Focal Segmental Glomerulosclerosis (FSGS)

Focal segmental glomerulosclerosis (FSGS) is a rare type of glomerular kidney disease that causes scarring in your kidneys’ tiny filters. These filters (glomeruli) help remove waste and extra water from your blood. These substances leave your body in your pee. But if you have FSGS, parts of your glomeruli scar or harden (sclerosis). This affects how well your kidneys work. It can lead to kidney damage and possibly kidney failure.

“Focal segmental glomerulosclerosis” is a big name. But what does it mean?

• Focal: Scarring affects some, but not all, of the glomeruli.
• Segmental: Scarring affects specific parts (segments) of the glomeruli.
• Sclerosis: There’s hardening of tissue.

There isn’t a cure for FSGS. The goal of treatment is to keep your glomeruli healthy for as long as possible. Your treatment options depend on what type of FSGS you have. It may include lifestyle changes, medicines and therapies. In severe cases, you may need dialysis or a kidney transplant.

Types

The different types of focal segmental glomerulosclerosis include:

• Primary (idiopathic) FSGS: There’s no known reason or obvious cause for having FSGS.
• Secondary FSGS: Another condition or drug causes FSGS. Examples include infections, medications, recreational drug use, sickle cell disease and obesity.
• Genetic (familial or hereditary) FSGS: You inherit a genetic variation from one of your biological parents or randomly develop one.
• Unknown FSGS: Experts can’t identify a genetic or secondary cause. But it also doesn’t meet the criteria for primary FSGS.

What are the symptoms of FSGS?

Common symptoms include:

• Swelling in your arms, legs or face
• Sudden weight gain due to extra fluids in your body
• Extreme tiredness
• Foamy pee

Your healthcare provider may also discover signs like:

• High levels of protein in your pee (proteinuria)
• Low levels of protein in your blood (hypoproteinemia)
• High blood pressure (hypertension)
• High cholesterol (hyperlipidemia)

Causes

Primary FSGS doesn’t have an obvious cause. Experts believe your immune system may attack podocytes in your kidneys. Podocytes are cells that help manage what stays and goes as your kidneys filter blood.

Secondary FSGS happens when too much blood flows to your glomeruli. It develops due to another disease, medication or condition. Examples include:

• Diseases, like sickle cell disease, diabetes and lupus
• Medications, like non-steroidal anti-inflammatory drugs (NSAIDs), interferon, bisphosphonates, calcineurin inhibitors (CNIs), mammalian target of rapamycin (mTOR) inhibitors, pamidronate, lithium and anthracyclines
• Recreational drugs, like anabolic steroids and intravenous heroin
• Viral infections, like HIV, cytomegalovirus, hepatitis B and C, and parvovirus B19
• A body mass index (BMI) greater than 25 (having overweight/obesity)
• High blood pressure

Genetic FSGS can happen when the APOL1 gene changes during fetal development. Experts sometimes call this APOL1-associated FSGS.

Other genetic variations can put you at risk of FSGS. But these variations won’t cause FSGS unless you have exposure to a certain trigger. In some cases, this may include exposure to environmental factors like pollution or certain chemicals.

What are the risk factors?

Anyone of any age can have focal segmental glomerulosclerosis. But you may be at a higher risk if you’re:

• Male
• Between the ages of 18 and 45
• Black, especially if you have West African ancestry

What are the complications?

FSGS can lead to:

• High blood pressure
• High cholesterol
• Anemia
• Infections that go away and come back
• Blood clots
• Kidney failure

How doctors diagnose FSGS

Your healthcare provider may suspect kidney disease if kidney function tests show these organs aren’t working as well as expected. But the only way they can make an official focal segmental glomerulosclerosis diagnosis is to perform a kidney biopsy. They’ll remove a small piece of your kidney and look for signs of FSGS under a microscope.

Your provider may also recommend:

• Genetic testing to help confirm genetic FSGS, though this type of testing isn’t common
• Antibody and viral tests to help rule out some causes of secondary FSGS

What are the stages?

Healthcare providers may stage FSGS according to the glomerular area it affects:

• Perihilar variant: It affects more than 50% of the glomeruli in the vascular pole (hilum), where the blood vessels enter the glomerulus.
• Cellular variant: There’s inflammation and crowding of the cells inside the glomerulus.
• Tip variant: The scarring occurs at the tip of the glomerulus, where the glomerulus meets the urine tube.
• Collapsing variant: There’s a severe collapse of the capillary loops and an overgrowth of the visceral epithelial cells (podocytes) inside the glomerulus.
• Not otherwise specified (NOS) variant: The scarring doesn’t meet the criteria for any of the other classes.

How is FSGS treated?

In general, treatments may include:

• ACE inhibitors and ARBs to treat high blood pressure and slow kidney damage
• Sparsentan to help decrease protein levels in your pee
• Diuretics to help treat high blood pressure and reduce swelling by making you pee more often
• Immunosuppressants, including corticosteroids or calcineurin inhibitors, to help stop your immune system from attacking your glomeruli
• Treating the underlying cause, which may include stopping or changing a certain medication or treating an infection

Your healthcare provider may also recommend lifestyle changes, including:

• Eating kidney-friendly foods that are low in animal protein, sodium (salt), phosphorus and potassium, and higher in vegetable protein
• Getting regular physical activity
• Quitting smoking
• Taking certain vitamins
• Maintaining a healthy that’s weight for you

Treatments and lifestyle changes won’t cure or reverse focal segmental glomerulosclerosis. But they can help slow it down. Your provider will create a treatment plan for you according to the type and cause of FSGS, your age and any other health conditions you have.

When should I see my healthcare provider?

Focal segmental glomerulosclerosis may not cause symptoms that you’ll easily notice on your own. But contact your provider if you have symptoms of severe kidney disease, including:

• Nausea
• Vomiting
• Loss of appetite
• Unexplained swelling in your arms, legs or face
• Foamy pee

What is the prognosis for FSGS?

There’s no cure, and the outlook varies. For some people, kidney function remains stable after treatment. For others, FSGS can be life-threatening if it progresses to kidney failure.

If FSGS causes kidney failure, you’ll need dialysis or a kidney transplant to stay alive. There’s a risk that it can come back after a kidney transplant. This is called recurrent FSGS. Your provider will schedule regular tests to check for any signs that it has returned. Recurrent FSGS treatment may include plasmapheresis.

Many people with FSGS still lead active lives. To help ensure the best outcome, it’s important to keep your appointments, take your medications exactly as prescribed, eat kidney-friendly foods and get plenty of physical activity.