Lessons in Dialysis, Dialyzers, and
Review
Dialysate
Robert Hootkins, MD, PhD
The author is Chief of Nephrology and Hypertension at The Austin Diagnostic Clinic, Austin, Texas. He is also a member of
D&T’s editorial advisory board.
H
emodialysis today has evolved
into a highly technical treatment
in which knowledge of the phys-
ics and chemistry of the dialysis
treatment system as well as knowledge of
individual patient’s pathology allows for a
better understanding of how the treatment
is best performed and individually modi-
fied. The “treatment prescription” is a set of
specific treatment parameters that includes
the treatment duration and frequency, the
choice of dialyzer, and the specifics of
the dialysate composition. It is imperative
that the nephrologist understand how to
deliver the most optimal treatment that is
additionally the most cost effective.
Dialysis
In short, hemodialysis is the process by
which a patient’s blood can be chemically
modified by driving it through a device
(dialyzer) that allows for the removal of
substances (blood solutes) as well as the
gain of substances (dialysate solutes) with
the additional option of the simultaneous
removal of plasma water. It has evolved
for almost a century but remains dependent
on the chemical properties of a semiper-
meable membrane that is selective to the
movement of solute and resistive to the
movement of solvent. The primary purpose
of dialysis is to eliminate uremic poisons
in patients with end-stage renal disease
and to modify serum electrolytes so as to
mimic the appropriate serum composition
of healthy individuals.
Dialyzers and Solute Clearance
A dialyzer can be classified based on prop-
erties of the chemical composition of its
membrane or based on its properties of sol-
ute removal (most commonly urea removal)
and solvent permeability (most commonly
water, termed hydraulic permeability) under
392 Dialysis & Transplantation September 2011
specific operating conditions (blood flow
rate [QB in mL/min] and dialysate flow rate
[QD in mL/min]). Some dialyzers are more
efficient at solute removal and are termed
high-efficiency, whereas other dialyzers have
lesser resistance to water movement and are
termed high-flux. Dialyzer membrane prop-
erties have been recently reviewed.1
Using a simple model of hemodialy-
sis operating conditions, the removal of a
solute like urea can be approximated by an
equation derived by Michaels2 in which the
removal of a solute K from blood can be
expressed by the clearance equation:
in which the dialyzer’s ability to remove
a solute K is proportional to the product of
the mass transfer coefficient of that dialyz-
er’s membrane (Ko) and the membrane sur-
face area (A). KoA is specific to a particular
solute (such as urea) and is independent of
QB and QD (assumption of the model). The
KoA of a particular dialyzer is provided by
the manufacturer, is determined in vitro in
aqueous solutions, and usually overesti-
mates by about 20% when compared with
in vivo blood-based solutions containing
proteins and red blood cells.
It is difficult to fully appreciate the
relationships among KoA, QB, and QD.
Figure 1 presents these relationships graph-
ically, depicting urea clearance K as a func-
tion of QB for a dialyzer KoA of 1,000 and
three separate QDs of 1,000, 500, and 400
mL/min (from the top curve down).
At lower QBs, the clearance (K) is
linear with QD, but as QB increases closer
to QD, there is a diminishing benefit of
increasing QB further (as QD becomes
clearance limiting).
Many insights can be obtained by an
analysis of the clearance equation. Table I
illustrates the effects on the overall clearance
of urea of changing a number of parameters.
The first observation is that the overall
clearance is simply determined by the low-
est of the three parameters KoA, QB, and
QD. Most high-efficiency, high-flux dia-
lyzers have a KoA for urea of 1,000-2,000.
Since QDs are typically in the range of 600-
800 mL/min. Dialyzer membrane proper-
ties have it is the lowest parameter, QB
(typically in the range of 400-500 mL/min)
that determines the overall clearance K. In
fact, the more general observation is that
clearance becomes limited as QB approach-
es either QD or KoA. Additionally, if the
magnitude of both QD and KoA are close
to QB, QB is even further diminished.
There are practical ramifications of
these observations. One lesson is that in
this current era of bundling and small finan-
cial margins, it makes sense not to spend
resources on dialyzers that have exces-
sively high KoAs in that their benefit will
be minimized by the QB, which is, in turn,
limited by access flow and needle resistance
limitations. In general, KoAs in excess of
1,000 are of marginal benefit. An additional
lesson is that with daily hemodialysis meth-
odologies that have reduced QDs of 150
mL/min (for example, NxStage) or contin-
uous veno-venous hemodialysis (CVVHD)
techniques with QDs of 50-100 mL/min,
there is no reason to employ higher QBs or
to use large dialyzers, as K will be limited
by QD.
Another example of an even greater
waste of financial resources is the use of
two dialyzers simultaneously, combined
either in-parallel (Figure 2A) or in-series
(Figure 2B) to effectively increase KoA.
Table II illustrates the overall effect on
clearance by use of these configurations.
Although a theoretical added clear-
ance of about 14-15% can be achieved, the
total dialysis treatment “dose” can often be
obtained more cost effectively by simply
DOI: 10.1002/dat.20609

