Chapter 1

Brief History of Clinical Dialysis: The Seattle

Experience

Although it was not until the 1960s that long-term dialysis in a clinical setting be-
came a reality, dialysis as a treatment for renal failure had been the focus of interest
for some time. By the end of the 1950s, Dr. B. H. Scribner had established an acute
dialysis program at the University of Washington. In 1960, a uremic comatosed
man who was thought to have acute renal failure was brought back to almost normal
active life with intermittent hemodialysis. However, he was found to have chronic
irreversible renal disease and had to be sent home to die; it became clear to the Seat-
tle team that if long-term vascular access could be maintained, long-term dialysis
would become a reality. This led to the development of the Scribner Shunt and the
advent of chronic hemodialysis.
The Seattle team developed an entire program to care for a population of pa-
tients who had a chronic disease and who were being kept alive on a new form of
treatment. New equipment and systems were developed and refined and solutions
for unexpected problems had to be devised—specifically, treatment of hyperphos-
phatemia, renal osteodystrophy, and hypertension. To make the treatment more prac-
tical, by reducing the bulk of the dialysate through the use of concentrated dialysate,
a proportioning system had to be developed and a substitute for bicarbonate was
used to prevent the precipitation of calcium carbonate. This was achieved by using
acetate. However, when acetate-related problems started to appear (due to the use
of more efficient dialyzers, in the mid-1970s), a double proportioning system was
developed to enable the use of bicarbonate again. As is often the case, the reso-
lution of one problem often led to other unexpected difficulties. The commitment
and ingenuity of the pioneers of dialysis treatment, however, meant that these hur-
dles were overcome and the success of dialysis as a treatment for end-stage renal
disease (ESRD) was assured. Later in the 1980s, another Scribner fellow, Joseph
Eschbach, developed and used recombinant erythropoietin, and anemia-related is-
sues became history. The pioneering work continues today; the most recent modifi-
cation in dialysate was the development of a citric acid-based acid concentrate for
dialysate. This is proving to be more beneficial to the patients than the currently
used acetic acid-based acid concentrate.

S. Ahmad, Manual of Clinical Dialysis, DOI 10.1007/978-0-387-09651-3 1, 1

c Springer Science+Business Media LLC 2009
2 1 Brief History of Clinical Dialysis: The Seattle Experience

The shortage of resources in the early days of dialysis necessitated the found-
ing of a patient selection committee to decide which of the needy patients would
be accepted into the program. This committee (thought by many to be the founda-
tion for the development of medical ethics) forced several actions with far-reaching
consequences, one of which was the development of home dialysis.
A young high-school student was found to have ESRD but was not accepted for
dialysis by the patient selection committee. The team decided that home dialysis was
a viable alternative if they could develop a smaller hemodialysis machine that could
be used at home. The collaborative effort of Dr. Scribner’s clinical team and the
engineering team of Dr. Albert L. Babb succeeded in building a home hemodialysis
machine in only 3 months. This home machine became the prototype of machines
in use currently.
In early 1960s, Dr. Fred Boen joined the Seattle group and began treating a pa-
tient using peritoneal dialysis (PD), with a closed system containing 20-l (and later
40-l) bottles. Henry Tenckhoff, a research fellow with Dr. Boen, treated patients at
home using Boen’s repeated puncture technique. This technique, however, required
aseptic access to the peritoneal cavity with a catheter each time dialysis was needed,
and meant that Dr. Tenckhoff had to visit each patient’s home at least three times a
week to insert the access device. Eventually, Dr. Tenckhoff developed the indwelling
peritoneal catheter and a sterile technique for its insertion, which made it possible
to use the new form of dialysis on a larger scale.
A detailed analysis of the Seattle experience with intermittent PD (IPD) revealed
the potential risk of under-dialysis and poor “technique survival rates” [1], suggest-
ing that the dialysis dose needed to be increased. In 1965, Dr. Robert Popovich
while in Seattle had become involved in the kinetics of the “middle molecule”
across the peritoneal membrane before moving to Texas and becoming a pioneer
of the continuous ambulatory PD (CAPD) technique. This continuous therapy im-
proved the dialysis dose and made PD a viable technique of renal replacement ther-
apy (RRT).
Encountering a patient who was dying of malnutrition due to bowel disease,
Dr. Scribner saw an opportunity to apply the group’s expertise in vascular access
to another area of medicine. The development of Broviac (and later on Hickman)
catheters and the “total parenteral nutrition” (TPN) program (operated by the
nephrology team at the University of Washington) was a result of the vision and
dedication of Dr. Scribner and his co-workers.
This very brief account of the Seattle experience shows that the commitment of
Dr. Scribner, his team, their collaborators, and community members accomplished
more than the development of a dialysis access device. Their efforts led to the de-
velopment of systems for dialysis, central venous catheters, parenteral nutrition,
long-term care of ESRD patients, community-based dialysis centers, home dialysis
programs, an early concept of dialysis dose calculation, and continued technological
improvement. The development of the dialysis program established nephrology as
a subspecialty and has also had far-reaching implications in the fields of bowel
disease, organ transplantation, oncology, and for all acutely ill patients. It is now
1.2 Mechanisms Involved in Molecular Movement 3

