{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T09:59:29Z","timestamp":1785578369926,"version":"3.56.0"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Hyperuricemia is common after kidney transplantation and frequently arises with calcineurin inhibitor exposure and reduced graft function. However, its role in development of interstitial fibrosis and tubular atrophy (IF\/TA) remains unclear. This study examined the association between post-transplant hyperuricemia and histologic fibrosis progression using clinical and in vitro analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We retrospectively analyzed 138 non-diabetic kidney transplant recipients in the Japan Academic Consortium of Kidney Transplantation (JACK) who underwent baseline and follow-up allograft biopsies (mean interval, 4.2 \u00b1 2.2 years). Hyperuricemia was defined as serum uric acid &gt;7 mg\/dL in men and &gt;6 mg\/dL in women at 6 months post-transplant. The primary outcome was fibrosis progression, defined as an increase of \u22652 Banff ci grades. In parallel, human proximal tubular epithelial (HK-2) cells were exposed to uric acid, and URAT1, \u03b1-smooth muscle actin (\u03b1-SMA), and E-cadherin expression was assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Hyperuricemia at 6 months was significantly associated with IF\/TA progression (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.16\u20133.77; p = 0.01) and remained significant after adjustment for serum creatinine and early T cell\u2013mediated rejection (adjusted HR, 1.99; 95% CI, 1.05\u20133.77; p = 0.04). No association was observed with arteriolar hyalinosis progression. In HK-2 cells, uric acid induced dose-dependent \u03b1-SMA upregulation and E-cadherin downregulation, consistent with epithelial\u2013mesenchymal transition(EMT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Hyperuricemia within the first 6 months after kidney transplantation was independently associated with interstitial fibrosis progression. Experimental data demonstrated EMT-related changes in tubular epithelial cells exposed to uric acid, suggesting a biological link between hyperuricemia and chronic allograft remodeling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.34067\/kid.0000001273","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T17:00:14Z","timestamp":1783616414000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Early Post-Transplant Hyperuricemia and Association with Histologic Fibrosis Progression and EMT-Related Changes in Proximal Tubular Cells"],"prefix":"10.34067","author":[{"given":"Mayuko","family":"Kawabe","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyuki","family":"Nakada","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9856-0852","authenticated-orcid":false,"given":"Izumi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akimitsu","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7309-0658","authenticated-orcid":false,"given":"Kohei","family":"Unagami","sequence":"additional","affiliation":[{"name":"Department of Organ Transplant Medicine, Tokyo Women's Medical University, Tokyo, Japan"},{"name":"Department of Nephrology, Tokyo Women's Medical University, Tokyo, Japan"},{"name":"Yocho-machi Clinic, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3343-6674","authenticated-orcid":false,"given":"Toshihito","family":"Hirai","sequence":"additional","affiliation":[{"name":"Department of Urology, Tokyo Women's Medical University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6137-4864","authenticated-orcid":false,"given":"Kazuya","family":"Omoto","sequence":"additional","affiliation":[{"name":"Department of Urology, Tokyo Women's Medical University, Tokyo, Japan"},{"name":"Yocho-machi Clinic, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8345-3627","authenticated-orcid":false,"given":"Tomokazu","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Organ Transplant Medicine, Tokyo Women's Medical University, Tokyo, Japan"},{"name":"Department of Urology, Tokyo Women's Medical University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1838-7998","authenticated-orcid":false,"given":"Takashi","family":"Yokoo","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1775-0943","authenticated-orcid":false,"given":"Toshio","family":"Takagi","sequence":"additional","affiliation":[{"name":"Department of Urology, Tokyo Women's Medical University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7370-4728","authenticated-orcid":false,"given":"Hideki","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Organ Transplant Medicine, Tokyo Women's Medical University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,7,9]]},"container-title":["Kidney360"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.34067\/KID.0000001273","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T09:03:29Z","timestamp":1785575009000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.34067\/KID.0000001273"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,9]]},"references-count":0,"URL":"https:\/\/doi.org\/10.34067\/kid.0000001273","relation":{},"ISSN":["2641-7650"],"issn-type":[{"value":"2641-7650","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,9]]},"assertion":[{"value":"2025-12-25","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-17","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}