APOL1-mediated kidney disease background
Kidney failure occurs in Black Americans about three times as much as it does in white Americans. There are many reasons for this increased risk, including genetic changes known as "risk variants" that were discovered in 2010 in the APOL1 gene.
What is APOL1?
APOL1 normally plays a role in immunity and is specifically protective against the trypanosoma parasite that causes African sleeping sickness. The APOL1 gene evolved specific changes over the past 10,000 years in people in parts of Africa that provide increased protection from this parasite. People who have moved outside of Africa have taken these genetic variants with them. While these APOL1 variants are protective from parasite infection, people with two APOL1variants, also known as “kidney risk variants,” have an increased risk for kidney disease.
Today, APOL1 risk variants occur in people of African ancestry who may self-identify as Black, African American, African, Afro-Caribbean, Hispanic, or Latino. It is important to think broadly about your ancestry since many people do not know their genealogy. Approximately 13% of Black Americans have two APOL1 kidney risk variants compared to less than 0.1% for other races. It is estimated that about 15 to 20 percent of patients with two APOL1 kidney risk variants will develop kidney disease in their lifetime.
What are the clinical signs of APOL1-mediated kidney disease?
APOL1-mediated kidney disease (AMKD) causes injury to the filtering portion of the kidney known as the glomerulus. This injury leads to proteinuria (high levels of protein in your urine) and declining kidney function which leads to symptoms, including swelling of the legs and feet, fatigue, and changes in urination, among others. APOL1-mediated kidney disease commonly is associated with high blood pressure but is usually not associated with diabetes.
How is APOL1-mediated kidney disease diagnosed?
Your doctor may decide to use different tests to diagnose APOL1-mediated kidney disease depending on your symptoms. Blood and urine tests can be used to measure kidney function and for proteinuria. A kidney biopsy can sometimes help to gain a better picture of the cause of kidney injury. Genetic testing for the APOL1 kidney risk variants is required to know with certainty if your kidney disease is APOL1-mediated kidney disease.
How is APOL1-mediated kidney disease treated?
There are no currently approved treatments specific to APOL1-mediated kidney disease. While there is a current standard of care treatments for kidney patients, there are no targeted therapies for AMKD and these patients often progress.
Why should a person undergo genetic testing if APOL1-mediated kidney disease is suspected?
Testing for APOL1 kidney risk variants is performed to further determine what is causing nondiabetic kidney disease in Black Americans before attributing it to other causes, like high blood pressure. The knowledge that APOL1 is the cause of disease would allow specific treatments and/or potential enrollment in clinical trials when they become available. Additionally, the diagnosis of APOL1-mediated kidney disease provides prognostic information and could be important in evaluating kidney donors with African ancestry. Vertex Pharmaceuticals is sponsoring the No Cost to Patient APOL1Genotyping Program to provide an Arkana Laboratories APOL1-risk variant test to eligible* patients.
What are the risks of genetic testing?
Genetic testing provides useful information about the underlying cause of disease. It is good to be aware that testing of multiple family members can rarely reveal unanticipated information about family member’s biological relationships. For example, the stated father of an individual may not be the true biological father.
*Who is eligible for the No Cost to Patient APOL1 Genotyping Program?
APOL1-risk variant testing is available at no cost to patients who meet all of the following criteria:
- Self-reported race as Black, African American, African, Afro-Caribbean, Hispanic, or Latino
- History of either protein in urine or decreased kidney function
- Absence of diabetes mellitus
- Not currently on dialysis and no history of kidney transplant