Study: Gene factors in kidney-transplant failures

Researchers at Wake Forest Baptist Medical Center have discovered a specific recessive gene that is a factor in the early failure of transplanted kidneys from black donors.

The discovery could greatly improve outcomes for potential kidney recipients and donors and could help identify whether some people have kidneys at greater risk of failure. The discovery also raises medical and ethical questions, such as whether a person should get a kidney knowing it’s likely to fail if it makes life better in the interim.

The report, timed for release today, is the result of a 12-year study of 136 kidneys from 106 deceased black donors. The report appears in the May issue of the American Journal of Transplantation.

“It’s been long observed that kidneys taken from some black donors just don’t last as long as those taken from nonblack donors,” said Dr. Barry Freedman, the senior investigator of the study.

“We now know these organs aren’t failing because they came from black donors, but rather because they came from individuals with two copies of a specific recessive gene.

“There is a need to do this study with live donors, but there is no reason to think the results would be different.”

According to MedicineNet.com, 95 percent of transplanted kidneys are working after one year and 80 percent after five years.

By comparison, the study found that half of the kidneys with the two copies of the recessive gene failed before two years, some within a few months. The race of the recipient did not matter.

“That’s a huge failure rate,” Freedman said.

The study focused on patients who received a kidney transplant from a donor whose genetic information had been recorded.

Researchers found that kidneys from donors who had specific coding changes in a gene called apolipoprotein L1 (APOL1) did not last as long after transplant as those from donors without these changes. The code changes are found in up to 12 percent of blacks.

The effect of having two copies of the gene dwarfed other factors, including genetic matching between donor and recipient, amount of time the organ was out of the body and antibody levels, Freedman said.

If the research is confirmed in other studies, it could help donors and recipients, Freedman said.

“It could revolutionize donor selection criteria, allowing transplant physicians the ability to identify kidneys that are likely to function for shorter periods of time,” Freedman said.

The screening tool could help doctors identify potential donors who carry the two copies of the gene and may be at risk of developing kidney disease later in life.

That knowledge could carry ethical and scientific challenges, health-care officials said. Such as:

Should a patient receive a kidney with two copies of the gene — knowing the kidney is likely to fail quicker — to improve quality of life in the interim?

Is it better for the patient to wait one to four more years for a kidney without the gene complication, enduring dialysis that limits quality of life?

Should a physician perform a transplant involving a living donor who has the gene complication, knowing it could put the person at higher risk of kidney failure?

Che Navey, a part-time intensive-care-unit nurse at Wake Forest Baptist, said she lives right in the middle of that gray area.

Navey is awaiting her third kidney transplant at age 38. She began to experience kidney failure at 15 after a case of strep throat she had at 12.

She received her first kidney at age 20 from a deceased donor. It failed nine years later. The second kidney came from her 18-year-old brother and lasted nine years.

Although she undergoes about eight hours of dialysis while she tries to sleep, Navey says she’s leading a quality life, including pursuing a master’s degree in nursing at UNC Greensboro. Her goal is to become a nurse practitioner.

Navey said she’s hopeful the study will provide a path to a better donor match because she’s aware her next transplant could be her last.

“I have been denied a third transplant by doctors at Carolinas HealthCare,” Navey said. “The doctors at Wake Forest Baptist are adamant about getting me another kidney.

“I’m hopeful a third kidney will be made available and will work for as long as possible.”

rcraver@wsjournal.com

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