Abstract
BACKGROUND: There is a need for objective biomarkers of dietary potassium. The mechanisms through which dietary potassium influences kidney health are incompletely understood. METHODS: Atherosclerosis Risk in Communities study participants at visit 3 (1993–1995) with dietary and proteomics data were randomly divided into discovery (N=6,814) and replication (N=3,380) sets. We examined associations between dietary potassium and 4,955 aptamers using multivariable linear regression, adjusting for sociodemographic factors, health behaviors, and estimated glomerular filtration rate, with a false discovery rate of 0.05. Then, we tested the prospective associations between potassium-related proteins and incident chronic kidney disease (CKD). RESULTS: Dietary potassium was significantly associated with 147 proteins in discovery, of which 85 (33 positive, 52 negative) replicated. Of 85 replicated proteins, 30 were selected by elastic net and improved prediction of high dietary potassium individually and collectively. Over a median follow-up of 21 years, 1,698 CKD cases developed. A score derived from 30 elastic net-selected dietary potassium-related proteins was associated with 7% lower risk of CKD (95% CI, 0.88–0.98, P=0.01). Of 85 potassium-related proteins from replication, 10 were associated with incident CKD. Specifically, pigment epithelium-derived factor and follistatin-related protein 3 were inversely associated with potassium and linked to 57% and 55% higher risk of CKD, respectively. Positively associated with potassium, TOM1-like protein 1 and serine/threonine-protein kinase pim-1 were associated with 28% and 26% lower risk of CKD, respectively. A score of 6 proteins mediated the association between potassium and CKD risk was associated with 13% lower risk of CKD (95% CI, 0.83–0.92, P=8.09×10(−7)). CONCLUSION: Proteins associated with dietary potassium and incident CKD represented biological pathways including iron metabolism, mitochondrial function, fibrosis, and immune-inflammatory responses, which help explain the impact of potassium intake on CKD.