Cardio-Kidney-Metabolic Syndrome: Unraveling Pathophysiological Cross-Talk and Novel Therapeutic Pathways

Cardio-kidney-metabolic (CKM) syndrome represents a unified clinical entity at the intersection of cardiovascular disease, chronic kidney disease, and metabolic disorders such as diabetes and obesity. These conditions share overlapping risk factors and interconnected pathophysiologic mechanisms that drive progression and adverse outcomes, making CKM syndrome one of the most pressing global health challenges.

A multitude of mechanisms underlie the development and progression of CKM syndrome. These include systemic inflammation, oxidative stress, neurohormonal activation, endothelial dysfunction, mitochondrial injury, fibrosis, and maladaptive metabolic signaling. Crosstalk between organs—such as the kidney–heart axis, heart–liver–adipose axis, and gut microbiome–immune system interactions—further amplifies disease burden. This intricate interplay opens new avenues for diagnostics and therapeutic innovations.

Until recently, management approaches were largely organ specific. A paradigm shift has emerged with the advent of drugs such as sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and the non-steroidal mineralocorticoid receptor antagonist (ns-MRA) finerenone, all of which demonstrate pleiotropic benefits across the cardiovascular, renal, and metabolic axes. Additional promising strategies include therapies targeting inflammation, fibrosis, hypoxia-inducible pathways, aldosterone synthase inhibitors, and novel modulators of metabolic signaling.

This Research Topic aims to deepen our understanding of CKM syndrome by integrating insights from mechanistic studies, pharmacologic and non-pharmacologic interventions, biomarker research, and clinical outcomes. We welcome manuscripts of original research, systematic reviews, mini-reviews, hypotheses, clinical trials, theory, and perspectives that address (but are not limited to) the following themes:

1. Pathophysiological crosstalk among cardiovascular, renal, and metabolic systems—mechanistic insights from preclinical and clinical studies.

2. Epidemiology and clinical outcomes of CKM syndrome in diverse populations, including those with obesity, diabetes, and advanced kidney disease.

3. Pharmacologic interventions: renin–angiotensin system inhibitors, SGLT2 inhibitors, GLP-1RAs, MRAs, and emerging therapies targeting inflammation, fibrosis, or metabolic reprogramming.

4. Precision medicine approaches—genomic, proteomic, metabolomic, and digital health applications for early diagnosis, risk stratification, and individualized treatment.

5. Multimodal and combination strategies for the integrated management of CKM syndrome across the continuum of care.

Topic Coordinator Dr. Elenjickal is supported by an educational grant from Pfizer and Topi Editor Prof. Jha reports consulting fees/honoraria from Bayer, Astra Zeneca, Boehringer Ingelheim, Baxter, Vera, Visterra, Otsuka, Novartis, Timberlyne, Biogen, Chinook, and Alpine under the policy of all payments going to the George Institute.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Technology and Code

Keywords: Cardio-Kidney-Metabolic Syndrome, Pharmacology, Therapeutics, Cardio, metabolism, CKM

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.