Effect of Treatment Duration and Frequency on Uremic Solute Kinetics, Clearances and Concentrations

The kinetics of uremic solute clearances are discussed based on two categories of uremic solutes, namely those that are and those that are not derived directly from nutrient intake, particularly dietary protein intake. This review highlights dialysis treatments that are more frequent and longer (high-dose hemodialysis) than conventional thrice weekly therapy. It is proposed that the dialysis dose measures based on urea as a marker uremic solute, such as Kt/V and stdKt/V, be referred to as measures of dialysis inadequacy, not dialysis adequacy. For uremic solutes derived directly from nutrient intake, it is suggested that inorganic phosphorus and protein-bound uremic solutes be considered as markers in the development of alternative measures of dialysis dose for high-dose hemodialysis prescriptions. As the current gap in understanding the detailed kinetics of protein-bound uremic solutes, it is proposed that normalization of serum phosphorus concentration with a minimum (or preferably without a) need for oral-phosphorus binders be targeted as a measure of dialysis adequacy in high-dose hemodialysis. For large uremic solutes not derived directly from nutrient intake (middle molecules), use of extracorporeal clearances for β₂ -microglobulin that are higher than currently available during thrice weekly therapy is unlikely to reduce predialysis serum β₂ -microglobulin concentrations. High-dose hemodialysis prescriptions will lead to reductions in predialysis serum β₂ -microglobulin concentrations, but such reductions are also limited by significant residual kidney clearance. Kinetic data regarding middle molecules larger than β₂ -microglobulin are scarce; additional studies on such uremic solutes are of high interest to better understand improved methods for prescribing high-dose hemodialysis prescriptions to improve patient outcomes.