Editorial: Cardiovascular–kidney–metabolic syndrome: interorgan crosstalk, pathophysiology, and therapeutics

against cisplatin-induced acute kidney injury by preserving mitochondrial integrity, highlighting mitochondrial function as a convergent point in CKM pathophysiology. This finding is particularly significant given that mitochondrial dysfunction has been implicated in insulin resistance, cardiac dysfunction, and renal injury-making it an attractive target for integrated CKM therapies 4,5. Yuan et al. showed that intermittent fasting mitigates high-fat diet-induced renal injury, with multi-omics analyses implicating thermogenesis, lipid metabolism, inflammation, and insulin resistance in its renoprotective effects. Bonnin-Marquez et al. used kinomic profiling in hyperlipidemic mice with adenine-induced CKD and showed that CKD progression is accompanied by stage-dependent alterations in renal kinase activity, involving pathways related to cell cycle regulation, inflammation, oxidative stress, lipid metabolism, and fibrosis. These mechanistic studies provide biological support for viewing CKM as an integrated disease spectrum and identify potential molecular targets for future therapeutic intervention.Building on these molecular insights, several studies further elucidated the interorgan communication pathways that drive CKM progression. Zhang et al. showed that hepatic ischemia-reperfusion injury in steatotic livers can lead to secondary acute kidney injury, and that inhibition of hepatic ferroptosis confers indirect renoprotective effects. This liver-kidney axis highlights how injury in one distant organ can propagate through systemic responses to affect others, with ferroptosis emerging as a potential therapeutic target. In addition, Zhu et al. found that intermittent exercise alleviates myocardial infarction-induced renal injury via IGF-1, suggesting that interventions targeting a single organ system may generate cross-organ benefits throughout the CKM network.Together, these bidirectional interactions underscore that CKM syndrome cannot be fully understood by considering individual organ systems in isolation, and they further highlight the need for integrated therapeutic strategies.It is also worth emphasizing that skeletal muscle may serve as a key regulator within the pathophysiological network of CKM syndrome. Hou et al. reported that myosteatosis is an independent predictor of both all-cause and cardiac mortality in incident dialysis patients. Li et al. showed that lower skeletal muscle density is independently associated with cardiac valve calcification. More notably, Li and colleagues further found that low skeletal muscle density also predicts constipation in maintenance dialysis patients, suggesting that the consequences of skeletal muscle dysfunction extend beyond traditional cardiovascular endpoints and may affect broader systemic functions. Taken together, these studies further support the view that skeletal muscle is not merely a target organ in the CKM pathophysiological network, but also an important active participant with potential regulatory roles.At the translational level, two studies improved the accuracy of cardiovascular risk prediction in patients with chronic kidney disease by applying advanced computational The 13 articles included in this Research Topic collectively illustrate both the complexity of CKM syndrome and the important progress that has been made in elucidating its pathophysiological mechanisms and advancing its clinical translation.Taken together, these contributions, spanning from fundamental molecular studies to clinical applications, point to several key directions that deserve further attention in future research. First, the foundational importance of mechanistic research cannot be overstated. The studies in this Topic addressing mitochondrial function and metabolic regulation provide a strong biological basis for viewing CKM as an integrated disease spectrum rather than a simple aggregation of coexisting disorders. Second, interorgan crosstalk is both a major challenge in understanding CKM and a potential point of therapeutic breakthrough. Studies of liver-kidney and heart-kidney interactions suggest that organ-specific, single-target approaches may be insufficient to meet the prevention and treatment needs of CKM syndrome, underscoring the need for network-based, system-oriented therapeutic strategies. Third, the recognition of skeletal muscle as a core participant in CKM syndrome opens new avenues for future research and intervention. Exercise-based strategies, nutritional support, and pharmacological therapies aimed at improving muscle quality may confer broad benefits across the entire CKM network. Fourth, the integration of multi-omics data with advanced computational methods provides powerful tools for identifying novel mechanistic pathways and therapeutic targets. The application of metabolomics, transcriptomics, and machine learning reflects a growing shift from mechanistic investigation toward precision translation. Finally, the promotion of clinical validation remains an urgent challenge. Although basic research has proposed several potential interventions, including ferroptosis inhibition and mitochondrial modulation, their clinical efficacy still requires further confirmation. In summary, future progress in the CKM field will require an integrated perspective that considers cardiovascular, renal, and metabolic dysfunction as an interconnected whole, thereby promoting deeper interdisciplinary and integrative research.