Principles of Hemodialysis

Ricardo A. Francisco, Jr., MD, MHA, FPCP, FPSN

Objective
1. To explain the basic principles of hemodialysis
2. To enumerate the different types of hemodialysis and discuss the principles behind
3. To discuss the indications for the different types of hemodialysis

Topic Outline
• Definition of Dialysis
• Principles of hemodialysis
o Diffusion
o Convection
o Ultrafiltration
o Blood Flow Rate
o Dialysis Flow Rate
o Dialyzers
• Types of Hemodialysis

Dialysis
• A process where the solute composition of a solution, A, is altered by exposing solution,
A to a second solution, B, through a semi permeable membrane
• Removes wastes or toxins and excess water from the blood to maintain their
concentrations at levels which they produce no uremic symptoms

Principles of Hemodialysis
• Solute Clearance
o Diffusive Transport
▪ Primary means of waste removal
▪ Interaction of blood with the dialysis fluid via pores of the dialysis
membrane
▪ Movement of solutes from regions of higher concentration to low
concentration
▪ Driving force for solute diffusion is transmembrane concentration
gradient
▪ Small molecules move at high velocity, collide with the membrane often,
high rate of diffusive transport
▪ Large molecules, diffuse through the membrane slowly and at law
velocity and collide less often
o Factors Affecting Diffusive Transport
▪ Concentration gradient
▪ Molecular weight of solute
▪ Velocity of solute in the solvent
 ▪ Membrane resistance
▪ Membrane surface area
▪ Pore size
▪ Duration
• Ultrafiltration
o Occurs when water is driven by a hydrostatic force and pushed through the
membrane.
o Water driven by either hydrostatic or osmotic pressure is published through the
membrane
o Transmembrane pressure (TMP) causes fluid to cross from the side of high
pressure (Blood compartment) to the side of low pressure (Dialysate
compartment)
o The rate of UF depends on the total pressure difference across the
compartments (TMP)
o Positive pressure from the blood with the negative pressure to the dialysate
compartment results in fluid removal from the patient

Convective Transport
o Water driven by either hydrostatic or osmotic pressure is pushed through the
membrane
o Solutes that can easily pass through the membrane are dragged with fluid across
the membrane (solvent drag)
o All ultra-filtered solutes below the membrane pore size are removed.
o Sieving coefficient – numerical assessment of the potential for convective
transport of a given solute
o Driving force for convection is transmembrane hydrostatic pressure
(ultrafiltration)
o One – solute passes completely
o Zero – solute is rejected

Components of HD
• Blood Flow
o As the blood flow rate (Qb) is increased to 300 ml/min, urea clearance increased
steeply, less steep for Qb of 400-500 ml/min
o Larger molecules, protein bound solutes removal is time dependent rather than
flow dependent as they diffuse more slowly; duration of dialysis is the major
determinant
• Dialysate Flow
o A faster dialysis solution flow rate (Qd) increase the efficiency of diffusion of
urea from blood to dialysate
o Dialysate flow rate should be countercurrent to the blood flow to maximize
concentration gradient between the two compartments
 • Semi-permeable membrane
o Type of membrane
▪ Cellulose-based membranes
▪ Synthetic membranes
o Mass transfer-area coefficient (KoA)
o KoA of a dialyzer describes the ability to eliminate substances
▪ Urea KoA – ability to remove low molecular weight substances
▪ Vitamins B12 and Beta microglubulin KoA – capacity to remove
higher molecular weight substances
o Ultrafiltration coefficient (KuF)
o KUf is a measure of dialyzer’s permeability to water
o Number of ml of fluid/hour that will be transferred across the membrane
per mmHg pressure gradient across the membrane

Definition of Terms (Dialysers)

• Flux
– Measure of ultrafiltration capacity (Kuf)
– Low : Kuf<10ml/h/mmHg
– High: Kuf>20ml/h/mmHg
• Permeability
– Measure of clearance of middle molecular wt mol (B2-microglobulin)
– Low: B2m clearance <10ml/min
– High: B2m clearance >20ml/min
• Efficiency
– Measure of urea clearance
– Low: KoA < 500ml/min
– High: KoA > 600 ml/min

High Efficiency Vs High Flux Dialyzers

• Improved solute and water clearance over that of standard HD
• Uses higher blood and dialyzate flows
• High Efficiency Dialyzers – higher KoA and higher clearance of smaller solutes like urea
than standard dialyzers
• High Flux Dialyzers- highly permeable membranes for larger molecules and higher Kuf
than High efficiency

Differences between High and Low-Efficiency Hemodiaysis

High efficiency Low efficiency
Dialyzer KoA ≥600 ml/min <500 ml/min
Blood flow ≥350 ml/min <350 ml/min
Dialysate flow ≥500 ml/min <500 ml/min
Bicarbonate dialysate Necessary Optimal
 BENEFITS OF LIMITATIONS OF
CAUSES OF HIGH-EFFICIENCY
HIGH- EFFICIENCY HIGH- EFFICIENCY
DIALYSIS FAILURE
DIALYSIS DIALYSIS
• Access-related Low BFR • Higher clearance of • Hemodynamic instability
• High recirculation rate urea, compared with • Low margin of safety if
• Patient/Staff not conventional dialysis short treatment time is
adherent to prescribe without increase in prescribed
time treatment time • Potential vascular access
• Failure to adjust time for • Better control of damage
conditions such as alarm, chemistry • Dialysis disequilibrium
dialysate bypass, and • Potentially reduced syndrome
hypotension morbidity
• Potentially higher patient
survival rates

