ASAIO GOLD
The 25 Landmark 'Milestone' Papers Published
by ASAIO
1955-2003
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Your Commentary --- Milestone Papers to Add
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Artificial
Kidney (Hemodialysis)
1.
Kolff, W.J.,
"The Artificial Kidney - Past, Present and Future," TASAIO, 1:1-7,
1955
Commentary: This article
is the first paper printed on Page 1 to 7 of Volume 1 of ASAIO Transactions by WJ Kolff. This transaction was typed by June Salisbury,
wife of Dr. Peter Salisbury, the founder of ASAIO and the third president of
ASAIO (1957-1958). The congress was held
in Hotel Chelsea in
Dr. WJ Kolff was the
founding president of ASAIO during 1955-1956.
Thus, this article should be considered as the first presidential
address of ASAIO. As everybody is well
aware, Dr. Kolff is credited with the first clinical
use of the artificial kidney in 1943 as well as currently promoting the
development of the wearable artificial kidney.
His achievements also include development of an artificial heart and
cardiac assist devices. He also has
interest and experience in organ preservation for transplantation, blood oxygenators, biomaterials, and artificial eyes and limbs.
Dr. Kolff, while truly the original pioneer of
artificial organs, remains in the forefront of modern artificial organ
development during the last 60 years.
Willem Kolff was born in The
Netherlands and received his M.D. in
This paper was voted as a top ASAIO publication
because after 50 years, approximately one million patients are being kept alive
with the technologies developed by Dr. Kolff. --
*****
Three
articles that forever changed dialysis– one million patients later.
-- C.M. Kjellstrand,
MD, PhD, FACP, FRCP(C); C.R. Blagg, MD, FRCP; T.S. Ing, MD. FACP, FRCP(
Commentary: It is rare,
for a single individual and group, to make as many contributions to medicine
and mankind, as came out of Dr. Scribner and his team in Seattle in the 1960’s
and 1970’s. Yet, all three articles, deemed the most important in dialysis by
the ASAIO membership, came from that team in the early 1960’s. Solutions to the
problems of providing long-term dialysis poured out of the
The development of dialysis for short-term treatment
of life-threatening acute uremia took over 30 years. It started in 1912 at the
Artificial internal organs are the practical
end-products of curiosity, hypothesis and laboratory experiments to verify or
reject the hypothesis. Some 230 years
ago, Hilaire-Marin Rouelle’s
curiosity of what is in urine led to boiling it dry and finding the white
residue, which he named urea. Fifty years later in
The practicalities of blood-thinning – leeches and
heparin - and durable and blood-friendly membranes followed and set the stage
for the apparatus developed by Abel, Rowntree and
Turner at
One dread we all had in those days was to start a
patient on dialysis and then find that renal function did not return. There are
only so many blood vessels sites that can be cut down for connection to an
artificial kidney and sooner or later these ran out. Several physicians sought
for the Holy Grail of endless connections of man to machine. Alwall tried using glass-cannulas
in an artery and vein and shunted with a piece of rubber tubing between
dialyses but this did not work. The material was wrong and the shunt stayed
open for only a couple of days even with the help of dangerous amounts of
heparin. Parsons tried using available plastic tubing in the late 1950’s but
the result was the same.
When Scribner was faced with the problem in 1960,
Teflon tubing had just become available.
It worked. Literally overnight the solution was there and soon the
number of patient began to grow beyond everybody’s predictions. Today more than
a million people are alive and on chronic dialysis, thanks to the observation,
perseverance, intelligence, clinical research and generosity of Dr. Scribner
and his team. The 1960’s were the glory days of nephrology before the era of
destructive patent fights and dialysis for profit. Not a penny for personal use
came from what was the most important discovery in modern nephrology!
The three papers selected below are among the most
important contributions to dialysis in the ASAIO Transactions and illustrate
the quick transition from discovery through experiment to practical
application.
2.
Quinton W, Dillard D, Scribner BH: Cannulation
of blood vessels for prolonged hemodialysis. Trans Am
Soc Artif Intern Organs 6:104-113, 1960. , AND, Scribner BH, Buri
R, Caner JEZ, Hergstrom R, Burnall JM: The treatment of chronic uremia by means of
intermittent hemodialysis:
A prelimninary report. TASAIO 6:: 114-122.
