Inflammation in cardiovascular-kidney-metabolic syndrome: key roles and underlying mechanisms-a comprehensive review

Area of Science:

• Cardiovascular Medicine
• Nephrology
• Metabolic Disorders
• Inflammation Research

Background:

• Cardiovascular-Kidney-Metabolic (CKM) syndrome is a systemic disorder defined by the interaction of diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD).
• Chronic inflammation is recognized as a key mediator in CKM syndrome, driving damage across multiple organs.
• Aberrant signaling pathways (NF-κB, Wnt, PI3K-AKT, JAK-STAT, PPAR) form an inflammatory network that links heart, kidney, and metabolic tissues.

Purpose of the Study:

• To systematically review the pathophysiological mechanisms of CKM syndrome.
• To emphasize the role of inter-organ inflammatory regulation mediated by key signaling pathways.
• To explore therapeutic strategies targeting inflammatory cytokines for CKM syndrome.

Main Methods:

• Systematic review of existing literature on CKM syndrome.
• Analysis of mechanistic investigations into inflammatory signaling pathways.
• Evaluation of clinical evidence for anti-inflammatory therapies.

Main Results:

• Key signaling pathways facilitate inter-organ inflammatory crosstalk, creating positive feedback loops.
• This crosstalk amplifies pathological processes including oxidative stress, endothelial dysfunction, and fibrosis.
• Therapeutic targeting of inflammatory cytokines (IL-1β, IL-6, TNF-α) shows translational potential.

Conclusions:

• CKM syndrome involves complex inter-organ inflammatory crosstalk driven by signaling pathways.
• Targeting inflammation offers a promising strategy to disrupt the pathological cycle of CKM syndrome.
• This review provides a framework for understanding and treating CKM syndrome.