Recent developments, current challenges and future perspectives on cellulosic hemodialysis membranes for highly efficient clearance of uremic toxins

Abstract

End stage renal disease (ESRD, or kidney failure) affects ∼10 % of the world’s population. Kidney transplantation, which best duplicates native kidney function, can extend the lifespan, but the number of available kidneys does not meet current demand; furthermore, the potential for organ rejection is ever-present, requiring life-long immunosuppression to address the associated risk of life-threatening infections. Hemodialysis (HD) is a life-sustaining extracorporeal blood purifying treatment for ESRD patients. However, this membrane-based therapy is associated with acute side effects, life-threatening chronic conditions, and unacceptably high morbidity and mortality. Current HD membranes are limited in terms of two key aspects: bio-incompatibility and poor clearance of middle-molecule (MM) uremic toxins. Renal Replacement Therapies (RRT) have several modalities, one of which involves the careful purification of patients’ blood volumes in dialyzers. These blood samples come in contact with non-physiologic dialyzer membrane materials with varying molecular structures, surface chemistries and symmetries. With cellulose HD membranes, health concerns of the complexities by their contact with blood have almost led to their complete discontinuity. For cellulose dialysis membranes, hydroxyl groups within their polymer chains initiates complement, leukocyte and even coagulation activations upon contact with blood, leading to several cardiovascular diseases. The principal factor behind some of these drawbacks has been addressed in this review, in an attempt to improve hemobiocompatibility and reduce health complications. Solutions are proffered within the bounds of material science, biomedicine and surface chemistry from outlined published experimental results in scientific investigations. This review focuses on biocompatibility as a factor that determines the consequences of surface/blood interactions during HD therapy, with special attention to the historical developments of cellulosic hemodialyzer membranes. The reintroduction of acetylated cellulose as well as the advantages of new generation cellulose triacetate (CTA) membranes have also been addressed. Recent progresses on the development of cellulose HD membranes has been vividly discussed while recent challenges and future perspectives have also been highlighted in line with selective removal of uremic toxins using cellulosic HD membranes. In the quest to improve quality of life for critically RRT patients undergoing HD, the use of membranes with sustainable biocompatibility are encouraged. This review centers beyond the different avenues of minimizing the health complications associated with biological pathways activation from cellulosic membrane materials. New approaches toward improvement of hemocompatibility have been reviewed to include the effect of complete acetylation of cellulose (CTA) membrane on inflammation. For instance, carbazate modified cellulosic membranes have supported the complete elimination of carbonylated proteins, and their effects on pH stability have been widely explained. In line with designing hybrid adsorption systems with hemodialysis membranes, this review has also highlighted beyond sustainable techniques for removing all uremic toxins in serum samples of chronic kidney disease (CKD) patients. New insights and perspectives have also been highlighted to focus on selective removal of uremic toxins using cellulose membranes.