Abstract
Is it reasonable to donate a kidney? Do we know enough about the risks to give proper informed consent? Has a long-term double-blind controlled study been done to compare persons who donated with persons, equally healthy and screened, who did not donate? No, and such a study cannot be done. However, 2 large studies1,2 published in 2014, one from Norway and one from the United States, highlight risks to living donors as compared with equally healthy nondonors. Results of those studies indicate that donors have a relative risk of end-stage renal disease (ESRD) of between 8 to 11 times the risk faced by healthy nondonors. This finding gives some pause to those enthusiastic about living donation. It is a relative risk, however, and not an absolute risk. In both studies, the absolute risk of ESRD was still less than 0.5% 15 years after kidney donation, and the lifetime risk was estimated at 0.9% in the US study. By comparison, the lifetime risk of dying in a motor vehicle accident in the United States is 1.2%. 3
Impressive as these studies were, they had limitations. In the Norwegian study, the accrual periods for donors and nondonors were different and the family histories of nondonors were not collected. 4 In the US study, the same nondonor controls were used multiple times to match with the greater number of donors, which may have led to underestimates of ESRD occurrence in nondonors because the definition of ESRD was different in the 2 groups.4–6 Further, blood pressure and body mass index were higher for donors at the time of donation. 7 Despite these limitations, these studies provide the best information to date on donor risks.
So, transplant centers now face the question: Do we have enough data to warrant making changes to clinical practice and informed consent processes? Or, should we wait for more data, or better data?
Given the relevance of these data to donors' decision making, it is essential to revise the informed consent process now. Doing this may sound simpler than it is. Given the big conceptual difference between absolute risk and relative risk, as well as how people perceive them, a number of questions arise about changing the informed consent process: What do we tell our potential donors? How should the information be conveyed in a way that optimizes donors' comprehension? In the following, we offer recommendations for risk disclosure, highlight new considerations about risk disclosure, and suggest avenues for further research on informed consent for living kidney donors.
We recommend that both absolute risk and relative risk be disclosed to maximize donors' understanding (see Table). Specifically, donors should be informed that the relative risk of ESRD is increased after kidney donation, especially in donors who are related to the recipient, according to the Norwegian study. The overall risk for ESRD in donors has been estimated as 8 to 11 times greater than the overall risk for ESRD in healthy nondonors. Additionally, although the relative risk is high, the absolute risk is still less than 0.5% at 15 years and 0.9% lifetime.
Although the absolute risk provides donor-related chances of kidney failure, relative risk helps to place absolute risk into greater context through comparison with other groups. However, a potential challenge with conveying relative risk is that risks to donors appear inflated and might be misinterpreted. These considerations when interpreting the meaning of relative and absolute risks should also be communicated to potential donors.
When presenting both forms of risk, caution is needed, however, because of framing effects. For example, research has shown that people prefer medicines with benefits presented in relative risks rather than in absolute risks. 9 Research is needed to identify best practice approaches for conveying such information that reduce potential confusion about donation risks.
Further, clinicians should inform donors that, although the 2 studies are good, they do have limitations and may not represent the final word on donor risks, and that future research may reinforce or uncover other information on risks donors face.
Donors may desire additional information and may wish to be apprised of the controversies or limitations surrounding these 2 studies or other studies. Thus, consent processes should be developed that layer information so that additional information can be provided according to the potential donor's specific information needs.
To be sure, disclosing both absolute and relative risk information as well as study limitations may overwhelm potential donors with too much information. Providing all of that information runs the risk of compromising, rather than affording, a more nuanced understanding of donor risks.
Donor risk of end-stage renal disease (ESRD): informing the patient
No empirical research has yet been done to evaluate the impact of disclosure of these new risks on donors' comprehension. Ultimately, the best approaches for disclosure of absolute and relative risks remain to be empirically determined through donor-centered research. That is, research should be done to identify the information content and delivery format that donors prefer.
A broader concern that these studies raise is whether donor risks remain medically acceptable. It would seem so (tissue and organ donation is safer than the lifetime risk of driving a car). Although the US and Norwegian studies provide a useful guideline, each donor's own risk profile must be weighed in relation to the benefits and risks to the recipient. Should we be more cautious with a 25-year-old African American donor whose mother has diabetic nephropathy? Yes. Should we be more careful with the potential young donor whose creatinine clearance is 90 mL/min as opposed to 120 mL/min? Probably yes, although this topic has not been adequately studied. The recent large studies on donor risks are useful in elucidating the relative risk of donation. It is reassuring that the absolute risks are not prohibitively high—more than 99% of donors will not end up with ESRD.
Disclosing donor risks is an important way to express respect for donors' autonomy in making treatment decisions consistent with donors' life goals, values, and beliefs. Updating the consent process now, and as new evidence arises, is important as a form of continuous quality improvement. Moreover, disclosing absolute and relative risks may coincide with the goals of precision medicine as recently unveiled by President Obama, in terms of providing personalized information to patients about their risk profile and treatment options. Accordingly, the Organ Procurement and Transplantation Network's policy 14.0 about living donation may need to be revised to cover the new data. 10
Communication is key to the informed consent process, and clinicians are pivotal to effectively disclosing information on risks that are material for donors' decision making. As other research shows, many clinicians do not comprehend risk information and do not feel competent obtaining patients' informed consent in the context of increased risk donor organs. 11 Thus, it is likely that clinicians will not have a firm grasp of donor risk information, which could compromise their ability to educate potential donors about the risks they face. Accordingly, the American Society of Transplantation's Living Donor Community of Practice Consensus Conference recommended that a process be developed
to ensure that transplant and dialysis team members attain competency in living donation risks, methods for communicating risks and benefits, and ways to provide guidance to transplant candidates on effective and ethical approaches to engaging potential donors. 10
Resources are therefore needed to help health care providers better understand and effectively explain risk information to potential living donors.
Living donors are generous and heroic. We owe it to them to provide the most accurate information regarding donor risk, especially the risk of ESRD. Past information available to us described donors' risk of ESRD as much lower than the risk in the general population. Newer data since 2014 comparing donors with healthy nondonors describe more accurately the relative and absolute risks of donation. These risks are not excessive, but the transplant community needs to incorporate the newer data into the consent process to inform prospective donors more fully.
Footnotes
Acknowledgments
An earlier version of this guest editorial was presented as a webinar through the American Society of Transplantation–sponsored Living Donor Community of Practice (LDCOP) on February 17, 2015.
None reported.