ArticlePloS one2022
Cardiovascular disease protein biomarkers are associated with kidney function: The Framingham Heart Study.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
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Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it, 5 citations in OpenAlex.
- Development and Validation of a Protein Risk Score for Mortality in Heart Failure : A Community Cohort Study.Annals of internal medicine · 2024Pooled it
- The multifaceted roles of MCAM in development, homeostasis, pathological conditions, and cancer.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Identification of plasma proteomic markers underlying polygenic risk of type 2 diabetes and related comorbidities.Nature communications · 2025Article
- Exploring the Plasma Proteome: Identifying Hub Proteins linking Aging, Homeostasis, and Organ Function.International journal of medical sciences · 2025Article
- Nontargeted Plasma Proteomic Analysis of Renal Disease and Pulmonary Hypertension in Patients with Sickle Cell Disease.Journal of proteome research · 2024Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundBiomarkers common to chronic kidney disease (CKD) and cardiovascular disease (CVD) may reflect early impairments underlying both diseases.
methodsWe evaluated associations of 71 CVD-related plasma proteins measured in 2,873 Framingham Heart Study (FHS) Offspring cohort participants with cross-sectional continuous eGFR and with longitudinal change in eGFR from baseline to follow-up (ΔeGFR). We also evaluated the associations of the 71 CVD proteins with the following dichotomous secondary outcomes: prevalent CKD stage ≥3 (cross-sectional), new-onset CKD stage ≥3 (longitudinal), and rapid decline in eGFR (longitudinal). Proteins significantly associated with eGFR and ΔeGFR were subsequently validated in 3,951 FHS Third Generation cohort participants and were tested using Mendelian randomization (MR) analysis to infer putatively causal relations between plasma protein biomarkers and kidney function.
resultsIn cross-sectional analysis, 37 protein biomarkers were significantly associated with eGFR at FDR<0.05 in the FHS Offspring cohort and 20 of these validated in the FHS Third Generation cohort at p<0.05/37. In longitudinal analysis, 27 protein biomarkers were significantly associated with ΔeGFR at FDR<0.05 and 12 of these were validated in the FHS Third Generation cohort at p<0.05/27. Additionally, 35 protein biomarkers were significantly associated with prevalent CKD, five were significantly associated with new-onset CKD, and 17 were significantly associated with rapid decline in eGFR. MR suggested putatively causal relations of melanoma cell adhesion molecule (MCAM; -0.011±0.003 mL/min/1.73m2, p = 5.11E-5) and epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1; -0.006±0.002 mL/min/1.73m2, p = 0.0001) concentration with eGFR. DISCUSSION/
conclusionsEight protein biomarkers were consistently associated with eGFR in cross-sectional and longitudinal analysis in both cohorts and may capture early kidney impairment; others were implicated in association and causal inference analyses. A subset of CVD protein biomarkers may contribute causally to the pathogenesis of kidney impairment and should be studied as targets for CKD treatment and early prevention.
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