Empagliflozin targets a renal neuro-epithelial-immune axis in heart failure

American Journal of Physiology-Cell Physiology 2026 Open access

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Authors: Jennifer Coelho, Livia C. Simonete, João Carlos Ribeiro-Silva, Erika F. Jesus, Andreia Boaro, Flavia L. Martins, Jose Wilson Correa do Nascimento, Larissa Ferreira dos Santos, Danúbia Silva dos Santos, Ednei L. Antonio, Raphael E. Szawka, Andrey J. Serra
+1 more Adriana C. C. Girardi
DOI: 10.1152/ajpcell.00209.2026
Cited by: 1
References: 56

Abstract

Our findings identify a renal neuro-epithelial-immune axis that may, at least in part, underlie empagliflozin-mediated renoprotection in heart failure. Empagliflozin selectively attenuated surrogate markers of renal sympathetic activity, lowering cortical and urinary norepinephrine without detectable changes in intrarenal renin-angiotensin system components. These changes were accompanied by a shift toward a reparative macrophage phenotype. In vitro, empagliflozin blocked norepinephrine-induced SGLT2 upregulation and IL-6 production, linking sympathetic signaling to tubular inflammation.

Fields of Study & Subjects

Renin-Angiotensin System Studies Diabetes Treatment and Management Heart Failure Treatment and Management

Publication details

Journal / source
American Journal of Physiology-Cell Physiology
Publisher
American Physiological Society
Volume
330
Issue
6
Pages
C1775–C1787
Publication date
12 May 2026
Language
EN