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In this issue, Feng and colleagues report that site-1 protease (S1P)-dependent cleavage of the (pro)renin receptor (PRR\/ATP6AP2) generates soluble PRR (sPRR), which functions as an inflammation amplifier in ischemic AKI. Remarkably, S1P inhibition pharmacologically or genetically suppresses sPRR production and attenuates macrophage infiltration and activation, blunting AKI. The work elevates sPRR from a putative biomarker to a mechanistically active mediator of AKI. It also couples innate immune programming to local renin\u2013angiotensin system engagement, suggesting an immuno-endocrine cross-talk and modulation in the kidney.<\/jats:p>","DOI":"10.1042\/cs20260223","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T09:22:32Z","timestamp":1773825752000},"page":"533-536","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["S1P\u2013sPRR axis in renal ischemia\u2013reperfusion injury: inflammation via a cut"],"prefix":"10.1042","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0555-4843","authenticated-orcid":false,"given":"Ying","family":"Fu","sequence":"first","affiliation":[{"name":"1Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3538-8095","authenticated-orcid":false,"given":"Zheng","family":"Dong","sequence":"additional","affiliation":[{"name":"1Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, China"},{"name":"2Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA, U.S.A."},{"name":"3Department of Research, Charlie Norwood VA Medical Center, Augusta, GA, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"2026031805222066100_B1","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/S0140-6736(24)02385-7","article-title":"Acute kidney injury","volume":"405","author":"Ostermann","year":"2025","journal-title":"Lancet"},{"key":"2026031805222066100_B2","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/s41581-025-01030-4","article-title":"The global epidemiology of acute kidney injury: challenges and opportunities","volume":"22","author":"Cerda","year":"2026","journal-title":"Nat. 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