Beyond Urea Kinetics: Balancing Tradeoffs in Dialyzer Design for the Next 50 Years

The 548,000 Americans who rely on dialysis to stave off death from kidney failure suffer from malnutrition, inflammation, immune defects, and vastly increased incidence of coronary thromboses and pulmonary embolisms. Conventional hemodialysis cartridges are designed to remove urea, because urea removal is fundamental to dialysis quality metrics. However, urea is a largely non-toxic stand-in for other waste products, and urea-focused efforts fail to capture the complexity of dialysis in renal failure. One class of uremic wastes that are thought to contribute to the illness of dialysis patients is called "protein-bound uremic toxins" (PBUTs), such as indoxyl sulfate, kynurenic acid, and p- cresyl. Because dialyzers do not allow albumin to pass from blood to dialysate, the toxins bound to albumin do not pass in appreciable quantities either. Dialyzer design has focused on urea removal. We hypothesize that increasing the residence time of blood in the dialyzer will allow for increased PBUT removal and eventually, better health for patients who depend on dialysis. Hemodialysis treatment is associated with an increased risk of clotting despite anemia, uremia, and chronic heparin use. The superphysiological shear stresses that platelets experience in hemodialysis appear to prime them to form clots inappropriately. We designed a parallel-plate dialyzer with tightly controlled shear forces. We will test whether platelet activation with this novel design reduces platelet activation, compared to conventional dialyzers.