Principle of Hemodialysis

dr Maruhum Bonar H Marbun

FKUI-RSCM
workshop PIT IPD 2013
 Modalities of
Renal Replacement Therapy

• Intermittent hemodialysis
• Continuous renal replacement therapy:
– CAVH/CAVHD/CVVHDF, CVVH/CVVHD/CVVHDF
• Peritoneal dialysis
Artificial kidney
 Terminology
• Hemodialysis (HD)
– transport process by which a solute passively diffuses
down its concentration gradient from one fluid
compartment (either blood or dialysate) into the other

• Hemofiltration (H)
– use of a hydrostatic pressure gradient to induce the
filtration (or convection) of plasma water across the
membrane of the hemofilter.

• Hemodiafiltration (HDF)
– dialysis + filtration.
– Solute loss primarily occurs by diffusion dialysis but 25 %
or more may occur by hemofiltration

• Hemoperfusion (HP)
– Removal of solutes by adsorption to charcoal or resin,
primarily for treatment of acute poisoning.
 HEMODIALYSIS
Diffusion

HEMOFILTRATION :
Convection
History
 1913:The First Hemodialysis
Experiment
90.0

67.5

45.0 East
West
North
22.5

0.0
1st 2nd3rd 4th
Qtr Qtr Qtr Qtr

Abel and Roundtree used a collodion hollow fiber tube arrangement, Dialysate, and Hirudin for anticoagulation
1926:The First Human Experiment

• George Haas used a

collodion tube
arrangement to
successfully dialyze
human subjects

• Allergic reactions to
impurities in Hirudin led
him to abandon his
experiments
1937: William Thalhimer
successfully lowers BUN
by performing
Hemodialysis in anephric
dogs

Thalhimer used Heparin anticoagulation, femoral Artery/Venous cannulation

and used a Cellophane tube as a dialyzer.
The tube was immersed in water to bring about a reduction in the BUN.
Dr Willem Kolff … father of dialysis

First Dialysis Machine — 1943: Kolff Rotating Drum

Kolff-Brigham Dialysis Machine: 1948
 Skeggs Leonards Plate Dialyzer: 1948

Leonard Skeggs and Jack Leonards, developed the first parallel flow artificial kidney
Milton-Roy Model A — First Machine Used for Nocturnal Home Hemo: 1964
Capillary Artificial Kidneys (Hollow Fiber Dialyzers): 1964-1967
Richard Stewart
 Principle of Hemodialysis

• Dialysis removes nitrogenous (and other)

waste products, and corrects the
electrolyte, water, and acid base
abnormalities associated with renal
failure.

• It requires the use of semi-permeable

membrane which allow the passage of
water and small molecular weight solutes,
but not large molecules.
 Dialysis: General Principles
• Diffusion
– Movement of solutes from an area of greater
concentration to lesser concentration

• Osmosis
– Movement of fluid from an area of lesser to an area of
greater concentration of solutes.

• Ultrafiltration (water & fluid removal)

– Movement of fluid across a semipermeable
membrane as a result of an artificially created
pressure gradient.
Diffusion
Ultrafiltration
 A B A B

Diffusion

Membrane
Membrane

t=0 t = equilibrium

A B A B

t=0 t = later
Ultrafiltration

The Process of diffusion (top) and ultrafiltration

 Solute Removal
from the Dialyzer Perspective
Hollow fiber Dialyzer
Hemodialysis Filter
 An Ideal dialyser should have :

• High clearance of small and medium molecular weight

molecules
• Adequate ultrafiltration
• Negligible loss of proteins and amino acids
• Non-toxic composition
• Minimal activation of cells or thrombotic pathways
• Minimal blood volume
• Reliability
• Re-usability
• Low cost

No single dialyser meets all these needs

Mechanisms of Solute Removal

1. Diffusion

2. Convection

3. Diffusion + Convection

4. Adsorbtion
 Solute Clearance
Blood Membrane Dialysate/Ultrafitrate
Diffusive Solute Clearance
Blood Membrane Dialysate/Ultrafitrate
Diffusive Solute Clearance

Blood Membrane Dialysate/Ultrafitrate

Convection
 Adsorption

ADSORPTION: molecular adherence to the surface or interior of the membrane.

