{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:29:43Z","timestamp":1786480183541,"version":"build-2736575974"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01-DK122212"],"award-info":[{"award-number":["R01-DK122212"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["1K08DK143343-01"],"award-info":[{"award-number":["1K08DK143343-01"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Kansas Intellectual and Developmental Disabilities Research Center","award":["U54 HD 090216"],"award-info":[{"award-number":["U54 HD 090216"]}]},{"name":"National Cancer Institute","award":["P30 CA168524"],"award-info":[{"award-number":["P30 CA168524"]}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01-DK122212"],"award-info":[{"award-number":["R01-DK122212"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["1K08DK143343-01"],"award-info":[{"award-number":["1K08DK143343-01"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Kansas Intellectual and Developmental Disabilities Research Center","award":["U54 HD 090216"],"award-info":[{"award-number":["U54 HD 090216"]}]},{"name":"National Cancer Institute","award":["P30 CA168524"],"award-info":[{"award-number":["P30 CA168524"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2026,7]]},"abstract":"\n Key Points<\/jats:title>\n \n \n \n High concentrations of tubular phosphate directly contribute to kidney mineral retention, tubular injury\/inflammation, and cyst growth in mice.<\/jats:p>\n <\/jats:list-item>\n \n Human polycystic kidney disease kidneys exhibit subclinical calcium-phosphate microcrystals that may be promoting kidney pathology in this setting.<\/jats:p>\n <\/jats:list-item>\n \n Phosphaturia and kidney mineral deposition may be novel and modifiable therapeutic targets to slow polycystic kidney disease progression.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n Accumulating evidence supports a direct contribution of abnormalities in phosphate homeostasis to progression of polycystic kidney disease (PKD); however, the mechanisms for these relationships remain undefined. A universal feature of nephron loss in all forms of kidney disease is increased urinary phosphate excretion by residual functional nephrons that helps to maintain systemic phosphate balance. To date, no studies have examined the direct contribution of urinary phosphate to kidney pathology in PKD.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We first examined the impact of dietary phosphate on kidney outcomes in\n Pkd1<\/jats:italic>\n RC\/RC<\/jats:sup>\n mice, an orthologous murine model of PKD. Next, to more specifically delineate the direct contribution of urinary phosphate to kidney pathology, we characterized kidney phenotypes in phosphaturic\n Slc34a1<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mice. We then investigated how increasing urinary phosphate excretion through\n Slc34a1<\/jats:italic>\n deletion affected cystic kidney disease progression in\n Pkd1<\/jats:italic>\n RC\/RC<\/jats:sup>\n mice. Finally, to define the relevance of our findings to human PKD, we conducted high-resolution imaging and trace mineral analysis of human PKD and control kidney specimens to assess the prevalence and composition of subclinical mineral deposition.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Pkd1<\/jats:italic>\n RC\/RC<\/jats:sup>\n mice fed a high phosphate diet exhibited kidney injury with activation of early fibrosis pathways, accelerated cyst growth, and phosphate-based crystal deposition that spatially colocalized with macrophages.\n Slc34a1<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mice demonstrated extensive nephrocalcinosis, tubular microcyst formation, and evidence of early kidney injury, inflammation, and fibrosis. Moreover, compound mutant\n Pkd1<\/jats:italic>\n RC\/RC<\/jats:sup>\n ,\n Slc34a1<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mice had increased kidney cyst burden accompanied by reduced kidney function compared with\n Pkd1<\/jats:italic>\n RC\/RC<\/jats:sup>\n ,\n Slc34a1<\/jats:italic>\n +\/+<\/jats:sup>\n controls. Finally, micro-computed tomography and trace mineral analyses of human kidneys revealed consistent deposition of calcium-phosphate microcrystals in PKD kidneys.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Increased urinary phosphate excretion directly contributes to kidney injury, cyst formation\/growth, inflammation, and fibrosis. Urinary phosphate excretion and tubular mineral solubility may represent novel therapeutic targets for slowing PKD progression in humans.<\/jats:p>\n <\/jats:sec>","DOI":"10.34067\/kid.0000001149","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T16:01:02Z","timestamp":1776960062000},"page":"1475-1488","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Phosphaturia Exacerbates Tubular Injury and Cyst Formation in Polycystic Kidney Disease"],"prefix":"10.34067","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8209-2943","authenticated-orcid":false,"given":"Kyle P.","family":"Jansson","sequence":"first","affiliation":[{"name":"The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas"},{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Kuluva","sequence":"additional","affiliation":[{"name":"The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Swanson","sequence":"additional","affiliation":[{"name":"The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0665-370X","authenticated-orcid":false,"given":"Timothy A.","family":"Fields","sequence":"additional","affiliation":[{"name":"The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas"},{"name":"Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine I.","family":"Swenson-Fields","sequence":"additional","affiliation":[{"name":"The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas"},{"name":"Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4616-7669","authenticated-orcid":false,"given":"Darren P.","family":"Wallace","sequence":"additional","affiliation":[{"name":"The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas"},{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Rowe","sequence":"additional","affiliation":[{"name":"The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas"},{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4580-5745","authenticated-orcid":false,"given":"Jason R.","family":"Stubbs","sequence":"additional","affiliation":[{"name":"The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas"},{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"issue":"10075","key":"B1-20260731","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/S0140-6736(16)32064-5","article-title":"Chronic kidney disease","volume":"389","author":"Webster","year":"2017","journal-title":"Lancet."},{"issue":"13","key":"B2-20260731","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1001\/jama.2019.14745","article-title":"Chronic kidney disease diagnosis and management: a review","volume":"322","author":"Chen","year":"2019","journal-title":"JAMA."},{"issue":"12","key":"B3-20260731","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1038\/ki.2011.47","article-title":"Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease","volume":"79","author":"Isakova","year":"2011","journal-title":"Kidney 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