{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:47:16Z","timestamp":1791380836910,"version":"4.3.3"},"reference-count":23,"publisher":"American Diabetes Association","issue":"1","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/100018696","name":"HORIZON EUROPE Health","doi-asserted-by":"publisher","award":["101095146"],"award-info":[{"award-number":["101095146"]}],"id":[{"id":"10.13039\/100018696","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>We evaluated the prognostic and clinical utility of kidneyintelX.dkd, a biomarker-based risk score, in patients with type 2 diabetes and a broad range of chronic kidney disease (CKD) by assessing its association with kidney outcomes at baseline and longitudinally, comparing it with the established Kidney Disease Improving Global Outcomes (KDIGO) risk classification, and examining its responsiveness to canagliflozin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>We measured tumor necrosis factor receptor-1 (TNFR-1), TNFR-2, and kidney injury molecule-1 (KIM-1) in banked plasma samples at baseline and year 1 and calculated kidneyintelX.dkd scores of participants with CKD G1-G3b from two large randomized controlled trials (Canagliflozin Cardiovascular Assessment Study [CANVAS] and Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation [CREDENCE]). We assessed concordance between KDIGO and kidneyintelX.dkd risk levels, evaluated associations of baseline and 1-year changes in kidneyintelX.dkd with kidney outcomes, and examined treatment effects of canagliflozin versus placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Mean kidneyintelX.dkd scores increased across higher KDIGO risk categories, but individual-level differences revealed improved risk reclassification. The kidneyintelX.dkd score was independently associated with kidney outcomes and more strongly predictive than KDIGO classification. At 1 year, canagliflozin significantly lowered kidneyintelX.dkd score versus placebo, and longitudinal reductions by 1 year were associated with lower subsequent risk of kidney outcomes, independent of changes in estimated glomerular filtration rate or urinary albumin-to-creatinine ratio. Absolute risk reductions with canagliflozin were largest among those at high kidneyintelX.dkd risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>The kidneyintelX.dkd score adds prognostic value beyond clinical classification, reflects canagliflozin treatment response, and helps identify individuals most likely to benefit from therapy. These findings support a role for the kidneyintelX.dkd score in personalized risk assessment and monitoring in type 2 diabetes and CKD in prospective studies and clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc25-1722","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T16:36:01Z","timestamp":1762878961000},"page":"92-98","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":4,"title":["Baseline Risk and Longitudinal Changes in kidneyintelX.dkd and Its Association With Kidney Outcomes in the CANVAS and CREDENCE Trials"],"prefix":"10.2337","volume":"49","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 of Groningen, University Medical Centre Groningen 1 , Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven G.","family":"Coca","sequence":"additional","affiliation":[{"name":"Barbara T. Murphy Division of Nephrology, Icahn School of Medicine at Mount Sinai 2 , New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Edwards","sequence":"additional","affiliation":[{"name":"Renalytix AI 3 , PLC, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendon L.","family":"Neuen","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, University of South Wales 4 , Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9370-9913","authenticated-orcid":false,"given":"Clare","family":"Arnott","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, University of South Wales 4 , Sydney, New South Wales, Australia"},{"name":"Department of Cardiology, Royal Prince Alfred Hospital 5 , Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan J.L.","family":"Bakker","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Groningen, University Medical Centre Groningen 6 , Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fergus","family":"Fleming","sequence":"additional","affiliation":[{"name":"Renalytix AI 3 , PLC, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-3730","authenticated-orcid":false,"given":"Hiddo J.L.","family":"Heerspink","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen 1 , Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"2026060411114978200_B1","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/S0140-6736(21)00519-5","article-title":"Chronic kidney disease","volume":"398","author":"Kalantar-Zadeh","year":"2021","journal-title":"Lancet"},{"key":"2026060411114978200_B2","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/s41581-024-00820-6","article-title":"Chronic kidney disease and the global public health agenda: an international consensus","volume":"20","author":"Francis","year":"2024","journal-title":"Nat Rev Nephrol"},{"key":"2026060411114978200_B3","doi-asserted-by":"crossref","first-page":"S117","DOI":"10.1016\/j.kint.2023.10.018","article-title":"KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease","volume":"105","author":"Stevens","year":"2024","journal-title":"Kidney Int"},{"key":"2026060411114978200_B4","article-title":"Urine as a source of biomarkers and biological knowledge in chronic kidney disease","author":"Vlahou","year":"2025","journal-title":"Nat Rev Nephrol."},{"key":"2026060411114978200_B5","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1186\/s12882-023-03339-3","article-title":"UK Kidney Association Clinical Practice Guideline: sodium-glucose co-transporter-2 (SGLT-2) INHIBITION IN ADULTS WITH KIDNEY DISEase 2023 update","volume":"24","author":"Roddick","year":"2023","journal-title":"BMC Nephrol"},{"key":"2026060411114978200_B6","doi-asserted-by":"crossref","first-page":"S219","DOI":"10.2337\/dc24-S011","article-title":"11. Chronic kidney disease and risk management: Standards of Care in Diabetes\u20142024","volume":"47","author":"American Diabetes Association Professional Practice Committee","year":"2023","journal-title":"Diabetes Care"},{"key":"2026060411114978200_B7","doi-asserted-by":"crossref","first-page":"102426","DOI":"10.1016\/j.eclinm.2024.102426","article-title":"Implementation of chronic kidney disease guidelines for sodium-glucose co-transporter-2 inhibitor use in primary care in the UK: a cross-sectional study","volume":"68","author":"Forbes","year":"2024","journal-title":"EClinicalMedicine"},{"key":"2026060411114978200_B8","doi-asserted-by":"crossref","first-page":"e230005","DOI":"10.1530\/EC-23-0005","article-title":"SGLT2 inhibitors for patients with type 2 diabetes and CKD: a narrative review","volume":"12","author":"Thomas","year":"2023","journal-title":"Endocr 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