Living Kidney Donors Face Some Excess Risk Over Time

Pam Harrison

January 29, 2018

Compared with nondonors, living kidney donors are at increased risk for several adverse health outcomes including end-stage renal disease (ESRD) and preeclampsia in female donors who become pregnant. However, the absolute risk for these adverse outcomes remains small, according to a systemic review and meta-analysis of mid- and long-term health risks for living donors.

The study, published online today in the Annals of Internal Medicine, did not find an excess risk for a number of other chronic diseases or all-cause mortality.

The estimates, however, should be interpreted with caution, Emilio Poggio, MD, from the Cleveland Clinic in Ohio and Peter Reese, MD, from the University of Pennsylvania, Philadelphia, write in an accompanying editorial.

"[A] close look at the data reminds us that long-term outcomes are uncertain and that precision medicine has not arrived for risk prediction in kidney donors," they write. "In the meantime, we should do our best to protect potential donors with careful selection, candor about harms, open discussion about unknowns, and a commitment to their lifelong health after nephrectomy."

Linda O'Keeffe, PhD, from the MRC Integrative Epidemiology Unit in the School of Social and Community Medicine at Oakfield House, Oakfield Grove, Bristol, United Kingdom, and colleagues identified 52 observational studies comparing a variety of health outcomes among living kidney donors and individuals who did not donate an organ. Mean or median follow-up for the studies was 10 years or more.

"Selection of the control population differed between studies, with 8 studies selecting control participants from population-based studies, 11 from the general population, 14 from siblings and other volunteers, and 19 from other sources," the investigators explain. This may be an important confounding, as the control groups are unlikely to have the same excellent health status that living kidney donors are expected to have.

Overall, Dr O'Keeffe and colleagues compared health outcomes between 118,426 donors and 117,656 control patients across all studies analyzed. Differences in health outcomes were expressed by standardized mean difference (SMD) within each study.

Living donors had poorer renal function, as reflected by a lower mean estimated glomerular filtration rate (SMD, −1.59; 95% confidence interval [CI], −1.86 to −0.33) than nondonors, as well as higher mean serum creatinine levels (SMD, 1.02; 95% CI, 0.44 - 1.60). In addition, donors had a higher mean diastolic blood pressure (SMD, 0.17; 95% CI, 0.03 - 0.34) and lower levels of high-density lipoprotein cholesterol (SMD, −0.29; 95% CI, −0.52 to −0.11) compared with nondonors, the researchers report.

Perhaps most strikingly, living kidney donors had an almost 9-fold greater relative risk (RR) for developing ESRD (relative risk [RR], 8.83; 95% CI, 1.02 - 20.93). However, the absolute risk for ESRD among donors was very low, with an incidence rate of 0.5 events (95% CI, 0.1 - 4.9 events) per 1000 person-years vs 0.1 event (CI, 0.0 - 0.6 event) among nondonors.

For female living donors, the RR for preeclampsia among those who become pregnant was 2.12 (CI, 1.06 - 4.27) compared with female control participants (absolute incidence, 5.9%% vs 3.1%% of pregnancies, respectively).

In contrast, the researchers found no clinically relevant or statistically significant differences in systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, triglycerides, or glucose levels between those who donated and those who did not.

Importantly, as well, at an average follow-up of between 5 and 15 years, the team found no increased risk for all-cause mortality, cancer, cardiovascular disease, type 2 diabetes, or hypertension among donors compared with nondonors.

Counseling Live Donors

Whereas the risks associated with live kidney donation must be discussed with all potential donors, there are good reasons to approach individual risk assessment with caution, the editorialists note.

For example, the risk for ESRD or other complications may depend on factors that were not examined in the current studies or that change with longer follow-up. Moreover, there is also no way that a physician counseling a potential donor can anticipate whether the potential donor might become obese and develop diabetes in the future, thereby compromising their own kidney health.

"In the absence of precision risk prediction, the transplant field has some immediate opportunities," Dr Poggio and Dr Reese suggest. The first tactic would be to select potential donors who are older and for whom the risk of developing ESRD, say, 15 years later is less of an issue than it would be for a 25-year-old donor.

The second is to make sure that patients are exposed to a "candid discussion" about the limitations of the data regarding what the long-term risks really are with live kidney donation. Physicians also need to determine what kind of information patients need to make a considered decision about donating a kidney, as well as about their own motives for wanting to do so.

"For many, kidney donation is affirming and meaningful," Dr Poggio and Dr Reese write. "We need to hear what donors feel, think, want, and understand about excess risk and how they use this information to reconcile long-term medical risk with psychosocial health and quality of life while making the decision," they add.

"[And] transplant programs and primary care physicians should help prior donors adopt healthy lifestyles to prevent and treat threats to kidney health after donation, such as diabetes, that may harm their kidneys later in life," the editorialists conclude.

The authors and Dr Poggio have disclosed no relevant financial conflicts. Dr Reese reports being associate editor for the American Journal of Kidney Diseases, as well as receiving grant support to the University of Pennsylvania from Merck. He also reports receiving research support from CVS Caremark and has served as a consultant with COHRDATA.

Ann Intern Med. Published online January 29, 2018. Article, Editorial

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