 Ultrafiltration

ULTRAFILTRATION:
The movement of fluid through a membrane caused by a pressure
Solute clearance : Convection vs Diffusion
Clearance

Convective
Clearance

Diffusive
Clearance

Molecular Weight
10 100 1,000 10,000
 Water movement during standard
hemodialysis

Intracellular fluid Extracellular fluid Dialyzer

step3
step1
280
Loss of urea
and water
Water movement
Osmolality
Osmolality 320 mosm/kg
320 mosm/kg Falling to
step2
290mosm/kg
as diffusion occurs

Compensatory refilling
 Hemodialysis circuit

• In practice, during dialysis, concentration

equilibrium is prevented, and the concentration
gradient between blood and dialysate is maximized,
by continuously refilling the dialysate compartment
with fresh dialysis solution and by replacing
dialyzed blood with undialyzed blood.

• Countercurrent flow  to maximize the

concentration different of waste products between
blood and dialysate in all parts of dialyzer.
 A “Standard” HD Delivery System
Informational Display Saline

PT = Pressure
Transducer Anticoagulant

PT
Blood from Patient

Dialysate / UF Out
(green / yellow)
Blood Leak Conductivity
Detector
PT
Meter
Mixing
Dialysate In System Pre-mixed or
sorbent
Water, Acid
PT regenerated
Concentrate,
dialysate
Bicarbonate
Concentrate In
Air Venous
Drip Chamber clamp
Detector

Blood return to
37
Patient
Solute Transfer & Ultrafiltration

C blood > C Dialysate

P blood
P blood >
≈PP Dialysate
Dialysate

Blood Dialysate
 Same direction movement

Ur Cr Ur Cr Ur Cr Ur Ur Ur Ur
Cr Cr
Cr
Ur Cr Ur Cr
Cr Ur Cr Ur Ur Ur Ur

A semi-permeable membrane

Ur Cr Ur Ur Ur
Ur Cr
Ur Cr
Ur Ur
Cr

START DIFFUSION SOME DIFFUSION NO DIFFUSION

 Same direction movement

Ur
Ur
Ur Ur
Ur Ur

A semi-permeable membrane

START DIFFUSION SOME DIFFUSION NO DIFFUSION

 Opposite direction movement

Ur Cr Cr Ur Cr Ur Cr Ur Ur
Cr Ur Cr
Cr Ur
Ur Ur Cr Cr Ur Ur Cr
Ur

A semi-permeable membrane

Ur Ur Ur Ur Ur
Cr Cr
Cr
Ur Ur Ur

DIFFUSION DIFFUSION DIFFUSION

 Opposite direction movement

Ur
Ur
Ur Ur
Ur Ur

A semi-permeable membrane

DIFFUSION DIFFUSION DIFFUSION

 Factors affecting the blood water urea clearance

The principal determinants are …..

• Blood flow rate: usually maintained at 200-500 ml/min.

Increasing blood flow, increases solute clearance

• Dialysis solution flow rate: usually approximately 500 ml/min.

Increasing dialysate flows rate, increases clearance, but only
marginally

• Dialyzer efficiency: membrane thickness, pore size, surface-

area, and architecture of the dialyzer will all affect clearance.
Efficiency is measured by the KoA (mass transfer urea
coefficient).

• Molecular weight of solute: urea-MW 60 (75%), creatinine-MW

113 (60%) B12–MW 1,355 (25%)
Relationship between dialysate
flow rate and clearance,
blood flow rate 200 ml/min.

Relationship between blood flow

rate and clearance,
dialysate flow rate 500 ml/min.
Dialysis fluid
 Components of dialysis fluid

• Buffer (stabilize any existing metabolic acidosis)

– Normally bicarbonate
• Electrolytes
– Sodium
– Potassium
– Calcium
– Magnesium
– Chloride
• Glucose : added to increase filtration of fluid
Hemodialysate

135 - 145

98 – 124

1.25 – 1.75
0.25 – 0.75

30 – 40
 Potassium
• Pre-dialysis potassium levels are usually high.
– Hyperkalemia causes arrhythmias (usually slow) and
can lead to cardiac arrest

• Post-dialysis potassium levels can be very low.

– Hypokalemia also causes arrhythmias (usually fast),
especially in elderly pts and those with heart
problems
– Rapid changes may also cause arrhythmias

• Patients may start dialysis with low serum K+

– Due to anorexia, sickness and/or diarrhoea
 Potassium
• A standard potassium level (e.g. 2.0 mmol/l) is
acceptable for most patients
– Unless the patient has problems with rapid
changes (heart disease, arrythmias)

• For pts with low pre-dialysis potassium  higher

dialysate potassium
– Alternatively: IV or oral K+ supplements

• Potassium checked before each session of

dialysis? increased to 3.0 mmol/l?
 Sodium

• Too high or low, shrinking or swelling of the brain

cells  confusion or coma

• Pre-dialysis usually close to lower end of normal

range
– Most patients have a ‘natural’ sodium level

• A dialysate sodium that is “too high” could cause

the patient to drink more to restore their ‘natural’
level
– Fluid overload and hypertension
 Calcium

