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Cardiovascular disease protein biomarkers are associated with kidney function: The Framingham Heart Study

BACKGROUND: Biomarkers common to chronic kidney disease (CKD) and cardiovascular disease (CVD) may reflect early impairments underlying both diseases. METHODS: We evaluated associations of 71 CVD-related plasma proteins measured in 2,873 Framingham Heart Study (FHS) Offspring cohort participants wit...

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Autores principales: Keshawarz, Amena, Hwang, Shih-Jen, Lee, Gha Young, Yu, Zhi, Yao, Chen, Köttgen, Anna, Levy, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9094507/
https://www.ncbi.nlm.nih.gov/pubmed/35544531
http://dx.doi.org/10.1371/journal.pone.0268293
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author Keshawarz, Amena
Hwang, Shih-Jen
Lee, Gha Young
Yu, Zhi
Yao, Chen
Köttgen, Anna
Levy, Daniel
author_facet Keshawarz, Amena
Hwang, Shih-Jen
Lee, Gha Young
Yu, Zhi
Yao, Chen
Köttgen, Anna
Levy, Daniel
author_sort Keshawarz, Amena
collection PubMed
description BACKGROUND: Biomarkers common to chronic kidney disease (CKD) and cardiovascular disease (CVD) may reflect early impairments underlying both diseases. METHODS: We 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. RESULTS: In 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/1.73m(2), p = 5.11E-5) and epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1; -0.006±0.002 mL/min/1.73m(2), p = 0.0001) concentration with eGFR. DISCUSSION/CONCLUSIONS: Eight 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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spelling pubmed-90945072022-05-12 Cardiovascular disease protein biomarkers are associated with kidney function: The Framingham Heart Study Keshawarz, Amena Hwang, Shih-Jen Lee, Gha Young Yu, Zhi Yao, Chen Köttgen, Anna Levy, Daniel PLoS One Research Article BACKGROUND: Biomarkers common to chronic kidney disease (CKD) and cardiovascular disease (CVD) may reflect early impairments underlying both diseases. METHODS: We 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. RESULTS: In 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/1.73m(2), p = 5.11E-5) and epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1; -0.006±0.002 mL/min/1.73m(2), p = 0.0001) concentration with eGFR. DISCUSSION/CONCLUSIONS: Eight 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. Public Library of Science 2022-05-11 /pmc/articles/PMC9094507/ /pubmed/35544531 http://dx.doi.org/10.1371/journal.pone.0268293 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Keshawarz, Amena
Hwang, Shih-Jen
Lee, Gha Young
Yu, Zhi
Yao, Chen
Köttgen, Anna
Levy, Daniel
Cardiovascular disease protein biomarkers are associated with kidney function: The Framingham Heart Study
title Cardiovascular disease protein biomarkers are associated with kidney function: The Framingham Heart Study
title_full Cardiovascular disease protein biomarkers are associated with kidney function: The Framingham Heart Study
title_fullStr Cardiovascular disease protein biomarkers are associated with kidney function: The Framingham Heart Study
title_full_unstemmed Cardiovascular disease protein biomarkers are associated with kidney function: The Framingham Heart Study
title_short Cardiovascular disease protein biomarkers are associated with kidney function: The Framingham Heart Study
title_sort cardiovascular disease protein biomarkers are associated with kidney function: the framingham heart study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9094507/
https://www.ncbi.nlm.nih.gov/pubmed/35544531
http://dx.doi.org/10.1371/journal.pone.0268293
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