What Is Focal Segmental Glomerulosclerosis (FSGS)?

Focal segmental glomerulosclerosis (FSGS) is a rare type of kidney disease marked by scarring (thickening or hardening) of your glomeruli, the tiny filters in your kidneys. This scarring leads to a buildup of waste products, which can lead to health issues such as kidney failure.

Types of FSGS

There are approximately one million glomeruli in the kidneys, but the scarring from FSGS doesn’t develop on all of them. The condition is known as “focal segmental glomerulosclerosis” because the scarring affects only some glomeruli (focal) and of these, only a portion of each glomerulus (segmental).

There are a few main types of FSGS.

• Primary (idiopathic) FSGS is thought to be associated with an immune system abnormality that damages or dysregulates podocytes, specialized cells that support glomeruli, although experts aren’t entirely sure.

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• Secondary FSGS develops from a wide range of other conditions, such as obesity, diabetes, sickle cell disease, HIV infection, heroin use, and other kidney diseases. Controlling or treating the underlying condition can often help treat secondary FSGS.

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• Genetic FSGS is a rare hereditary form of FSGS caused by genetic mutations. You can develop genetic FSGS if both of your parents carry one or both copies of the altered gene, even if they do not have FSGS.

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Signs and Symptoms of FSGS

FSGS doesn’t always cause noticeable symptoms, but most people experience one or more of the following signs or symptoms.

• Foamy or bubbly urine (caused by excess protein)

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• Edema (swelling) in the legs, ankles, feet, or around the eyes
• Sudden, unexplained weight gain
• Fatigue
• Loss of appetite
• Increased risk of infection

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• High blood pressure
• High cholesterol

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Causes and Risk Factors of FSGS

There are several different causes of FSGS, which differ by type.

• Obesity
• Sickle cell disease
• Systemic diseases like diabetes, lupus, and high blood pressure
• Intravenous heroin use
• Other drug use, including lithium, anabolic steroids, and chemotherapy drugs called anthracyclines
• HIV and other viral infections, such as hepatitis B and C, parvovirus, and COVID-19
• Other kidney diseases

With genetic FSGS, certain mutations can affect the glomeruli, particularly mutations on the APOL1 gene. This can increase a person's risk of FSGS.

How Is FSGS Diagnosed?

• Urine tests to measure the amount of protein and other substances in your urine
• Blood tests to assess your kidney function and the levels of waste products in your blood
• Estimated glomerular filtration rate (eGFR), a specific blood test that measures how well your kidneys are filtering wastes from your body

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• Kidney biopsy, during which a tiny tissue sample is collected from your kidney and inspected under a microscope. This is the only way to definitively diagnose FSGS
• Genetic testing, rarely, to determine whether you have genetic FSGS

Treatment and Medication Options for FSGS

FSGS is treatable, but not curable, since scarred glomeruli cannot be repaired. The current FSGS treatments work by helping to control symptoms and protect glomeruli, which can slow disease progression and achieve remission.

Medication Options for FSGS

Immunosuppressants

If steroids are not fully effective or the side effects are too severe, your doctor may recommend another type of immunosuppressant drug called calcineurin inhibitors (CNIs), which includes cyclosporine (Gengraf, Neoral, Sandimmune) and tacrolimus (Astagraf XL, Envarsus XR). These drugs require close monitoring.

• mycophenolate mofetil (Cellcept, Myhibbin)
• rituximab (Riabni, Rituxan)
• obinutuzumab (Gazyva)
• cyclophosphamide (Cytoxan)
• adrenocorticotropic hormone (ACTH)

Medications for Symptom Management

• Angiotensin-converting enzyme (ACE) inhibitors or angiotensin 2 receptor blockers (ARBs) to reduce blood pressure and proteinuria (these drugs should not be used with sparsentan)
• Diuretics to remove excess salt and water from the body, decreasing swelling and blood pressure
• Antibiotics like penicillin to prevent or treat infections

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• Statins or other medications to lower cholesterol

Other Treatment Options

If FSGS progresses, you may require treatments such as a kidney transplant. Sometimes, FSGS comes back after a kidney transplant, which is known as recurrence. If this occurs, you may receive plasmapheresis or other medications.

Kidney Transplant

A kidney transplant is a procedure that places a healthy kidney from a living or deceased donor into a person whose kidneys are no longer working effectively (for example, in someone who has kidney failure).

Plasmapheresis

Lifestyle Changes and Prevention of FSGS

There are no preventive measures for primary and genetic FSGS. But you can take steps to reduce your risk of some forms of secondary FSGS, such as by maintaining a healthy weight, treating underlying conditions that may cause FSGS, and avoiding heroin use.

• Quit smoking.
• Avoid certain medications that may harm the kidneys (unless recommended by your provider), such as over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen, blood-thinners or anticoagulants, and antimicrobial drugs.

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• Maintain a healthy weight for your body.
• Exercise regularly.
• Follow a kidney-healthy diet that’s high in fruits and vegetables and low in sodium.
• Monitor your intake of sodium, protein, fat, cholesterol, and fluid, maintaining levels recommended by your provider or a registered dietitian.
• Keep blood sugar levels under control.

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• Reduce alcohol consumption.
• Manage stress levels.

FSGS Prognosis

Complications of FSGS

• High blood pressure
• Anemia (low levels of healthy red blood cells)
• Blood clots in the veins (venous thromboembolism)
• Blood clots in the capillaries or arteries (thrombotic microangiopathy)
• Recurrent infections
• Malnutrition

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• Nephrotic syndrome
• Kidney failure or end-stage kidney disease

The Takeaway

• FSGS is a potentially life-threatening disease that affects the kidneys. Without adequate treatment, it can lead to kidney failure.
• It’s not known what causes all types of FSGS, but some are caused by genetic mutations, while others are caused by secondary conditions such as viral infections and obesity.
• While there is no cure for FSGS and the prognosis can vary, there are treatments available that can help you achieve partial or complete remission.