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However, the majority of currently available fluorescent probes are preferentially taken up by the liver or only respond to a single analyte, resulting in limited accuracy in renal imaging and severely impairing their performance in renal function imaging. Herein, based on a novel \u201ctwo birds with one stone\u201d strategy, we report the renal-clearable and nitroreductase (NTR)\/viscosity dual-activated fluorescent probe V-NTR for precise in vivo kidney disease imaging and diagnosis. Notably, the probe displays a remarkable 31.3-fold fluorescence enhancement upon dual stimulation by NTR and elevated viscosity, significantly improving detection specificity. In vivo NIR fluorescence imaging and in vitro urine analysis studies have collectively demonstrated that V-NTR enables precise imaging of RCC and real-time monitoring of injury induced during the early ischemic phase of renal IRI. Thus, this study not only provides a novel and reliable molecular tool for the early diagnosis and real-time monitoring of kidney diseases, but also offers a generalizable chemical design platform for the development of kidney-specific molecular imaging probes.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c04500","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:26:40Z","timestamp":1787070400000},"page":"25413-25422","source":"Crossref","is-referenced-by-count":0,"title":["Renal-Clearable\nNitroreductase and Viscosity Dual-Activated\nHemicyanine Probes for Precise\n                    <i>In Vivo<\/i>\n                    Kidney Disease\nImaging and Diagnosis"],"prefix":"10.1021","volume":"98","author":[{"given":"Zhangkang","family":"Lv","sequence":"first","affiliation":[{"name":"Guangxi Normal University , , ,","place":["Guilin, P. R. China, 541004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrong","family":"Lin","sequence":"additional","affiliation":[{"name":"Guangxi Normal University , , ,","place":["Guilin, P. R. China, 541004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingting","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangxi Normal University , , ,","place":["Guilin, P. R. China, 541004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangxi Normal University , , ,","place":["Guilin, P. R. China, 541004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Shen","sequence":"additional","affiliation":[{"name":"Guangxi Normal University , , ,","place":["Guilin, P. R. China, 541004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7116-6919","authenticated-orcid":true,"given":"Xing-Can","family":"Shen","sequence":"additional","affiliation":[{"name":"Guangxi Normal University , , ,","place":["Guilin, P. R. China, 541004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6331-7377","authenticated-orcid":true,"given":"Hua","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangxi Normal University , , ,","place":["Guilin, P. R. 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Nephrol."},{"issue":"7620","key":"2026090306471161200_cit6","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/537S97a","article-title":"Kidney cancer","volume":"537","author":"Owens","year":"2016","journal-title":"Nature"},{"issue":"8031","key":"2026090306471161200_cit7","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1038\/s41586-024-07812-3","article-title":"Mitochondrial complex\nI promotes kidney cancer metastasis","volume":"633","author":"Bezwada","year":"2024","journal-title":"Nature"},{"issue":"8013","key":"2026090306471161200_cit8","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1038\/s41586-024-07368-2","article-title":"Geographic variation\nof mutagenic exposures in kidney cancer genomes","volume":"629","author":"Senkin","year":"2024","journal-title":"Nature"},{"issue":"1","key":"2026090306471161200_cit9","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1182\/blood-2025-1282","article-title":"Novel protective role of factor XII\nin kidney ischemia\/reperfusion injury in a rat model","volume":"146","author":"Sharma","year":"2025","journal-title":"Blood"},{"issue":"10","key":"2026090306471161200_cit10","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1038\/s41581-023-00762-5","article-title":"Propagation\nof acute kidney injury","volume":"19","author":"Allison","year":"2023","journal-title":"Nat. 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Sci."},{"key":"2026090306471161200_cit46","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202524057","article-title":"Molecularly engineered\nphenoxazinone-skeleton cascade-activated NIR\nprobes for monitoring Fe2+\/Viscosity in ferroptosis-mediated\nparkinson\u2019s disease","volume":"13","author":"Guo","year":"2026","journal-title":"Adv. Sci."},{"issue":"4","key":"2026090306471161200_cit47","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1038\/s41563-025-02462-w","article-title":"Cell viscosity\ninfluences\nhaematogenous dissemination and metastatic extravasation of tumour\ncells","volume":"25","author":"Gensbittel","year":"2026","journal-title":"Nat. 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Rev."},{"issue":"24","key":"2026090306471161200_cit51","doi-asserted-by":"publisher","first-page":"12080","DOI":"10.1039\/D3CS01118F","article-title":"Twisted intramolecular\ncharge transfer (TICT) based\nfluorescent probes and imaging agents","volume":"54","author":"Wu","year":"2025","journal-title":"Chem.\nSoc. Rev."},{"issue":"22","key":"2026090306471161200_cit52","doi-asserted-by":"publisher","first-page":"12656","DOI":"10.1039\/D1CS00239B","article-title":"Twisted intramolecular\ncharge transfer (TICT) and twists beyond TICT: from mechanisms to\nrational designs of bright and sensitive fluorophores","volume":"50","author":"Wang","year":"2021","journal-title":"Chem. Soc. Rev."},{"key":"2026090306471161200_cit53","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2021.214336","article-title":"Recent advances in\nmultifunctional fluorescent probes for viscosity and analytes","volume":"453","author":"Yang","year":"2022","journal-title":"Coord. Chem. 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