Toward a conceptual framework for systemic effects of continuous renal replacement therapy in critical illness

Continuous renal replacement therapy (CRRT) is traditionally used for solute and fluid removal in critically ill patients with acute kidney injury. Emerging evidence suggests that CRRT may also influence systemic biological networks, including inflammation, vascular function, immunity, and metabolism. In sepsis and critical illness, these systems are dynamically dysregulated, involving fluctuating inflammatory mediators, endothelial alterations, immune dysfunction ranging from hyperinflammation to immunoparalysis, and metabolic reprogramming that varies with disease stage. We propose a conceptual framework in which CRRT modulates these interconnected processes. Beyond solute and cytokine removal, CRRT may affect the distribution of circulating mediators, attenuate concentration peaks, influence endothelial stability, and modulate immune and metabolic states, thereby contributing to systemic network regulation. However, CRRT has bidirectional effects. While it may help restore homeostasis by removing harmful mediators, it may also eliminate beneficial molecules and induce inflammatory or oxidative responses due to extracorporeal circulation. Therefore, its overall impact is likely context-dependent and influenced by treatment settings and patient condition. Although direct evidence for systemic reprogramming remains limited, this framework provides a basis for future research. Integrative biomarker-based and phenotyping approaches may support the development of individualized and adaptive CRRT strategies in critical care.