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Bacteria typically synthetize long chains, while human platelets harbor exclusively medium chains. PolyP-mediated lung and liver-injury have been reported in experimental mouse models but their effects on the kidney remain undefined. Here, we assessed kidney histopathology and cytokine levels following intravenous administration of medium-chain (P100) and long-chain (P700) PolyPs and their synergistic effects with lipopolysaccharides (LPS) in mice. We found that P700 induced albuminuria, renal transcription of Kim-1 and Lcn2, focal renal damage with glomerular microthrombi, tubular degeneration, granular phenotype of slit diaphragm components nephrin and ZO1 (also known as TJP1), and enlarged electron-dense vesicles in podocyte cytoplasm indicating lysosome swelling. P700 combined with LPS induced marked multifocal acute tubular necrosis in the cortex and augmented LPS-induced pro-inflammatory cytokine levels. No notable effects were seen with P100, indicating that development of PolyP-mediated kidney injury is dependent on chain length. We conclude that P700 PolyPs may play a procoagulant role in kidney injury development, by inducing microthrombi characteristic of thrombotic microangiopathy and augmenting cytokine levels under inflammatory conditions.<\/jats:p>","DOI":"10.1242\/dmm.052361","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T11:22:40Z","timestamp":1770376960000},"source":"Crossref","is-referenced-by-count":0,"title":["Long-chain polyphosphates induce glomerular microthrombi and exacerbate LPS-induced acute kidney injury in mouse"],"prefix":"10.1242","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1567-6834","authenticated-orcid":false,"given":"Anniina","family":"Pirttiniemi","sequence":"first","affiliation":[{"name":"Folkh\u00e4lsan Institute of Genetics, Folkh\u00e4lsan Research Center 1 , 00290 Helsinki ,","place":["Finland"]},{"name":"University of Helsinki and Helsinki University Hospital 2 Department of Nephrology , , 00290 Helsinki 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,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6960-5505","authenticated-orcid":false,"given":"Krishna","family":"Adeshara","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Institute of Genetics, Folkh\u00e4lsan Research Center 1 , 00290 Helsinki ,","place":["Finland"]},{"name":"University of Helsinki and Helsinki University Hospital 2 Department of Nephrology , , 00290 Helsinki ,","place":["Finland"]},{"name":"University of Helsinki 3 Program for Clinical and Molecular Metabolism, Faculty of Medicine , , 00290 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jere","family":"Lind\u00e9n","sequence":"additional","affiliation":[{"name":"University of Helsinki 4 Department of Veterinary Biosciences , , 00014 Helsinki ,","place":["Finland"]},{"name":"HiLIFE, University of Helsinki 5 Finnish Centre for Laboratory Animal Pathology , , 00014 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4189-2415","authenticated-orcid":false,"given":"Sanna","family":"Lehtonen","sequence":"additional","affiliation":[{"name":"University of Helsinki 3 Program for Clinical and Molecular Metabolism, Faculty of Medicine , , 00290 Helsinki ,","place":["Finland"]},{"name":"University of Helsinki 6 Department of Pathology , , 00014 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4322-6942","authenticated-orcid":false,"given":"Niina","family":"Sandholm","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Institute of Genetics, Folkh\u00e4lsan Research Center 1 , 00290 Helsinki ,","place":["Finland"]},{"name":"University of Helsinki and Helsinki University Hospital 2 Department of Nephrology , , 00290 Helsinki ,","place":["Finland"]},{"name":"University of Helsinki 3 Program for Clinical and Molecular Metabolism, Faculty of Medicine , , 00290 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4055-6954","authenticated-orcid":false,"given":"Per-Henrik","family":"Groop","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Institute of Genetics, Folkh\u00e4lsan Research Center 1 , 00290 Helsinki ,","place":["Finland"]},{"name":"University of Helsinki and Helsinki University Hospital 2 Department of Nephrology , , 00290 Helsinki ,","place":["Finland"]},{"name":"University of Helsinki 3 Program for Clinical and Molecular Metabolism, Faculty of Medicine , , 00290 Helsinki ,","place":["Finland"]},{"name":"Central Clinical School, Monash University 7 Department of Diabetes , , Melbourne, VIC 3004 ,","place":["Australia"]},{"name":"Baker Heart and Diabetes Institute 8 , Melbourne, VIC 3004 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8414-7285","authenticated-orcid":false,"given":"Markku","family":"Lehto","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Institute of Genetics, Folkh\u00e4lsan Research Center 1 , 00290 Helsinki ,","place":["Finland"]},{"name":"University of Helsinki and Helsinki University Hospital 2 Department of Nephrology , , 00290 Helsinki ,","place":["Finland"]},{"name":"University of Helsinki 3 Program for Clinical and Molecular Metabolism, Faculty of Medicine , , 00290 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"2026033111265174100_DMM052361C1","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1001\/jama.290.2.238","article-title":"Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: 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