Historical Article
The First Human Renal Transplants
John M. Barry*,† and Joseph E. Murray
From the Division of Urology and Renal Transplantation, The Oregon Health & Science University, Portland, Oregon (JMB), and
Department of Surgery, Harvard Medical School, Brigham & Women’s Hospital, The Childrens’ Hospital, Wellesley Hills, Massachusetts
(JEM)
Key Words: kidney transplantation, history, Nobel prize
he 2 authors are separated by a generation. One is a
T Nobel laureate transplant surgeon who was associ-
ated with the first successful monozygotic twin kidney
transplant, the first successful dizygotic twin kidney trans-
plant, the first successful deceased donor renal transplant
and the training of scores of transplant surgeons. The other
is in the autumn of a renal transplant career that has
spanned 33 years at the institution where Joseph E. Mur-
ray, J. Englebert Dunphy and Clarence Hodges led the do-
nor and recipient surgical teams for a successful kidney
transplant from one 12-year-old monozygotic twin to an-
other on October 9, 1959. The 2 authors met at the 40th
anniversary of that program in Portland, Oregon and have
been correspondents since.
The first human renal allograft was done by Yu Yu
Voronoy in the Ukraine on April 3, 1933.1 The patient was a
26-year-old woman with type O blood who had attempted
suicide by ingesting corrosive sublimate (mercuric chloride).
The donor was a 66-year-old man with type B blood whose
kidney was removed 6 hours after death. With the patient
under local anesthesia, the renal vessels were anastomosed
to the femoral vessels and a cutaneous ureterostomy was
performed. A small amount of bloodstained urine appeared
but the patient died 2 days after the procedure. Although
technically successful the procedure was doomed from the
time of renal revascularization because of prolonged warm
ischemia time and ABO blood group incompatibility.
In 1945 Landsteiner, Hufnagel and Hume transplanted a
human cadaver kidney to the brachial artery and cephalic
vein of a young woman with acute renal failure at the Peter
Bent Brigham Hospital in Boston.2,3 The woman’s own kid-
neys recovered a few hours later and the allograft was re-
moved without demonstration of significant function. Five
years later the first intra-abdominal human renal trans-
plant was done in Chicago by a team led by Lawler.4 After
removal of the recipient’s left polycystic kidney, a cadaver
kidney’s vessels were anastomosed to her renal vessels, and
a stented ureteroureterostomy was done. Her serum creati-
nine decreased from a preoperative value of 2.3 to 1.2 mg/dl
3 months later. An indigo carmine test on postoperative day
52 showed excretion from the side of the allograft and from
Submitted for publication March 27, 2006.
* Correspondence: Division of Urology and Renal Transplantation,
The Oregon Health & Science University, Portland, Oregon 97239
(telephone: 503-494-8470; FAX: 503-494-8671; e-mail: barryj@ohsu.
edu).
† Financial interest and/or other relationship with Astellas.
0022-5347/06/1763-0888/0
THE JOURNAL OF UROLOGY®
Copyright © 2006 by AMERICAN UROLOGICAL ASSOCIATION
the remaining native kidney. Seven months later function
had ceased.5
In Paris in January 1951, 3 human kidney transplants
were performed by 3 separate teams.6 Rene Kuss went on to
perform 4 more transplants that year. The kidneys were
transplanted by an extraperitoneal approach into the con-
tralateral iliac fossa onto the iliac vessels, and a cutaneous
ureterostomy was done to monitor renal function. Cadaver
kidneys were obtained from decapitated criminals who had
agreed to postmortem renal donation. The kidneys were
removed within minutes of decapitation, flushed with Ring-
er’s solution and transported to the hospital for transplan-
tation. Living donor kidneys with moderate abnormalities
were removed as free kidneys and transplanted into ABO
blood group compatible recipients in an adjacent operating
room. Some of the kidney transplants produced urine but no
immunosuppression was used, and all kidneys failed within
weeks of implantation. Except for urinary tract reconstruc-
tion by ureteroneocystostomy or ureteroureterostomy, the
principles of renal transplantation surgery into the iliac
fossa had been established.
