A History of Transplant Nephrology at UCSF

By William Amend

1962-1974 Background
Clinical renal transplantation was initiated in 1962 by the Department of Surgery
– Dr. J.Engleburt Dunphy, chairman. He appointed a young faculty member, Dr. John
Najarian, to learn the surgical techniques from Thomas Starzl, then in Denver. Dr.
Najarian performed the first UCSF living donor transplant in 1964 assisted by Dr. Folkert
Belzer, another young Dunphy-trainee. Because of the scarcity of hemodialysis, a
Selection Committee (consisting of MDs, social workers and nurses along with
religious/psychiatry input) rigorously chose persons with chronic renal failure – only
approving a patient to receive dialysis if he/she was a transplant candidate. At the time,
both life-saving treatments were on a self-pay basis.
Besides having few possible living-donors, there were similar barriers to the use
of deceased donors – procurement and recipient surgeries had daunting logistical
problems. To address this obstacle, Dr. Belzer did landmark research utilizing cold
storage and pulsatile perfusion in cadaver procurement and preservation.
During this time, immunosuppressants included only corticosteroids, azathioprine
and the occasional use of crude antilymphocyte preparations. Since there was not a good
clinical alternative (chronic dialysis was often unavailable), over-immunosuppression
often resulted. Sometimes transplants (two or more) were serially performed in desperate
attempts to save the patient following graft failure. It is not surprising that Infectious
Disease consults provided the brunt of posttransplant medical care. The nephrologists at
that time were simply utilized to take care of any kidney transplant-failure.
When Dr. Najarian went to the University of Minnesota (1967), the new chief of
the UCSF transplant service was Dr. Samuel Koontz, a PhD who was not only a surgeon
but a clinical immunologist as well. He and Dr. Belzer enjoyed great success with their
complementary research interests.
Beginning in 1967, UCSF received a 10-year NIH center grant: “Clinical Utility
of Kidney Transplantation,” the purpose of which was to explore how various renal
disease-states might affect clinical outcomes. Since the surgical procedure had no
insurance coverage and was self-pay, the research funding allowed for the rapid growth 
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of the program. Although UCSF soon became one of the largest kidney transplant
programs in the world, nephrology participation remained limited.
Dr. Kent Cochrum, DVM, of the Immunology Laboratory developed the threeday mixed lymphocyte culture (MLC). It was only useful prospectively with living
donors but provided retrospective information in the cases of deceased-donor
transplantation. This test turned out to be the in-vitro biologic correlate of what later
became known as Class II HL-A (DR-locus) compatibility.
Dr. Koontz was also a consummate activist. While at UCSF (and subsequently at
Downstate SUNY as chairman of surgery), he: 1. Functionally defined the term “Endstage renal disease” (ESRD) = when a person is chronically so uremic that he needs
dialysis or a transplant to remain alive; 2. Helped develop the Uniform Anatomic Gift
Act which led to developing criteria of brain death; 3. Served as a major advocate to get
Congressional approval of Medicare coverage for persons with ESRD (1972). This last
advance catalyzed the proliferation of chronic dialysis programs and kidney transplant
services throughout the U.S.
Dr. Koontz departed in 1972, Dr. Belzer to U. Wisconsin in 1974 and the surgical
directorship was assumed by Dr. Oscar Salvatierra, a highly respected urologist.
Dr. Salvatierra was a trainee of Drs. Koontz and Belzer. His initial contributions
included making kidney transplant available to a wide variety of “high risk” diseasestates (e.g. diabetes); developing techniques for very young pediatric patients (en-bloc
procedures); and formulating the principle of limiting immunosuppression – a truly
unique philosophy at the time. This strategy, coupled with an increased access to dialysis,
allowed the kidney transplant patient to have substantially lower morbidity and mortality
without any effect on overall graft success rates.
1974-1983 Nephrology Association with the Kidney Transplant Service
By 1974, the UCSF program had grown from 20/year to 100 surgeries/year and
the pre- and post transplant clinic had burgeoned. Dr. Salvatierra, Chief of Surgery (Dr.
Paul Ebert), Chief of Medicine (Dr. L.H. Smith) and the Division of Nephrology Director
(Dr. Floyd Rector) recognized the need for a nephrologist who would be assigned full
time to this important university program. 