Differences between High-and Low-Flux Hemodialysis

High Flux Low Flux
Dialyzer KoA Variable Variable
Blood flow ≥350 ml/min <350 ml/min
Dialysate flow ≥500 ml/min <500 ml/min
Bicarbonate dialysate Necessary Optimal

Characteristics of High-Flux Dialysis

• Dialyzer membranes are characterized by a high ultrafiltration coefficient (Kuf > 20
mL/h/mm Hg)
• High clearance of middle molecular weight molecules occurs (B2-microglobulin)
• Urea clearance can be high or low, depending on the urea KoA of the dialyzer
• Dialyzers are made of either synthetic or cellulosic membranes
• High-flux dialysis requires an automated ultrafiltration control system

Potential benefits of High-Flux Dialysis

• Delayed onset and risk of dialysis-related amyloidosis because of enhanced B2-
microglobulin clearance
• Increased patient survival resulting from higher clearance of middle molecular weight
molecules
• Reduced morbidity and hospital admissions
• Improved lipid profile
• Higher clearance of aluminum
• Improved nutritional status

Limitations of High-Flux dialysis

• Enhanced drug clearance, requiring supplemental dose after dialysis
• High cost of dialyzers
 • Back filtration, or reverse filtration - movement of fluid in the direction opposite to that
of the designed ultrafiltration which carries endotoxins (ET) from dialysate to blood.

Different Types of Renal Replacement Therapies

• Conventional HD (iHD)
• SLED
• Convective Therapies (HF/HDF)
• CRRT

Types of RRT
• Hemodialysis
• Hemofiltration (HF)
o Large amount of UF is coupled with infusion of a replacement fluid in order to
remove solutes.
o Comparable in removing small solutes with HD
o More effective in larger and poorly diffusible solutes
• Hemodiafiltration (HDF)
o combines the diffusive and convective solute transport (HD plus HF) using high
flux membrane with Kuf >20ml and sieving coefficient for beta 2 microglobulin of
greater than 0.6.
o Fluid is removed by ultrafiltration and the volume of filtered fluid exceeding the
desired weight loss is replaced by sterile, pyrogen-free infusion solution.
o Convective transport is achieved by an effective convection volume of at least
20% of the total blood volume processed.
o Benefits of HDF
▪ Optimize small solute removal
▪ Significant removal of uremic solutes with middle and larger molecular
weights
▪ Post dilution Online HDF reduces the risk of all-cause mortality, CV
mortality and infection related mortality (Maduell F et. Al, JASN Feb
2013)
• Slow Continuous Ultrafiltration (SCUF)
o Designed to remove up to 6 to 7 L of fluid/day without requiring replacement
fluid.
o Useful in patients with refractory heart failure.
o Acid-base disturbances and electrolyte imbalances need to be corrected by
adjusting the compositions of IV infusions.
o Potential advantages/ indications
▪ Hemodynamically well tolerated
▪ Better control of azotemia, electrolyte and acid-base balance; correct
abnormalities as they evolve
▪ Highly effective in removing fluid
 ▪Facilitates administration of parenteral nutrition and obligatory IV meds
by creating unlimited “space” by virtue of continuous UF
▪ Less effect in ICP
▪ New user-friendly machines are available
• Continuous Renal Replacement Therapy (CRRT)
o Mainstay of RRT in critically ill patients who often cannot tolerate standard HD
due to hemodynamic instability
o Dialysis (Diffusion-based solute removal)
o Filtration (Convection-based solute and water removal)
o “Go Slow Dialysis”
o Continous Veno-Venous or Arterio-venous Techniques
▪ CVVHD/CVVHDF
▪ CAVHD/CAVHDF
o Efficacy is realized when done throughout the 24 hour period without interruption

iHD CRRT

Hemodynamic Stability Daily or alternate Dose. Daily dose of dialysis with slow
Rapid fluid and solute removal – rate of solute and fluid removal.
hypotension – abrupt fall in Posm- ECF Effectively removing excess fuid
vol depletion promoting osm in hypotensive patients.
movement into the cells Relative protection
Solute Removal 160 ml/min in 4 hrs 17 ml/min in 24-48 hrs
Removal of Less porous membranes – less efficient Effectively removes molecules.
immunomodulatory in removing middle to large molecules Do not induce mediator
substances in sepsis activation.
Effect on Mortality No modality of RRT on the critically ill SAME
patients has been clearly shown to
have a survival benefit.

Primary Therapeutic Goal Clinical condition Renal replacement therapy

Solute removal Stable, catabolic Hemodialysis

Unstable, catabolic CRRT, SCUF + HD
Unstable, non-catabolic CRRT, SCUF + HD
Fluid removal Stable IIUF
Unstable IIUF, SCUF
Solute and Fluid removal Stable Hemodialysis
Blood Detoxification Unstable CRRT, IIUF + HD
Unstable CRRT
Non-Renal Indications for CRRT
• Pulmonary edema
• Sepsis
• ARDS
• Hepatic failure
• Severe burns
• Cerebral edema
• Tumor lysis syndrome
• Cardiopulmonary bypass
• Chemotherapy
• Lactic Acidosis
• Drug overdose with a toxin removable by extracorporeal therapy

Take Home Message

• The choice of dialytic technique is dependent upon a variety of factors:
▪ Expertise of the clinician
▪ Hemodynamic stability
▪ Comorbid conditions
▪ Degree to which solutes and/or fluid must be removed.
• The major advantage of continuous therapy is the slower rate of solute or fluid removal
per unit time.