1960
Commentary: All is there –
the dimensions; the detailed instructions for using the heating contraption for
bending Teflon tubing and extruding the vessel tip that caused burns on so many
nephrologists’ pinkies; the care needed to cut the tip just right to fit it to
the size of the blood vessel while avoiding any frayed edges and the little
pliers that allowed one to do so; the arm plate; the complicated “Swagelok” connectors that were plumbing supplies; a careful
description of the surgical technique; and the histological proof that the cannula did not set up any destructive tissue
reactions. It is all there in crystal
clear terse prose. The paper is only 6
pages long, double-spaced and in large print, with three pages of
illustrations. This was the solution to
the problem of repeated dialyzer connections that
previously had frustrated everyone.
What is less well known is that this paper was never
presented at the ASAIO Annual Meeting.
The shunt was first used on March 9th of 1960, but the
program for the ASAIO meeting that April was already complete. Scribner took the patient, Clyde Shields,
Preceding the cannulation
paper in the 1960 Transactions is a detailed description of the technique of prolonged
continuous hemodialysis that was presented at the
meeting. In 1959, Paul Teschan had reported the benefits of prophylactic
intermittent hemodialysis in the treatment of acute
renal failure. Scribner thought that an
alternative approach would be continuous hemodialysis
for 24 hours at a time and developed a system to provide this. With development of the Teflon shunt this was
used to treat the first patients with chronic renal failure. -- C.M. Kjellstrand, MD, PhD, FACP, FRCP(C); C.R. Blagg, MD, FRCP; T.S. Ing, MD.
FACP, FRCP(
3.
Scribner BH, Caner JEZ, Buri
R, Quinton WE: The technique of continuous hemodialysis.
Trans Am Soc Artif Intern Organs 6:88-93, 1960
Commentary: The team
describes the technique in great detail, including the mathematical
considerations of urea removal underlying the use of the huge 15 cubic foot
home freezer tank, and the reasoning behind choosing a low resistance
parallel-plate dialyzer so as to allow enough blood
flow without the use of a blood pump. Dialyses were done with dialysate at 4o C as this cold temperature
inhibited bacterial growth and also reduced clotting in the extracorporeal
circuit. The report details how to connect the Teflon cannulas
to the very long 20 feet of blood tubing that allowed the arterial line to pass
through the dialysate tank to cool blood entering the
dialyzer and let the venous line pass through a
warming bath before returning to the patient.
It also allowed the patient to move around during the very long dialysis
runs. Some acute patients were hooked up
to the system for up to 14 days! The
paper includes a brief description of the ten patients with acute renal failure
and eight with chronic renal failure that provided the clinical basis for the
metabolic calculations. Twenty grams of nitrogen, corresponding to a combined
catabolic/dietary intake load of 120 grams of protein, was removed daily.
These two papers were the shots heard around the world
of physicians dealing with uremia that was the start of the revolution against
the early death of end-stage renal disease.
The
Thirteen years later, hearings in the US Congress
resulted in the incorporation of dialysis and kidney transplantation into
Medicare. At that time there was no comprehension of the magnitude of the
program that would result. The latest
forecast from the US Renal Data System suggests the need to provide care to
600,000 patients in the
4.
Eschbach JW, Jr.,
Wilson WE, Jr., Peoples RW, Wakefield AW, Babb AL, Scribner BH: Unattended
overnight home hemodialysis. Trans Am Soc Artif Intern Organs 12:346-362, 1966
Commentary: Dialysis was very expensive – and when this
paper was published seven years before the Congress acted it was out of reach
of almost anyone but the richest patient.
The obvious solution was to send the patients home for dialysis. The
The equipment used was the first single patient system
using proportioning pumps to make dialysate. Three monitors were developed to solve the
problem of patient safety in the home: a blood leak detector, a negative
pressure monitor in the dialysate compartment and an
arterial blood pressure monitor in the extracorporeal circuit. The equipment, training, maintenance and
medical supervision are described. It is
hard today not to laugh out loud or to develop acute depression on reading the
cost analysis that showed the initial cost of equipment, home remodeling and
two months of training came to all of $12,800 and from then on the yearly cost
was $4,150 - physician payment and laboratory costs were each $200! The paper details the various medical,
technical and psychological problems of the first eight patients and the ways
to deal with them. The patient who had been on the system the longest had 24
months of experience and total experience for the whole program was 94 patient
months. The difficulties of performing remote monitoring - two of the patients
were in
It would take another 30 years before this experience
was reproduced in
Many
of the lessons taught by the
One cannot help but marvel at the unprecedented and
tantalizing accomplishments and feel one’s spirits buoyed, while reviewing the
heydays and trailblazing of dialysis so exquisitely illustrated by these three
landmark publications that began the effort to banish death from chronic renal
failure from the list of hopelessly incurable diseases! -- C.M. Kjellstrand, MD, PhD, FACP, FRCP(C); C.R. Blagg, MD, FRCP; T.S. Ing, MD.
