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However, current imaging strategies are hindered by a lack of fluorophores that combine rapid renal clearance with high signal\u2010to\u2010background ratios. Here, we report CS\u2010CY5\u2010PEG, a renal\u2010clearable NIR\u2010II fluorophore (\u03bb\n                    <jats:sub>em<\/jats:sub>\n                    = 1035\u00a0nm) designed to overcome aggregation\u2010caused quenching (ACQ) via polyethylene glycol (PEG) modification. CS\u2010CY5\u2010PEG exhibits remarkable brightness (\u03a6\n                    <jats:sub>F<\/jats:sub>\n                    \u00a0\u00d7\u00a0\u03b5 = 55.4\u00a0M\n                    <jats:sup>\u2212<\/jats:sup>\n                    <jats:sup>1<\/jats:sup>\n                    \u00b7cm\n                    <jats:sup>\u2212<\/jats:sup>\n                    <jats:sup>1<\/jats:sup>\n                    ), offering a 6.4\u2010fold improvement over ICG in aqueous solution. Its compact hydrodynamic diameter (\u223c3.1\u00a0nm) and optimized hydrophilicity (log\u00a0D = \u20130.83) enable efficient glomerular filtration and 80% renal clearance within 1 h. Importantly, CS\u2010CY5\u2010PEG sensitively detects renal injury in adenine\u2010induced CKD models, allowing dynamic tracking of kidney function from mild to severe disease stages. By leveraging this property and tracking its localized visible emission (\n                    <jats:italic>\u03bb<\/jats:italic>\n                    <jats:sub>em<\/jats:sub>\n                    \u2248 530\u00a0nm), we further investigated the underlying mechanisms of renal injury in CKD. Our findings elucidate how functional impairment in the glomeruli leads to abnormal retention of exogenous substances within renal tissues. These results position CS\u2010CY5\u2010PEG as a versatile platform for noninvasive renal diagnostics and nephrotoxicity evaluation in preclinical research.\n                  <\/jats:p>","DOI":"10.1002\/smll.202514874","type":"journal-article","created":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T18:19:49Z","timestamp":1778437189000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Development of Renal\u2010Clearable NIR\u2010II Fluorescent Probes via Hydrophilicity Tuning for Imaging of Chronic Kidney Disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Yuxin","family":"Xie","sequence":"first","affiliation":[{"name":"State Key Laboratory of Chemo and Biosensing College of Chemistry and Chemical Engineering Hunan University  Changsha P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yuan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chemo and Biosensing College of Chemistry and Chemical Engineering Hunan University  Changsha P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5774-8306","authenticated-orcid":false,"given":"Tian\u2010Bing","family":"Ren","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chemo and Biosensing College of Chemistry and Chemical Engineering Hunan University  Changsha P. R. 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