• In the past most patients needed extra Ca from

dialysis
– Used of high dialysate Ca concentrations (
1.75 mmol/l).
– This could lead to “adynamic bone disease”

• Use of vitamin D and Ca-based phosphate

binders has reduced Ca requirement
– Low dialysate Ca concentrations ( 1.25
mmol/l) allow higher doses of Ca-based
 Calcium
• For most pts, 1.5 mmol/l
– Some absorption of Ca during dialysis
– Some suppression of PTH post-dialysis

• For pts with high Ca, taking Ca based phosphate binders,

1.25 mmol/l
– Minimal absorption of Ca during dialysis

• For pts with low Ca and high PTH, 1.75 mmol/l

– Ca absorbed during dialysis
– Transient high post dialysis Ca suppresses PTH
production
 Magnesium

• High concentrations ( 0.75 mmol/l).

• Suppress PTH and impede arterial calcification
• Increase pruritus and contribute to renal bone
disease

• Low concentrations ( 0.25 mmol/l)

• Improve bone mineralisation and resolve bone pain
• Increase PTH levels and cause cramps during
dialysis

• Levels around 0.5 mmol/l are normally used

 Glucose
• Glucose will diffuse out of the blood if a zero glucose
dialysis fluid is used
– Losses of 14 to 31 g per session
– May cause hypoglycaemia
• Diabetic patients may need IV or oral glucose
supplements

• Physiologically normal glucose levels reduce symptoms

in diabetics (and may for all patients)
• hypoglycaemia were reduced by > 90% when the
dialysate glucose was increased from 0 to 5.5
mmol/l
– Higher levels may be needed to reduce symptoms in
diabetics
 Continuous Renal
Replacement Therapy
(CRRT)
 Definition of CRRT
• Either
– Dialysis (diffusion-based solute removal) or
– Filtration (convection-based solute and water removal) treatments
– that operate in a continuous mode(24hr/day)
• The major advantage
– slower rate of solute or fluid removal per unit of time.
– generally better tolerated than conventional therapy
– since many of the complications of IHD are related to the
rapid rate of solute and fluid loss
Mechanisms of solute removal in IHD and CRRT

IHD CRRT

Small solutes (< 300 D) Diffusion Convection (CVVH)

Diffusion (CVVHD)
Middle molecules (500-5000) Diffusion Convection
Convection Diffusion
LMW protein (5000-50 000) Convection Convection
Diffusion Adsorption
Adsorption
Large molecules (> 50 000 Convection Convection
 Vascular access - Arteriovenous
(AV)

• Advantage
– Not need blood pump
– Not need air detector, easy to control system

• Disadvantage
– Problem of arterial catheter e.g. ischemia,
atheroembolism, bleeding and
pseudoaneurysm
– Unstable blood flow
 Vascular access - Venovenous (VV)

• Advantage
– No complications from arterial catheter
– Blood pump – better blood flow

• Disadvantage
– Complicated – need blood pump and safety systems
• Venous bubble trap chamber
• Air detector, clamp and automatic stop blood pump
• Pressure monitor with alarm
– Air embolism and life threatening bleeding still occur
 Modalities of CRRT
• Blood Access
– Arteriovenous
• Continuous arteriovenous hemofiltration, (CAVH)
• Continuous arteriovenous hemodialysis (CAVHD)
• Continuous arteriovenous hemodiafiltration (CAVHDF)
– Venovenous
• Continuous venovenous hemofiltration (CVVH)
• Continuous venovenous hemodialysis (CVVHD)
• Continuous venovenous hemodiafiltration (CVVHDF)
– Slow continuous ultrafiltration (SCUF)
• Peritoneal Access
– Continuous equilibrium peritoneal dialysis
 Choice of therapy
• Dependent upon several factors including
– availability,
– the expertise of the clinician,
– hemodynamic stability,
– vascular access, and
– primary need? (fluid and/or solute removal)

• SCUF, CVVH, or CAVH

– can be used if fluid removal is the primary goal
– generally prefer venovenous access (more predictable BFR)
– However, arteriovenous access can be used if blood pumps are not available.

• CAVHD
– will probably be more effective than CAVH in the highly catabolic patient with a large
small solute load.

