Metabolome-derived kidney function scores as prognostic readouts of cardiovascular-kidney-metabolic health.
Year: 2026
Type: preprint
Abstract: Kidney disease is a rapidly growing global health concern, tightly linked to cardiovascular and metabolic disease within the recently defined cardiovascular-kidney-metabolic (CKM) syndrome. Routine clinical assessment of kidney function primarily relies on creatinine-based estimated glomerular filtration rates (eGFRcr) which can be affected by non-renal factors and declines only after substantial kidney damage. Using data from the MetaCardis study (N=1,723), we derived metabolomic kidney function gaps (mKFGs)-the difference between metabolome-predicted eGFRcr and measured eGFRcr. A physiology-guided feature-selection strategy - anchored on three cardiometabolic markers (haemoglobin, albumin and the Neutrophil-to-Lymphocyte Ratio) that associate with mKFGs but not with eGFRcr - yielded compact sex-stratified metabolite panels (40-98 out of 1,514 metabolites) that tracked cardiovascular-kidney-metabolic risk. Machine-Learning models revealed distinct metabolic signatures, including biomarkers of meat consumption and androgens, highlighting potential sex-specific pathways linked to CKM health. External validation in the general-population Canadian Longitudinal Study on Aging (N=9,958) and German Chronic Kidney Disease Study (N=5,113) cohorts revealed that mKFGs added incremental predictive value for future CKM events and all-cause mortality beyond eGFRcr and established risk equations. Our findings open new avenues for personalised risk stratification for CKM disease progression and targeted interventions based on metabolically defined kidney health.
Source: medRxiv
Authors: Petros Andrikopoulos, Janis M Nolde, Rima Chakaroun, Manyi Jia, Sofia K Forslund-Startceva, Judith Aron-Wisnewsky, Trine Nielsen, Elena Butz, Peggy Sekula, Sara Vieira-Silva, Gwen Falony, Angelos Manolias, Antonis Myridakis, Julien Chilloux, Kanta Chechi, Elliot Murphy, Francesc Puig-Castellvi, Christine Rouault, Christine Poitou, Pierre Bel Lassen, Romina Pacheco-Tapia, Ines Castro-Dionicio, Eugeni Belda, Emmanuelle Le Chatelier, Matthias Blueher, Jens Nielsen, Jeroen Raes, Peer Bork, Lars Koeber, Henrik Vestergaard, Torben Hansen, Philippe Froguel, Jean-Daniel Zucker, Mark Lathrop, Parminder Raina, Kai-Uwe Eckardt, Jean-Michel Oppert, S. Dusko Ehrlich, Fredrik Backhed, Anna Koettgen, Michael Stumvoll, Oluf Pedersen, Karine Clement, Marc-Emmanuel Dumas
Institutions: Imperial College London, University of Freiburg, Leipzig University, Max Delbrück Center, Sorbonne Université, University of Copenhagen, Johannes Gutenberg University Mainz, Wageningen University & Research, Université de Lille, Université Paris-Saclay, Chalmers University of Technology, KU Leuven, European Molecular Biology Laboratory, European Molecular Biology Laboratory, McGill University, McMaster University, Charité – Universitätsmedizin Berlin, University College London, University of Gothenburg
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7225749847
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