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WEDNESDAY, July 9, 2003 (HealthDayNews) -- Something old and something new could help doctors better predict which kidney transplant patients are most likely to reject their new organs -- and perhaps lead to genetically tailored ways of preventing rejection in those at high risk of the reaction.
What's old is a souped-up version of ultrasound, which shows that stifled blood flow to the kidneys raises the odds of rejection. What's new are computer chips that detect differences in gene activity linked to the severity of a patient's immune response to the donor organ.
Last year, a record 14,769 kidney transplants were performed in the United States, according to the United Network for Organ Sharing.
Although advances in drugs to suppress the immune system have driven down rejection rates for kidney grafts -- 10 percent versus 30 percent a decade ago -- transplant failure remains a significant hurdle for patients. Failure is now the fourth leading cause of end-stage kidney disease in this country.
Doctors have therefore been looking for better ways to improve the odds that transplant recipients will keep their new organs as long as possible and with the fewest hardships.
To that end, two studies appear in the July 10 issue of the New England Journal of Medicine. In one, German researchers showed that using a modern twist on conventional ultrasound to measure blood flow in a transplanted organ can accurately predict which is most likely to fail in the short term.
Patients whose flow was most restricted three months after surgery -- the result of a blocked or kinked renal artery -- were nine times more likely than those with freer flow to suffer a serious rejection or die. The average survival after surgery was 2.5 years in the group with restricted blood flow to the organ, but 23 years for patients with low resistance.
"Prior to this study it wasn't appreciated that this commonly used tool could predict outcomes," says Dr. Philip Marsden, a kidney specialist at the University of Toronto. "Now we recognize that [blood] flow within the kidney is telling us something about how the graft will do in the years ahead."
In the second study, researchers at Stanford University in California used "gene chip" technology to analyze the activity of more than 12,400 genes in the kidney cells of childhood transplant patients. Gene chips are glass or plastic slides that can read genes in a tissue sample and determine which are more or less prominent, providing in the process genetic "signatures" for certain cell types, such as highly aggressive tumors.
The chip found clear patterns in grafts that were healthy and those that were troubled, giving a genetic picture of the risk of organ rejection and response to anti-rejection steroid therapy. A group of 1,340 genes appeared to be most closely related to rejection.
The analysis revealed at least three genetically distinct forms of rejection, based on the nature of the patients' immune cells. These differences weren't visible under a light microscope, the conventional way of examining kidney biopsies. A closer look at these forms found that people with particularly high numbers of immune system B cells in their kidney tissue had a strong risk of severe organ rejection and failure.
"We're pretty excited by what could be the potential practical implications" of the study, says Dr. Minnie Sarwal, a Stanford pediatrician and kidney expert who led the research. "You could actually differentiate which rejection episodes may be the ones with the worst outcomes, which we currently can't do."
B cells had been thought to be mere bystanders in the immune response to an organ transplant, but Sarwal's study changes that view. The immune system "uses these B cells to turbo-charge the T cells [that attack the graft] and makes the rejection response very malignant," she says. Ironically, the success of immune-suppressing drugs makes it possible for B cells to be so potent, she adds.
Marsden, author of an editorial accompanying the journal articles, says neither study holds all the answers to the problem of transplant rejection.
The German research gives doctors a fairly simple tool to predict severe rejection, but it offers nothing to stop it from occurring. The California study shows gene profiles can sort patients into groups with varying degrees of rejection risk and by their response to anti-rejection drugs. But gene chip analysis isn't currently available to most doctors or patients, nor is the function of all the genes in the kidney cells understood.
Still, gene chips hold the promise of leading to customized therapies to prevent organ rejection. As the new study suggests, Marsden says, one of these might involve targeting B cells in certain patients.
More information
Try the United Network for Organ Sharing or the National Kidney Foundation.
