Language
English
Publication Date
6-1-2023
Journal
Journal of the American Society of Nephrology
DOI
10.1681/ASN.0000000000000108
PMID
36890639
PMCID
PMC10278823
PubMedCentral® Posted Date
3-9-2023
PubMedCentral® Full Text Version
Post-print
Abstract
Significance statement: We describe circulating proteins associated with albuminuria in a population of African American Study of Kidney Disease and Hypertension with CKD (AASK) using the largest proteomic platform to date: nearly 7000 circulating proteins, representing approximately 2000 new targets. Findings were replicated in a subset of a general population cohort with kidney disease (ARIC) and a population with CKD Chronic Renal Insufficiency Cohort (CRIC). In cross-sectional analysis, 104 proteins were significantly associated with albuminuria in the Black group, of which 67 of 77 available proteins were replicated in ARIC and 68 of 71 available proteins in CRIC. LMAN2, TNFSFR1B, and members of the ephrin superfamily had the strongest associations. Pathway analysis also demonstrated enrichment of ephrin family proteins.
Background: Proteomic techniques have facilitated understanding of pathways that mediate decline in GFR. Albuminuria is a key component of CKD diagnosis, staging, and prognosis but has been less studied than GFR. We sought to investigate circulating proteins associated with higher albuminuria.
Methods: We evaluated the cross-sectional associations of the blood proteome with albuminuria and longitudinally with doubling of albuminuria in the African American Study of Kidney Disease and Hypertension (AASK; 38% female; mean GFR 46; median urine protein-to-creatinine ratio 81 mg/g; n =703) and replicated in two external cohorts: a subset of the Atherosclerosis Risk in Communities (ARIC) study with CKD and the Chronic Renal Insufficiency Cohort (CRIC).
Results: In cross-sectional analysis, 104 proteins were significantly associated with albuminuria in AASK, of which 67 of 77 available proteins were replicated in ARIC and 68 of 71 available proteins in CRIC. Proteins with the strongest associations included LMAN2, TNFSFR1B, and members of the ephrin superfamily. Pathway analysis also demonstrated enrichment of ephrin family proteins. Five proteins were significantly associated with worsening albuminuria in AASK, including LMAN2 and EFNA4, which were replicated in ARIC and CRIC.
Conclusions: Among individuals with CKD, large-scale proteomic analysis identified known and novel proteins associated with albuminuria and suggested a role for ephrin signaling in albuminuria progression.
Keywords
Humans, Female, Male, Albuminuria, Proteome, Cross-Sectional Studies, Proteomics, Glomerular Filtration Rate, Renal Insufficiency, Chronic, Hypertension, Risk Factors
Published Open-Access
yes
Recommended Citation
Kiernan, Elizabeth; Surapaneni, Aditya; Zhou, Linda; et al., "Alterations in the Circulating Proteome Associated with Albuminuria" (2023). Faculty, Staff and Students Publications. 6668.
https://digitalcommons.library.tmc.edu/baylor_docs/6668
Graphical Abstract