{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:48:37Z","timestamp":1791820117424,"version":"4.3.4"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"abstract":"<jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Afferent vagus nerve stimulation (aVNS) suppressed maladaptive renal sympathetic nerve activity after ischemic injury by engaging kidney-associated vagal\u2013autonomic circuits identified by transsynaptic tracing.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Full renoprotection by aVNS required an intact spleen, revealing an integrated vagal\u2013renal\u2013splenic neuroimmune reflex<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>aVNS protected kidney function, whether delivered as preconditioning before injury or 72 hours after ischemia-reperfusion injury, defining a clinically therapeutic window.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>AKI is associated with maladaptive increases in renal sympathetic nerve activity (RSNA) and frequently progresses to CKD. Neuromodulatory strategies that suppress sympathetic outflow may provide therapeutic benefit. We tested whether afferent vagus nerve stimulation (aVNS) mitigates ischemic AKI by modulating RSNA through central autonomic circuits and splenic neuroimmune signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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 aVNS. Bilateral renal ischemia-reperfusion injury was used to assess therapeutic efficacy. Mechanistic studies included subdiaphragmatic vagotomy, renal denervation controls, splenectomy, ganglionic blockade, and c-Fos mapping.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Pseudorabies virus tracing identified polysynaptic pathways linking the kidney to nodose ganglia, dorsal root ganglia, and central autonomic nuclei, with controls supporting tracer specificity. aVNS produced frequency-dependent and sustained suppression of RSNA. In ischemia-reperfusion injury, aVNS attenuated RSNA surges, preserved GFR, reduced tubular injury markers including neutrophil gelatinase\u2013associated lipocalin and kidney injury molecule-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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>aVNS engages kidney-associated vagal\u2013autonomic pathways that suppress RSNA and require splenic signaling for full renoprotection after ischemic AKI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.0000001196","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T16:02:40Z","timestamp":1785945760000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["A Vagal\u2013Renal\u2013Splenic Reflex Suppresses Renal Sympathetic Nerve Activity and Preserves Kidney Function after Ischemic Injury"],"prefix":"10.1681","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6728-1930","authenticated-orcid":false,"given":"Mazher","family":"Mohammed","sequence":"first","affiliation":[{"name":"Milton and Carroll Petrie Department of Urology, Icahn School of Medicine at Mount Sinai, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9962-5371","authenticated-orcid":false,"given":"Ubong","family":"Ekperikpe","sequence":"additional","affiliation":[{"name":"Barbara T. Murphy Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3039-523X","authenticated-orcid":false,"given":"Sujit S.","family":"Nair","sequence":"additional","affiliation":[{"name":"Milton and Carroll Petrie Department of Urology, Icahn School of Medicine at Mount Sinai, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7290-0786","authenticated-orcid":false,"given":"Eric","family":"Lazartigues","sequence":"additional","affiliation":[{"name":"Cardiovascular Center of Excellence, Louisiana State University Health Science Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3146-4524","authenticated-orcid":false,"given":"Ashutosh K.","family":"Tewari","sequence":"additional","affiliation":[{"name":"Milton and Carroll Petrie Department of Urology, Icahn School of Medicine at Mount Sinai, New York, New York"},{"name":"Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0985-3213","authenticated-orcid":false,"given":"Babu J.","family":"Padanilam","sequence":"additional","affiliation":[{"name":"Milton and Carroll Petrie Department of Urology, Icahn School of Medicine at Mount Sinai, New York, New York"},{"name":"Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"issue":"4S","key":"B1-20261012","first-page":"S1","article-title":"Kidney Disease: Improving Global Outcomes Diabetes Work Group. 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