Focal Segmental Glomerulosclerosis (FSGS)

Authors: Tejwinder Sandhu, Touro University - California, US

What are the kidneys and what do they do?

The kidneys are two bean-shaped structures located on either side of the backbone. Kidneys play a very important role in the human body.

Each kidney has a million little filters (called glomeruli) that act as a sieve. As blood flows through these filters, the good things (like red blood cells, protein, sugar, etc.) are retained while excess water and waste products are removed via urine.

The kidneys also maintain our blood pressure, provide building blocks to maintain our red blood cells (hemoglobin), and also activate vitamin D to maintain healthy bones.

What is Focal Segmental Glomerulosclerosis (FSGS)?

Focal segmental glomerulosclerosis (FSGS) is a collection of many types of kidney disorders characterized by scarring of glomeruli, which are tiny filters in the kidneys that help remove waste and excess fluids from the blood. FSGS is one of the leading causes of glomerular disease in the United States and is the second leading cause globally. The exact number of people with this disease is difficult to measure. However, new cases of FSGS have been increasing around the world.

“Focal” and “segmental” describe where the scarring occurs. Focal means that only a few glomeruli in the kidneys are affected. Segmental means only a portion of the individual glomerulus is scarred. Sclerosis means scar. Therefore, Focal Segmental Glomerulosclerosis affects a few of all glomeruli and only scars a portion of these glomeruli. This scarring ultimately results in the leakage of protein into the urine and progressive loss of kidney function.

What are the causes of FSGS?

There are many causes of FSGS. Some of the leading causes are:

Primary FSGS: This is due to an autoimmune reaction and can respond to therapy if diagnosed early.
Genetic FSGS: The disease occurs due to a defective gene. Several genes and genetic mutations have been identified that can lead to FSGS.
APOL1-mediated kidney disease: One of the mutations includes a defect in the APOL1 gene which is more commonly seen in people of recent African descent. The presence of mutations in this gene protects against infection from trypanosomes but, unfortunately, increases susceptibility to kidney injury due to other events (other infections, inflammation, lupus), leading to kidney damage over the lifetime.
Drug-induced FSGS: Certain medications and illicit drugs can cause FSGS.
Viruses: Certain viral infections can result in FSGS.
Adaptive FSGS: There are many causes of adaptive FSGS, such as diabetes, high blood pressure, obesity, birth defects in the kidney, and sickle cell anemia.

Who is at risk for FSGS?

Depending on the cause, FSGS can be seen in men and women of all ages and ethnicities. Children and young patients are more likely to have genetic forms of FSGS, whereas patients of recent African descent are more likely to have APOL1-mediated kidney disease. FSGS is also linked to various diseases and conditions, including diabetes, obesity, sickle cell disease, viral infections, and certain medications and drugs.

What are the signs and symptoms of Focal Segmental Glomerulosclerosis or APOL1-mediated kidney disease?

Signs and symptoms of focal segmental glomerulosclerosis or APOL1-mediated kidney disease may include:

Foamy urine due to protein present in urine
Swelling (edema) throughout the body, including legs and face
Weight gain due to excess fluid in the body
High blood cholesterol
High blood pressure
Fatigue

How can I prevent developing FSGS?

There is no known preventative therapy for FSGS, but clinical trials are underway. However, following a healthy lifestyle that includes a low-fat and low-sodium diet will improve kidney health and could control symptoms of FSGS. It is essential to manage underlying diseases such as diabetes, sickle cell anemia, obesity, and viral infection to protect kidneys from developing FSGS.

What tests will my doctor perform to diagnose Focal Segmental Glomerulosclerosis and APOL1-mediated Kidney Disease?

FSGS is a pattern of injury to the kidney filters observed on a kidney biopsy. A kidney biopsy is a procedure where a doctor will take a small sample of kidney tissue using a needle and study the sample under a microscope. Your doctor will put these findings together with your clinical presentation to identify the underlying cause of the disease.

To confirm whether the FSGS seen on the biopsy is due to a genetic mutation in the APOL1 gene (APOL1-mediated kidney disease) or due to other genetic causes, genetic testing needs to be performed.

Your doctor will arrange for specific blood and urine tests along with a kidney ultrasound scan and a kidney biopsy to confirm the diagnosis and determine a possible cause.

Treatment of FSGS

Treatment for FSGS is dependent on the cause of the disease, either primary or secondary such as due to genetic cause.

Typically primary FSGS treatment involves immunosuppressive medications. Sometimes, several immunosuppressive medications may be required.

For APOL1-mediated kidney disease, several clinical trials are currently under way to find a treatment.

For secondary forms of the disease, treatment is usually directed at the underlying cause. For example, if your doctor suspects an infection causes the disease, treatment is targeted at the infection.

For any form of FSGS, your doctor will likely give you medications to control your blood pressure, reduce the amount of protein leaking into the urine, reduce swelling (using diuretics), maintain your cholesterol levels, and prevent blood clots (using anti-coagulant medications). Your doctor will also advise you to maintain a healthy lifestyle, follow a low-salt diet, quit smoking, and exercise regularly.

If the disease progresses or presents in an advanced stage, your doctor will discuss kidney replacement therapy options with you, including dialysis and kidney transplantation. Your doctor may also offer you the option of enrolling in a clinical trial.

It is important for anyone experiencing symptoms suspicious of FSGS to see a doctor for proper diagnosis and treatment. Early intervention may help prevent complications and improve the chances of a successful outcome.

Will I develop kidney failure if I have FSGS?

Developing kidney failure is, unfortunately, a possibility for those suffering from FSGS. Depending on the underlying cause, about 40-50% of patients may not have an adequate response to treatment and may progress to kidney failure, in which case your doctor will discuss the options of dialysis and/or kidney transplantation.

Your doctor will also discuss the risk of the disease recurring after kidney transplantation (this risk is often high in those with primary FSGS but unlikely for genetic or secondary causes).

Clinical trials for FSGS:

New treatments and therapies are being developed for kidney diseases. Ask your doctor if you are interested in participating in a clinical trial for Focal Segmental Glomerulosclerosis. More information is available at: www.enrollmypatient.org