Living kidney donors are at increased risk for end-stage renal disease (ESRD) and cardiovascular and all-cause mortality, according to a new study.

Investigators led by Hallvard Holdaas, MD, of Oslo University Hospital in Oslo, Norway, compared 1,901 individuals who donated a kidney from 1963 to 2007 with a control group of 32,621 potentially eligible kidney donors. The median follow-up for the donors and controls was 15.1 and 24.9 years, respectively.

Compared with controls, kidney donors had a significant 11.4 times increased risk of ESRD, 1.4 times increased risk of cardiovascular death, and 1.3 times increased risk of death from any cause, after adjusting for potential confounders.

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ESRD developed in 9 donors (0.47%). The median time from donation was 18.7 years. ESRD was mainly caused by immunologic renal diseases.

“Our findings raise some medical and ethical considerations regarding live-kidney donation,” the authors wrote in Kidney International (2014;86:162-167). “The present study indicates potential increased long-term risks for kidney failure and mortality in kidney donors. However, this has to be put into perspective.”

Living donor transplantation, they noted, has been a necessary and essential part of providing ESRD patients with freedom from dialysis and enabling transplant recipients to enjoy a superior quality of life. “Most potential living donors are willing to accept a degree of risk when the recipient is a family member of a close friend.”

Previous studies have suggested that living kidney donors maintain long-term renal function and have no increase in cardiovascular or all-cause mortality, Dr. Holdaas’ group stated. Most investigations, however, have included control groups that were less healthy than the living donor population and have had relatively short follow-up periods, they pointed out.

The researchers said their findings will not change their opinion about promoting live kidney donation. “However,” they pointed out, “potential donors should be informed of increased risks, although small, associated with donation in short-term and long-term perspective.”

In an editorial accompanying the new report (pp. 20-22), Neil Boudville, MD, of the University of Western Australia in Perth, and Amit X. Garg, MD, of Western University in London, Ontario, pointed out that the elevated risk of ESRD in living kidney donors found by Dr. Holdaas and colleagues is comparable to that found in a study by Abimereki D. Muzaale, MD, MPH, of Johns Hopkins University School of Medicine in Baltimore, and colleagues.

The study, published in the Journal of the American Medical Association (2014;311:579-586), compared 96,217 living kidney donors with 20,024 participants in the Third National Health and Nutrition Examination Survey (NHANES III). In this study, the incidence rate of ESRD was 8-fold higher in the donor cohort.

“The findings of these two studies are very important and should influence the information we provide to potential donors,” Drs. Boudville and Garg wrote.

They noted that the findings may impact criteria for donor selection. “We will likely want a higher level of pre-donation kidney function … for younger individuals who are expected to live 50 or more years with one kidney (recognizing we do not have ideal evidence to inform what is the optimal acceptance threshold),” they wrote.