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protocol streamlines therapy that makes more
Kidney Transplants possible
Newswise — A new therapy developed at
Cedars-Sinai Medical Center improves
transplant rates and outcomes for patients
awaiting living- and deceased-donor kidney
transplantation, according to a study
published in the July 17 issue of the New
England Journal of Medicine.
The therapy may provide an option for many
patients “sensitized” to transplant antigens
(human leukocyte antigens, or HLA) who
previously would not have been candidates
for transplantation because of their intense
immune response to these HLA targets.
HLA exposure can come through blood
transfusions, previous transplantation or
Once exposed, the immune system is
sensitized to those antigens and develops
antibodies to fight them. If a donor organ
with the antigens is later transplanted, the
antibodies respond, increasing the risk of
rejection and loss of the organ.
Antibodies to HLA were previously considered
an absolute contraindication to
transplantation – the risk was too high for
transplantation to be an option.
About 30 percent of the 74,000 patients on
the transplant waiting lists for a
deceased-donor kidney are sensitized, and
those with exceptionally high antibody
levels are considered especially poor
candidates for transplantation.
In fact, each year only 6.5 percent of
highly sensitized patients receive a
transplant. Most remain on dialysis
indefinitely, without hope for a life-saving
“From a quality-of-life perspective, as well
as from the financial standpoint,
transplantation is a much better option than
years of dialysis,” said Stanley C. Jordan,
M.D., director of the Division of Nephrology
and medical director of the Renal Transplant
Program at Cedars-Sinai.
The senior author of the journal article,
Jordan developed high-dose intravenous
immunoglobulin (IVIG) therapy to
“desensitize” highly sensitized patients and
increase their chances of successful
The approach became a Medicare-approved
therapy in 2004 at the conclusion of a
National Institutes of Health-funded
Cedars-Sinai is a national leader in
desensitization for the highly HLA
sensitized patient, offering therapy for
those awaiting both living-donor and
The New England Journal article describes a
Phase I/II safety and limited efficacy trial
of a combination of IVIG and rituximab, a
monoclonal antibody – an antibody engineered
to bind to a specific protein.
The combination of IVIG and rituximab
appears to offer superior benefits to IVIG
alone, improving transplant rates to 80
percent of treated patients. The one-year
patient and graft survival rates were 100
percent and 94 percent, respectively.
Based on these results, the new protocol is
less costly than IVIG alone yet appears to
be highly effective in reducing antibody
levels and improving transplantation rates.
Larger, multicenter trials are necessary to
confirm these findings.
Because nearly one-third of kidney failure
patients are highly sensitized and few
transplant centers specialize in
desensitization therapy, many potential
candidates are told that a transplant simply
is not possible.
“Patients who are on dialysis and those who
are progressing toward renal failure should
be considered for a kidney transplant.
"Ideally, they would be referred to a
transplant center for evaluation even before
they start dialysis because data show that
those who get transplanted before starting
dialysis do better,” Jordan said.
“However, for the highly sensitized patient,
transplantation is not an option unless
desensitization therapies are used.”
Jordan estimates that about 40 percent of Cedars-Sinai’s kidney transplant
patients are highly sensitized and are
referred or self-referred to the program
because of their highly sensitized state.
For many patients, especially those awaiting
a deceased-donor transplant, the combination
of IVIG and rituximab appears to offer an
alternative to ongoing dialysis.
The New England Journal of Medicine article
is accompanied by an editorial written by
Ron Shapiro, M.D., of the Thomas E. Starzl
Transplantation Institute at the University
He concludes his comments by saying, “As the
authors note, their observations need to be
confirmed and validated by other centers and
in larger numbers of patients and during
longer periods of follow-up.
"However, their approach may represent a
breakthrough in the care of sensitized
patients awaiting transplantation and may
have the potential to help thousands of
patients who are languishing on waiting
lists around the world.
Citation: The New England Journal of
Medicine, “Rituximab and Intravenous Immune
Globulin for Desensitization during Renal
Transplantation,” July 17, 2008.
Disclosure/conflicts: Study supported by
Genentech and Biogen Idec, which also
provided drugs used in the study. Dr.
Reinsmoen received lecture fees from Cylex.
Dr. Jordan receives consulting fees and
grant support from Talecris and
Bristol-Myers Squibb and lecture fees from
Genentech. Cedars-Sinai owns a patent: “Use
of IVIG in Desensitization.” No other
potential conflicts of interest relevant to