Proteins Associated with Risk of Kidney Function Decline in the General Population
Copyright © 2021 by the American Society of Nephrology..
BACKGROUND: Proteomic profiling may allow identification of plasma proteins that associate with subsequent changesin kidney function, elucidating biologic processes underlying the development and progression of CKD.
METHODS: We quantified the association between 4877 plasma proteins and a composite outcome of ESKD or decline in eGFR by ≥50% among 9406 participants in the Atherosclerosis Risk in Communities (ARIC) Study (visit 3; mean age, 60 years) who were followed for a median of 14.4 years. We performed separate analyses for these proteins in a subset of 4378 participants (visit 5), who were followed at a later time point, for a median of 4.4 years. For validation, we evaluated proteins with significant associations (false discovery rate <5%) in both time periods in 3249 participants in the Chronic Renal Insufficiency Cohort (CRIC) and 703 participants in the African American Study of Kidney Disease and Hypertension (AASK). We also compared the genetic determinants of protein levels with those from a meta-analysis genome-wide association study of eGFR.
RESULTS: In models adjusted for multiple covariates, including baseline eGFR and albuminuria, we identified 13 distinct proteins that were significantly associated with the composite end point in both time periods, including TNF receptor superfamily members 1A and 1B, trefoil factor 3, and β-trace protein. Of these proteins, 12 were also significantly associated in CRIC, and nine were significantly associated in AASK. Higher levels of each protein associated with higher risk of 50% eGFR decline or ESKD. We found genetic evidence for a causal role for one protein, lectin mannose-binding 2 protein (LMAN2).
CONCLUSIONS: Large-scale proteomic analysis identified both known and novel proteomic risk factors for eGFR decline.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:32 |
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| Enthalten in: |
Journal of the American Society of Nephrology : JASN - 32(2021), 9 vom: 31. Sept., Seite 2291-2302 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Grams, Morgan E [VerfasserIn] |
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| Links: |
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| Themen: |
ESKD |
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| Anmerkungen: |
Date Completed 12.11.2021 Date Revised 03.02.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1681/ASN.2020111607 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Proteins Associated with Risk of Kidney Function Decline in the General Population |
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| 500 | |a Date Revised 03.02.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 by the American Society of Nephrology. | ||
| 520 | |a BACKGROUND: Proteomic profiling may allow identification of plasma proteins that associate with subsequent changesin kidney function, elucidating biologic processes underlying the development and progression of CKD | ||
| 520 | |a METHODS: We quantified the association between 4877 plasma proteins and a composite outcome of ESKD or decline in eGFR by ≥50% among 9406 participants in the Atherosclerosis Risk in Communities (ARIC) Study (visit 3; mean age, 60 years) who were followed for a median of 14.4 years. We performed separate analyses for these proteins in a subset of 4378 participants (visit 5), who were followed at a later time point, for a median of 4.4 years. For validation, we evaluated proteins with significant associations (false discovery rate <5%) in both time periods in 3249 participants in the Chronic Renal Insufficiency Cohort (CRIC) and 703 participants in the African American Study of Kidney Disease and Hypertension (AASK). We also compared the genetic determinants of protein levels with those from a meta-analysis genome-wide association study of eGFR | ||
| 520 | |a RESULTS: In models adjusted for multiple covariates, including baseline eGFR and albuminuria, we identified 13 distinct proteins that were significantly associated with the composite end point in both time periods, including TNF receptor superfamily members 1A and 1B, trefoil factor 3, and β-trace protein. Of these proteins, 12 were also significantly associated in CRIC, and nine were significantly associated in AASK. Higher levels of each protein associated with higher risk of 50% eGFR decline or ESKD. We found genetic evidence for a causal role for one protein, lectin mannose-binding 2 protein (LMAN2) | ||
| 520 | |a CONCLUSIONS: Large-scale proteomic analysis identified both known and novel proteomic risk factors for eGFR decline | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a ESKD | |
| 650 | 4 | |a proteomics | |
| 700 | 1 | |a Surapaneni, Aditya |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jingsha |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Linda |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Zhi |e verfasserin |4 aut | |
| 700 | 1 | |a Dutta, Diptavo |e verfasserin |4 aut | |
| 700 | 1 | |a Welling, Paul A |e verfasserin |4 aut | |
| 700 | 1 | |a Chatterjee, Nilanjan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jingning |e verfasserin |4 aut | |
| 700 | 1 | |a Arking, Dan E |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Teresa K |e verfasserin |4 aut | |
| 700 | 1 | |a Rebholz, Casey M |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Bing |e verfasserin |4 aut | |
| 700 | 1 | |a Schlosser, Pascal |e verfasserin |4 aut | |
| 700 | 1 | |a Rhee, Eugene P |e verfasserin |4 aut | |
| 700 | 1 | |a Ballantyne, Christie M |e verfasserin |4 aut | |
| 700 | 1 | |a Boerwinkle, Eric |e verfasserin |4 aut | |
| 700 | 1 | |a Lutsey, Pamela L |e verfasserin |4 aut | |
| 700 | 1 | |a Mosley, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Feldman, Harold I |e verfasserin |4 aut | |
| 700 | 1 | |a Dubin, Ruth F |e verfasserin |4 aut | |
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| 700 | 1 | |a Lee, Hongzhe |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Zihe |e verfasserin |4 aut | |
| 700 | 1 | |a Coresh, Josef |e verfasserin |4 aut | |
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