The most commonly applied technique is hemodialysis (HD). In HD blood and a “cleansing fluid” called dialysate are exposed to each other separated by a semipermable membrane. The sieving properties of the membrane exclude all solutes above a certain threshold from crossing the membrane. Solutes within the permeability range of the membrane pass it while diffusing along existing concentration gradients.
The selectivity of the dialysis process is low. It mainly depends on the above mentioned membrane sieving properties and the various concentration gradients. This situation reflects the uncertainty regarding “real“uremic toxins. A solute, which is present at both sides of the membrane in equal concentration will not contribute to transmembrane flux.
Diffusion is not only used to remove solutes from the blood of the patient but also allows to transport specific substances into the blood (e.g., buffer for acidosis correction). Blood and dialysate flow through the dialyzer in counter current mode to maintain optimized concentration gradients over the whole length of the dialyzer. Diffusion based dialysis is an efficient technique to remove small molecular weight solutes from the blood. However, efficacy quickly decreases with increasing solute MW.
In clinical routine the dialysis process is always accompanied by removal of excessive body water (ultrafiltration). Water flux is achieved by applying a hydrostatic pressure from the blood side into dialysate.
Solute transfer across semipermeable membranes along concentration gradients (diffusion)
Counter current flow for optimized efficacy
Low (dialysate composition)
High for small molecular weight substances (urea, creatinine, electrolytes, buffer…)
Low for higher molecular weight substances (small proteins, mediators, etc.)
The figure below shows the typical solute removal pattern for HD as it results from the performance of commonly used dialyzers (high flux type – bright colors, low flux type – darker colors).
HD efficacy for small MW solutes is mostly determined by extracorporeal blood flow. Efficacy – or, in other words, clearance – is blood flow limited. The impact of blood flow quickly decreases with the molecular weight of the solute considered. For these substances efficacy is membrane limited. Consequently, increasing blood flow alone to increase dialysis efficacy mostly affects small MW solutes but has nearly no effect on solute balances for higher MW solutes.
High flux dialyzers in general provide higher efficacies compared to low flux dialyzers. The difference being larger with increasing solute molecular weight.
Extracorporeal clearance has a very limited meaning for the net effect of dialysis, which is better is described by the term “patient clearance”. Discrepancies between extracorporeal clearance and effective patient clearance result from the compartment structure of the human body, various differences in terms of intercompartmental transfer resistances and tissue perfusion rates. Phosphate management in dialysis patients is a typical example where the net effect of dialysis is low despite considerable extracorporeal clearances. Improved phosphate elimination is immediately achieved when attention is paid to the specific solute kinetics by increased treatment times and/or treatment frequency.