Gene Finding May Influence Kidney Transplant Outcomes
Variants in ABCB1 may raise risk of delayed graft function in renal transplant patients
WEDNESDAY, May 27 (HealthDay News) -- Kidney transplant recipients who have T allelic variants in exons 21 or 26 of the ABCB1 gene may have a greater likelihood of several adverse events related to cyclosporine A, according to research published online May 21 in the Journal of the American Society of Nephrology.
Dario Cattaneo, Ph.D., of the Ospedali Riuniti in Bergamo, Italy, and colleagues analyzed data from 147 patients who underwent renal transplant. Cyclosporine A is a standard treatment to reduce graft rejections, and it serves as a substrate of an efflux transporter encoded by the ABCB1 gene.
The researchers found that 37 percent of the subjects had the wild-type ABCB1 genotype in exon 12 or 21, and 36 percent in exon 26. After a median of 65.5 months of follow-up, those with T allelic variants in exons 21 or 26 had almost a three-fold higher risk of delayed graft function compared to those with the wild-type genotype. Their incidence of new-onset diabetes and cytomegalovirus reactivation was also significantly higher. However, the authors note, incidence of acute rejection and mean cyclosporine A blood levels were similar.
"We suggest that delayed and impaired kidney function recovery in carriers of T allelic variants in ABCB1 exons 21 or 26 might be the consequence of a more severe reperfusion injury. Conceivably, oxidative stress in grafts given to carriers of the T allelic variants could have been amplified by reactive oxygen species generated and released in increased amounts by infiltrating lymphocytes, polymorphonuclear cells, and other host leukocytes," the authors write.