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Hemodialysis (HD): overview

AKA: intermittent hemodialysis (iHD), haemodialysis

A general overview of the principles of hemodialysis therapy in pediatric patients

Basic setup

  • Blood from the patient perfuses an extracorporeal circuit and enters the tiny capillaries of the hollow fiber dialyzers
  • Dialysate passes on opposite side of membrane
  • High efficiency system: blood and dialysate move at rapid speeds, so particles move quickly
  • Particle removal is mostly by diffusion
  • Fluid removal by
    (hydrostatic pressure across the dialyzer membrane)
    • Small particles are also forced across the membrane by hydrostatic pressure

Effect of pore size on membrane selectivity

  • Small and middle sized (based on molecular weight) molecules tend to traverse the membrane fairly easily
    • “Small” molecules are <500 Da
    • “Middle” molecules are 500-60,000 Da
    • “Large” molecules >60,000 Da
  • Small molecules may be bound to larger molecules such as albumin
    • When this is the case, the small molecules will behave like the larger molecules they are bound to

Underlying concepts

Ultrafiltration (UF)

  • The removal of plasma water from whole blood across a semipermeable membrane (the dialysis filter) down a pressure gradient
    • There is positive pressure in the blood compartment and negative pressure in the dialysate compartment; the difference between these two is the transmembrane pressure (TMP)
    • To increase the UF rate in HD, we decrease the pressure of the dialysate, which increases the hydrostatic pressure gradient (TMP)
      • When moving down this pressure gradient, the movement of water “drags” the dissolved solutes along with it (this “solvent drag” is called convective mass transfer)
        • Ultrafiltrated water is isotonic
          • Contrast this with loop diuretics, which produce a hypotonic urine
        • Solids and large molecules are left behind; the exact composition of the ultrafiltrated fluid depends on the TMP and on the characteristics of the filter membrane
  • In dialysis, we use the term ultrafiltration to quantify the net removal of water


  • In dialysis, convection refers to the mass transfer of solutes down a pressure gradient in ultrafiltrated fluid
    • Pressure is applied to one side of the semipermeable membrane, forcing water and the dissolved molecules across the membrane
      • To establish this pressure gradient, one can apply positive pressure on one side of the membrane or negative pressure to the other side; in dialysis, we apply negative pressure on the dialysate side of the membrane to force water and solutes over from the blood side of the membrane
    • Unlike diffusion, particle movement is not dependent on size: if molecules can fit through the pores of the membrane, they will flow equally well
      • Membrane pore size limits the convective transfer of molecules larger than 20-50 kDa

Diffusion (hemodialysis)

  • Diffusion is the movement of particles down a concentration gradient
    • Particles move from an area of higher concentration (on one side of the membrane) to an area of lower concentration (on the other side of the membrane)
    • Particles move through random (Brownian) motion
    • Small molecules diffuse more quickly than larger molecules
    • Diffusion occurs in both directions across the membrane
    • If the concentration of the molecules are the same on both sides (i.e., equilibrium), the net movement is zero
  • Diffusion is the main form of solute removal in HD.

Convection (hemofiltration) vs Diffusion (hemodialysis) vs Combination (hemodiafiltration)

  • Given the same dose of dialysis, diffusion and convection are similarly effective at removing small solutes, but convection is better at clearing large molecules

Removing molecules and fluids

Permeability surface area product (K0A)

  • K0A (“K-O-A”) is a property of the dialyzer
  • Product of permeability (K0) & surface area (A): K0A = K0 & A
    • Permeability (K0) = transfer coefficient of the membrane for a given solute
      • Dependent upon pores per surface area, thickness of the membrane, and design of the dialyzer (i.e., degree of contact between blood and dialysate columns across the membrane)
  • Describes maximum ability of dialyzer to “clear” a given substance (how well the filter allows molecules to move from the blood into the dialysate)
  • The in vitro K0A is specified by the manufacturer of the dialyzer
  • In vitro K0A is often 20-30% higher than in vivo measurements
  • K0A urea is the maximum possible urea clearance (mL/min) at infinite QB and QD
  • High efficiency dialyzers have a urea K0A >600 mL/min, whereas conventional dialyzers have a urea K0A of <500

Clearance (KD)

  • Clearance (KD) describes ability of a dialyzer to remove a substance from the blood under a given set of circumstances (the dialysis prescription)

    • Some define high efficiency dialyzers as having a Kurea of >210 mL/min
  • Clearance is a function:

    • Size and permeability of the filter selected (K0A)
    • Blood flow rate (QB)
    • Dialysate flow rate (QD)
  • At higher blood flow rates, larger dialyzers are able to achieve better clearance (greater efficiency) than smaller dialyzers at the same blood flow rates

  • At lower blood flow rates (<100 mL/min), there is no advantage to using a large dialyzer

    • In children, we may not be able to achieve a high blood flow rate, so a smaller dialyzer may be more appropriate
      • Smaller dialyzers require smaller extracorporeal blood volume - less blood outside of the patient that is liable to clot
  • Smaller molecules (e.g., urea) diffuse easily, and clearance (KD) increases with QB and QD

  • Larger molecules (e.g., vitamin B12) diffuse slowly, and clearance does not increase as much as blood or dialysate flow rates increase

    • In other words, large molecules have a lower KD (relative to small molecules) for a given QB and QD

Ultrafiltration (UF)

  • Removal of water due to the effects of hydrostatic pressure
  • Solutes are removed by convection at the same time
    • The composition of the solutes in the water is determined by the characteristics of the dialyzer (flux)
      • The flux of the dialysis membrane is how “leaky” it is: high flux membranes allow mid-sized molecules through, whereas low-flux filters only permit small molecules.
        • High flux dialyzers are arbitrarily defined as having a β2-microglobulin clearance of >20 mL/min
          • Low flux dialyzers have a β2-microglobulin clearance of <10 mL/min
          • Vitamin B12 (MW 1.335 kD) is used as a surrogate for middle molecules and β2-microglobulin (MW 11.8 kD) is used a surrogate for large weight molecules
  • Ultrafiltration coefficient (KUF) describes the
    capability of a dialyzer
    • KUF is expressed in mL/hour/mmHg
      • As this suggests, one can increase
        rate by using a larger/more porous dialyzer (higher KUF) or by increasing the transmembrane pressure (TMP) across the membrane
        • However, too much TMP can crack the dialyzer