The first long-term success with human kidney trans-
plantation in which the patient survived for more than a
year occurred in Boston on December 23, 1954, when a
kidney from one 24-year-old twin was transplanted into the
other twin, who had end stage renal disease.7 The recipient
had been prepared with hemodialysis, and monozygosity
was confirmed by the successful exchange of full thickness
skin grafts between the twins. The left kidney was trans-
planted into the right iliac fossa, and a transvesical uretero-
neocystostomy with a submucosal tunnel was done. A small
polyethylene catheter was passed up the transplant ureter
and brought out through a suprapubic cystostomy. Bladder
drainage was by a suprapubic mushroom catheter. Dr. Jo-
seph Murray led the recipient’s surgical team and Dr. J.
Hartwell Harrison led the donor’s team. After renal revas-
cularization, Doctor Harrison came into the recipient’s op-
erating room and assisted with the urinary tract reconstruc-
tion. The kidney functioned in the operating room and the
patient was discharged on postoperative day 37 with blood
urea nitrogen 14 mg/dl. He had good kidney function until
cardiac death 8 years later.8
After years of failed renal allografts and the conclusion in
a 1955 publication by Hume et al that, “At the present state
of our knowledge, renal homotransplants do not appear to be
justified in the treatment of human disease,” there were
finally 2 long-term successful engraftments.2 The first oc-
888 Vol. 176, 888-890, September 2006
Printed in U.S.A.
DOI:10.1016/j.juro.2006.04.062
 FIRST HUMAN RENAL TRANSPLANTS
curred in 1959 in Boston between dizygotic twins, and the
second occurred in Paris later that year.3,9 Both recipients
had been prepared with total body irradiation and both
survived for more than a decade. By 1960 the technical
principles of renal transplantation, the importance of histo-
compatibility and the dangers of total body irradiation for
immunosuppression had been established, and it was time
for the next step: pharmacological immunosuppression.
In the summer of 1960 a 26-year-old woman underwent
kidney transplantation from her brother-in-law by Rene
Kuss’ team in Paris.6 She had been prepared with total body
irradiation and additional irradiation to the spleen. Two
months later a rejection crisis was confirmed by biopsy, and
50 mg 6-mercaptopurine daily and 40 mg hydrocortisone
daily were prescribed along with graft irradiation and addi-
tional total body irradiation. Eight months after transplan-
tation renal function began to deteriorate and she died of
renal failure 16 months after transplantation. This was
probably the first successful use of pharmacological immu-
nosuppression in a human kidney transplant recipient. In
that same year Willard Goodwin successfully used glucocor-
ticoids to reverse a kidney transplant rejection in a patient
treated with cyclophosphamide.10 In 1961 azathioprine was
used clinically at the Peter Bent Brigham Hospital, where
the first long-term successful cadaver kidney transplant was
performed in 1962.3 On June 3, 1963 a patient in Belgium
with a head injury and profound coma was pronounced dead
while the heart was still beating.11 A kidney was removed
from this, probably the first, brain-dead renal donor, and
transplanted into a patient with uremia who experienced
immediate renal function but died of sepsis 3 months later.
Immunosuppression consisted of azaserine and actinomycin
D. In 1966 Starzl’s team used antilymphocyte globulin clin-
ically, and antilymphocyte antibody induction therapy, aza-
thioprine with glucocorticoid maintenance therapy, and
high dose glucocorticoid administration with or without
graft irradiation for kidney transplant rejection became
common in kidney transplant immunosuppression proto-
cols.12
The direct cross-match between donor lymphocytes and
recipient serum was introduced in 1966, and this nearly
eliminated hyperacute renal transplant rejection due to pre-
formed antidonor antibodies in kidney transplant recipi-
ents.13 In the late 1960s human renal preservation over 24
hours became possible with either pulsatile machine perfu-
sion or simple cold storage after an ice-cold intracellular
electrolyte flush.14,15
What was it like to perform kidney transplants on a
urology service in the early 1970s? Patients with end stage
renal disease were supported with hemodialysis, usually
through plastic shunts, sometimes through the relatively
new arteriovenous fistulas, or with chronic peritoneal dial-
ysis. Preemptive renal transplantation was rare. Kidney
transplant candidates and prospective living renal donors
were admitted to the transplant ward for evaluations. Donor
evaluations included excretory urograms and selective renal
arteriograms. Only kidneys were removed for transplanta-
tion from deceased donors, first separately and later, en bloc.
