A Vagal-Renal-Splenic Reflex Suppresses Renal Sympathetic Nerve Activity and Preserves Kidney Function After Ischemic Injury.

Authors

Mazher Mohammed, Ubong Ekperikpe, Sujit S Nair, Eric Lazartigues, Ashutosh K Tewari, Babu J Padanilam

Published in

Journal of the American Society of Nephrology : JASN. Aug 05, 2026. Epub Aug 05, 2026.

Abstract

Acute kidney injury (AKI) is associated with maladaptive increases in renal sympathetic nerve activity (RSNA) and frequently progresses to chronic kidney disease. Neuromodulatory strategies that suppress sympathetic outflow may provide therapeutic benefit. We tested whether afferent vagus nerve stimulation mitigates ischemic AKI by modulating renal sympathetic nerve activity through central autonomic circuits and splenic neuroimmune signaling.
Retrograde transsynaptic pseudorabies virus tracing was used to identify neural pathways linking the kidney to vagal sensory circuits in C57BL/6J mice. RSNA, arterial pressure, and heart rate were recorded during intermittent afferent vagus nerve stimulation. Bilateral renal ischemia-reperfusion injury (IRI) was used to assess therapeutic efficacy. Mechanistic studies included subdiaphragmatic vagotomy, renal denervation controls, splenectomy, ganglionic blockade and c-Fos mapping.
Pseudorabies virus tracing identified polysynaptic pathways linking the kidney to nodose ganglia, dorsal root ganglia, and central autonomic nuclei, with controls supporting tracer specificity. Afferent vagus nerve stimulation (aVNS) produced frequency-dependent and sustained suppression of RSNA. In IRI, aVNS attenuated RSNA surges, preserved GFR, reduced tubular injury markers including NGAL and KIM-1, and limited fibrosis. Protection was observed with both preconditioning and delayed treatment, including stimulation initiated up to 72 hours after injury. Ganglionic blockade abolished acute aVNS responses. Splenectomy eliminated the full RSNA-lowering and renoprotective effects of aVNS, while aVNS reduced systemic norepinephrine and altered splenic signaling.
Afferent vagus nerve stimulation engages kidney-associated vagal-autonomic pathways that suppress renal sympathetic nerve activity and require splenic signaling for full renoprotection after ischemic AKI.

PMID:
42555213
Bibliographic data and abstract were imported from PubMed on 06 Aug 2026.

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