Arteriovenous Sampling for Organ-Specific Metabolic Insights in CKM Syndrome

Cardiovascular-kidney-metabolic (CKM) syndrome recognises connections among obesity, diabetes, chronic kidney disease, and cardiovascular disease, describing the close metabolic links and shared risk factors including dyslipidemia, hypertension, and metabolic dysfunction. While the concentrations of circulating metabolites have been frequently measured in these varied pathophysiological conditions, the flux of metabolites between and across organs is not easily captured. Arteriovenous sampling provides a transformative approach to metabolite gradient measurements offering new insights into organ-specific regulation of lipid, lipoprotein, and small molecule metabolism. Here, arteriovenous sampling was used to determine organ-specific metabolic differences between the heart and kidney compared with peripheral venous differences. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and nuclear magnetic resonance (NMR) analysis was performed to assess lipids, lipoproteins and small molecules in peripheral venous, coronary sinus (CS), renal vein and radial artery samples collected from 18 participants with stage 1-2 CKM. Paired arterial-CS and arterial-renal vein gradients revealed significant differences in lipid and lipoprotein metabolism. The heart exhibited net uptake of long-chain fatty acids (e.g., FA(18:0), FA(20:3)) and very-low-density lipoprotein (VLDL) subfractions (e.g., VLFC, VLAB), along with a net release of lysophosphatidylethanolamine (LPE(18:2)). In contrast, the kidney showed net uptake of diacylglycerols (DG), fatty acids (e.g., FA(14:0), FA(16:1)), and lysophospholipids (e.g., LPE(20:4)). Significant differences in glutamine, citric acid, lactic acid, and pyruvic acid gradients between the heart and kidneys were noted, with each analyte showing a net uptake by its respective organ. Our findings highlight the comprehensive changes in organ-specific metabolites and lipids that occur between the heart and kidneys. These data indicate the value of arteriovenous sampling in understanding the metabolic differences between the heart and kidneys, and its potential to explore bidirectional metabolic crosstalk between these organs.