{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T10:11:42Z","timestamp":1792231902484,"version":"4.4.0"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"HORIZON EUROPE Reforming and enhancing the European Research and Innovation system","award":["101095146"],"award-info":[{"award-number":["101095146"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2026,10]]},"abstract":"\n Key Points<\/jats:title>\n \n \n \n Lower urinary EGF levels, normalized to urinary creatinine, reflected impaired tubular health and were associated with higher kidney risk across CKD.<\/jats:p>\n <\/jats:list-item>\n \n Sodium-glucose cotransporter 2 inhibitors attenuated the decline in urinary EGF-creatinine ratio observed with placebo, supporting a role in maintaining tubular health.<\/jats:p>\n <\/jats:list-item>\n \n Early increases in urinary EGF-creatinine ratio were linked to lower kidney risk, adding prognostic value beyond albuminuria.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n Urinary EGF is a marker of tubular repair capacity. Lower urinary EGF-creatinine ratio (uEGF\/Cr) levels associate with kidney disease progression in patients with type 2 diabetes at early stages of CKD. In these patients, sodium-glucose cotransporter 2 inhibitors (SGLT2is) are associated with increased tubular EGF expression. In this study, we aimed to extend these findings to a broad CKD population with and without type 2 diabetes at various stages of CKD.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We measured EGF in stored urine samples at baseline and year 1 in participants from the Canagliflozin Cardiovascular Assessment Study (CANVAS), Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), and Dapagliflozin and Prevention of Adverse Outcomes in CKD (DAPA-CKD) clinical trials. Associations of baseline and longitudinal uEGF\/Cr with the composite kidney outcome (sustained \u226540% eGFR decline, kidney failure, or kidney-related death) were assessed using multivariable Cox regression, and associations with annual eGFR decline using a two-slope linear mixed-effects model. Treatment effects of SGLT2i on uEGF\/Cr over time were analyzed with analysis of covariance.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In participants with type 2 diabetes from the CANVAS and CREDENCE trials (\n N<\/jats:italic>\n =5978), higher baseline uEGF\/Cr was associated with a lower risk of the composite kidney outcome (hazard ratio per two-fold higher uEGF\/Cr, 0.87 [95% confidence interval, 0.80 to 0.94]). SGLT2i attenuated the decline in uEGF\/Cr over 1 year compared with placebo by 6.7% (95% confidence interval, 2.5 to 10.8). Increases in uEGF\/Cr from baseline to year 1 were independently associated with a lower risk of the kidney outcome, even after accounting for 1-year changes in albuminuria, eGFR, and other clinical variables. Replication analyses showed similar results in the DAPA-CKD trial (\n N<\/jats:italic>\n =2450), with consistent findings in participants with and without diabetes.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n These results extend previous findings, supporting uEGF\/Cr as a robust, independent biomarker of tubular health and kidney risk across diverse CKD populations. SGLT2i attenuated uEGF\/Cr decline, and early changes in uEGF\/Cr provided prognostic information beyond albuminuria.<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.0000001086","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T16:04:28Z","timestamp":1775145868000},"page":"2210-2220","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":4,"title":["Association of Urinary EGF with Kidney Outcomes and Effects of Sodium-Glucose Cotransporter 2 Inhibition"],"prefix":"10.1681","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3983-5136","authenticated-orcid":false,"given":"Erik","family":"Moedt","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9432-2427","authenticated-orcid":false,"given":"Akihiko","family":"Koshino","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"},{"name":"Department of Nephrology and Rheumatology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0882-3656","authenticated-orcid":false,"given":"Niels","family":"Jongs","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9136-8454","authenticated-orcid":false,"given":"Wenjun","family":"Ju","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viji","family":"Nair","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4064-0582","authenticated-orcid":false,"given":"Matthias","family":"Kretzler","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0062-0520","authenticated-orcid":false,"given":"Michael K.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, LLC, Spring House, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9370-9913","authenticated-orcid":false,"given":"Clare G.","family":"Arnott","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, Sydney, New South Wales, Australia"},{"name":"Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0745-3478","authenticated-orcid":false,"given":"David C.","family":"Wheeler","sequence":"additional","affiliation":[{"name":"Department of Renal Medicine, University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1531-4294","authenticated-orcid":false,"given":"Peter","family":"Rossing","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0928-9168","authenticated-orcid":false,"given":"Steven G.","family":"Coca","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Hammarstedt","sequence":"additional","affiliation":[{"name":"Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2529-4477","authenticated-orcid":false,"given":"Peter J.","family":"Greasley","sequence":"additional","affiliation":[{"name":"Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5160-2947","authenticated-orcid":false,"given":"Petter","family":"Bjornstad","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3356-6791","authenticated-orcid":false,"given":"Stephan J.L.","family":"Bakker","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The 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