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Dr. William Amend was recruited after completing a nephrology fellowship with
Dr. John Merrill in Boston, and soon joined by a second surgeon, Dr. Nicholas Feduska
(1975) and a second nephrologist, Dr. Flavio Vincenti (1976). With a growing
collegiality between the four, the clinical experience was enriched. Given the limited
types of immunosuppression, the unit’s numerous publications included descriptions (and
management) of infections, aseptic necrosis, cancer, gastrointestinal problems, cataracts
and the many other complications, which affected the patients. Since 1974, renal fellows
at UCSF have rotated through the kidney transplant service.
The surgeons and two nephrologists developed a unique (for UCSF and other
academic centers at the time) team-approach . . . each providing a particular expertise to
each patient. Since it was such an unusually closely-knit arrangement, it was of little
surprise that a concern was raised during a Medicare-audit looking at billing practices
(1978). The auditor asked one of the nephrologists: “How many surgeries did you do last
year?” (‘None’) ; then: “Well, do you split the surgical fees?” (‘No’); followed by: “What
do you do, then, on a surgical service?” (‘I do nephrology consultation at the request of
the surgeons on kidney transplant.’); then: “What does this mean?” (‘I assess dialysis
need, manage hypertension, treat diabetes, diagnose infections, etc.’ before adding, ‘I
guess I am doing transplant nephrology.’)The interchange ended with the auditor
concluding: “Then you’re not a surgeon?” (‘Sometime I wish I were but no,no,no! I’m a
nephrologist.’). Satisfied, the auditor sat back and stated: “Then I’ll write down here that
you are a ‘transplant nephrologist’.” (The term stuck).
During this time, Amend and collaborators in the School of Pharmacy published
studies of prednisone and azathioprine in attempts to improve their use. Dr. Vincenti
published the large UCSF experience (1978-NEJM) – it was sobering: <70-85% living
donor 2year graft success and <47% cadaver donor graft success. In addition, the initial
hospitalization was 30 days with frequent readmissions.
Dr. Juliet Melzer joined the surgical faculty in 1983 to assist handling the surgical
load that had increased to nearly 200 kidney transplants per year.
Immunologic advances included the use of a more potent, less toxic polyclonal
rabbit-ATG, collaboration with Drs. Terasaki and Opelz (UCLA) regarding overall
benefits of blood transfusions and importantly, a unique, surprisingly successful series of 
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living (mismatched) donor transplants following pretransplant donor- specific
transfusions (the DST-story). The protocol, devised by Drs. Salvatierra and Cochrum,
had the downside risk, however, of potential recipient sensitization.
In the early 1980s, clinical management advances took hold. The widespread use
of certain antimicrobials and newer antivirals in the first month post transplant markedly
reduced the incidences of CMV, PCP, Candidiasis and postoperative infections.
Collaboration with the Department of Radiology led to the increased use of
sonographically guided transplant renal biopsies.
Dr. Marvin Garovoy was recruited from the Peter Bent Brigham to run a newly
formed UCSF Histocompatibility Lab. Under his direction, the flow-activated cell sorting
technique (FACS) was invented for precise cross matching. The two nephrologists and
Garovoy became founding members of the American Society of Transplant Physicians, in
1982, which initially numbered 30; the successor AST now has nearly 3,000. In 2003, Dr.
Vincenti served as the President of the American Society of Transplantation.
1983-1988
The biggest paradigm shift in clinical immunosuppression followed the discovery
of cyclosporine A. The agent was extremely effective in clinical trials but had frequent
nephrotoxicity. Within one month of the drug’s approval (1983), the UCSF staff noted
striking differences in outcomes – patients had earlier discharges and the rejection rate
was halved. The task now was to differentiate rejection from acute CSA toxicity.
Biopsies were increasingly utilized along with studies of non-invasive surveillance.
Dr. Stephen Tomlanovich joined the UCSF Transplant Nephrology faculty in
1985. His renal fellowship research at Stanford with Dr. Bryan Myers included several
investigations in the nephrotoxicity of cyclosporine. His expertise and clinical skills
would prove invaluable. Drug levels using an immunoassay were performed at Stanford
before an HPLC assay was developed at UCSF. In 1986, Drs. Melzer and Tomlanovich
published the large UCSF CSA-treated transplant outcomes. Their analysis showed a
doubled success rate and lowered morbidities compared to only a decade previously. The
pre- and post-CSA eras were thereafter referenced as such. 
