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Solute removal in hemodialysis occurs through a combination of diffusion, convection, and adsorption.
The uremic solutes removed by hemodialysis are divided into three main categories
  • Small water soluble compounds such as urea with an upper molecular weight of < 500 Da that can be removed with any dialysis membrane by diffusion
  • Larger middle molecular weight molecules (500 to 15,000 Da) which can only be removed through dialyzer membranes with enhanced transport capacity and large enough pores (high flux)
  • Protein bound molecules, mostly with a molecular weight of 500 Da, but larger and more difficult to remove because of being bound to proteins

    The efficiency of solute clearance through diffusion is expressed as KoA for a particular dialyzer and a given solute, where Ko is the mass transfer coefficient and A is membrane surface area.

    KoA values for urea are provided by dialyzer manufacturers, but if those values are determined in vitro, then they should be reduced by approximately 20% to better replicate in vivo membrane exposure to blood.

    The manufacturer in vitro data must not be used in urea kinetics to determine the dialysis prescription.

    Convective separation of solutes and low molecular weight proteins from large serum proteins and blood elements is achieved with high flux dialyzers through increased porosity and efficiency of mass transfer.

    Adsorption is the adhesion of macromolecules and proteins to the membrane surface without penetration, and it primarily depends upon the internal pore structure and the hydrophobicity of the membrane.
    A highly adsorptive membrane may also have negative consequences by reducing the diffusive and convective capacities. Therefore, a moderate level of protein adsorption combined with the ability to bind protein bound uremic toxins appears to be recommended features in a membrane.

    Clearance may be considered the most important characteristic of a dialyzer because it is a critical factor in determining the dialysis prescription.

    Urea clearance is the most commonly used measure, since it is used to calculate the dialysis dose.
    Phosphate clearance and uric acid clearances are not always reported but can be helpful when treating significantly high phosphate or uric acid levels.
    Because phosphate is an intracellular ion, using a dialyzer with a high phosphate clearance can cause the plasma value to decrease rapidly without a major impact on its total removal.

    Enlarging membrane pore size beyond that of conventional low-flux dialyzers has led to increased B2-M clearance, and because it is easy to measure, B2 M is now considered a surrogate marker for middle molecular weight solutes.
    The membrane sieving coefficient for B2 M has gained acceptance by both dialyzer manufacturers and the medical community to assess

    Dialyzers are considered highflux if their ultrafiltration coefficient (Kuf) is > 15 ml/h/mmHg and their ability to clear B2M > 20 ml/min.

    In Japan, however, the classification of dialyzers refers to five types, from I to V, based on the clearance of B2-M of less than 10, 30, 50, 70, and more than 70 ml/min, respectively, at a blood flow rate of 200 ml/min and a dialysate flow rate of 500 ml/min.

    Types IV and V are considered to be super high-flux dialyzers, with molecular weight cutoffs closer to that of the human kidney (65,000 Da), thus allowing for efficient removal of middle and large size uremic toxins, and greater clearance of inflammatory cytokines than conventional highflux membranes.

    A Cochrane review based upon 3820 patients with end stage renal disease, from all available RCTs, could not determine overall efficacy and safety of high-flux compared with low-flux HD, but did conclude that high-flux HD may reduce cardiovascular mortality by about 15% in people requiring HD.
    In the Hemodialysis (HEMO) study, highflux HD provided significantly lower rates for cardiac and cerebrovascular mortality after 3.7 years on HD, as compared with lowflux HD.

    In the Membrane Permeability Outcome (MPO) study, highflux HD provided higher survival rates for patients with serum albumin ≤ 4g per dl, improved survival for diabetics, and even for low risk patients, as compared with lowflux HD.

    Aside from research findings, one should consider that backfiltration almost never occurs in low flux dialysis, and its occurrence during high flux treatments depends on the transmembrane pressure used.
    This is a crucial safety concern because any contamination of dialysate or wash out from the membrane can reach the blood side.

    Forward and backfiltration coefficients are different in vitro and even more so in vivo because of the protein layer in the blood compartment and the structure of the membrane.

    Additionally, correcting an interdialytic weight gain of more than 5 kg within a dialysis session of less than 3 hours with high flux dialysis could lead to a significant increase in the risk for hypotension, especially in patients with poor cardiac function or autonomic neuropathy.