Kidney transplantation is a life-saving procedure and is associated with at least a doubling in life expectancy of transplant recipients.¹ Live-donor kidneys provide better kidney function and longer transplant survival than those from deceased donors. However, live donation is not entirely without risk, and several recent studies have demonstrated an increase in risk of end-stage kidney disease (ESKD) in live donors.² 

While the lifetime absolute risk of ESKD after kidney donation remains very low, estimated at less than 1%,² there are subgroups such as African Americans and younger donors, where the risk may be higher. Accurate identification of those at increased risk is critical to minimize the risk of complications in those who give this incredibly generous gift to their loved ones.

Recently, several research groups have developed risk calculators to estimate the future risk of ESKD in potential live-donor candidates. In 2016, Grams et al. published a study in NEJM,³ where they examined data from 5 million healthy patients and developed a model to estimate their risk of ESKD based on risk factors, including age, sex, race, smoking status, hypertension, and diabetes.

Using this calculator, they estimated that in these selected healthy patients, who might be potential kidney donors, the risk of developing ESKD within 15 years was very low.  This estimate give insights into the risk related to demographic and health characteristics, but no estimate of the risk specifically related to donating. The rationale is that to understand an individual’s risk from donation, we must first estimate their baseline ESKD risk, so we can safely exclude those at unacceptable long-term risk.

Using the Grams calculator, the lowest risk group was white women, followed by white men, with higher rates seen in black women, and the highest risk of future ESKD was for black men.

Table: Baseline estimated risk of ESRD at 15 years in healthy patients (who have not donated)³

They then applied this model to 58,000 live donors, whose incidence of ESKD at 15 years post donation was known. The observed increase in relative risk following donation was 3-5 fold in this model. Other studies, using different healthy populations, have estimated a relative risk of developing ESKD of 4-8 fold in prior kidney donors.^2,4

Massie et al. took a slightly different approach. They studied data from >130,000 live donors and linked it with ESKD status, as identified from CMS data. They developed a model, to characterize risk factors for ESKD in live donors and produce risk estimates for ESKD at 5, 10, 15, and 20 years after donation.⁵ This calculator, although based on a smaller number of patients (only 331 cases of ESKD post donation), may give an estimate of the risk following donation and is complementary to the estimate of baseline risk provided by the Gram’s calculator.

In this study, they found in addition to male sex (HR 1.88) and black race (HR 2.96), higher BMI and biological relationship to the recipient were associated with increased risk (HR 1.6 and 1.7 respectively). Increased age also conferred increased risk, with HR for ESKD of 1.4 per 10-year increase in age. The C statistic of the model was 0.71, indicating a moderate correlation. However, they observed a very wide range of risk where donors at the lowest predicted risk of ESKD at 20 years post-donation of 7/10,000 as compared to the highest predicted risk who had estimates of nearer 256/10,000.⁵ As a comparator, the lifetime risk of ESKD in healthy nondonors has been estimated at 14/10,000.²

So how is this information useful? Using the Gram’s calculator, we can get a sense of the baseline risk for each individual of developing ESKD. Data presented in the paper on several hypothetical ‘patients’ emphasize that the sum of several subtle abnormalities can notably increase long-term risk of developing ESKD, even in the absence of donation. Massie’s calculator gives an assessment of long-term risk in those who have donated. However, it is based on a relatively small number of ESKD events, and incorporates a large number of variables to estimate risk. The risk estimates are extremely wide, which could be due to small numbers of events influencing the estimates, given that the number of patients with ESKD was small. Further validation in a larger population will be necessary to assess if this calculator provides an accurate assessment of post donation risk.