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.
||Iran in 2006 became
the first country to legalize the selling of kidneys. The
Economist, reporting on the development, said if just .06%
of healthy Americans aged 19 to 65 donated or sold one kidney,
the U.S. wait list would disappear.
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 Bray.
“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 a transplant.
“Kidney transplantation is the optimal
treatment for end-stage renal disease, and being able to offer transplantation
to this population is a significant advance,” says Pearson.
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
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.”
||A survey of 232
renal disease and kidney transplant recipients at the University
of Glasgow, Scotland, found only 6% agreed with the current
U.K. and U.S. policy to allocate to a patient not on dialysis
who had been on the wait list longer than a patient already
on dialysis. Only 24.6% of the participants agreed with U.K.
and U.S. policies that designate allocation to a good HLA match
who had been waiting two years in preference to a patient waiting
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
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
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.”