difficult to imagine that less than 50 years ago, patients with ESRD had only one
prognosis—death—and that patients with renal failure were connected to patients
with liver failure so that each could be kept alive by the healthy organ of the
other.

1.1 Definition of Dialysis

In broad terms, the process of dialysis involves bidirectional movement of molecules

across a semipermeable membrane. Clinically, this movement takes place in and out
of blood, across a semipermeable membrane. If the blood is exposed to an artificial
membrane outside of the body, the process is called hemodialysis (HD) or hemofil-
tration (HF). If the exchange of molecules occurs across the peritoneal membrane,
the process is called peritoneal dialysis (PD).

1.2 Mechanisms Involved in Molecular Movement

The movement of molecules follows certain physiological and physicochemical

principles that are outlined below (see Fig. 1.1a).
4 1 Brief History of Clinical Dialysis: The Seattle Experience

Fig. 1.1 a Diffusion, osmosis, and osmotic ultrafiltration by osmotic pressure. b Hydrostatic ul-
trafiltration. D diffusion, O osmosis, OU osmotic ultrafiltration, UF ultrafiltration by hydrostatic
pressure, C convection

1.2.1 Diffusion

If two solutions of different concentrations are separated by a semipermeable mem-

brane, solute will move from the side of higher to the side of lower solute concentra-
tion. This process of solute movement on a concentration gradient is called diffusion
and is caused by the random movement of the solute molecules striking and moving
across the membrane. Several factors influence this random movement and thus the
rate of diffusion. The transport of any solute or solvent molecule is dependent on
the physical size of the molecule relative to the size of the pores in the membrane.
Any molecules larger than the pores of the membrane cannot pass through. Sim-
ilarly, the electrical charge and the shape of the molecule also determine the rate
of transport across the membrane. If the membrane has a negative charge, particles
with a like charge will have limited transport as compared with those with a positive
or a neutral charge.

1.2.2 Ultrafiltration

A solvent such as water can be forced across a semipermeable membrane on a pres-

sure gradient, from higher to lower pressures (see Fig. 1.1). The pressure could be
a result of osmotic force (see below) or of mechanical hydrostatic pressure. The
1.3 Clearance 5

solvent carries with it the dissolved solute molecules small enough to pass through
the membrane pores (see below). This movement of molecules across a semiperme-
able membrane, caused by a pressure difference, is called ultrafiltration (UF). If the
pressure is hydrostatic, the process is called “hydrostatic UF.” Conversely, the UF
caused by osmotic pressure is called “osmotic UF.”

