{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:31:55Z","timestamp":1786480315221,"version":"build-2736575974"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["K23 DK132680"],"award-info":[{"award-number":["K23 DK132680"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institute of Diabetes and Digestive and Kidney Institutional Network Award","award":["U2CDK136780-01A1"],"award-info":[{"award-number":["U2CDK136780-01A1"]}]},{"name":"NIH-NHLBI","award":["R01 HL167233"],"award-info":[{"award-number":["R01 HL167233"]}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["K23 DK132680"],"award-info":[{"award-number":["K23 DK132680"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institute of Diabetes and Digestive and Kidney Institutional Network Award","award":["U2CDK136780-01A1"],"award-info":[{"award-number":["U2CDK136780-01A1"]}]},{"name":"NIH-NHLBI","award":["R01 HL167233"],"award-info":[{"award-number":["R01 HL167233"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Kidney injury molecule-1 and soluble urokinase plasminogen activator receptor are associated with retinal microvascular changes in individuals without CKD, diabetes, or cardiovascular disease.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Tubule biomarkers may reveal microvascular pathways linking kidney dysfunction to cardiovascular risk beyond eGFR or albumin-to-creatinine ratio.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>CKD is strongly associated with cardiovascular disease (CVD), yet the etiology responsible for this link remains elusive. Novel blood and urine biomarkers reflecting kidney tubule dysfunction and injury may provide novel insights to mechanisms linking the kidney to CVD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In 470 participants of the Multi-Ethnic Study of Atherosclerosis without type 2 diabetes, CVD, or CKD, we measured six plasma (kidney injury molecule-1 [KIM-1], monocyte chemoattractant protein-1, soluble urokinase plasminogen activator receptor, tumor necrosis factor receptor 1 and 2, and anti\u2013chitinase-3-like protein 1) and six urinary (\n                      <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                      1 microglobulin, EGF, KIM-1, monocyte chemoattractant protein-1, anti\u2013chitinase-3-like protein 1, and uromodulin) kidney tubule health biomarkers. To assess microvascular health, we used retinal microvascular measurements assessed from fundus photography: central retinal arteriolar and venular equivalents (central retinal artery equivalent [CRAE] and central retinal venular equivalent [CRVE], respectively). Multivariable linear regression evaluated associations of tubule biomarkers and kidney function with CRAE and CRVE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The mean participant age was 60\u00b110 years with 52% female. The racial and ethnic distribution was 46% White, 24% Black, 18% Hispanic, and 11% Chinese. The mean eGFR was 92.1\u00b113.3 ml\/min per 1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      , and the median urine albumin-to-creatinine ratio was 4.7 mg\/g (interquartile range, 3.0\u20139.4). Higher plasma KIM-1 (\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      , \u22125.14; 95% confidence interval [CI], \u22129.84 to \u22120.45) and urine KIM-1 (\n                      <jats:italic toggle=\"yes\">\u03b2,<\/jats:italic>\n                      \u22125.68; 95% CI, \u221210.15 to \u22121.22) concentrations were individually associated with narrower CRAE, while plasma soluble urokinase plasminogen activator receptor concentrations were individually associated with wider CRAE (\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      , 9.15; 95% CI, 0.89 to 17.4) and CRVE (\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      , 21.49; 95% CI, 9.39 to 33.59). There were no significant associations between the remaining tubule health biomarkers and CRAE or CRVE nor were there associations between eGFR or urine albumin-to-creatinine ratio with CRAE and CRVE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this study of community-living individuals without CKD, diabetes, or CVD, selected kidney tubule health markers are associated with retinal microvascular changes. These findings suggest that kidney tubule biomarkers may reflect or contribute to systemic microvascular dysfunction, above and beyond glomerular damage. Tubular biomarkers may help elucidate the shared microvascular mechanisms linking CKD and CVD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.34067\/kid.0000000970","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T16:06:37Z","timestamp":1757088397000},"page":"2157-2165","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Associations of Biomarkers of Kidney Tubule Health with Retinal Microvascular Signs"],"prefix":"10.34067","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7711-2356","authenticated-orcid":false,"given":"Armin","family":"Ahmadi","sequence":"first","affiliation":[{"name":"Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Gorji","sequence":"additional","affiliation":[{"name":"Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5646-2663","authenticated-orcid":false,"given":"Sanskrita","family":"Shashikant","sequence":"additional","affiliation":[{"name":"Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7723-7469","authenticated-orcid":false,"given":"Ronit","family":"Katz","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfons J.H.M.","family":"Houben","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9553-3202","authenticated-orcid":false,"given":"Robert N.","family":"Weinreb","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of California San Diego, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Allison","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, University of California San Diego, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5484-2535","authenticated-orcid":false,"given":"Stacy M.","family":"Meuer","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2379-976X","authenticated-orcid":false,"given":"Barbara E.","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2046-4350","authenticated-orcid":false,"given":"Mary Frances","family":"Cotch","sequence":"additional","affiliation":[{"name":"Office of Vision Health and Population Sciences, National Eye Institute, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6593-3571","authenticated-orcid":false,"given":"Orlando M.","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Sarnak","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9559-204X","authenticated-orcid":false,"given":"Michael","family":"Shlipak","sequence":"additional","affiliation":[{"name":"Department of Medicine, Kidney Health Research Collaborative, San Francisco VA Healthcare System, University of California, San Francisco, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8084-9869","authenticated-orcid":false,"given":"Joachim H.","family":"Ix","sequence":"additional","affiliation":[{"name":"Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"issue":"11","key":"B1-20260109","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1038\/s41591-019-0627-8","article-title":"Glomerular filtration rate by differing measures, albuminuria and prediction of cardiovascular disease, mortality and end-stage kidney disease","volume":"25","author":"Lees","year":"2019","journal-title":"Nat Med."},{"issue":"5","key":"B2-20260109","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1053\/j.ajkd.2021.03.026","article-title":"The promise of tubule biomarkers in kidney disease: a 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