FIGURE 1. Dialysis clearance equation. K versus QB for QD = 1,000, 500, 400 [KoA = 1,000].
extending the dialysis treatment time
using a single dialyzer by an additional
15-30 minutes with a minimal added cost
of dialysate consumption! To employ the
other configurations, additional connec-
tors must also be purchased, increasing
the costs associated with the treatment.
Additionally, these configurations also
result in greater dialysis disequilibrium
(faster rate of solute removal, which is
proportional to K/V); depending on the
methodology of the urea kinetic modeling
utilized, this can lead to greater overesti-
mation of solute removal and a false sense
of security that enough dialysis is being
performed.
It is important to know that the clear-
ance equation only applies under a set of
ideal circumstances including the absence
of convection (ultrafiltration). For the
removal of urea, this is a fair approxima-
tion since it is primarily eliminated by
diffusion, not convection, and Fick’s law
TABLE I. Dialysis clearance equation.
KoA QB QD
1,000 400 800
1,000 400 1,000
1,000 1,000 800
10,000 400 800
applies. In most dialysis treatments, how-
ever, the ultrafiltration rate can be sig-
nificant. A more general equation can be
derived that includes the effects of both
diffusion and ultrafiltration but is beyond
the scope of this article.3 Fortunately,
however, in the limit of solutes that are
large enough to be cleared predominantly
by ultrafiltration and not diffusion (for
example, vancomycin), the more general
equation3 simplifies to:
K = (1  ) QF + KoA.
The sigma () relates to the permeabil-
ity of the dialysis membrane to a particular
solute. This equation is the equation of
a straight line, and if one experimentally
measures the clearance of a molecule as
a function of ultrafiltration rate, QF in
mL/min, the  and KoA can be determined
from the slope (1   )and the intercept
(KoA).3 Doing this for the clearance of
vancomycin (molecular weight of 1,486)
Clearance % Increase
333
341 2%
469 41%
400 20%
for a specific dialyzer (Fresenius F80)
results in the determination of  of 0.9 and
a KoA of 20. Graphing the clearance (here
defined as D́) of vancomycin as a function
of QB and QF (Figure 3) demonstrates that
it is removed more effectively with lower
QBs and higher QFs.
For larger solutes cleared by convec-
tion, the greater the time of the dialysis
membrane exposure (slower QB) and the
greater the pressure gradient across the
dialyzer membrane (higher QF), the greater
the clearance. The opposite of this is true as
well. For example, to minimize vancomy-
cin clearance, faster QBs and smaller QFs
will clear less of the antibiotic for a given
dialysis prescription.
Additional Degrading Factors
That Reduce the Actual
Clearance of Substances
As a result of dialysis being performed in a
in-parallel fashion, there is the generation
of both an access recirculation (AR) and
a cardiopulmonary recirculation (CPR).
The dialyzer operating in-parallel with the
peripheral access results in AR, and the
peripheral access operating in-parallel with
the systemic venous circulation results in
CPR (Figure 4).
AR and CPR effectively prevent the
dialyzer from actually receiving blood with
systemic concentrations of solute; instead,
a “diluted” sampling of systemic venous
blood with solute cleared blood is received
(Figure 5). (The extraction efficiency of
a dialyzer is proportional to the incident
concentration of the solute to be removed).
The mathematics of these effects has been
worked out by Schneditz et al.4 As a conse-
quence, the actual removal of solute is not
only based on the dialysis treatment pre-
scription but is also dependent on patient
specific parameters that include cardiac
output and venous flow through the periph-
eral access.
Another barrier to our effectively elim-
inating urea from a patient’s body results
from the fact that the storage of urea occurs
primarily in the skeletal muscle and its
