Protein adsorption phenomena in hemodialysis membranes: Mechanisms, influences of clinical practices, modeling, and challenges

Abstract Kidney failure affects a significant part of the world's population where more than 2 million people currently undergoing some sort of treatment for end-stage kidney disease (ESKD). One of the most common treatments is hemodialysis (HD) which consists of an extracorporeal membrane-based therapy that can retain toxins and remove excess fluid. However, patients can experience short- and long-term life-threatening complications associated with protein adsorption to the HD membrane. Upon contact between blood and membrane, protein adsorption takes place incautiously promoting the build-up of a cake layer and activation of complex reactions called biochemical cascades. The mechanisms of protein adsorption can be complex due to the highly heterogeneous composition of blood and are still not fully understood. Membrane properties such as biocompatibility and surface roughness play a critical role in protein adsorption since it influences the affinity between membrane material and blood components. Also, the HD operating conditions in the clinical practices can significantly influence protein adsorption and play a critical role in the cell rupture pathway which can enhance the adsorption process. Modeling and predicting membrane fouling and protein adsorption in HD have a great potential to guide the definition of adequate operating conditions for HD treatment but still limited. Predictive models can indicate how to manipulate blood and dialysate flow rate, operating pressure, and treatment time to yield better control of protein adsorption, reducing the side effects that are linked to unacceptably high morbidity and mortality rates. This critical review will focus on a comprehensive understanding of the protein adsorption phenomenon, including its mechanisms, its influential factors, and the blood activations and the consequences associated with this phenomenon. Also, and current models and challenges for predicting protein adsorption and membrane fouling are reviewed. Moreover, this review will cover how there is a distinct lack of knowledge when it comes to currently hypothesized mechanistic aspects and their translation into mathematical concepts and models to predict protein adsorption and hemodialysis membrane performance. The models seen so far lack in describing multiprotein adsorption as a function of hemodialysis operating conditions and correlation with patient outcomes.