{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T06:27:47Z","timestamp":1773815267668,"version":"3.50.1"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Early identification of patients with high cardiorenal risk and timely targeted interventions are critical in managing type 2 diabetes (T2D). Although we previously developed a multivariable risk score to predict diabetic kidney disease (DKD), its ability to stratify cardiorenal risk in T2D patients with established high cardiovascular risk remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this\n                      <jats:italic>post-hoc<\/jats:italic>\n                      analysis of the ELIXA trial, 2,635 T2D participants without baseline DKD were stratified into different risk groups (low-, moderate-, high-, and very high-risk group) using the previously developed risk score (incorporating nine simple clinical indicators: age, body mass index, hemoglobin A1c, systolic blood pressure, high-density lipoprotein cholesterol, triglycerides, smoking, diabetic retinopathy, and urinary albumin-to-creatinine ratio [UACR]). Patients were followed for renal outcomes (DKD incidence and progression) and cardiovascular outcomes (major adverse cardiovascular events [MACEs] and heart failure [HF]).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The risk score demonstrated strong, graded associations with cardiorenal outcomes. Over 108 weeks of renal follow-up, a progressive increase in DKD incidence was observed across risk strata (52.5% vs. 13.5% in the very high- vs. low-risk groups; relative risks [RR] 3.89, 95% confidence interval [CI] 2.82\n                      <jats:bold>\u2013<\/jats:bold>\n                      5.38,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001). This graded pattern extended to other key events of renal disease progression: macroalbuminuria (5.1% vs. 0.8%; RR 9.37, 95% CI 2.41\n                      <jats:bold>\u2013<\/jats:bold>\n                      36.46,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.001), a \u226540% decline in estimated glomerular filtration rate (eGFR, 3.4% vs. 0.2%; RR 17.72, 95% CI 1.58\n                      <jats:bold>\u2013<\/jats:bold>\n                      198.82,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.020), and rapid renal function decline (44.2% vs. 29.5%; RR 1.89, 95% CI 1.06\n                      <jats:bold>\u2013<\/jats:bold>\n                      3.37;\n                      <jats:italic>P<\/jats:italic>\n                      = 0.032). Higher-risk groups exhibited earlier and progressively worsening renal dysfunction, with eGFR decline evident as early as week 24 and UACR elevation becoming significant by week 76, both persisting through week 108. During the 224-week cardiovascular follow-up, the combined high\/very high-risk group had significantly greater risks of both MACEs (15.2% vs. 6.8%; hazard ratio [HR] 1.86, 95% CI 1.26\n                      <jats:bold>\u2013<\/jats:bold>\n                      2.74,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.001) and HF (2.8% vs. 0.5%; HR 4.58, 95% CI 1.41\n                      <jats:bold>\u2013<\/jats:bold>\n                      14.9,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.011) compared to the low-risk group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This practical risk score identifies high-risk T2D patients with cardiorenal risk, including early renal function decline, to guide targeted intervention.<\/jats:p>\n                  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China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyu","family":"Wang","sequence":"additional","affiliation":[{"name":"NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongmei","family":"Li","sequence":"additional","affiliation":[{"name":"NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology","place":["Tianjin, 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China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongai","family":"Gao","sequence":"additional","affiliation":[{"name":"NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingli","family":"Cheng","sequence":"additional","affiliation":[{"name":"NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juhong","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang, Institute 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