What a Gene and Its Risks Could Mean for Kidney Transplants

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Kidneys from Black donors are automatically downgraded in transplant assessments, but studying a gene variant could help change that.

Transplant specialists, when evaluating kidneys that come from donors, try to work out how likely it is that the kidney will fail after being transplanted into a recipient. Their risk calculations consider factors including the donor’s age, height, weight and history of diabetes. And, to the dismay of some researchers, it also includes the donor’s race.

Kidneys from Black donors, living or dead, are automatically downgraded as higher risk.

Some experts are now asking if there is a better way of evaluating kidneys from Black donors, one that can rely more on genetic screening rather than race to assess the risk of failure.

The proposed genetic screening would check whether donors carry two copies of variants in a gene, APOL1, that are strongly associated with kidney disease. Because most Black donors do not have those genetic variants, the experts argue, their kidneys should not be automatically downgraded.

But before instituting that change, researchers say they have to determine if, in fact, kidneys from donors that have the risk variants of APOL1 are more likely to fail.

The first hint came from a study by Dr. Barry Freedman, of Wake Forest University in North Carolina involving 1,153 deceased donor kidney transplants performed at 113 different transplant programs. It found that kidneys from deceased donors with two risk variants were twice as likely to fail rapidly compared with kidneys from donors who have one gene variant or none.

But that finding will need to be replicated in a bigger research effort. It is getting underway with APOLLO, a large study sponsored by the National Institutes of Health, to assess living and deceased donors. Study researchers are testing kidney donors for APOL1 and following the fate of thousands of transplant patients who have received kidneys from Black American donors at more than 97 transplant programs.

In the study, living donors can decide if they want to learn the result of their genetic test and if they want the recipient of their kidney to know the result as well. Medical privacy regulations forbid doctors from telling kidney transplant candidates if a living donor has the variants without the donor’s consent.

Dr. Freedman said that whatever results come from the research, more transplant centers are broaching the idea of genetic testing people who want to donate kidneys.

Until recently, he added, “many transplant centers said they don’t want to talk about it.”