Chronic kidney disease in African Americans: Puzzle pieces are falling into place
ABSTRACT
Recent decades have seen great advances in the understanding of chronic kidney disease, spurred by standardizing disease definitions and large-scale patient surveillance. African Americans are disproportionately affected by the disease, and recently discovered genetic variants in APOL1 that protect against sleeping sickness in Africa provide an important explanation for the increased burden. Studies are now under way to determine if genetic testing of African American transplant donors and recipients is advisable.
KEY POINTS
- Patients with chronic kidney disease are more likely to die than to progress to end-stage disease, and cardiovascular disease and cancer are the leading causes of death.
- As kidney function declines, the chance of dying from cardiovascular disease increases.
- African Americans tend to develop kidney disease at a younger age than whites and are much more likely to progress to dialysis.
- About 15% of African Americans are homozygous for a variant of the APOL1 gene. They are more likely to develop kidney disease and to have worse outcomes.
Genetic testing advisable?
Genetic testing for APOL1 risk variants is on the horizon for kidney transplant. But at this point, providing guidance for patients can be tricky. Two case studies27,28 and epidemiologic data suggest that donors homozygous for an APOL1 variant and those with a family history of end-stage kidney disease are at increased risk of chronic kidney disease. Even so, most recipients even of these high-risk organs have good outcomes. If an African American patient needs a kidney and his or her sibling offers one, it is difficult to advise against it when the evidence is weak for immediate risk and when other options may not be readily available. Further investigation is clearly needed into whether APOL1 variants and other biomarkers can predict an organ’s success as a transplant.
The National Institutes of Health are currently funding prospective longitudinal studies with the APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) to determine the impact of APOL1 genetic factors on transplant recipients as well as on living donors. Possible second hits will also be studied, as will other markers of renal dysfunction or disease in donors. Researchers are actively investigating these important questions.
KEEPING SCIENCE RELEVANT
In a recent commentary related to the murine knockout model of APOL1-associated kidney disease, O’Toole et al offered insightful observations regarding the potential clinical impact of these new genetic discoveries.23
As we study the genetics of kidney disease in African American patients, we should keep in mind 3 critical questions of clinical importance:
Will findings identify better treatments for chronic kidney disease? The AASK trial found that knowing the genetics did not affect outcomes of routine therapy. However, basic science investigations are currently underway targeting APOL1 variants which might reduce the increased kidney disease risk among people of African descent.
Should patients be genotyped for APOL1 risk variants? For patients with chronic kidney disease, it does not seem useful at this time. But for renal transplant donors, the answer is probably yes.
How does this discovery help us to understand our patients better? The implications are enormous for combatting the assumptions that rapid chronic kidney disease progression reflects poor patient compliance or other socioeconomic factors. We now understand that genetics, at least in part, drives renal disease outcomes in African American patients.
