{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T16:58:28Z","timestamp":1780937908448,"version":"3.54.1"},"reference-count":45,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Nephrol"],"abstract":"<jats:p>Introduction: KIM-1, TNFRSF1A, and TNFRSF1B have been accepted as early risk markers in diabetic kidney disease by the US Food and Drug Administration. Whether they may be useful in identifying high-risk patients for cardiovascular\/kidney clinical trial enrollment in other important subgroups is uncertain. Methods: We evaluated the potential prognostic enrichment of KIM-1, TNFRSF1A, and TNFRSF1B in four cohorts: the Atherosclerosis Risk in Communities (ARIC) (N = 4,594, mean age 76 years, 55% women, mean eGFR 68 mL\/min\/1.73 m2), African American Study of Kidney Disease and Hypertension (AASK) (N = 705, mean age 55 years, 39% women, mean mGFR 46 mL\/min\/1.73 m2), Chronic Renal Insufficiency Cohort (CRIC) (N = 2,943, mean age 59 years, 45% women, mean eGFR 35 mL\/min\/1.73 m2), and Boston Kidney Biopsy Cohort (BKBC) (N = 434, mean age 54 years, 48% women, mean eGFR 51 mL\/min\/1.73 m2). We evaluated three outcomes: 40% glomerular filtration rate (GFR) decline, kidney failure, and incident cardiovascular disease (CVD) overall and in two subgroups historically underrepresented in clinical trials: participants with no diabetes, and those with albuminuria &lt;200 mg\/g. Results: Published models (40% decline tool, kidney failure risk equation, and PREVENT) using clinical variables had moderate to strong risk discrimination in each cohort: 40% GFR decline, AUROC range: 0.78\u20130.90; kidney failure, C-statistic range: 0.75\u20130.93; and CVD, C-statistic range: 0.59\u20130.79. After addition of biomarkers, there was a small but significant improvement in the meta-analyzed overall population: change in AUROC in 40% GFR decline: 0.02, p &lt; 0.001; change in C-statistic for kidney failure: 0.01, p = 0.02; change in C-statistic for CVD: 0.01, p = 0.03. Among participants without diabetes, the change was statistically significant only for 40% decline; among patient with albuminuria &lt;200 mg\/g, the change was statistically significant only for the two kidney outcomes. Conclusion: KIM-1, TNFRSF1A, and TNFRSF1B may not be strong prognostic enrichment biomarkers over and above clinical risk estimates. Clinical trials should test whether they help with predictive enrichment.<\/jats:p>","DOI":"10.1159\/000547138","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T12:02:45Z","timestamp":1751284965000},"page":"328-339","source":"Crossref","is-referenced-by-count":0,"title":["Circulating Proteins for Prediction of Kidney Disease Progression and Cardiovascular Outcomes: Individual Participant Data Meta-Analysis of Four Cohorts"],"prefix":"10.1159","volume":"57","author":[{"given":"Carolina","family":"Lopez-Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Surapaneni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Coresh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa 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