FSGS: A rare kidney disease without targeted therapies

Focal Segmental Glomerulosclerosis (FSGS) is a long name for what’s essentially a serious filtering problem.

Without proper treatment, this rare kidney disease can lead to Nephrotic Syndrome, a disorder that causes too much protein to filter into urine. Nephrotic Syndrome leads to a host of other problems, ranging from malnutrition to high blood pressure to acute kidney failure.

Currently, we have medications to control symptoms. Aggressive therapies lead to remission in about 50% of cases¹. That researchers don’t know the precise cause of FSGS makes drug development that much more challenging.

What is FSGS?

The “glomerulosclerosis” of FSGS means scarring of the glomeruli. The glomeruli are tiny filters that circulate blood through the kidney. When the glomeruli become damaged, they can’t filter as well, which causes more protein to pass through to the urine.

“Focal” and “segmental” refer to the fact that not all glomeruli are damaged (focal), and not the entire glomeruli (segments) are scarred.

Who gets FSGS?

Both children and adults can get FSGS. It affects males slightly more often than females. In adults, it most often manifests at age 45 years or older. It occurs about twice as often in African Americans than Caucasians. People with a family member with FSGS have an increased risk of developing the disease.

FSGS accounts for about 40% of adults and 20% of children with Nephrotic Syndrome. About 5% to 20% of people with end-stage renal failure have FSGS.

FSGS currently affects about 80,000 people in the United States. However, studies show the number of people diagnosed with FSGS is climbing.

What causes FSGS?

No one knows for sure—a frustrating situation.

Doctors divide FSGS into two types: primary and secondary. Primary FSGS happens on its own for mysterious reasons. Researchers speculate that affected individuals have proteins called permeability factors in their blood that damage podocytes. That damage causes the glomeruli to leak protein into the urine.

Secondary FSGS manifests (possibly) from another medical condition such as:

• Kidney defects from birth
• Obesity
• Obstructive Sleep Apnea
• A disease such as Sickle Cell Anemia, Lupus, or Diabetes
• Viruses such as HIV
• Drugs, such as anabolic steroids, interferon and bisphosphonates
• A previous kidney injury

What are the signs and symptoms of FSGS?

In addition to an unknown cause, someone with FSGS may not have symptoms. As the disease progresses, however, they may experience the following:

• Swelling in the legs, ankles, around your eyes (edema).
• Large amount of foamy protein in urine (proteinuria).
• High fat lipid (cholesterol) levels in the blood.
• Low protein levels in the blood.
• High blood pressure in some cases.
• Kidney failure may occur around 10 years post-diagnosis.

How do doctors diagnose FSGS?

Doctors suspect FSGS when blood tests show elevated cholesterol levels, lowered protein levels and waste products in the blood. Blood tests can also determine glomerular filtration rate (GFR). The lower the GFR, the worse the kidney function. Urine tests show elevated levels of protein and possibly blood in the urine.

If blood and urine tests indicate the possibility of FSGS, the patient will undergo a kidney biopsy. A pathologist evaluates samples under a microscope to look for FSGS signs. Genetic testing can confirm or deny abnormal gene variants that may cause the disease.

How is FSGS treated?

There is no specific FSGS treatment. The overreaching goal is to improve proteinuria, which helps lower the odds of kidney disease or failure.

Supportive therapy helps control symptoms. A few therapies include:

• Corticosteroids, to suppress immune system activity.
• Immunosuppressive drugs, particularly if the disease has developed into Nephrotic Syndrome.
• Renin-angiotensin-aldosterone system (RAAS) inhibitors, angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) to control blood pressure, which helps lower the amount of protein in the urine.
• Rituximab, a cancer drug, sometimes used to treat patients with steroid-resistant Nephrotic Syndrome with FSGS.
• Diuretics, to relieve water retention (edema)
• A low-sodium diet, to relieve edema and possibly reduce blood pressure

Researchers are studying a few new and existing drugs to treat FSGS. For example, investigators are also testing two drugs—rosiglitazone (Avandia) and adalimumab (Humira)—as possible FSGS treatments.

FSGS needs a novel medication that regulates both high body fats and inflammasome inhibition via upstream innate immune system to block intracellular initiation of inflammatory cascade and extra cellular inflammation. If you’re pursuing this path, Biorasi can help.

Over the past five years, nearly 30% of Biorasi-initiated or ongoing studies involved chronic kidney disease. Our experience allows us to develop successful nephrology clinical trials.

Interesting in discussing rare kidney disease therapies? Get in touch.

Resources

1. Korbet, Stephen M. Treatment of Primary FSGS in Adults. JASN Nov. 2012, 23 (11) 1769-1776; DOI: https://doi.org/10.1681/ASN.2012040389