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These CSA-associated kidney transplant successes kindled an enthusiasm for the
development of ‘nephew’ programs at UCSF in the areas of liver, pancreas, pulmonary
and heart transplants – all as treatments of various “end-stage organ failures.” The UCSF
kidney transplant program served as a model for the formation of combined surgicalmedical programs with similar cross-disciplinary participation (including pods of other
committed specialists and researchers). As an example, Dr. Melzer began the pancreaskidney transplant service in (1988) with assistance of diabetologists and the
nephrologists.
1988-2005
Drs. Nancy Ascher and John Roberts from the U.Minnesota joined the faculty in
1988. Dr. Ascher initiated the surgical transplant fellowship program with 5 subsequent
trainees becoming surgical faculty – Drs. Peter Stock, Chris Friese, Sandy Feng, Ryo
Hirose, Sang-Mo Kang and Andrew Posselt. As well, Drs. Tomlanovich and Vincenti
developed an intensive kidney transplant fellowship for board-qualified nephrologists
interested in this career-track.
Dr. Ascher and Roberts formed the UCSF Liver Transplant Service as a combined
service with interested hepatologists (soon known as ‘transplant hepatologists’). The
UCSF transplant nephrologists have routinely consulted on this and other solid organ
transplant services and continue to coauthor many conjoint publications.
Following Drs. Salvatierra’s and Feduska’s departures in the late ‘80’s, the heads
of the UCSF surgical services became: Dr. Ascher – chair of Surgery and Dr. Roberts –
head of the Renal & Liver Transplant Program. Dr. Tomlanovich was appointed as the
Kidney Transplant Program’s Medical Director in 1995. Dr. Garovoy moved to a
biotechnology firm and Dr. Lee-Anne Baxter was subsequently appointed head of the
UCSF Immunogenetics Lab.
Dr. Deborah Adey joined the transplant nephrology section in 1997 and was
instrumental in the education of medical students, residents and fellows. Dr. Adey’s
research interest focused on approaches to highly sensitized recipients and on the
detection of polyoma (BK) virus infections. She left in 2005 and currently is on faculty at
UC Davis. 
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Dr. Amend retired in 2005.
2005-present
During the previous decade, and continuing since, Dr. Vincenti, Tomlanovich and
other colleagues initiated many clinical drug trials involving a variety of unique
immunosuppressants: OKT3 (a murine antibody), tacrolimus, mycophenolate, rapamycin,
and costimulatory signal blockers (belatacept and daclizumab). All of these studies led to
the approval of important immunosuppressive therapies. As an offshoot, Dr. Vincenti has
retained a special interest in studying the pathogenesis of (and treatments for) FSGS
because of the condition’s propensity to recur in allografts. Dr. Vincenti has held the
Faiman Chair of Medicine & Surgery since 2007.
Dr. Tomlanovich has spearheaded the development of a referral network within
Northern California. This has allowed better access to clinical care and participation in
many of UCSF’s ongoing transplant research studies. He and Dr. Roberts have helped
create a national network-system to deal with incompatible living donor-recipient pairs.
For the past 35 years, residents and general nephrology fellows have rotated
through the Kidney Transplant Service. This involves experiences in kidney transplant
inpatient-care (15 pts./day), nephrology consultation on non-renal solid organ recipients
(5-6/day) and rotation through the kidney transplant clinic (1-2 half-day/week). As
mentioned, there has also been an AST-certified fellowship trainee(s) for the past fifteen
years.
In 2010, the transplant clinic and offices were relocated to a new, state-of-the-art
facility at the UCSF Parnassus Campus – the Connie Frank Transplant Center.
The transplant nephrology faculty (with their research interests) now includes:
Sindhu Chandran (serial analyses of transplant biopsy phenotypes and their predictive
value on long term outcomes), Brian Lee (studies involving renal donors and
posttransplant development of diabetes), Allison Webber (newer techniques of immune
monitoring), and David Wojciechowski (studies of more effective diagnosis and
management of posttransplant infections). 
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Current and comparative data of the UCSF clinical program (case loads and
outcomes) may be best obtained by accessing the Scientific Registry of Transplant
Recipients website: SRTR.org.
Dr. Bill Amend, Professor Emeritus of Nephrology at UCSF, 2010