09/13/93
CONTACT: Stanford University News Service (650) 723-2558
STANFORD -- African American dialysis patients wait twice as long for a kidney transplant as whites, partly because federal guidelines place more emphasis than is medically justified on genetic similarity between kidney donors and recipients, say two doctors and two law professors in an article to be published in the Sept. 15 issue of the Journal of the American Medical Association.
The JAMA paper, which proposes changes in the federal policy, was authored by University of Alabama at Birmingham nephrologist Dr. Robert S. Gaston; Dr. Arnold Diethelm, who directs that university's transplant center; Stanford University law Professor Ian Ayres; and Valparaiso University law Professor Laura G. Dooley.
Genetic similarity between the donor and the recipient improves the chance of transplant success when six specific proteins on the surface of cells match, but partial matching of these proteins, known as HLA antigens, has no persuasive impact on transplant success and is likely to make it more difficult for black patients to qualify for transplantation, the authors say.
Black patients, on average, have fewer matched antigens with the kidney donor than do white patients, the authors say. However, new immuno-suppressant therapies are destroying the historic disparity between the survival of transplanted organs in black and white recipients. (See comparison graphs at the end of this release.)
More than 100,000 people in the United States suffer from kidney failure, a condition doctors call end-stage renal disease, or ESRD. "About one-third of ESRD patients in this country are African American, three times more than representation of this racial group in the general population," Gaston said.
Many ESRD patients are treated with ongoing kidney dialysis, but the optimal treatment is a kidney transplant from either a living relative or a dead donor. Because of a shortage of organ donors, only about 8,000 of the 23,000 people waiting for a suitable cadaveric kidney receive transplants each year. And most of the donors are white, making it difficult for black patients to find an HLA match.
African Americans, 31 percent of the patients on waiting lists for cadaveric kidney transplants in 1990, received only 22 percent of the kidneys allocated. They have a median waiting time of 13.9 months versus 7.6 months for whites on the waiting list, the study found.
While Gaston and his colleagues agree that possible causes of racial disparity in cadaveric transplantation are numerous, they say that a previously unacknowledged factor - the federal government's organ allocation policy - plays a key role in perpetuating inequitable racial access.
Some hospitals and regional hospital networks agree that partial matching of HLA antigens is no longer a significant survival factor and have sought exemptions from the federal organ allocation policy. For example, the California Transplant Donor Network, which includes five San Francisco Bay Area hospitals that perform kidney transplants, no longer allocates kidneys on the basis of partial antigen matches. The network will begin allocating cadaveric kidneys to patients Jan. 1 on the basis of their length of waiting time on a regional waiting list, rather than to separate hospital waiting lists. This will make length of wait an even more important factor in regional kidney allocation decisions, said Phyllis Weber, executive director of the network.
In general, however, federal regulations control the allocation of scarce donated kidneys among prospective recipients, Gaston said.
"Since 1972, Medicare has covered the costs of virtually all kidney transplants," he said. "To qualify for Medicare reimbursement, transplanting hospitals must abide by rules formulated by the federal Organ Procurement and Transplantation Network, also called the United Network for Organ Sharing."
The current policies for cadaveric allocation give strong preference to potential recipients who are genetically similar to the donor. That genetic determination is made by identifying antigens located on the surface of cells. An antigen is a protein on the surface of tissues that can stimulate an immune response.
Specific antigens called HLA antigens enable white blood cells - the primary immunologically active cells of the body - to distinguish between self and foreign tissue, Gaston said.
"Unless suppressed by drug therapy, the immune system will attack tissue that it recognizes as foreign, but ignore self tissue," he said. "If kidney tissue bearing specific antigens is transplanted into a person whose tissue does not bear those antigens, then the immune system of the recipient will attack the transplanted tissue in a process known as rejection."
However, "the immune system can be suppressed by drugs, enabling transplanted kidneys to survive, even in the presence of foreign antigens," Gaston said. Recent improvements in such drugs played a pivotal role in the development of the researchers' analysis of kidney allocation policies.
"The rules say that if all six antigens in a potential recipient match those of a donor organ anywhere in this country, then that patient gets the kidney. This is mandatory," Gaston said. The researchers say they don't dispute this rule, because there is strong evidence of greater transplant survival rates when all six antigens match.
More problematic, they say, is a point system that gives great weight to partial antigen matches, especially since newer immuno- suppressant drug therapy has improved the rate of success in unmatched transplantations. New drugs undergoing trials in kidney recipients may reduce the significance of antigen matching even further, the researchers said.
The point system for partial matches "tends to favor potential recipients who resemble the donors, and disfavor those who don't," Gaston said. Because kidney failure disproportionately affects African Americans and the donor population is predominately white in the United States, he said, the net result is an allocation system that, in an attempt to improve outcomes for all recipients, inadvertently limits access to transplantation for otherwise worthy African American candidates.
"The current system gives a lot of points for partial matching when there isn't any persuasive evidence of medical benefit and there is evidence of racial detriment," said Ayres, a Stanford law professor who models the disparate impact of laws and regulations.
"At minimum," he said, "the government regulations should decrease reliance on partial antigen matching and increase reliance on time spent on the waiting list in deciding which ESRD patients should qualify for transplantation."
Some commentators have suggested that the racial discrepancy in access to kidneys should be tackled by increasing African American donors, Ayres said. However, because a larger proportion of blacks suffer from kidney failure, the donation rate for blacks - for both cadaveric and living related organs - would have to increase to five times its current rate and more than four times the current rate for whites. "Increases of this magnitude are unlikely," he said.
The racial implications of the current system were "unintentional and unforeseen," Gaston said.
"The UNOS [United Network for Organ Sharing] allocation system was implemented in good faith as a response to medical evidence linking success in kidney transplantation to antigen matching," he said. "However, from its inception, while antigen matching accurately predicted outcomes in living-related transplantation, its role where cadaveric donors are concerned has been controversial."
The medical community remains divided on whether antigen matching is appropriate for organ allocation, Ayres said. For example, researchers who favor tissue typing called for an expanded emphasis on matching in a 1991 New England Journal of Medicine article.
Rules for allocating scarce medical resources, such as kidneys, are likely to need periodic amendment, Ayres said, as medical advances lead to new techniques that will likely change success ratios for some patients more than others.
Some may argue that scarce medical resources should be allocated only on the basis of likely medical success, he said, but kidney transplantation is a case where the government has already attempted to include some equity concerns as well as medical success in its criteria.
Patients whose immune systems have rejected one kidney transplant, for example, are awarded extra points under the federal cadaveric allocation system, in order to give them a chance at getting a second kidney transplant, despite the increased odds that a second transplant won't be successful.
"To ignore the equity concerns of African Americans," Ayres said, is "selective indifference."
-kpo-
930913Arc3150.html
This is an archived release.
This release is not available in any other form.
Images mentioned in this release are not available online.
Stanford News Service has an extensive library of images,
some of which may be available to you online.
Direct your request by EMail to newslibrary@stanford.edu.