1.2.3 Osmosis

As solute concentration increases, solvent concentration correspondingly decreases

and vice versa. If a semipermeable membrane separates solutions of different con-
centrations, solvent along with dissolved small solutes will flow from the side with
the higher solvent concentration to the side with the lower solvent concentration.
This process is called osmosis (see Fig. 1.1).

1.2.4 Convection

As solvent molecules move on a pressure gradient, the dissolved solute molecules

are dragged along (solvent drag); this process of solute movement is called convec-
tion. The ease with which the solute is dragged along is determined by the size of
the solute molecule relative to the size of the membrane pores. Smaller solutes are
transported easily and the entire solution can sieve across the membrane without any
change in concentration. In contrast, larger solutes move more slowly and the rate
of convective transport is slower. Thus, the convective transport of a solute depends
on the porosity of the membrane. This porosity, known as the “sieving coefficient of
the membrane,” can be calculated by dividing the concentration of solute on side A
by the concentration on side B.

1.3 Clearance

In a clinical setting, the removal of a solute is measured in terms of clearance, the

term being defined as the volume of blood or plasma from which the solute is com-
pletely removed in unit time. Let us assume that the blood urea concentration across
a hemodialyzer drops from 100 mg/dl at the inlet to 10 mg/dl at the outlet. This 90%
decline represents the diffusion of urea from blood into the dialysate and depends
largely on the concentration gradient between these fluids. However, the magnitude
of the “cleaning” of blood also depends on blood flow rates (Qb). Thus, in the above
example, a blood flow rate of 100 ml/min means that 90 ml of the blood was cleared
of urea. However, for a blood flow of 200 ml/min, 180 ml of blood is cleared of urea
each minute (see the example below for a more accurate calculation). Clearance
measures the magnitude of blood cleaning, independent of the concentration of the
solute entering the dialyzer.
6 1 Brief History of Clinical Dialysis: The Seattle Experience

1.3.1 Blood vs Plasma Clearance

During transit across the dialyzer, most solutes are removed from plasma water
(about 93% of blood volume, depending on plasma protein concentration). If the
solute is not in the blood cells or if the movement of solute out of these cells is slow,
the clearance of the solute decreases as the hematocrit increases (since the plasma
volume decreases). Urea is often used as a solute to measure dialysis efficiency (it
is present in plasma water as well as in erythrocytes), and the flux of urea across the
erythrocyte membrane is reasonably fast. This means that urea is cleared from whole
blood during dialysis and is not affected greatly by the hematocrit. The following
example clarifies these concepts:

Example

Qb = 200 ml/min, hematocrit = 35%

Plasma flow rate = 200ml/min × (1 − 0.35) = 130 ml/min
Plasma water flow rate = 130 ml/min × 0.93 (93% of plasma is water) =
121 ml/min
Erythrocyte flow rate = 200 ml/min − 130 ml/min = 70 ml/min
Erythrocyte water flow rate = 70 ml/min × 0.80 (about 80% of erythrocyte
volume is water [containing diffusible urea]) = 56 ml/min
Thus, the whole blood water flow rate effective for urea clearance =
121 ml/min+ 56 ml/min = 177 ml/min
If the blood water concentration of urea = 100 mg/dl at dialyzer inlet and
10 mg/dl at outlet, the urea clearance of whole blood = 177 ml/min ×
{1−[(10 mg/dl)/ (100 mg/dl)]} = 159 ml/min
This means that 159 ml of blood is cleared of urea each minute.

1.3.2 Clinical Factors Influencing Dialysis Urea Clearance

The three major determinants of urea clearance during hemodialysis are:

Blood flow rate (Qb)
Dialysate flow rate (Qd)
Membrane (dialyzer/peritoneal membrane) efficiency

Reference

1. Ahmad S, Gallagher N, Shen F. Intermittent peritoneal dialysis: status reassessed. Trans Am

Soc Artif Intern Organs 1979, 25:86–89.