(P39-20-26) Proteomic Biomarkers of Inflammation and Their Associations With Diet, Incident Kidney Disease, and Death

Objectives: To characterize inflammatory proteins associated with a healthy dietary pattern and investigate their associations with incident kidney disease and all-cause mortality.

Methods: We assessed cross-sectional associations between Alternate Healthy Eating Index (AHEI) scores and plasma proteins in Atherosclerosis Risk in Communities (ARIC) Carotid MRI substudy participants with diabetes (2005-06; n=245) using multivariable linear regression. Dietary intake was assessed using a 148-item food frequency questionnaire. Immune-related proteins were profiled using the NULISAseq Inflammation Panel 250 (Alamar) and log₂ transformed for analysis. We examined prospective associations between AHEI-related proteins, incident kidney disease, and death using Cox proportional hazards regression. Incident kidney disease was defined based on: eGFR < 60 ml/min per 1.73 m², accompanied by ≥25% eGFR decline from baseline; kidney disease-related hospitalization or death; or initiation of dialysis or transplantation. Statistical significance was evaluated at a false discovery rate q < 0.05.

Results: Participants (58% female, 100% White) had a mean age of 72 years and eGFR 76 mL/min/m³. Higher AHEI scores were associated with lower levels of 17 proteins. Considering AHEI scoring components individually, trans fat intake was associated with the most proteins (7 of 17). Among participants with baseline eGFR >60 mL/min/m³ (n=190), incident kidney disease occurred in 87 people over 11 years median follow-up. Five AHEI-related proteins were associated with incident kidney disease, including two members of the tumor necrosis factor receptor superfamily. Ranked by p-value, signaling lymphocytic activation molecule (SLAMF1) was most strongly associated with kidney disease. Over 14 years median follow-up, 167 deaths occurred. Fourteen AHEI-related proteins were associated with mortality. Hepatocyte growth factor and interleukin 10 receptor subunit beta (IL10RB) were most strongly associated with mortality.

Conclusions: Higher adherence to the AHEI was associated with lower levels of inflammatory proteins, many of which were linked to a higher risk of incident kidney disease and mortality. These proteins may represent immune-related mechanisms underlying effects of a healthy dietary pattern.

Funding Sources: NIH