• One of the forms of HDF, with its convective removal of larger solutes,
– may be desirable in the patient with sepsis in whom an ancillary goal is the removal
of inflammatory mediators
 Choice of therapy
• Slow Continuous Ultrafiltration (SCUF)
– Vol control, minimal solute clearance
• Continuous Hemofiltration (CH)
– Convective solute removal
• Continuous Hemodialysis (CHD)
– Diffusive solute removal
• CHDF(Continous hemodiafiltration)
– Convective + Diffusive solute removal
 CRRT :
Slow Continuous Access
Ultrafiltration
Return
QB (50-100 mL/min)

High permeable filter

Vol control, minimal solute clearance!!

Ultrafiltration vol = Pt’s Wt loss QUF (100-300 mL/hr) or
(2-6 mL/min)
Effluent
 CRRT :
Continuous Hemofiltration Access

QB (50-200 mL/min) Return

Predilution

High permeable filter

Replacement
QR
Postdilution

Convective solute removal

Clearance for all solutes =UF
QUF (500-2000 mL/hr)

Effluent
 CRRT :
Continuous Hemodialysis Access

QB (50-200 mL/min)

Low permeable dialyzer with

QDo
Countercurrent flow through
Dialyzer compartment

Diffusive solute removal

Limited small solute Return

Dialysate
QDi

QUF = Q Di – Q Do
(100-300 mL/hr)
 CRRT :
Continuous Access
Hemodiafiltration
Predilution

QDo
High permeable dialyzer with
Countercurrent flow through
Replacement Dialyzer compartment
QR
Return
Convective + Diffusive solute removal Postdilution
Small to large molecule Dialysate
QDi

QUF = Q Di – Q Do
(100-300 mL/hr)
 Comparison of different CRRT Modalities

CRRT Blood Replacement Urea Urea Middle simplici

pump Fluid (RF) molecule
Dialysate (D) clearan clearan clearance ty
ce ce
(L/day) (ml/mi
n)
SCUF Y/N N 1-4 1-3 + +
CAVH 10-15
N RF 7-10 ++ +
CVVH 22-24 15-17
Y RF +++ ++
CAVHD 24-30
N D 17-21 - +
CVVHD 24-30 17-21
Y D - ++
CAVHDF 36-38 25-26
N RF + D +++ +++
CVVHDF 36-38 25-26
Y RF + D +++ +++
 Comparison of different CRRT Modalities

SCUF CH CHD CHDF

Vascular access AV or VV access AV or VV access AV or VV access AV or VV access
BFR 50-100 50-200 50-200 50-200
Urea clearance + 12-36 14-36 20-40
(L/day)
UFR 2-5 8-25 2-4 8-12
Diffusive - - +++ ++
clearance
Convective + +++ + ++
clearance
Hemofilter/ highly permeable highly permeable Low permeable highly permeable
hemofilter hemofilter dialyzer dialyzer
dialyzer
UF goal = excess fluid > excess fluid = excess fluid > excess fluid
Replacement fluid - pre / postdilution - pre / postdilution

Goal Fluid removal middle and large small molecule small to large
molecule clearance > clearance molecule clearance
CHD
 RECENT TECHNICAL INNOVATIONS

• High volume hemofiltration (HVHF)

– Sepsis dose vs Renal dose
– 3L/hr vs 1.4~2.4L/hr Standard renal dose in CVVH (70kg)
– Not yet proven, cost, technical problem…

• Sustained low-efficiency dialysis or extended daily dialysis (SLED)

– “Hybrid therapy”(form of CVVHD)
– Standard IHD equipment and accessory
– Lower solute clearance and UFR maintained for prolonged periods of
time.
– Higher Qd and Urea clearance
– High dose of dialysis, minimal urea disequilibrium, on-line bicarbonate
dialysate, excellent electrolyte control, good UF tolerance.
 Sustained Low-Efficiency Dialysis
• SLED was introduced July 1998 at the University of Arkansas
for Medical Sciences and involves application of the Fresenius
2008H machine with reduced dialysate and blood flow rates
for 12-hour nocturnal treatment.
• Dialysate and blood flow rates can be set between 100 and
200ml/min
• A 8-12 hour duration can be prescribed to allow for a low
ultrafiltration rate, provide good solute clearance and
coincide with ICU nursing shifts
• Use a low-flux polysulfone hemodialysers
Peritoneal dialysis
 Layers of the PD Membrane
Solute and water must cross these 5 barriers to move
from the blood into peritoneal cavity)

1. Capillary endothelium
2. Endothelial cell basement membrane
3. Interstitium
4. Base membrane of the mesothelium
5. Mesothelium of the visceral peritoneum
 Solute and Water Transport Mechanism in PD
Substance Mechanism
removed

