Plasma Proteomic Profile of Dietary Potassium and Incident CKD

Key Points We identified ten plasma proteins associated with dietary potassium and CKD risk in a US adult population. These proteins highlighted mechanisms involving iron deposition, mitochondrial function, kidney inflammation, and fibrosis. Promoting the consumption of potassium-rich foods could be an effective strategy for CKD prevention. 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 =6814) and replication ( n =3380) sets. We examined associations between dietary potassium and 4955 aptamers using multivariable linear regression, adjusting for sociodemographic factors, health behaviors, and eGFR, with a false discovery rate of 0.05. Then, we tested the prospective associations between potassium-related proteins and incident 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, 1698 CKD cases developed. A score derived from 30 elastic net-selected dietary potassium-related proteins was associated with 7% lower risk of CKD (95% confidence interval, 0.88 to 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% confidence interval, 0.83 to 0.92; P = 8.09×10 −7 ). Conclusion Proteins associated with dietary potassium and incident CKD represented biologic pathways including iron metabolism, mitochondrial function, fibrosis, and immune-inflammatory responses, which help explain the effect of potassium intake on CKD.