{"doi":"10.1159/000547138","title":"Circulating Proteins for Prediction of Kidney Disease Progression and Cardiovascular Outcomes: Individual Participant Data Meta-Analysis of Four Cohorts","abstract":"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 <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: 0.78-0.90; kidney failure, C-statistic range: 0.75-0.93; and CVD, C-statistic range: 0.59-0.79. 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 < 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 <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.","journal":"American Journal of Nephrology","year":2025,"id":569370,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":232664,"name":"Aditya Surapaneni","orcid":"0000-0003-4978-5980","position":1,"is_corresponding":false},{"id":23021,"name":"Josef Coresh","orcid":"0000-0002-4598-0669","position":2,"is_corresponding":false},{"id":378741,"name":"Teresa K. 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Kimmel","orcid":null,"position":12,"is_corresponding":false},{"id":228813,"name":"Sarah J. Schrauben","orcid":"0000-0003-2557-5161","position":13,"is_corresponding":false},{"id":241229,"name":"Chirag R. Parikh","orcid":"0000-0001-9051-7385","position":14,"is_corresponding":false},{"id":34474,"name":"Joseph V. Bonventre","orcid":"0000-0001-7144-386X","position":15,"is_corresponding":false},{"id":292966,"name":"Mirela Dobre","orcid":"0000-0002-9059-9998","position":16,"is_corresponding":false},{"id":277170,"name":"Panduranga S. Rao","orcid":"0000-0002-4699-5395","position":17,"is_corresponding":false},{"id":348121,"name":"Ana C. Ricardo","orcid":"0000-0001-8670-3644","position":18,"is_corresponding":false},{"id":244987,"name":"Matthew R. Weir","orcid":"0000-0001-8820-5702","position":19,"is_corresponding":false},{"id":73169,"name":"Morgan E. Grams","orcid":"0000-0002-4430-6023","position":20,"is_corresponding":false},{"id":283357,"name":"the CRIC Study Investigators","orcid":null,"position":21,"is_corresponding":false},{"id":1285389,"name":"Carolina Lopez-Silva","orcid":null,"position":0,"is_corresponding":true}],"reference_count":1,"raw_metadata":null,"created_at":"2026-07-19T02:56:59.652443Z","pmid":"40587944","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}