Proteins Associated with Risk of Kidney Function Decline in the General Population.
ESKD
proteomics
Journal
Journal of the American Society of Nephrology : JASN
ISSN: 1533-3450
Titre abrégé: J Am Soc Nephrol
Pays: United States
ID NLM: 9013836
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
16
11
2020
accepted:
22
04
2021
entrez:
1
9
2021
pubmed:
2
9
2021
medline:
16
11
2021
Statut:
ppublish
Résumé
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. 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. 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 Large-scale proteomic analysis identified both known and novel proteomic risk factors for eGFR decline.
Sections du résumé
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
CONCLUSIONS
Large-scale proteomic analysis identified both known and novel proteomic risk factors for eGFR decline.
Identifiants
pubmed: 34465608
pii: 00001751-202109000-00022
doi: 10.1681/ASN.2020111607
pmc: PMC8729856
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2291-2302Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR000439
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000424
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002548
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK061021
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK060990
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK060963
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL086694
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004402
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700005I
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL134320
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK060902
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM109036
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR025005
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK060984
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK089174
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700001I
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK060980
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700004I
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK119199
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL059367
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700002I
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000003
Pays : United States
Organisme : NCRR NIH HHS
ID : M01 RR016500
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700003I
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK060990
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK108803
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK124399
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024131
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK085689
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL087641
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK061022
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000433
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR029879
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK106981
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK061028
Pays : United States
Informations de copyright
Copyright © 2021 by the American Society of Nephrology.
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