Eryptosis in Peritoneal and Hemodialysis: Pathophysiology, Mechanisms, Triggers, and Translational Perspectives

Eryptosis is a programmed cellular death that leads to the removal of defective red blood cells (RBCs). It is driven by convergent intracellular pathways centered on cytosolic Ca2+ overload, ceramide formation, caspase and calpain activation, disruption of membrane phospholipid asymmetry, and the externalization of phosphatidylserine on the cell surface, which marks the cell for clearance by macrophages. In hemodialysis (HD), intermittent extracorporeal circulation exposes erythrocytes to mechanical stress, bio-incompatible membrane surfaces, and rapid osmotic and ionic shifts. Experimental evidence indicates that osmotic shock induces eryptosis through synergistic Ca2+ influx and sphingomyelinase-dependent ceramide generation, providing a mechanistic framework for intradialytic erythrocyte injury. Clinical studies report heterogeneous eryptotic responses during HD, reflecting the balance between toxin removal and procedure-related stress. In contrast, peritoneal dialysis (PD) imposes sustained exposure to hyperosmolar, glucose-based solutions and is strongly influenced by inflammation and residual kidney function. Clinical and experimental data consistently demonstrate increased eryptosis in PD patients, with marked amplification during peritonitis and close associations with inflammatory mediators. This review integrates mechanistic and clinical evidence on eryptosis in HD and PD, highlights modality-specific triggers converging on shared downstream pathways and discusses translational implications and research priorities for improving dialysis biocompatibility and anemia management.