{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T17:58:40Z","timestamp":1785261520332,"version":"3.55.0"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"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":"\n Background:<\/jats:title>\n Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder leading to accumulation of 2,8-dihydroxyadenine (DHA) in the kidneys, causing urinary stones and progressive chronic kidney disease. This study aimed to characterize the renal histological changes in APRT deficiency, and immunohistochemical expression of selected potential mediators of kidney injury.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n Kidney biopsy (n=3) and nephrectomy specimens (n=2) from five patients with APRT deficiency, along with three control nephrectomy specimens were included in the study. All kidney tissue samples, obtained from the Landspitali University Hospital Biobank, were assessed for DHA crystal localization, degree of inflammation and\/or fibrosis, and other indicators of tissue damage. Tissue samples were classified as DHA\n high<\/jats:sup>\n and DHA\n low<\/jats:sup>\n based on DHA crystal tissue burden. The expression of APRT, xanthine oxidoreductase, E-cadherin, N-cadherin, CD44, NGAL, KIM-1 and collagen I and III was assessed by immunohistochemistry (IHC).\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n Kidney tissue from patients with APRT deficiency showed birefringent DHA crystals within tubular lumina, inside tubular epithelial cells, and in the interstitium. DHA\n high<\/jats:sup>\n samples displayed marked inflammation and tubular atrophy, with interstitial fibrosis, whereas DHA\n low<\/jats:sup>\n samples exhibited only localized injury around the limited crystal deposits. No crystals, inflammation, or fibrosis were observed in the control tissue. IHC confirmed absent APRT, reduced N-cadherin in DHA\n high<\/jats:sup>\n samples, and increased collagen III expression in all samples, suggesting early fibrotic remodeling. CD44 expression tended to be higher in kidney sections from patients with APRT deficiency, consistent with crystal-induced inflammation.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n \n DHA crystal deposits were seen in renal tubular lumina, within epithelial cells, and in the interstitial space. The degree of inflammation and fibrosis noted in kidneys of individuals with APRT deficiency was associated with the burden of DHA crystal deposits observed. The IHC findings, together with previously published data, support a likely pathobiological chain of events mediating DHA crystal-induced kidney injury in APRT deficiency\n .<\/jats:bold>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.34067\/kid.0000001299","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T17:02:06Z","timestamp":1785258126000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["2,8-Dihydroxyadenine Crystal Nephropathy and Mediators of Kidney Injury in Adenine Phosphoribosyltransferase Deficiency"],"prefix":"10.34067","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5139-9010","authenticated-orcid":false,"given":"Hildur Run","family":"Helgudottir","sequence":"first","affiliation":[{"name":"Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1826-1383","authenticated-orcid":false,"given":"Hrafnhildur Linnet","family":"Runolfsdottir","sequence":"additional","affiliation":[{"name":"Internal Medicine Services"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0331-9029","authenticated-orcid":false,"given":"Sverrir","family":"Hardarson","sequence":"additional","affiliation":[{"name":"Section of Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6763-1702","authenticated-orcid":false,"given":"Runolfur","family":"Palsson","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland"},{"name":"Section of Nephrology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4204-9342","authenticated-orcid":false,"given":"Vidar Orn","family":"Edvardsson","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland"},{"name":"Children\u2019s Medical Center and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9645-9665","authenticated-orcid":false,"given":"Thorarinn","family":"Gudjonsson","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland"},{"name":"Section of Laboratory Hematology, Landspitali University Hospital, Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,7,28]]},"container-title":["Kidney360"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.34067\/KID.0000001299","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T17:02:06Z","timestamp":1785258126000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.34067\/KID.0000001299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":0,"URL":"https:\/\/doi.org\/10.34067\/kid.0000001299","relation":{},"ISSN":["2641-7650"],"issn-type":[{"value":"2641-7650","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,28]]},"assertion":[{"value":"2026-01-20","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-21","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}