#264 Kidney function and the metabolome in the general population

Abstract Background and Aims A reduction in kidney function cause metabolites that normally are cleared by the kidney to accumulate. These metabolites could potentially link kidney function to an increased risk of cardiovascular disease. To assess the relationships between creatinine-based estimated glomerular filtration rate (eGFR) and the metabolome (791 endogenous metabolites) in the general population, with particular focus on the cortisol to cortisone ratio. Method Three population-based cohorts, Epihealth, PIVUS and POEM (total n = 3444), were used with a discovery/validation approach. Metabolomics was measured by mass spectroscopy. eGFR was calculated using the 2021 CKD-EPI creatinine-based equation. Multivariate linear regression was used to assess the correlations between each metabolite concentration and eGFR adjusting for sex, % fat mass, cardiovascular risk factors and medications. A pathway enrichment analysis was performed using MetaboAnalyst 6.0. Results In the fully adjusted regression model, 227 metabolites were significantly related to eGFR. Six of these were positively while the remaining were inversely correlated. Creatinine was the strongest negatively and cortisone the strongest positively correlated metabolite. The cortisol/cortisone ratio was significantly negatively related with eGFR (FDr = 0.021). Pathway enrichment analysis found 11 significantly enriched pathways (see table 1). The majority of these involved amino acid metabolism. Conclusion In this study of kidney function vs metabolome in a general population with only mild to moderately reduced kidney function, several metabolites, including the cortisol to cortisone ratio, related also to risk of cardiovascular disease were associated with kidney function.