A single variant in a single gene in a donor (and therefore in his or her donated kidney) could make a difference in survival of the transplant by affecting how the new kidney pumps out the anti-rejection drugs, according to research led by a U.K. hospital.
The immunosuppressant drugs that prevent rejection of the new organ have a rather ironic toxicity--they can damage the kidney. A team of scientists, led by Richard Borrows of Queen Elizabeth Hospital Birmingham in the U.K., has looked at genetic variants in donors to see how these affect the kidney's ability to process the drugs. The results were published in the Journal of the American Society of Nephrology.
The team looked at 811 immunosuppressant-treated kidney transplant recipients, testing for 52 single-nucleotide polymorphisms (SNPs; single-letter changes in the genetic code). They found that a single-letter variant in the multidrug resistance 1 (MDR-1) gene in donors was linked to a 69% increased risk for long-term failure of transplanted organs. This gene codes for the drug transporter P-glycoprotein, which protects cells by pumping harmful substances out and therefore can cause drug resistance by pumping therapeutics out of the cells, too.
In what the researchers describe as the largest study of its kind, they validated this genetic biomarker in another 3,660 donors.
"The study of donor, as opposed to recipient, gene variation is relatively uncommon in the field of transplantation, and it certainly warrants more attention," Borrows said.
This single genetic change is unlikely to be solely responsible for rejection, but could form part of a network of genes that could influence the process. Using biomarkers of this type could help select the best kidneys for transplantation or suggest which recipients should be monitored most closely, especially as demand for organs for transplantation already far outstrips supply. They could also be used as targets for developing new anti-rejection drugs.
- read the press release
- see the abstract