The rationale to develop hemofiltration (HF) was to overcome the reduced efficacy of diffusion for larger MW solutes. HF has the advantage of removing solutes small enough to pass through the ultrafilter in proportion to their plasma concentration rather than their concentration gradient, as with diffusion. The driving force is a pressure gradient rather than a concentration gradient. The rate of solute removal is proportional to the applied pressure that can be adjusted to meet the needs of the clinical situation.
HF requires a large flux of water across a semipermable membrane. This water flux is induced by a pressure gradient from the blood side to the so-called filtrate side of the membrane. The water flux drags solutes across the membrane. The selectivity of the process is determined exclusively by the sieving properties of the membrane.
The removal of large amounts of plasma water from the patient requires volume substitution. Substitution fluid, typically a buffered electrolyte solution close to plasma water composition, can be administered pre or post filter (pre-dilution mode, post-dilution mode).
Convective transport is favorable for larger MW solutes but not that efficient for smaller substances. To match HF small MW transport with HD performance, large amounts of exchange volume are needed.
Filtration minus substitution provides the required weight loss of the patient.
- Solute transfer across semipermeable membranes by pressure induced water flow (convection, "solute drag")=>
- Volume substitution (pre or post filter)
- Improved for higher molecular weight solutes (small proteins, mediators, etc.)
- Reduced for small molecular weight substances (urea, creatinine, electrolytes, buffer base)
The amount of convective transport is a direct funtion of the respective water flux. Whether or not a certain solute can cross a membrane depends on various conditions; solutes can be transported
c) not at all.
The major impact comes from the solute size in comparison to the membrane pore size. Molecular mass is a good first-order estimation for solute size. Further influencing factors include molecular shape / configuration and possible charge effects from the solute as well as from the membrane.
Convective Transport Across Membranes: Determinants
- Water flux across the membrane
- Pore size and pore size distribution of the membrane
- Molecular size (molecular mass)
- Molecular shape and configuration
- Charges (solutes and membranes)
Membrane passage of a solute is described by means of the sieving coefficient S, which is the ratio from solute filtrate concentration cf to the respective solute plasma concentration cp. A sieving coefficient of S=1 indicates unrestricted transport while there is no transport at all at S=0. For a given membrane each solute has its specific sieving coefficient. Sieving coefficients typically are plotted versus increasing molecular mass to show the sieving coefficient curve.
This graph shows sieving coefficient curves for different membrane types. However, it is obvious that artificial kidney membranes over the years became more and more permeable for higher MW solutes targeting the sieving characteristics of glomerular filtration. Shifting sieving coefficient curves further to higher MWs in parallel required steeper shapes at the end to prevent significant protein transport in the order of magnitude of albumin and above. Whether or not preventing transport at or above albumin is really a required strategy is an open question. From time to time scientific literature speculates about the potential beneficial effects of slightly albumin leaking membranes.
Sieving coefficient curve and MW cutoff
Convective clearance for a certain solute “x” is described as the product from the respective sieving coefficient and the total water flux.
In summary, HF is based on convective transport to remove solutes from the blood of uremic patients. This process requires large amounts of sterile infusion fluid to compensate for the fluid loss from the patient. HF is characterized by increased solute removal capabilities for higher MW solutes, but is less efficient for small MW solutes when compared to HD. This difference can be compensated by increased exchange volumes. HF has not been widely used in the routine treatment of chronic uremia due to the relative high cost associated with high volumes of infusion fluids. It is currently experiencing a revival in terms of daily short HF at home. However, the costs remain high.