removal may depend on the vascular “com-
munication” of this compartment with the
central venous system.
This provides one theory of why
exercise during dialysis improves the
September 2011 Dialysis & Transplantation 393
 Review
FIGURE 2. A) Operational configuration of 2 dialyzers placed in-parallel; B) Operational configu-
ration of 2 dialyzers placed in-series. Reprinted from AJKD (reference 7), copyright 2003, with
permission from Elsevier.
quality of urea removal: it allows for great-
er vascular flow (improved communica-
tion) with the skeletal compartment and
a subsequent higher central venous con-
centration of urea. Table III illustrates a
comparison between two patients with an
394 Dialysis & Transplantation September 2011
identical extracorporeal dialysis treatment
prescription but different cardiac output
and access flows.
Patient A is relatively healthy with
a normal cardiac output and no signifi-
cant access pathology. Patient B has mild
FIGURE 3. K vs QB [QF = 20  100]
[  = 0.9, K0A = 20, QD = 500]. From
reference 3.
anemia, a cardiomyopathy, and poorly
functioning access flow. Ultimately, patient
B receives 30% less dialysis in spite of
having the same identical treatment pre-
scription. The lesson here is that the actual
delivered amount of dialysis can be signifi-
cantly less than the theoretically prescribed
dialysis. Flow recirculations (AR and CPR)
and a patient’s individual physiology (urea
trapping in skeletal muscle and cardiac out-
put) and access health result in a delivered
clearance dependent on factors out of our
prescriptive control. Careful consideration
of a patient’s cardiac status and access
health may indicate a need for additional
clearance beyond that predicted by an a
simple analysis of his or her urea kinetic
modeling.
Dialysate
Dialysis machines employ a proportioning
system that mixes an acid concentrate with a
bicarbonate concentrate and purified water.
This allows for the generation of a dialysate
with a physiologic pH and minimizes the
possibility of forming a precipitate between
bicarbonate containing alkaline solutions
and calcium. The acid concentrate contains
dextrose and is the source of electrolytes
including potassium, calcium, magnesium,
and acetic (or citric) acid. The bicarbonate
concentrate may contain sodium chloride
as well as sodium bicarbonate (36.83)
or may contain only sodium bicarbon-
ate (35/45). The nomenclature of the
commonly used Fresenius 45x system is
derived from the fact that the proportion-
ing system mixes 1 part acid concentrate to
1.72 parts bicarbonate concentrate to 42.28
parts water, which adds up to 45 “parts.” It
is important to understand that modifying
the prescription for sodium or bicarbonate
 in real time during rounding will alter all
TABLE II. Effect on clearance of using two dialyzers. electrolyte concentrations of the dialysate
Operating conditions: KoA = 1,000 solution. Most current equipment will show
QB = 400, QD = 800 the effects of changing the dialysate pro-
portioning in real time.
Single dialyzer: K = 333 mL/min It is also of importance that the total
Two dialyzers in series: K = 380 mL/min (+14%) buffer in this system include bicarbonate as
Two dialyzers in parallel: K = 383 mL/min (+15%) well as acetate (or citrate), which can add
an additional 2.0-8.0 mEq/L buffer. If one
prescribes a dialysate bicarbonate delivery
of 35 mEq/L, the total delivered buffer will
be the sum of the bicarbonate and the ace-
tate (or citrate) from the acid concentrate
(which is metabolized to bicarbonate in the
liver). Therefore, the total delivered base
(TDB) to a patient has to include consid-
eration of both bicarbonate and acetate (or
citrate) buffers. Consequently, on longer
dialysis treatments using high bicarbonate
concentrations (40 mEq/L), we can induce
a chronic metabolic alkalosis, which can
have adverse effects on patient mortality
(based on mortality data obtained by sev-
eral large dialysis providers).