FACP, FRCP(
*****
5.
Henderson LW, Besarb A,
Michaels A, Bluemle Jr:
Blood purification by ultrafiltration and fluid
replacement (diafiltration). TASAIO 13:216-225 , 1967.
Commentary: Medical
therapy is an interdisciplinary field, and advances evolve at the interface of
basic science, engineering and medicine. Physicians and bioengineers make
progress in disease therapy by borrowing technologies and applying them to
solve certain problems. In this paper Henderson and others clearly describe the
problem with use of diffusion for removal of uremic
substances in hemodialysis devices. Especially for
larger solutes, diffusion is a significant limitation to their removal. Up to
the time of this publication, ultrafiltration was “a
familiar process” for removal of fluid and water during dialysis. These authors
for the first time explained the potential for hemofiltration
membranes to remove large toxins at rates equal to that of small toxins, up to
the m.w. cutoff of the membranes. Beyond merely
providing an hypothesis,
the authors outlined details on everything needed to make hemofiltration workable: the membranes (newly developed
flat sheet Diaflo membranes of net neutral charge),
the proposed chemical components of sterile replacement fluid (reconstitution
fluid), and how to obtain any desired ultrafiltration
rate from blood. In addition there is elegant testing to demonstrate a near
zero reflection coefficient for uremic toxins and a
high reflection coefficient for plasma proteins. A theoretical model is
provided to predict required membrane surface area of a clinical hemofiltration device to give 300 ml/min ultrafiltrate. In
spite of all of the elements described in this paper, hemofiltration
wouldn’t be practical until the membranes were produced in hollow fiber rather
than sheet form. Prophetically, Lipps and others
first described “The Hollow Fiber Artificial Kidney” at this same ASAIO meeting
and in this volume of ASAIO Transactions, page 200. -- Stephen
R. Ash, MD, FACP
*****
6.
Menno, AD, Zizzi J, Hodson J, McMahon J., "An Evaluation of the Radial Arterio-Venous Fistula as a Substitute for the Quinton
Shunt in Chronic Hemodialysis," TASAIO 13:62-76,
1967.
Commentary: When we look
at medical practice in
retrospect, commonplace things and practices that seem obvious
now to us were almost never obvious at the time of invention. The arterio-venous fistula for chronic dialysis access is one
example. In 1960, Quinton,
Scribner and others first published on the “silastic-teflon
bypass cannula” arteriovenous
shunt, in ASAIO Transactions (see Gold Journal Papers #3). This access was
clearly an “engineer’s solution,” hydraulic and mechanical in design, a
permanent transcutaneous device with separable parts.
The AV shunt was somewhat cumbersome and occasionally risky though when placed
properly quite successful, and the device established the first practical blood
access for chronic hemodialysis. Nothing could have been
more contrary to this device, or a more purely “biological” approach, than the arteriovenous fistula. Instead of creating a permanent transcutaneous tract, the AV fistula changed native
anatomy, allowing enlarged veins to be intermittently and easily cannulated with needles that were placed for dialysis then
removed.
By
the next year’s ASAIO meeting, Menno, Zizzi, Hodson and McMahon from Deaconess in
Commentary: Throughout the 1960s and 1970s surgical residents
learned the tedious details of construction, management, declotting,
and replacement of Quinton Scribner shunts.
Although the external silicone rubber shunt made chronic intermittent hemodialysis possible, the hardware needed constant
tending. This paper by Meno and others was one of the first to describe creation
of a forearm arterial-venous fistula to provide access for intermittent chronic
hemodialysis.
As the AV fistula matured, the ready accessibility of the large, tough,
pulsating veins on the surface of the forearm gradually made the external
prosthetic shunt obsolete. When this paper was presented in 1967 the idea of such an invasive
procedure simply to dialyze the few patients dependent on chronic hemodialysis seemed rather outrageous. Not even the most optimistic nephrologist anticipated the fact that hundreds of
thousands of patients with chronic renal failure would be managed in this
fashion decades later. –
*****