Focal segmental glomerulosclerosis (FSGS): symptoms, causes and treatment

What is focal segmental glomerulosclerosis (FSGS)?

FSGS is a rare kidney disease that causes scarring in the tiny filters in your kidneys, called glomeruli, that clean your blood. When some of these filters become scarred, your kidneys cannot work as well to filter waste and extra fluid from your blood. Over time, it may be harder for your kidneys to function, and can lead to kidney failure, also called end-stage renal disease (ESRD) or end-stage kidney disease (ESKD). 

While FSGS can occur in children and adults, men are slightly more likely to develop FSGS, and it is more common in people who are Black or African American. 

What are the signs and symptoms of FSGS?

In the early stages of FSGS, you may not notice any symptoms. 

As FSGS gets worse, you may start to notice:

• Swelling in your legs, ankles, feet or around your eyes
• Sudden weight gain from fluid buildup
• Feeling more tired than usual from waste buildup
• Foamy or bubbly urine (pee) from protein loss in urine
• Dark or cola-colored urine

Some people may also develop high blood pressure, which can further damage your kidneys if not treated.

FSGS can cause nephrotic syndrome. Nephrotic syndrome is a group of symptoms, such as edema or swelling in your legs, feet and ankles or in your face and hands, foamy urine and weight gain, that happen when your kidneys are leaking large amounts of protein. Nephrotic syndrome can also cause high fat levels in your blood (hyperlipidemia), an increased risk of blood clots (hypercoagulability), and an increased risk of infections.

 Your doctor can find signs of disease through tests that look at: 

• Protein in your urine (proteinuria)
• Low protein levels in your blood (hypoproteinemia)
• High cholesterol or high fat levels in your blood 

Having one or more of these symptoms does not mean you have FSGS. If you start to notice one or more of these symptoms, it's important that you talk to your doctor. If you notice worsening swelling, very foamy urine or sudden weight gain, call your doctor right away.

Will I have kidney failure because of FSGS?

FSGS is a long-term (chronic) condition with scarring and kidney damage that cannot be reversed. However, many people are able to slow disease progression and protect their kidney function with treatment and regular follow-ups.

Over half of people with FSGS develop kidney failure over time, but this can depend on the type of FSGS you have, how early it is found and how well treatments work for you. 

If FSGS progresses to kidney failure, treatment options like dialysis or a kidney transplant may help you. FSGS can sometimes come back after a kidney transplant. This is called recurrence and happens in about 50% of people with primary FSGS. If it comes back, treatments such as plasma exchange and certain medicines may help control it. 

What causes FSGS?

FSGS is a rare kidney disease. Doctors diagnose about 7 out of every 1 million people each year. The exact causes of FSGS can vary. Some people develop FSGS for reasons that are still unknown. Other people may have inherited it from one's family or developed it because of another health condition, certain medicines, infections, or changes and problems in their kidneys structure.

What are the different types of FSGS?

Doctors group FSGS into different types based on what causes it: 

Primary FSGS: Happens without a clear or known cause. It is immune-mediated, which means the immune system attacks and damages podocytes (the cells that filter waste from the blood in the kidneys).

• Primary FSGS can cause:
• high levels of protein in the urine
• low levels of protein in the blood
• high cholesterol
• swelling
• high blood pressure

Secondary FSGS: Happens because of another health condition or outside factor, such as:

• How your kidneys are formed at birth
• Certain medicines, like non-steroidal anti-inflammatory drugs (NSAIDs), lithium, anti-cancer drugs, interferon, or bisphosphonates for bone health
• Viral infections like human immunodeficiency viruses (HIV), Cytomegalovirus (CMV), Parvovirus, or COVID-19
• Use of recreational drugs, like heroin and anabolic steroids
• Obesity (can increase stress on the filters of the kidneys)
• High blood pressure
• Sickle cell disease

In secondary FSGS, treating and managing the underlying cause can help to slow down ongoing kidney damage. 