Sometimes deceased donor kidneys that were removed sep-
arately were discarded because of minor anatomical abnor-
malities such as multiple renal arteries or duplicate ureters
because of concerns about technical complications in the
recipient. This was the transition period when the concept of
889
brain death was defined as death of the individual. Some
organs were retrieved after the heart had stopped beating
and others were retrieved from brain-dead donors with in-
tact renal circulations. All living donor nephrectomies were
performed with open procedures. Kidney preservation was
by flushing with an ice-cold electrolyte solution followed by
simple cold storage or by pulsatile machine perfusion. The
latter method was preferred for kidneys from circulatory
arrest donors. After brain death became accepted, simple
cold storage became the preferred method of cadaver kidney
preservation by most centers. Splenectomies and bilateral
nephrectomies, either at or before the time of kidney trans-
plantation, were commonly done, the first to reduce antibody
production, and the second because of concern that the orig-
inal renal disease might occur in the kidney transplant, or to
assist in the management of hypertension. The surgical
principles developed in the 1950s were applied: minimize
warm ischemia time, use the extraperitoneal approach,
anastomose the renal vessels to the iliac vessels, place the
kidney into the opposite iliac fossa so the collecting system is
the most medial of the hilar structures, do an antireflux
ureteroneocystostomy for primary urinary tract reconstruc-
tion, and leave the better of 2 kidneys with the living kidney
donor.
After the transplant procedure the recipients were admit-
ted to the transplant ward and placed in isolation. Flow
sheets were taped on the doors of the patient rooms to
monitor laboratory results and immunosuppression. Blood
was drawn by gowned, gloved and masked house staff or
nurses. Locally prepared antilymphocyte antibody was in-
jected intramuscularly by the resident. Local reactions were
universal and systemic reactions were common. Mainte-
nance immunosuppression consisted of with azathioprine
and prednisone. Rejection crises were treated intravenously
with up to a gram of methylprednisolone daily for up to 2
weeks. Lymphoceles were usually treated by opening the
wound to allow healing by secondary intention, and some-
times by open marsupialization into the peritoneal cavity.
Renal biopsies were all done with an open procedure in the
operating room, and with the patient under local anesthesia.
The usual hospital stay for a recipient was more than a
month. Of the deceased donor kidneys 30% failed within the
first 3 months and 30% of the recipients of those kidneys did
not survive the first year.16 The resident call schedule was
12 days on and 2 days off.
What did the future hold? Immunological conditioning
with blood products for deceased and living donor renal
transplants became part of standardized pretransplant im-
munological conditioning protocols for renal transplanta-
tion, only to be abandoned in the calcineurin inhibitor era
when the beneficial effects of random blood transfusions and
donor specific blood transfusion protocols were difficult to
prove, and transfusion protocols became associated with
donor specific sensitization and the transmission of viral
illnesses. Medicare coinsurance for patients with end stage
renal disease was passed into law in 1972 and instituted in
1973. This meant that the treatment of end stage renal
disease with dialysis or transplantation was no longer ex-
perimental in the United States. In the mid 1970s brain
death laws were passed, allowing organ retrieval from beat-
ing heart deceased donors, reducing warm ischemia time,
improving the quality of deceased donor kidney grafts, and
opening the door for the retrieval of vital organs such as the
890 FIRST HUMAN RENAL TRANSPLANTS
heart and the liver. The first clinical trials of cyclosporine
were reported in 1978,17 followed 3 years later by reports of
the successful use of a monoclonal antibody for the treat-
ment of renal allograft rejection in humans.18 In 1984 Con-
gress passed the National Transplant Act, which authorized
a national organ sharing system and grants for organ pro-
curement. The University of Wisconsin solution, introduced
in the late 1980s, provided a solution for the preservation of
all transplantable abdominal organs. Recombinant erythro-
poietin became available in 1989, which significantly im-
proved the quality of life for patients on maintenance dial-
ysis and reduced the need for blood transfusions. This
decreased the risks of blood borne viral infections and the
development of anti-human leukocyte antigen antibodies in
potential kidney transplant recipients. Laparoscopic donor
nephrectomy was introduced in the mid 1990s and this
decreased disincentives for living donor nephrectomy.
More than 15,000 renal transplants are now performed
annually in the United States, and the 1-year deceased
donor kidney transplant and patient survivals are expected
to be 90% and 95%, respectively.19 It is notable how different
the current figures are compared to the 36% and 42% corre-
sponding survival figures from 1951 to 1966.16 To our col-
leagues in surgery, medicine, histocompatibity and govern-
ment, “well done,” and “thank you.”
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