Blood proteomics profiles are associated with progression of chronic kidney disease over 9 years: A prospective...

Chronic kidney disease (CKD) is a major health burden, yet its underlying mechanisms and early predictors remain poorly understood.

This prospective study identified serum proteins associated with incident CKD and examined their upstream determinants related to inflammation and diet.

A total of 2,182 participants with baseline serum proteomic data and repeated measurements of estimated glomerular filtration rate (eGFR) over four 3-year intervals were included. Proteins associated with incident CKD were identified using multivariable-adjusted models, with internal validation from repeated measurements and external replication in the UK Biobank (UKB). Associations of CKD-related proteins with serum inflammatory markers, inflammation-related dietary indices, and serum carotenoids were also examined.

Twenty-two proteins were associated with 9-year CKD risk (11 positively and 11 inversely; adjusted p < 0.05). A combined protein score predicted CKD with an area under the curve (AUC) of 0.75 in the discovery cohort, 0.76 in the internal validation using averaged protein data, and 0.70 in the UKB replication using 15 overlapping proteins. Standardized hazard ratios of CKD risk ranged from 1.31 to 1.66 for the top 4 risk proteins (PEDF, CFAD, RET4, APOH) and from 0.77 to 0.80 for the top 4 protective proteins (A1BG, A2AP, ENAM, GPX3) (all adjusted p < 0.01). Inflammatory markers (e.g., C-reactive protein) were positively associated with deleterious proteins and inversely associated with protective ones. Higher serum carotenoid concentrations and DASH diet scores were associated with lower inflammatory markers and more favorable CKD-related protein profiles.

We identified 22 serum proteins associated with CKD incidence, supporting their potential for early prediction and mechanistic insight. Systemic inflammation was adversely associated with, whereas circulating carotenoids were beneficially associated with, CKD-related protein profiles.