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Back to Nephrology Articles
Wednesday 5th October, 2005
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The results could pave the way to a national matching registry
enabling patients to exchange donors with a stranger.
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A preliminary study suggests that kidney paired donation
transplantation, in which incompatible donor/recipient pairs
exchange kidneys so that each recipient receives a compatible
kidney, had graft survival rates equivalent to compatible live
donor transplants, according to a study in the October 5 issue
of JAMA.
The number of patients waiting for a
kidney transplant
continues to increase at an alarming pace and any significant
gains in closing the gap between organ supply and demand are
likely to come from the increased use of live donors. The two
most significant barriers to greater use of live donors are
blood type incompatibility and human leukocyte antigens (HLA)
antigen sensitization. Based on blood group frequencies in the
United States, there is a 36 percent probability that any two
individuals will be blood type incompatible, eliminating up to
one-third of the potential live donor pool. In about 30 percent
of the patients on the deceased donor waiting list, HLA antigen
sensitization is present due to exposure to foreign tissue in
the form of previous
transplants, pregnancies, or blood
transfusions.
An alternative strategy is kidney paired donation (KPD)
transplantations. In KPD transplants, incompatible
donor/recipient pairs exchange kidneys so that each recipient
receives a compatible organ. The KPD transplant program
represents a cost savings compared with desensitization, which
is significantly less costly than if an individual continues to
undergo dialysis. While logistically challenging, a broader
implementation of KPD on a regional or national scale could
provide compatible organs for a substantial number of the
estimated 6,000 patients on the waiting list who currently have
incompatible donors.
In the study, published in the Oct. 5 issue of The Journal of
the American Medical Association, Hopkins surgeons report
successfully performing KPD transplants on 21 out of 22 kidney
patients whose willing donors were incompatible by matching them
up with other incompatible pairs. Robert Montgomery, M.D.,
Ph.D., the director of the Comprehensive Transplant Center at
Hopkins and lead researcher in the study, said the results could
pave the way to a national matching registry that would enable
hundreds and perhaps thousands of patients who cannot receive a
kidney from a loved one to be
transplanted by exchanging donors
with a stranger.
Dr. Montgomery conducted a study to determine the feasibility
and effectiveness of KPD for the management of patients with
incompatible donors. Paired donations were matched and
transplanted from a pool of blood type or crossmatch
incompatible donors and recipients with end-stage renal disease
(6 conventional and 4 unconventional KPD transplants) between
June 2001 and November 2004.
A total of 22 patients received
transplants through 10 paired
donations including 2 triple exchanges. At a median follow-up of
13 months, the patient survival rate was 100 percent and the
graft survival rate was 95.5 percent. Twenty-one of the 22
patients have functioning grafts with a median 6-month serum creatinine level of 1.2 mg/dL. There were no instances of
antibody-mediated rejection despite the inclusion of 5 patients
who were highly sensitized to HLA antigens due to previous
exposure to foreign tissue. Four patients developed acute
cellular rejection (18 percent).
The complexity and potential benefits of an unconventional
KPD transplant are demonstrated by the triple exchange. Based on
blood type and HLA antigen antibody reactivity, the probability
of finding a suitable donor in the deceased donor pool for each
of the 3 recipients was 0.029, 0.033 and 0.008.
"This study demonstrates that KPD transplants can be
performed with outcomes similar to compatible living donor
kidney transplants. The cost savings and decrease in waiting
time that could be realized by a wider application of this
concept are substantial. Because the likelihood of finding a
suitable match is dependent on the size of the pool, a national
list could enable many more transplants. We estimate that about
half of the incompatible pairs could receive transplants using a
national KPD transplant scheme with blood type compatible,
negative crossmatch kidneys, including as many as 14 percent of
the highly sensitized patients," the authors write.
"Patients unable to be matched by KPD could undergo
desensitization with their intended donor. Those who were not
deemed acceptable for desensitization due to high titer or
immunologic risk could participate in a less restricted KPD
search in which a more favorable, but not completely compatible,
donor could be identified. This single center experience
demonstrates that KPD is feasible, successful, and if applied to
larger donor pools capable of expanding access to
renal
transplantation," the researchers conclude.
(JAMA.2005; 294:1655-1663.)

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Editorial: The Importance of Innovative Efforts to Increase
Organ Donation
In an accompanying editorial, Arthur J. Matas, M.D., and
David E. R. Sutherland, M.D., Ph.D., of the University of
Minnesota, Minneapolis, examine the findings by Montgomery et
al.
"The individual organ recipients who undergo a successful
transplantation have greatly improved expectations compared with
those individuals who continue to undergo
dialysis. Removing
candidates from the transplant waiting list shortens the waiting
time for the remainder of patients. One of the limitations of
paired exchange is the small number of eligible donor/recipient
pairs at each center, making finding a matched pair difficult.
Regional or national matching programs would make finding pairs
more probable, but including the highly sensitized blood type O
candidates would require extensive laboratory testing."
"However, there are several important cautions. While
transplant physicians see the tremendous benefit that organ
recipients derive from a successful transplant, organ
transplantation raises numerous ethical issues involving
protection of the donor, informed consent, and equity in organ
allocation. To date, only a limited number of long-term outcome
and quality-of-life follow-up studies have been performed
concerning conventional donors. Paired exchange leads to
additional concerns. For example, what if one kidney fails early
but the other functions well? Those involved in such programs
must pay careful attention to the informed consent process and
should be conducting formal follow-up studies of donors."
"Kidney transplantation remains a success story, but its
promise and future continue to be threatened by the ongoing lack
of suitable organ donors. While new methods to overcome this
problem are welcome, the transplant community must face up to
the new ethical issues that surround every advance," the authors
conclude.
(JAMA.2005; 294:1692-1693.)
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