Abstract
Hemodialysis is a form of extracorporeal kidney replacement therapy for patients with end-stage renal disease. Successful delivery hemodialysis requires a knowledge of the mechanisms involved in solute clearance and fluid removal as well as the rationale behind writing a hemodialysis prescription for a particular patient. This chapter provides the reader with a theoretical as well as a practical overview of most relevant aspects of hemodialysis.
Keywords
hemodialysis, hemofiltration, hemodialfiltration, dialyzer, dialysate, diffusion, convection, ultrafiltration, dialysis dose, clearance
Hemodialysis (HD) is an extracorporeal therapy that is prescribed to reduce the signs and symptoms of uremia and to partially replace a number of the key functions of the kidneys when kidney function is no longer sufficient to maintain an individual’s well-being or life. Although HD is one of several therapies (peritoneal dialysis, hemofiltration [HF]/hemodiafiltration [HDF], transplantation) that can be used for the treatment of acute or chronic end-stage kidney disease (ESKD), this chapter focuses primarily on HD. Peritoneal dialysis and transplantation are covered in detail elsewhere in the Primer.
Principal Functions of Hemodialysis
HD for the treatment of ESKD is effective in (1) reducing the concentration of uremic toxins, particularly small and medium-sized molecules, primarily by diffusion; (2) removing excess fluid volume by convection; and (3) correcting some of the metabolic abnormalities, such as acidosis and hyperkalemia, by the use of dialysate solutions with variable solute concentrations. The two major components of the HD procedure that will be discussed are the dialyzer and the dialysate.
Dialyzer
Structure
The most commonly used device for the performance of HD is the hollow fiber dialyzer, composed of several thousand hollow fibers made of thin, semipermeable membranes. These fibers are encased in a plastic tubing device that allows blood to be pumped from the patient through the hollow fibers while an aqueous solution, the dialysate, is pumped outside the fibers, typically in the opposite direction of the blood flow (countercurrent), to maximize the diffusion gradients across the membranes and along the length of the dialyzer.
There are generally two types of dialysis membranes ( Fig. 57.1 ). The first are called “low-flux” membranes and are made up of fibers with small pore sizes, which allow the diffusion of small solutes such as urea and water but not the passage of larger molecules such as β2-microglobulin. “High-flux” membranes, the second type, have larger pore sizes that allow the passage of larger molecules such as β2-microglobulin. Because of these larger pores, the rate of water transfer (ultrafiltration coefficient) is much higher than that for low-flux membranes.
The manufacturing process of these membranes is such that, regardless of whether it is a low-flux or a high-flux membrane, the pore sizes are not uniform, and there is a distribution of pore sizes that allows the diffusion or removal of differently sized molecules at different rates ( Fig. 57.2 ). It is important to note that the distribution of pore sizes for high-flux membranes is such that it does not allow for the passage of albumin.
Principal Functions of the Dialyzer
Diffusion
Diffusion describes the movement of solutes from a milieu with high concentrations across a semipermeable membrane into a milieu where it is in lower concentration. The rate and amount of solute that diffuses across the membrane in either direction depend on the difference in concentration between the blood and dialysate compartments; the molecular size of the solute; the characteristics of the membrane including its surface area, thickness, and porosity; and the conditions of flow (e.g., turbulent or smooth). These membrane characteristics are generally labeled mass transfer characteristic or coefficient of diffusion and are specific for the membrane used and the solute under consideration.
Using urea as an example of a small molecular solute, HD allows the movement of urea from the blood compartment, where it is in high concentration, to the dialysate compartment across the hollow fiber membranes. Thus, as blood is pumped and traverses through the dialyzer inside hollow fibers, the urea concentration of the blood is reduced; concurrently, the urea concentration of the dialysate increases as it flows outside the hollow fibers in the opposite direction. If the blood and dialysate were to flow in the same direction, then the urea concentration gradient between the blood and dialysate compartments would be considerably reduced at the exit site of the dialyzer, whereas a countercurrent flow ensures a maximum difference in concentration along the entire dialyzer length and therefore higher flux of solute from the blood compartment into the dialysate compartment.
The principles of diffusion apply not only to urea and other solutes that have a higher concentration in the blood than dialysate, but also to the diffusion of substances that have a higher concentration in the dialysate than blood. An example of the latter is the diffusion of bicarbonate from the dialysate into the blood compartment. The rate of diffusion (R) of a small blood solute like urea across the dialyzer membrane is proportional to the blood solute concentration (C) and is governed by laws of first-order kinetics. Based on this concept, R is proportional to C, or R = KC and therefore K = R/C, where K is a constant referred to as clearance . K of any solute across the dialyzer membrane is an expression of the effectiveness of dialysis. It remains constant during intermittent treatments as both blood concentrations of small solutes (C) and solute removal rates (R) decrease simultaneously. A useful way to express K is:
K = Q B ( C A − C V ) C A
K of a solute from the blood compartment (in mL/min) is expressed as the difference in the amount of a solute at the inlet (Q B × C A , where Q B is the blood flow rate in mL/min and C A is the concentration in mg/mL at the inlet or “arterial” side of the dialyzer) and the amount of solute at the outlet (Q B × C V , where C V is the concentration at the outlet or “venous” side of the dialyzer), divided by the concentration at the inlet (C A ).
Convection
The simple equation for solute clearance mentioned above does not take into account convective clearance of solutes. Convection refers to the mass transport of solutes along with the fluid it is dissolved in (plasma water) and is driven by the higher hydrostatic pressures in the blood compartment generated by the blood pump. The amount of solute removed by convection is not dependent on the concentration gradient of the solute, but rather on the difference in hydrostatic pressure between the blood and dialysate compartment and a specific membrane characteristic, termed the “sieving coefficient.” The sieving coefficient (S) represents the ratio of the concentration of the solute in the ultrafiltrate and the concentration in plasma water, with values ranging from 0 (membrane impermeable to solute) to 1 (membrane freely permeable to the solute).
The relative contribution of convective transport to overall clearance depends on the pore size of the membrane as well as the size and charge of the solute. In general, the relative contribution of convective transport to the overall clearance for small molecules, such as urea, is minor, but it is more substantial for larger molecules (e.g., β2-microglobulin) because of the low diffusive clearance.
Therefore a more complete representation of solute clearance incorporating both diffusion and convection is:
K = Q Bi × C A − Q Bo × C V C A ≈ Q Bo ( C A − C V ) C A + Q uf
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