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SIMPLE LAW OF ECONOMICS: when demand outweighs supply, the price
of a commodity rises. But what if the commodity is a human kidney,
which by law cannot be sold? Who should receive first priority?
The person who has waited the longest or the one who is the sickest?
What about the person who is the best biologic match for the kidney,
regardless of wait time?
The answers are far from black and
white. Of the more than 65,000 people in the United States on the
waiting list for a kidney transplant, approximately 4,000 will die
this year because they were unable to receive an organ in time.
Current national policy in matching kidneys to recipients tends
to favor patients who have spent the longest time on the wait list.
Researchers at Emory have long worked
toward a better method of kidney allocation, and they have developed
a new system that gives hope to one of the most disadvantaged groups
on the waiting list, so-called sensitized patients. Sensitized patients
are those who have developed antibodies against human leukocyte
antigens (HLAs), which play an important role in the body’s
immune response to foreign tissue. Such antibodies usually result
from a prior pregnancy, blood transfusion, or previous transplant.
The Emory Algorithm, as the new method for kidney allocation is
known, may even change the way kidneys from deceased donors are
allocated in this country.
The United Network for Organ Sharing
(UNOS) coordinates the nation’s transplant system through
a point system based primarily on wait time, sensitization, and
HLA matching. When a kidney becomes available anywhere in the country,
the UNOS computer creates a list that prioritizes recipients based
on these criteria. When a “perfect match” occurs, the
kidney is offered to the person at the top of the national list.
If there are no perfect matches on the national list, the kidney
is next made available to transplant centers in the region from
which it came, and in turn each of those centers runs a match list.
While many transplant centers replicate the UNOS allocation policy,
some regions have received permission to deviate from the standard.
The Emory Algorithm takes a different
approach, while still following these guidelines. For the sensitized
patients (who make up approximately 50% of Georgia’s wait
list), the Emory Algorithm predicts which patients on the list will
be compatible with any given donor. The algorithm’s developers—immunologists
Robert Bray and Howard Gebel and transplant surgeons Christian Larsen
and Thomas Pearson—say the method may help level the playing
field for sensitized patients, who rarely make it to surgery because
a compatible match is seldom identified. In the United States, although
sensitized patients represent one-third of the wait list, on average
they receive approximately 15% of deceased-donor kidney transplants
each year. Using the Emory Algorithm, its developers found they
could raise the rate of transplants to 25% in sensitized patients.
The results of their five-year study appeared in the October 2006
issue of the American Journal of Transplantation.
than a best guess
The Emory Algorithm uses a relatively new technology of single-antigen
bead assays, which give a more specific analysis of HLA antibodies.
With the degree of specificity the assays provide—identifying
a single antibody versus general groups of antibodies—immunologists
can inform transplant surgeons with a high degree of confidence
whether a kidney from a deceased donor is a compatible match with
a given recipient. No more making a “best guess,” says
“Each of us has a constellation
of HLAs, with six major ones related to kidney transplantation,”
Bray says. “With the older technique of cross-matching HLA
cells with the blood of a potential recipient, we couldn’t
always identify which HLAs the antibodies were targeting. False
readings could occur.”
Everyone has an A, B, and DR antigen
from each parent, making up the six antigens important to transplantation.
Within each antigen group are numerous specific antigens, sometimes
dozens. There are nearly 50 B antigens alone. Studies have shown
the more A, B, and DR antigens a donor and recipient share, the
better the survival rate of the transplanted kidney.
Emory’s Algorithm incorporates
a filtering process into the match, effectively removing patients
with antibodies against the donor because antibodies to HLAs are
what really matter, Pearson says. A poorly HLA-matched kidney without
antibodies is better than a well-matched kidney with antibodies.
And the single-antigen bead assay test is key to determining which
HLA antibodies are present.
A decade ago, Bray and Gebel helped
One Lambda, an HLA diagnostic company in California, develop and
test its single-antigen bead assays. Each bead is coated with a
single HLA antigen produced by recombinant DNA technology. Different
HLA molecules are bound onto different antigen bead assays. The
beads are mixed with the recipient’s blood and then placed
in a flow cytometer, a machine the size of a window air-conditioner.
Inside the flow cytometer, a laser reads what antibodies, if any,
are attached to the HLA molecules on the beads. A computer then
collects and organizes the results. The process takes less than
four hours, from start to finish.
While some transplant centers use
these same single assay tests to identify HLA antibodies, they fail
to incorporate the data into their match run. Thanks to the Emory
Algorithm, sensitized patients have an increased chance of receiving
“Kidney transplantation is the
optimal treatment for end-stage renal disease, and being able to
offer transplantation to this population is a significant advance,”
Pearson says the Emory Algorithm showcases
how technology can be used to define nature’s barriers to
improve transplantation—essentially helping you work better
with what you’ve been given.
Other methods that break down barriers
before transplantation, such as plasmapheresis—a blood-filtering
process that removes a recipient’s antibodies in preparation
for a transplant from a living donor—are costly and carry
a high risk of complications.
Within the Emory study, the survival
rate of a kidney transplant in sensitized patients after five years
was almost identical to that of unsensitized recipients—66%
versus 70%, respectively. “There is a perception in the literature
that patients who are highly sensitized have poor outcomes,”
says Gebel, “but that’s not our experience.”
the national policy
Based on results of the Emory study, a UNOS committee is looking
at the algorithm as UNOS reevaluates its kidney allocation system.
The committee is expected to make recommendations this year, according
to Mark Stegall, a transplant surgeon at the Mayo Clinic and the
committee chair. Pearson also sits on the committee.
“I hope the algorithm process
will become national policy as part of an overall kidney allocation
policy,” Stegall says. “Eighty percent of transplant
programs are using the single-antigen bead technology, but relatively
few are using that data to allocate kidneys to sensitized patients.
Emory has been a thought leader in this for many years. They’ve
provided a great resource to the transplant community.”
Still Stegall is not ready to commit
to a system based only on organ compatibility as determined by antibodies.
“Kidneys are a scare resource,” he says. “We have
to put sensitization in perspective. There is always an unsensitized
patient out there.”
No allocation system for kidney transplants
can be 100% fair to every patient, Pearson says, although the Emory
Algorithm helps equalize the allocation scheme. With this system,
everyone on the waiting list would be considered for an available
kidney, but only the best match would receive it.
“There is no ‘right’
answer and no ‘fair’ as long as the number of patients
with kidney failure far exceeds the number of kidneys available
for transplant,” Pearson says. “We have to balance priorities
to try and help as many people as possible.”