Molecular Mechanisms of Blood–Membrane Interactions in Hemodialysis: Advances in Anti-Inflammatory Surface Modifications

The development of novel hemodialysis membranes aims not only to enhance dialysis efficiency but also to improve hemocompatibility, an important determinant of treatment safety and tolerability. This narrative review provides a comprehensive overview of the molecular mechanisms underlying blood–membrane interactions during hemodialysis, focusing on key processes such as protein adsorption, complement activation, platelet and leukocyte responses, oxidative stress, and inflammatory mediator release. These interconnected processes can contribute to acute blood–material incompatibility and thrombo-inflammatory responses during dialysis, although their contribution to long-term clinical outcomes remains multifactorial and incompletely defined. Furthermore, the review critically examines current surface-modification strategies, including hydrophilic and antifouling modifications, antithrombotic and complement-directed interfaces, and antioxidant functionalization. Particular emphasis is placed on distinguishing mechanistic and surrogate findings from clinically meaningful evidence and on considering hemocompatibility together with membrane transport performance. By integrating molecular mechanisms, modification strategies, and translational evidence, this review aims to provide a framework for the development and evaluation of safer and more effective hemodialysis membranes, while avoiding overinterpretation of isolated biomarker changes as established clinical benefit.