{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T22:58:41Z","timestamp":1785279521425,"version":"3.55.0"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive metabolic disorder caused by pathogenic variants in\n                    <jats:italic>AGXT<\/jats:italic>\n                    , leading to hepatic oxalate overproduction, recurrent nephrolithiasis, nephrocalcinosis, progressive kidney dysfunction, and, in advanced stages, systemic oxalosis. Here, we report a family in which two brothers developed recurrent nephrolithiasis and progressed to end-stage kidney disease (ESKD) in young adulthood. The proband, a 32-year-old man, presented with bilateral kidney stones, rapidly progressive renal failure, and extensive extra-renal tissue oxalate deposition on follow-up imaging. Genetic testing identified a homozygous\n                    <jats:italic>AGXT<\/jats:italic>\n                    variant, c.740T&amp;gt;G, p.(Leu247Arg), in both affected siblings, while the proband\u2019s mother and daughter were heterozygous carriers, consistent with autosomal recessive inheritance. Plasma oxalate levels were markedly higher in the proband than in his brother and in non-PH ESKD controls. During follow-up, the proband received maintenance hemodialysis alone, whereas his older brother underwent combined hemodialysis, hemofiltration, and hemoperfusion, and appeared to achieve better plasma oxalate control. These findings suggest that intensified blood purification may serve as a potential bridging strategy in advanced PH1 while definitive treatment is being arranged. This report expands the genotypic and phenotypic spectrum of PH1 and underscores the importance of early genetic evaluation in patients with recurrent or early-onset nephrolithiasis, especially when accompanied by rapid renal decline or a positive family history.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2026.1865152","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T22:10:21Z","timestamp":1785276621000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: A rare AGXT pathogenic variant associated with young-adult-onset end-stage kidney disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Hui","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Nephrology, Longyan First Affiliated Hospital of Fujian Medical University","place":["Longyan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuzhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Longyan First Affiliated Hospital of Fujian Medical University","place":["Longyan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senqing","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Longyan First Affiliated Hospital of Fujian Medical University","place":["Longyan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senchao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Longyan First Affiliated Hospital of Fujian Medical University","place":["Longyan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuping","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Longyan First Affiliated Hospital of Fujian Medical University","place":["Longyan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxiu","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Longyan First Affiliated Hospital of Fujian Medical University","place":["Longyan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e70079","DOI":"10.1111\/petr.70079","article-title":"Hidden in CAKUT: post-transplant diagnosis of primary hyperoxaluria type 1 and rescue management using lumasiran","volume":"29","author":"Bahbah","year":"2025","journal-title":"Pediatr. Transpl."},{"key":"B2","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1097\/mnh.0000000000000790","article-title":"New therapeutics for primary hyperoxaluria type 1","volume":"31","author":"Dejban","year":"2022","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1056\/NEJMoa2021712","article-title":"Lumasiran, an RNAi therapeutic for primary hyperoxaluria type 1","volume":"384","author":"Garrelfs","year":"","journal-title":"N. Engl. J. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e69","DOI":"10.1056\/NEJMc2107661","article-title":"Lumasiran, an RNAi therapeutic for primary hyperoxaluria type 1. Reply","volume":"385","author":"Garrelfs","year":"","journal-title":"N. Engl. J. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.bbrc.2023.01.042","article-title":"Biochemical and cellular effects of a novel missense mutation of the AGXT gene associated with primary hyperoxaluria type 1","volume":"645","author":"Gatticchi","year":"2023","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B6","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/s41581-022-00661-1","article-title":"Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope","volume":"19","author":"Groothoff","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1111\/scd.12968","article-title":"Primary hyperoxaluria: description of a new oral finding and review of literature","volume":"44","author":"Hassona","year":"2024","journal-title":"Spec. Care Dent."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1007\/s40265-022-01735-x","article-title":"Improving treatment options for primary hyperoxaluria","volume":"82","author":"Hoppe","year":"2022","journal-title":"Drugs"},{"key":"B9","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1007\/s40265-024-02014-7","article-title":"Correction: lumasiran: a review in primary hyperoxaluria type 1","volume":"84","author":"Kang","year":"2024","journal-title":"Drugs"},{"key":"B10","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1053\/j.ajkd.2022.05.012","article-title":"Lumasiran for advanced primary hyperoxaluria type 1: phase 3 illuminate-C trial","volume":"81","author":"Michael","year":"2023","journal-title":"Am. J. Kidney Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"3143","DOI":"10.1007\/s00467-024-06328-2","article-title":"Diagnosis and management of primary hyperoxalurias: best practices","volume":"39","author":"Michael","year":"2024","journal-title":"Pediatr. Nephrol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1002\/ajmg.c.31991","article-title":"Systematic assessment of monogenic etiology in adult-onset kidney stone formers undergoing urological intervention-evidence for genetic pretest probability","volume":"190","author":"Schonauer","year":"2022","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"B13","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1093\/ndt\/18.2.273","article-title":"Primary hyperoxaluria type 1 in the Netherlands: prevalence and outcome","volume":"18","author":"van Woerden","year":"2003","journal-title":"Nephrol. Dial. Transpl."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2407","DOI":"10.1093\/ndt\/16.12.2407","article-title":"Oxalate removal by daily dialysis in a patient with primary hyperoxaluria type 1","volume":"16","author":"Yamauchi","year":"2001","journal-title":"Nephrol. Dial. Transpl."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1007\/s00345-022-03934-3","article-title":"A comparison of the clinical characteristics of pediatric urolithiasis patients with positive and negative molecular diagnoses","volume":"40","author":"Zhao","year":"2022","journal-title":"World J. Urol."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1865152\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T22:10:26Z","timestamp":1785276626000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1865152\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,29]]},"references-count":15,"alternative-id":["10.3389\/fgene.2026.1865152"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2026.1865152","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,29]]},"article-number":"1865152"}}