• Genetic (familial or hereditary) FSGS: Caused by a gene mutation (change) that can be passed down through your family. If any of your family members have FSGS or show symptoms of it, it may be genetic. Genetic FSGS can appear early in life with more severe symptoms or show up later with milder symptoms. Genetic testing and counseling can help identify this type.

How will I know if I have FSGS?

The only way to confirm FSGS is with a kidney biopsy. During a kidney biopsy, your doctor will perform a procedure using a needle and imaging, such as an ultrasound or CT, to take a tiny piece of your kidney tissue to look at it closely under a microscope.

This is important because many kidney diseases can look similar on lab tests. A kidney biopsy can tell your doctor if you have FSGS and help identify the exact type to decide the best treatment for you. 

Your doctor may also do other tests, including:

• Blood tests –eGFR (estimated glomerular filtration rate) to check how well your kidneys are working.
• Urine tests –
  • uACR: (albumin-to-creatinine ratio) to measure the amount of albumin (a type of protein) in your urine compared to the level of creatinine (a waste product) to determine how well your kidneys are working.
  • uPCR (protein-to-creatinine ratio) to measure all total proteins, including albumin, in your urine compared to the level of creatinine to determine how well your kidneys are working
• Genetic testing- to see if you were born with a change (or mutation) in your DNA that determines your risk of certain gene variants, like the APOL1 gene, that can cause FSGS. There are multiple genetic causes of FSGS, including APOL1-Mediated Kidney Disease (AMKD).
• Serology or viral testing to rule out secondary causes of FSGS

Primary FSGS treatment

Treatment usually includes immunosuppressants, which are medicines that help lower the activity of the immune system and reduce inflammation. These may include glucocorticoids (often called "steroids") or calcineurin inhibitors. 

Secondary FSGS treatment

During treatment can include:

• Treating the underlying condition that caused FSGS, such as stopping a certain medicine or treating an infection.
• Managing health conditions like high blood pressure or obesity
• Anti-retroviral (ARV) medicines for HIV-associated FSGS
• Stopping or changing a certain medicine that is affecting kidney function

Recurring FSGS treatment

If you have recurring FSGS (FSGS that returns after a transplant) your doctor may recommend a procedure called plasmapheresis (also known as plasma exchange or "PLEX") as a treatment option. This is a procedure where a plasmapheresis machine separates plasma (the liquid part of the blood) from the blood cells and it may involve placing a central venous catheter, or "central line," which is when a thin flexible tube is placed in a vein to draw blood. 

During this procedure, blood is taken from the body and sent through the machine that separates the plasma from the rest of the blood. The old plasma is removed (which may contain harmful substances), and it is then replaced with plasma from a donor (which includes helpful substances like albumin, clotting factors, and other fluids). The treated blood and new plasma are then returned to the body. This procedure has been shown to help decrease protein loss in the urine (proteinuria) and may also help to improve response to other FSGS treatments. Some people may have several treatments over a few weeks, depending on the response to the treatments. Plasma exchange is a safe procedure, but some people may have side effects that include low calcium levels, low body temperature and low blood pressure. 

Other treatments for recurring FSGS include Lipoprotein apheresis (also called LDL apheresis), which removes certain fats and substances from the blood, and medicines, such as rituximab, that help control the immune system. Your transplant team will monitor you closely after surgery so that if recurrence happens, treatment can begin as soon as possible. 

Your treatment plan will be unique to you and your condition. Talk with your doctor about other medicines and your options to help treat FSGS.

Living with FSGS

Living with FSGS means working closely with your healthcare team and taking steps to protect your kidneys. Taking your medicines exactly as your doctor tells you, watching for changes in swelling or weight, staying active and following a kidney-friendly eating plan can help you manage symptoms and support your overall health.

It's important to have regular visits with your doctor to monitor your health and check for any changes. This can help catch problems early and adjust your treatments. Your doctor may also have you do regular blood and urine tests to track how well your kidneys are working. 

Where can I learn more about FSGS?

• UNC Kennedy Center
• Mayo Clinic
• Clinical trials