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.
HemofiltrationThe 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.
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 transporteda) unrestricted,b) restricted,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.
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).
nglish: Scheme of filtration barrier (blood-urine) in the kidney.A. The endothelial cells of the glomerulus; 1. pore (fenestra)B. Glomerular basement membrane: 1. lamina rarainterna 2. lamina densa 3. lamina raraexternaC. Podocytes: 1. enzymatic and structural protein 2. filtration slit 3. diaphragmaPolski:Schematbarieryfiltracyjnej (krew-mocz) w nerce.A. Okienkowyśródbłoneknaczyńwłosowatychkłębuszkanerkowego; 1. por (okienko)B. Błonapodstawna: 1. blaszkajasnazewnętrzna. 2. blaszkagęsta 3. blaszkajasnawewnętrznaC. Podocytu (wypustki): 1. białkaenzymatyczneistrukturalne 2. szczelinafiltracyjna, 3. przeponaszczeliny
Figure 2: Techniques available today for renal replacement in the intensive care unit. CAVH, continuous arteriovenous hemofiltration; CHP, continuous hemoperfusion; CPFA, plasmafiltration coupled with adsorption; CPF-PE, continuous plasmafiltration – plasma exchange; CVVH, continuous veno-venous hemofiltration; CVVHD, continuous veno-venous hemodialysis; CVVHDF, continuous veno-venous hemodiafiltration; CVVHFD, continuous high flux dialysis; D, dialysate; HVHF, high-volume hemofiltration; K, clearance; Pf, plasmafiltrate flow; Qb, blood flow; Qd, dialysate flow; Qf, ultrafiltration rate; R, replacement; SCUF, slow continuous ultrafiltration; SLEDD, sustained low efficiency daily dialysis; UFC, ultrafiltration control system.Mentions: The evolution of technology did not stop, however, and the recent demand for higher efficiency and exchange volumes has spurred new interest in a further generation of machines with better performance, integrated information technology and easy to use operator interfaces. An example of such technological evolution is represented by the passage from CAVH systems to the BSM 22 and Prisma machines to the most recently developed Prismaflex machine (Gambro Dasco, Mirandola, Italy; Fig. 1). A schematic drawing of different techniques available today for the therapy of the critically ill patient with renal and other organ dysfunction is given in Fig. 2. The last generation of machines available on the market today and representing the evolution of the past decade of research and development is shown in Fig. 3.
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
Hemodialysis training course Bahrain Specialsit Hospital June 2013
Hemodialysis Training Course
29th of June 2013
Solute transfer across semipermeable membranes along concentration
Counter current flow for optimized efficacy
Low (dialysate composition)
High for small molecular weight substances (urea, creatinine, electrolytes,
Low for higher molecular weight substances (small proteins, mediators, etc.)
- Solute transfer across semipermeable membranes
by pressure induced water flow (convection, "solute
- 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)
Water flux across the membrane.
Pore size and pore size distribution.
Molecular size (molecular mass).
Molecular shape and configuration.
Charges (solutes and membranes).
Convective Transport Across
Rate of removal (diffusion) of small molecules. As Urea
Rate of removal (convection) middle molecule. B2microglob.
Ultrafiltration Coefficient (removal of water).
Mass Area Transfer KoA.
Filter membrane specifications
Flux Dialyzers Urea KoA
Low Conventional <450 <150 <12 <10
Low High efficiency >600 >200 variable Variable
High High flux variable variable >12 >20
High Hemofilters variable variable >12 >20
Performance of different Dialyzers