What is APOL1-mediated kidney disease (AMKD)?

The APOL1 gene is part of the APOL gene family, which plays a role in immunity, our body’s built-in system to fight threats. We all have the APOL1 gene, and it’s present in many tissues, including the kidneys. APOL1 stands for apolipoprotein L1.

Over the past 3,000 to 10,000 years, the gene evolved in specific ways in people who lived in Western and Central Africa, to protect them from resistant forms of the parasite that causes African human trypanosomiasis.

As people from these regions have migrated around the world, they have taken these certain genetic variants in the APOL1 gene with them. Today, people of African ancestry may carry these APOL1 variants, including (but not limited to) people who identify as Black, African American, Afro-Caribbean and Latino/Latina.

Having two variants in the APOL1 gene is associated with increased risk of kidney disease, known as APOL1-mediated kidney disease (AMKD). AMKD can have various clinical presentations including (but not limited to) focal segmental glomerulosclerosis (FSGS), hypertension-attributed kidney disease, membranous nephropathy, or nephrotic syndrome.

What is AMKD? 

AMKD is a genetic kidney disease associated with certain variants of the APOL1 gene, which exert a toxic effect on kidney cells, leading to cell injury, cell death, and damage to glomeruli (which filter blood to the kidney). This damage leads to loss of protein in the urine and deteriorating kidney function. This can cause a number of symptoms, including fatigue, swelling in the legs and feet, and weight gain.

There are currently no approved treatments that address the underlying cause of AMKD. Even with treatment, people with AMKD often progress to kidney failure. Kidney failure is treated with frequent, long-term dialysis or a kidney transplant. Both require lifelong treatment and follow-up and carry a high mortality risk.

How is AMKD diagnosed? 

Tests to diagnose AMKD usually include blood and urine tests (to check for proteinuria and to measure kidney function). A kidney biopsy may be required to better understand the nature of the kidney injury, and a genetic test is needed to identify whether a person has two APOL1 variants.

What is the underlying cause of disease? 

In people living with two APOL1 variants, an inflammatory exposure (like an infection) can increase the toxic activity of the APOL1 protein in the kidney, which can lead to kidney cell injury, cell death and damage to the glomeruli (which filter blood in the kidney). This leads to abnormal amounts of protein in the urine (or proteinuria) and decreased ability of the kidney to function.

Summary

We have described what is APOL1-mediated kidney disease (AMKD). We hope it has been helpful.

Other resource

This is a good review article: Daneshpajouhnejad, 2022