Specific Dialysate Electrolytes:

Sodium and Calcium
High dialysate sodium concentrations can
lead to sodium loading, increased thirst,
and subsequent high weight gains and
hypertension. A chronic state of volume
FIGURE 4. Origin of AR and CPR as depicted by parallel blood flows from dialyzer to access, and overload and hypertension ultimately leads
access to the systemic circulation. to left ventricular hypertrophy and cardiac
dysfunction. Sodium is removed from the
patient both by ultrafiltration (for patients
with large weight gains) and by diffusion.
Consequently, the total fluid removed as
well as the sodium gradient between the
patient and the dialysate at the initiation
of the treatment are both critical factors. It
has been suggested that individualizing the
dialysis sodium concentration to be slightly
less than a patient’s historic sodium con-
centration may be the best way to prevent
sodium loading.5
Much controversy exists over the opti-
mal calcium concentrations in dialysate. A
concern exists that calcium loading may be
harmful to patients and that many hemodi-
alysis patients are constantly exposed to a
state of positive calcium balance between
the oral ingestion of calcium in foods and
FIGURE 5. Reduced efficiency from AR adn CPR results from blood effectively cleared of urea binders as well as from a positive calcium
nitrogen by dialysis being mixed with blood with high urea nitrogen from its primary source (skeletal
influx from the dialysate. This positive
muscle tissue). This mixing reduces the concentration of urea nitrogen returning back to the central
venous compartment and leads to reduced urea nitrogen concentration in the blood incident to calcium balance may contribute to calcium
the dialyzer. deposition in arterial vessels and heart

September 2011 Dialysis & Transplantation 395

 Review

ensure the correct dialysate delivery to each

TABLE III. Comparison between two patients with the same dialysis patient’s dialyzer by sampling dialysate at
but different cardiac output and access flows. the first and last chair of each distribution
Parameter Patient A Patient B loop. Most dialysis specialty labs can mea-
sure electrolytes on non-blood samples and
Hct 35% 30%
provide this as a safety check. D&T
CO 10 L/min 6 L/min
Access flow 1,000 500
References
Access recirculation 1% 15%
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Dial. 2011;24:65-71.
QB 400 400
2. Michaels AS. Operating parameters and perfor-
QD 800 800 mance criteria for hemodialyzers and other mem-
brane-separation devices. Trans Am Soc Artif
QF 10 10 Intern Organs. 1966;12:387-392.
3. Hootkins R, Bourgeois B. The effect of ultrafil-
% Reduction from theoretical K 4% 30% tration on dialysis: mathematical theory and
experimental verification. ASAIO Trans. 1991;37:
M375-377.
4. Schneditz D, Kaufman A, Polaschegg D,Levin
valves. A recent mathematical analysis of as prescribed. Unfortunately, a number of NL, Daugirdas J. Cardiopulmonary recirculation
this issue by Gotch et al.6 suggests that variables can affect the proportioning sys- during hemodialysis. Kidney Int. 1992;42:1450-
1456.
dialysate concentrations below 2.5 mEq/L tem, one being the inlet pressure of the
5. Penne EL, Sergeyeva O. Sodium gradient: a tool
may be necessary to limit calcium influx dialysis concentrates and water entering to individualize dialysate sodium prescription
from the dialysate. into the dialysis machine. Depending on in chronic hemodialysis patients? Blood Purif.
2011;31:86-91.
the open or closed loop nature of the distri-
6. Gotch F, Levin NL, Kotanko P. Calcium balance in
Is the Dialysate Delivered the bution system, inlet pressures to the dialysis is best managed by adjusting dialysate
machines can significantly vary even by calcium guided by kinetic modeling of the inter-
Dialysate Prescribed? relationship between intake, dose of vitamin d
position within the loop. To promote a analogs and the dialysate calcium concentration.
One assumes that if the hemodialysis more consistent pressure, a gravity feed Blood Purif. 2010;29:163-176.
machine is set appropriately with the cor- system is often utilized. Perhaps one of the 7. Fritz BA, Doss S, McCann LM, Wrone EM. A com-
parison of dual dialyzers in parallel and series
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396 Dialysis & Transplantation September 2011