The APOL1 test and its role in driving greater health equity

Although the US passed a significant milestone in 2022—more than 1 million organ transplants completed since recordkeeping on them began—the stark reality is that 104,000 people in American need an organ transplant right now, and 92,000 of them—88%—are waiting for a kidney.¹

Based on decades of experience working in this field, it’s clear that a lack of matching donor profiles is not the only factor that has contributed to this waiting list. Good potential donor candidates for transplant often aren’t given basic information about becoming involved in this process. This information gap is especially wide among minority patient groups. In my experience, there is far too little outreach and education for this group about what the donation process looks like.

This information gap is particularly challenging among African Americans. These groups are not well represented in transplant match programs, and organ donations from these groups for transplants are relatively rare. Yet this is the same community that require kidney transplants the most because of the increased incidence of conditions like end stage renal disease and associated comorbidities.

The good news is that recent developments in a genetic area specific to certain minority populations offer health systems and hospitals an opportunity to change this dynamic, and may contribute to health equity in the process.

Although the 2 disease-causing APOL1 genetic variants arose in humans in sub-Saharan Africa several thousand years ago, the APOL1 gene itself was only discovered in 1997. Thirteen years later, the additional discovery was made that inheriting 2 copies of the G1/G2 variants of this gene carried strong association with increased risk of chronic kidney disease (CKD) and end stage renal disease.

These APOL1 variants are most common among those with western sub-Saharan African ancestry, such as West African, African American, South American (particularly Brazilian), and African and Hispanic Caribbean. Approximately 10% to 15% of African American individuals have a high-risk APOL1 genotype. 

APOL1 genotype information is important for both kidney donors and recipients to know. At least one study has shown that living kidney donors with high-risk APOL1 genotypes may have greater declines in post-donation renal function compared to donors with low-risk genotypes. Transplant recipients’ post-donation renal function can be adversely impacted by donors with the high-risk APOL1 genotype as well. Studies such as NIH’s APOLLO are ongoing and should determine more specifically the effect of APOL1 gene risk variants in living donors and recipients.

In the meantime, there are 3 critical steps that health systems and hospitals can take to leverage APOL1 insights—which, by extension, will create a better understanding of kidney disease in African American population.

1. Education
   The first—and often missing—step is education. Health systems and hospitals should be raising awareness among their patient populations about APOL1 so they can make more educated decisions. This is especially important education for potential donors in the ethnic subgroups described above. One of the most significant publications thus far, the KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors, recommends that APOL1 genotyping be offered to donor candidates with sub-Saharan African ancestors. Donor candidates should be informed that having 2 APOL1 risk alleles increases the lifetime risk of kidney failure, and that that patients should be tested for the APOL1 risk variant and educated on the relative risk of kidney donation.
   
   An important note is that the risk of CKD, while real, is relatively low. Many kidney transplants from deceased donors with a high risk APOL1 genotype show good kidney function for a prolonged period. Lack of education about these issues creates a vacuum, and with donation rates among these ethnicities significantly lower than the rest of the general American population, it’s important to create an environment of open information sharing so potential donors and/or recipients don’t come to foregone conclusions about their odds of success.
   
   
2. Testing
   Testing for APOL1 is now widely available, though options do vary. Utilizing dual PCR Sanger sequencing delivers faster results compared to the next-generation sequencing (NGS) methodology. If your reference lab uses Sanger sequencing, confirm that they are also deploying several different dual primer sets for PCR amplification to verify the results.
   
   Of course, your reference lab also must have deep and demonstrable experience with genetic testing, so patients and nephrologists understand and receive proper instructions for sample collection: what sample type to collect, how to collect it, and when to collect it.
   
   
3. Communication
   The significance of the APOL1 test results varies significantly among different clinical settings and is still being actively studied. The APOL1 process is far from over when the test results are in. That’s why your reference lab should have an experienced genetic counselor team on staff, as well as pathologists and lab directors, who can accurately and sensitively answer all the questions which may arise before the test is ordered and after the physician has evaluated the results. This level of professional communication is key to creating a successful patient experience.

New information about risk can be interpreted as an opportunity. In the case of APOL1, there is such an opportunity for transplant clinicians, nephrologists, and other caregivers to start the conversation about where APOL1 fits into the bigger picture, specifically for African American and Hispanic Caribbean individuals and audiences.

This conversation includes creating clarity—this test is important and available; you must have 2 risk variants in APOL1, not just 1, to be higher-risk genotype—as well as context about crucial factors like comorbidities. Here, too, the health and economic benefits of discussing ways to decrease the incidence of comorbidities and the potential for future chronic disease through actions like diet and exercise apply to both donors and recipients.  

When we have conversations about topics like APOL1, we can begin to have a very real, positive impact not just on the lengthy kidney transplant waiting list, but also on the improvements to the overall health of donor and recipient as well.