Oral Presentation AUS-oMicS 2025

Arteriovenous sampling for organ-specific metabolic insights in CKM syndrome (#38)

Dana Hicks 1 2 , Natalie C Ward 3 , Bu Yeap 4 5 , Girish Dwivedi 4 6 , Julien Wist 1 , Markus Schlaich 3 7 , Nicola Gray 1 2
  1. Australian National Phenome Centre, Murdoch University, Australian National Phenome Centre, Health Futures Institute, Murdoch University, Murdoch, WA, Australia
  2. Computational and Systems Medicine, Health Futures Institute, Murdoch University, Perth, WA , Australia
  3. Dobney Hypertension Centre, Medical School - Royal Perth Hospital Unit, The University of Western Australia, , Perth, WA, Australia
  4. Medical School, University of Western Australia, Perth, WA, Australia
  5. Department of Endocrinology and Diabetes, Fiona Stanley Hospital , Perth, WA, Australia
  6. Department of Cardiology, Fiona Stanley Hospital, Perth, WA, Australia
  7. RPH Research Foundation, Perth, WA, Australia

Introduction

Cardiovascular-kidney-metabolic (CKM) syndrome includes interconnected conditions like obesity, diabetes, chronic kidney disease, and cardiovascular disease, which are closely linked through metabolic processes often arising from shared mechanisms and risk factors. To better understand the roles of lipids, lipoproteins, and small molecules in these biological processes, examining organ-specific arteriovenous gradients (AVG) between the heart and kidney can help develop targeted therapies and improve patient outcomes.

Methods

Samples from a double-blind crossover trial were analysed to assess metabolic disparities between the heart and kidneys. Participants (n=18) with Stage 2 CKM received Empagliflozin or a placebo daily for 4 weeks, followed by a 4-week washout, then swapped treatments for another 4 weeks. At the end of each phase, coronary sinus, renal vein, and radial artery samples were obtained via catheterisation. Lipidomic analysis was performed using liquid chromatography-mass spectrometry, and lipoprotein and small molecule analysis using nuclear magnetic resonance spectroscopy. Significant analytes identified by the Friedman test, paired Wilcoxon signed-rank test, and VIP scores >1 from PLS-DA were further investigated. Heart and kidney AVGs from paired samples were determined to assess organ-specific differences.

Results

Significant differences were observed between the heart and kidneys, as indicated by AVG analysis. Specifically, the subfractions of very-low-density lipoproteins showed a net uptake by the heart, while no significant lipoproteins were associated with the kidney. The heart and kidney also demonstrated significant uptake of distinct long-chain fatty acids. Additionally, the kidney showed a net uptake of diacylglycerol and lysophosphatidylethanolamine species. Small molecule analysis showed the heart's glutamic acid and acetoacetic acid uptake. In contrast, the kidney took up glutamine and citric acid while releasing acetoacetic acid.

Conclusion

This study is the first to use arteriovenous sampling for metabolic phenotyping analysis to reveal organ-specific metabolic activity in the heart and kidney associated with Stage 2 CKM.