Proteins Associated with Risk of Kidney Function Decline in the General Population.

TitleProteins Associated with Risk of Kidney Function Decline in the General Population.
Publication TypeJournal Article
Year of Publication2021
AuthorsGrams, ME, Surapaneni, A, Chen, J, Zhou, L, Yu, Z, Dutta, D, Welling, PA, Chatterjee, N, Zhang, J, Arking, DE, Chen, TK, Rebholz, CM, Yu, B, Schlosser, P, Rhee, EP, Ballantyne, CM, Boerwinkle, E, Lutsey, PL, Mosley, T, Feldman, HI, Dubin, RF, Ganz, P, Lee, H, Zheng, Z, Coresh, J
JournalJ Am Soc Nephrol
Volume32
Issue9
Pagination2291-2302
Date Published2021 09
ISSN1533-3450
KeywordsAge Factors, Aged, Cohort Studies, Female, Glomerular Filtration Rate, Humans, Male, Middle Aged, Proteomics, Renal Insufficiency, Chronic, Risk Factors
Abstract

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

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 -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.

DOI10.1681/ASN.2020111607
Alternate JournalJ Am Soc Nephrol
PubMed ID34465608
PubMed Central IDPMC8729856
Grant ListUL1 TR000439 / TR / NCATS NIH HHS / United States
UL1 TR000424 / TR / NCATS NIH HHS / United States
UL1 TR002548 / TR / NCATS NIH HHS / United States
U01 DK061021 / DK / NIDDK NIH HHS / United States
U24 DK060990 / DK / NIDDK NIH HHS / United States
U01 DK060963 / DK / NIDDK NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
R01 HL134320 / HL / NHLBI NIH HHS / United States
U01 DK060902 / DK / NIDDK NIH HHS / United States
P20 GM109036 / GM / NIGMS NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
U01 DK060984 / DK / NIDDK NIH HHS / United States
R01 DK089174 / DK / NIDDK NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
U01 DK060980 / DK / NIDDK NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
R01 DK119199 / DK / NIDDK NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
UL1 TR000003 / TR / NCATS NIH HHS / United States
M01 RR016500 / RR / NCRR NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
U01 DK060990 / DK / NIDDK NIH HHS / United States
R01 DK108803 / DK / NIDDK NIH HHS / United States
R01 DK124399 / DK / NIDDK NIH HHS / United States
UL1 RR024131 / RR / NCRR NIH HHS / United States
U01 DK085689 / DK / NIDDK NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
U01 DK061022 / DK / NIDDK NIH HHS / United States
UL1 TR000433 / TR / NCATS NIH HHS / United States
UL1 RR029879 / RR / NCRR NIH HHS / United States
U01 DK106981 / DK / NIDDK NIH HHS / United States
U01 DK061028 / DK / NIDDK NIH HHS / United States