments lasted for 90 days. As an add-on to losartan, Ly normalized blood pressure and albuminuria, and prevented CKD progression more effectively than eplerenone. This effect was associated with strong stimulation of PRA and aldosterone. Despite exhibiting higher affinity for the MR than either eplerenone or spironolactone, Ly caused no hyperkalemia. Ly may become a novel asset in the effort to detain the progression of CKD. (AU)

FAPESP's process: 12/10926-5 - Pathogenesis and treatment of chronic kidney disease: role of innate immunity in glomerular, tubular and interstitial injury
Grantee:Roberto Zatz
Support Opportunities: Research Projects - Thematic Grants