{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T18:13:47Z","timestamp":1779300827888,"version":"3.51.4"},"reference-count":58,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"850","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22207130"],"award-info":[{"award-number":["22207130"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22474160"],"award-info":[{"award-number":["22474160"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010256","name":"Guangzhou Municipal Science and Technology Project","doi-asserted-by":"publisher","award":["2025A04J7148"],"award-info":[{"award-number":["2025A04J7148"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the National Key R&D Program of China","award":["2022YFA0912700"],"award-info":[{"award-number":["2022YFA0912700"]}]},{"name":"The Key Research and Development Plan of Guangzhou City","award":["202206080007"],"award-info":[{"award-number":["202206080007"]}]},{"name":"the introduced innovative R&D team project of \u201cThe Pearl River Talent Recruitment Program\u201d","award":["2021ZT09Y544"],"award-info":[{"award-number":["2021ZT09Y544"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,5,20]]},"abstract":"<jats:p>\n                    Fibrosis is a hallmark and common outcome of progressive chronic kidney disease (CKD). Noninvasive and accurate diagnosis of kidney fibrosis remains unavailable in clinics, limiting effective patient management. Here, we report the development of fibrogenesis sensing reporters (FSRs) for sensitive in vivo near-infrared fluorescence imaging and ex vivo translational urinalysis of kidney fibrosis. FSR achieves enhanced diagnostic accuracy by engaging two crucial, concurrently up-regulated biomarkers in fibrotic kidneys: lysyl oxidase\u2013derived allysine (Lys\n                    <jats:sup>Ald<\/jats:sup>\n                    ) and transglutaminase 2 (TG2). Engineered to be intrinsically nonfluorescent with excellent renal clearance, injected FSRs preferentially target kidneys through covalent binding to Lys\n                    <jats:sup>Ald<\/jats:sup>\n                    and are robustly cleaved by TG2, which is elevated in the fibrotic kidney, to unquench a renal-clearable fluorophore, enabling fluorescence \u201cturn-on\u201d for sensitive fibrosis detection by both kidney imaging and urine assays. Leveraging the high specificity of urinary TG2, FSR-based urinalysis distinguished kidney fibrosis from nonfibrotic acute kidney injury and was not confounded by extrarenal fibrosis (such as pulmonary and hepatic), providing diagnostic insights unattainable with routine kidney function tests. In a clinical cohort (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u00a0=\u00a035), FSR-based urinalysis discriminated patients with CKD from healthy controls with 84% sensitivity and 94% specificity and provided discrimination between histological mild versus severe fibrosis. In contrast, traditional clinical metrics such as the estimated glomerular filtration rate, serum creatinine, and blood urea nitrogen were not able to classify mild versus severe fibrosis cases. This noninvasive activatable reporter holds translational potential for early identification of renal fibrosis and patient stratification of CKD to improve clinical management and patient outcome.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adz6929","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T18:02:30Z","timestamp":1779300150000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Urinary fluorogenic reporters for noninvasive detection and staging of kidney fibrosis"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0265-4575","authenticated-orcid":true,"given":"Lijuan","family":"Zhu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China."},{"name":"Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3332-4294","authenticated-orcid":true,"given":"Fang","family":"He","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Urological\u200c Metabolism and Immunoecology Laboratory, First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8402-7280","authenticated-orcid":true,"given":"Weiliang","family":"Deng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China."},{"name":"Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China."},{"name":"Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8280-6846","authenticated-orcid":true,"given":"Yuyan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaogang","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Urological\u200c Metabolism and Immunoecology Laboratory, First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4012-4406","authenticated-orcid":true,"given":"Jiaguo","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China."},{"name":"Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 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