http://news.medill.northwestern.edu/chicago/news.aspx?id=186028Genes, not race, determine kidney transplant success
BY PRISCILLA KUNAMALLA
Doctors have long observed that kidneys taken from African-American donors have an increased risk of early failure, but a study released today suggests that race has nothing to do with the problem.
Researchers at Wake Forest Baptist Medical Center found that individuals with two copies of a recessive gene called apolipoprotein L1, or APOL1, which is associated with kidney disease, occurs in 10 to 12 percent of African-Americans but is virtually absent in Caucasians.
The mutation plays a major role in early kidney transplant failure, researchers said Tuesday.
“This is a game changer in the field of transplantation,” said Dr. Barry I. Freedman a nephrologist at the Wake Forest Baptist Medical Center in North Carolina and the study’s senior investigator. “The fact is that the mutations in this gene that cause kidney disease are almost exclusively in the African-American population, but it’s not about the race of the donors. It’s about the donor’s genetic predisposition and genetic makeup.”
To study the APOL1 gene linked to the problem, the researchers pulled medical records dating back to 1998 for patients who received a kidney transplant from a deceased black donor. They analyzed 106 donors from whom one or both kidneys had been transplanted, resulting in 136 donated kidneys.
They found that kidneys donated by individuals with two copies of the APOL1 gene, one from their mother and one from their father, had higher rates of early failure than kidneys from donors with one copy of the gene or none.
“We found that kidneys from black donors who didn’t have two risk copies of the APOL1 gene survived very well.” Freedman said.
According to Freedman, the effect of having two copies of the APOL1 gene played a far stronger role in transplant failure than the standard, accepted risk factors such as general genetic matching between the donor and recipient, the amount of time the kidney was out of the body, and the antibody levels.
Early failure means that patients may need to return to dialysis. They can get another transplant down the road, but other complications can then develop. The patient can become more sensitized and it could be more difficult to get the next kidney transplant.
“The study needs to be replicated in other centers but, immediately upon replication, we think this has powerful implications for transplant physicians and patients.” Freedman said.
Based on the study, doctors may be able to genetically screen for donor kidneys that have the best chance of long-term functioning. The new screening tool could also help doctors identify potential donors who may be at risk for kidney disease Freedman said.
“If we know a kidney has a very high likelihood of not functioning for a long time, that may change the procedure. We may not do that transplant and instead wait for a kidney with a better outlook.” Freedman said.
However, for kidney transplant recipients, their first kidney transplant is their best shot for long-term transplant success, said Dr. Amber Reeves-Daniel, the study’s junior investigator, also at Wake Forest.
Transplanted kidneys take over the work of the two kidneys that have failed and patients will not longer need dialysis according to the National Institutes of Diabetes and Digestive and Kidney Diseases.
According to Freedman, the reason the gene became so common in the African-American population is because having one copy of the gene offered protection from an African parasitic disease called African sleeping sickness, while two copies today could lead to early kidney transplant failure.
A number of factors need to assessed together before a kidney can be transplanted, including the donor’s age, whether the donor is living and if they have diseases such as high blood pressure or diabetes that put them at risk for kidney problems, according to Dr. Edward F. Hollinger a kidney and pancreas surgeon at Rush University Medical Center.
“Any tools that we can have that can predict how well a donor kidney is going to do will be very useful,” said Hollinger, who is also surgical director of the living donor kidney and pancreas transplant programs at Rush. “It will be interesting to see if the findings can be replicated in future studies and if researchers can develop a practical system to make it useful.”
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