People who donate one of their kidneys have an increased risk of developing end-stage renal disease (ESRD), although the overall magnitude of that risk is small, researchers found.

In an analysis of National Health and Nutrition Examination Survey (NHANES) data paired with outcomes from CMS, the estimated risk of ESRD over 15 years was 30.8 per 10,000 in kidney donors compared with 3.9 per 10,000 in matched healthy nondonors (P<0.001), Dorry Segev, MD, PhD, of Johns Hopkins University, and colleagues reported in the Feb. 12 issue of the Journal of the American Medical Association.

"Even with the observed increased risk of ESRD for donors compared to healthy nondonors, we are still talking about a cumulative incidence of ESRD of about three per 1,000 at 15 years, which is pretty low," Kerry Willis, PhD, senior vice president for scientific affairs at the National Kidney Foundation, told MedPage Today. "I do think prospective donors should be aware of this, but overall the study is reassuring because it is the most rigorous to date in terms of sample size and carefully matching the health of the comparator nondonor group to that of the donors."

Other nephrologists contacted by MedPage Today warned that the study's observational nature couldn't determine causality. Other factors could be responsible for the association, they said.

"The elephant in the room is family history. The most common reason people donate organs is that it is a loved one in need," said Joel Topf, MD, of St. John Providence Health System in Farmington Hills, Mich. "Spouses do not share genetic risk of kidney failure but children, parents, uncles, siblings, nieces, and cousins all share genetic predisposition to ESRD. Genetics is a powerful risk factor and, until it is taken into account, it is difficult to blame the nephrectomy for the increased risk."

He said a more accurate way to assess outcomes would be to have a control group of relatives who do not donate an organ.

"I would have liked to see them break out the risk of ESRD by relationship to the recipient," Topf said. "I suspect we would see a much lower rate among spouses and unrelated donors than among blood relatives."

Although familial risks could be due to environmental exposures, researchers are learning more about the genetics of kidney disease, which may also be at play, according to Rajnish Mehrotra, MD, of the University of Washington in Seattle. It's known that polymorphisms in the APOL1 gene increase the risk of kidney disease, especially among black patients, he said.

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