Serum Metabolomic Markers of Dietary Potassium and Risk of CKD

Key Points We identified metabolomic markers of dietary potassium and diet-related metabolites that were associated with incident CKD in US adults. These metabolites may be prioritized for elucidating mechanisms that could be modified by dietary strategies to prevent CKD. Background Discovering metabolomic markers of dietary potassium may help improve dietary assessment of potassium and trace the effect of dietary potassium on CKD development. Methods We included adults from the Atherosclerosis Risk in Communities study without CKD at visit 1 ( N =3812). Cross-sectional associations between dietary potassium and serum metabolites were assessed using multivariable linear regression models. Cox regression models estimated hazard ratios for potassium-related metabolites and incident CKD. Incident CKD was defined as eGFR (<60 ml/min per 1.73 m 2 and ≥25% decline), CKD-related hospitalization or death, or KRT identified using the United States Renal Data System registry from visit 1 (1987–1989) through December 31, 2020. Results There were 33 significant associations between dietary potassium and serum metabolites, including pyridoxate, N -methylproline, stachydrine, pantothenate, and scyllo-inositol. During more than two decades of follow-up (median: 23 years, 25th–75th percentile: 14–30), 1616 (42%) of participants developed incident CKD. Ten of the 33 potassium-related metabolites were significantly associated with incident CKD. Metabolites involved in phenylalanine and tyrosine metabolism—3-(4-hydroxyphenyl)lactate and 3-phenylpropionate—were significantly associated with dietary potassium and CKD. In addition, glycerate, involved in glucose metabolism, was positively associated with dietary potassium ( β =0.09, P = 4.01×10 −17 ) and inversely associated with CKD (hazard ratio, 0.77; 95% confidence interval, 0.69 to 0.85; P = 8.57×10 −7 ). There was a significant trend for CKD risk across quartiles of 3-(4-hydroxyphenyl)lactate, 3-phenylpropionate, and glycerate. Conclusions Dietary potassium was associated with 33 serum metabolites. 3-(4-hydroxyphenyl)lactate 3-phenylpropionate and glycerate are candidate markers of dietary potassium's effect on CKD.