Proteomics of CKD progression in the chronic renal insufficiency cohort.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 10 2023
10 10 2023
Historique:
received:
03
03
2023
accepted:
13
09
2023
medline:
27
10
2023
pubmed:
11
10
2023
entrez:
10
10
2023
Statut:
epublish
Résumé
Progression of chronic kidney disease (CKD) portends myriad complications, including kidney failure. In this study, we analyze associations of 4638 plasma proteins among 3235 participants of the Chronic Renal Insufficiency Cohort Study with the primary outcome of 50% decline in estimated glomerular filtration rate or kidney failure over 10 years. We validate key findings in the Atherosclerosis Risk in the Communities study. We identify 100 circulating proteins that are associated with the primary outcome after multivariable adjustment, using a Bonferroni statistical threshold of significance. Individual protein associations and biological pathway analyses highlight the roles of bone morphogenetic proteins, ephrin signaling, and prothrombin activation. A 65-protein risk model for the primary outcome has excellent discrimination (C-statistic[95%CI] 0.862 [0.835, 0.889]), and 14/65 proteins are druggable targets. Potentially causal associations for five proteins, to our knowledge not previously reported, are supported by Mendelian randomization: EGFL9, LRP-11, MXRA7, IL-1 sRII and ILT-2. Modifiable protein risk markers can guide therapeutic drug development aimed at slowing CKD progression.
Identifiants
pubmed: 37816758
doi: 10.1038/s41467-023-41642-7
pii: 10.1038/s41467-023-41642-7
pmc: PMC10564759
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
6340Subventions
Organisme : NHLBI NIH HHS
ID : U01 HL096812
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK108809
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL096917
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK060963
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL096902
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024131
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK061022
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700004I
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000439
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL096814
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700003I
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR029879
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK061028
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000433
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM129781
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK060984
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 DK060980
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK119199
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700002C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700001I
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000003
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000424
Pays : United States
Organisme : NCRR NIH HHS
ID : M01 RR016500
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM109036
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK060902
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK124399
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK060990
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700005C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700001C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700003C
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL096899
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700004C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700002I
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700005I
Pays : United States
Informations de copyright
© 2023. Springer Nature Limited.
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