African-Americans have a four-to-five-times higher rate of end-stage renal disease than populations without African ancestry. In this population two genetic changes (risk variants) in the APOL1 gene known as G1 and G2 account for nearly all of the increased risk of non-diabetic kidney disease. These variants are common in African Americans (30% with a single risk variant; 13% with two risk variants), but rare in individuals without African ancestry. The G1 and G2 risk variants never occur on the same genetic string (chromosome) and therefore an individual can carry no more than two risk alleles (i.e. G1/G1, G1/G2, or G2/G2). The risk of APOL1-mediated kidney disease increases with the number of risk alleles (i.e. dose-related pattern): no risk for zero variants (G0/G0), lower risk for single risk variants (G1/G0, G2/G0) and high risk for two risk variants (G1/G1, G2/G2 and G1/G2).

A genetic change in the APOL1 gene designated “M1” or “N264K” was recently found to be protective against the G2 risk variant when present on the same chromosome. This combination is designated G2-M1. Testing for this variant is warranted in patients identified to have G1/G2 or G2/G2 high-risk genotypes as G1/G2-M1, G2/G2-M1, and G2-M1/G2-M1 clinically behave as lower risk genotypes.

Reasons to test for APOL1 genotyping include:

• Determining the cause of kidney disease in patients with possible African ancestry
• Determining risk status in patients with possible African ancestry
• Individuals being considered for kidney donation
• Determination of APOL1 status in a family member
• Biopsy findings that suggest APOL1-mediated kidney disease

No Cost to Patients APOL1 Genotyping Test Program

Arkana Laboratories and Vertex Pharmaceuticals are working together to increase awareness of APOL1-mediated kidney disease by making it possible for healthcare providers to order APOL1-risk variant testing at no cost in qualifying patients.

For more information on this program or to download the No Cost to Patients APOL1 Genotyping Test requisition form, click the links below.

Information for physicians on No Cost to Patient APOL1 Genotyping Test

Information for patients on No Cost to Patient APOL1 Genotyping Test

APOL1-Mediated Kidney Disease Background

Kidney failure occurs in Black Americans about four 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 APOL1 variants, 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.

The reason why only some individuals with two risk variants develop APOL1-mediated kidney disease (AMKD) is not completely known but is felt to be due to a combination of 1) an individual’s other potentially protective genetic factors and 2) exposure to environmental triggers. Along these lines, a DNA change was recently identified that was protective against one of the APOL1 risk variants.

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 (abnormal levels of protein in your urine) and declining kidney function which can lead 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 and sometimes 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 kidney disease in patients with African ancestry 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 APOL1 Genotyping 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 of the risks of genetic testing as well. These risks will be discussed in detail during your pre-test genetic counseling appointment with your genetic counselor. Any individual considering genetic testing should understand these factors before deciding to pursue genetic testing.