Diffusion Solute - Via mid-size pores

(e.g. urea, - Most important
creatinine, - From high conc. (blood) to low conc.
potassium) (dialysate)
- Proportional to the concentration gradient
(Highest at beginning, decrease during the
dwell time) ; Best for clearance of small
molecules

Convect Solute - Movement in response to a positive

(e.g. protein, transmembrane pressure
ion sodium) - Less dependent on molecular size
 Solute and Water Transport Mechanism in PD
Substance Mechanism
removed

Ultrafiltra Water - Movement from low osmotic conc.(blood) to

tion high osmotic conc. (dialysate), via aquaporin-1
- The higher the conc. the more water is removed
- Highest at the beginning, ceases when
osmolarity has decreased to equal serum
osmolarity (due to dextrose absorption)
- Reabsorbtion of water occurs if dialysate
isallowed to dwell beyond the time past when
osmotic equilibrium is reached
 Peritoneal Membrane Characteristics
% Membrane 4-Hr D/P Characteristics Suggestion
Type Creatinine
Patients
• Very efficient membrane Best suited for short
frequent cycles
• Transports solutes quickly
.82 - 1.03 APD/standard CAPD
• Increased glucose absorption
HIGH + Icodextrin
• May have difficulty achieving UF
10% • At risk for low serum albumin

• Efficient membrane Standard CAPD

HIGH .65-.81
• Transports solutes well
AVERAGE
53% • Ultrafilters well
• Less efficient membrane Standard CAPD
31% LOW .50-.64
• Transports solutes somewhat slowly
AVERAGE
• Ultrafilters well
* Inefficient membrane If no RRF, PD may
6% LOW .34-.49 not be adequate
• Transports solutes slowly
Peritoneal dialysis
HD vs. PD
Thank You
 SCUF
• Slow Continuous Ultra-
Filtration

• Arterio-venous or veno-venous
• Slow convection
• Filtrate flow < 5 ml/min
(< 3 l/d) Measuring
device
• No replacement fluid
• Treatment time less than one
day Filtrate
 CAVH Replace-
ment
fluid

• Continuous-Arterio-Venous
Hemofiltration

• Arterio-venous circuit
• High permeable membrane
• Ultrafiltration flow ~ 6 ml/min
(9-12 l/day) Measuring
• Requires MAP > 50 mmHg device

(Flow = 50-90 ml/min)

• Replacement fluid
Filtrate
 Replac

CVVH e-ment
fluid

• Continuous-Veno-Venous
Haemofiltration

• Veno-venous circuit
• High permeable membrane
• Ultrafiltration flow > 10ml/min
( > 15 l/day) Measuring
device
• At least a blood pump (Flow >
50 ml/min) required
• Replacement fluid Filtrate

pre-dilution, post-dilution, or pre-/post- dilution

 CVVHD
• Continuous-Veno-Venous
Haemo-Dialysis
• High permeable membrane
• Ultrafiltration rate ~ 0 Dialysate

• No replacement fluid Measuring

device
• At least a Blood pump and
a pump for Dialysat (10-30
ml/min) required Filtrate
 CAVHDF
Replace-
ment
fluid

• Continuous-Arterio-Venous
Haemo-Dia-Filtration

• High permeable membrane

Dialysate

• Ultrafiltration flow > 6 ml/min

Measuring
device
( 9-12 l/day)
• 1 pump for dialysate
(10-30 ml/min) Filtrate

• Replacement fluid
 CVVHDF Replace-
ment fluid

• Continuous Veno-Venous
Haemo-Diafiltration
• High permeable membrane
• Ultrafiltration flow > 10 ml/min
(14-24 l/day)
• A Blood pump (Flow = 50 -150
ml/min) required Dialysate
Dialysat

• A replacement pump (10-30

ml/min) and a Pump for
Dialysate (10-30 ml/min)
required Filtrate +
Dialysate
• A filtrate pump required

requires administration of substitution fluid, which is typically delivered in the post-dilution mode
Therapeutic Plasma Exchange (TPE)

• Membrane is used to separate whole blood into plasma and

cellular components, the plasma removed may be replaced
with fresh plasma and/or plasma substitutes

• Clinical indications
– Hepatic failure
– Autoimmune diseases
– Hypercholesterolaemia
– Immuno-suppression
– Drug intoxication
Arteriovenous access
Femoral artery  Femoral vein
Molecular weight in Dalton of some nonionic substances

Substance Molecular weight

(in Dalton)
BUN 28
Urea 60
Creatinine 113
Ethanol 46
Methanol 33
Glucose 180
Vit B12 1355
Albumin 68000