The identification of APOL1-related kidney disease and recognition of its large contribution to excess risk of end-stage kidney disease (ESKD) in people of West African origin has been one of the biggest stories in nephrology over the past 2 decades (2-time NephMadness champion, 2015 and 2017).
The presence of 2 APOL1 risk variants (G1:G1, G1:G2, or G2:G2) confers a higher risk of kidney disease and studies have reported inferior allograft outcomes in deceased donors with a high risk genotype. Arguably of more concern is the potential for donors harboring high-risk APOL1 alleles to develop accelerated kidney disease post-donation.
Should we employ APOL1 testing as a tool to stratify risk in potential donors of African origin? This question and its ethical and clinical consequences are explored in a recently published Perspective by Mohan et al. The authors pose some provocative questions, including:
- Who to test?
- Should testing be mandatory (what if a patient refuses)?
- What to do with the results (would high risk status be an absolute contraindication to donation)?
Mohan et al also discuss ethical issues regarding informed consent and access to and sharing of the test result between donors, recipients, and transplant programs.
When considering these questions, it’s important to consider the following points:
- Many African Americans do not have West African sub-Saharan origin. Moreover, others who do not necessarily identify as black may harbor risk alleles (particularly those from Caribbean islands including Dominican Republic and Haiti).
- The implications of the test are not known. Most people with high-risk APOL1 alleles will not develop kidney disease and the natural history of kidney donation in these circumstances remains unclear.
- Like any genetic test, the result may have significant implications for family members.
- The rollout of APOL1 testing in black donors will likely lead to a shrinking of the donor pool in this population.
APOL1 Long term Kidney Transplantation Outcomes (APOLLO) is a national prospective study which will explore the impact of the APOL1 risk variants in both living and deceased donor kidney transplantation and will hopefully inform practice. We need more clarity on attributable risk associated with presence of risk variants and how other risk factors, such as age, blood pressure, and body weight, help stratify this risk. However, the results of APOLLO are some years away and individual transplant programs are already performing APOL1 testing in donor candidates and presumably making decisions based upon genotype.
While Mohan et al quite rightly emphasize the reasons to have a considered approach rather than rush to testing without regard for consequences, we all appreciate that donor safety is paramount. In that regard, donor APOL1 testing may become a useful tool in donor selection. This will likely occur at the expense of declining some donors, although hopefully appropriately. Either way, as stated by the authors, significant engagement with the black community in the United States is needed before establishing a policy on testing.
Interestingly, in a recent study by Gordon et al which surveyed black donors regarding APOL1 testing, there was widespread support for testing, although donors did fear the consequences of having a high-risk genotype identified.
This Perspective is a thought-provoking piece discussing the complex ethical and clinical issues regarding donor APOL1 testing. In many ways this issue highlights in general the struggle we have in actively promoting live kidney donation while at the same time striving for the utmost donor safety.
Title: APOL1 Genetic Testing in Living Kidney Transplant Donors
Authors: Sumit Mohan, Ana S. Iltis, Deirdre Sawinski, and James M. DuBois