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

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 ex...

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Autores principales:	Clarice K. Fujihara, M. C. Kowala, M. D. Breyer, Claudia R. Sena, Mariliza V. Rodrigues, Simone C. A. Arias, Camilla Fanelli, Denise M. Malheiros, P. K. Jadhav, Chahrzad Montrose-Rafizadeh, Jose E. Krieger, Roberto Zatz
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/780f96a202214d06a07005c8f676b540
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spelling	oai:doaj.org-article:780f96a202214d06a07005c8f676b5402021-12-02T12:32:37ZA Novel Aldosterone Antagonist Limits Renal Injury in 5/6 Nephrectomy10.1038/s41598-017-08383-22045-2322https://doaj.org/article/780f96a202214d06a07005c8f676b5402017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08383-2https://doaj.org/toc/2045-2322Abstract 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.Clarice K. FujiharaM. C. KowalaM. D. BreyerClaudia R. SenaMariliza V. RodriguesSimone C. A. AriasCamilla FanelliDenise M. MalheirosP. K. JadhavChahrzad Montrose-RafizadehJose E. KriegerRoberto ZatzNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Clarice K. Fujihara M. C. Kowala M. D. Breyer Claudia R. Sena Mariliza V. Rodrigues Simone C. A. Arias Camilla Fanelli Denise M. Malheiros P. K. Jadhav Chahrzad Montrose-Rafizadeh Jose E. Krieger Roberto Zatz A Novel Aldosterone Antagonist Limits Renal Injury in 5/6 Nephrectomy
description	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.
format	article
author	Clarice K. Fujihara M. C. Kowala M. D. Breyer Claudia R. Sena Mariliza V. Rodrigues Simone C. A. Arias Camilla Fanelli Denise M. Malheiros P. K. Jadhav Chahrzad Montrose-Rafizadeh Jose E. Krieger Roberto Zatz
author_facet	Clarice K. Fujihara M. C. Kowala M. D. Breyer Claudia R. Sena Mariliza V. Rodrigues Simone C. A. Arias Camilla Fanelli Denise M. Malheiros P. K. Jadhav Chahrzad Montrose-Rafizadeh Jose E. Krieger Roberto Zatz
author_sort	Clarice K. Fujihara
title	A Novel Aldosterone Antagonist Limits Renal Injury in 5/6 Nephrectomy
title_short	A Novel Aldosterone Antagonist Limits Renal Injury in 5/6 Nephrectomy
title_full	A Novel Aldosterone Antagonist Limits Renal Injury in 5/6 Nephrectomy
title_fullStr	A Novel Aldosterone Antagonist Limits Renal Injury in 5/6 Nephrectomy
title_full_unstemmed	A Novel Aldosterone Antagonist Limits Renal Injury in 5/6 Nephrectomy
title_sort	novel aldosterone antagonist limits renal injury in 5/6 nephrectomy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/780f96a202214d06a07005c8f676b540
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A Novel Aldosterone Antagonist Limits Renal Injury in 5/6 Nephrectomy

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