Focal segmental glomerulosclerosis: Understanding a rare kidney disease

Focal segmental glomerulosclerosis (FSGS) describes a “pattern of injury” that is observable with a microscope when examining a biopsy of kidney tissue. Namely, this specific pattern of injury appears as scar tissue in the glomeruli — the tiny blood vessels that filter waste from the blood.

FSGS is not a specific disease process. Rather, it can be the result of a wide array of other conditions. There are a few different ways experts refer to FSGS. You may hear it called a kidney disease or glomerular disease, or you may hear a healthcare professional describe it as a lesion or a pattern of injury in the kidney. What’s important to understand is that scar tissue is developing, and that may affect kidney function over time.

The National Organization for Rare Diseases reports that, out of every 1 million people, only 7 are estimated to have FSGS. And although the condition is most common in adults over age 45, children also can be affected.

If you’re a caregiver or family member of a child with FSGS, you may feel overwhelmed by the diagnosis. You may wonder how FSGS will affect your child’s life, what medicines are available or why your child developed kidney issues in the first place. But the more you understand about FSGS, the easier it can be to make a plan and understand the treatment options available.

Below, Fernando C. Fervenza, M.D., Ph.D., a nephrologist and FSGS researcher at Mayo Clinic in Rochester, Minnesota, answers your questions.

FSGS affects the kidney’s glomeruli and, as a result, it is considered a type of glomerular disease.

Glomerular diseases affect the kidneys’ glomeruli — the dense network of tiny blood vessels the kidneys use to filter waste from the blood. Other glomerular diseases include IgA nephropathy and complement 3 glomerulopathy.

FSGS happens when the glomeruli harden or develop scar tissue. The term “sclerosis” in glomerulosclerosis refers to the hardening, scarring or thickening of tissue. As this scar tissue builds up, the glomeruli may be unable to filter the blood as efficiently.

Symptoms of FSGS include:

• Edema, which is swelling in the legs, ankles, face and other body parts.
• Weight gain.
• Low protein (albumin) levels in the blood.
• Proteinuria, which is too much protein in the urine. This gives urine a foamy appearance.

As a note of caution, Dr. Fervenza says that if your child has foamy urine, blood in the urine, increased swelling in the legs and feet, or facial swelling — especially upon waking in the morning — you should contact your child’s healthcare team immediately. These are all signs of nephrotic syndrome, a potential complication of FSGS. Nephrotic syndrome develops when too much protein is passed in the urine. Nephrotic syndrome may lead to increased risk of blood clots and high cholesterol. FSGS causes an estimated 20% of all nephrotic syndrome occurrences in children.

Finally, it’s important to understand that scar tissue can lead to progressive kidney damage and, in some situations, kidney failure. Kidney failure means the kidneys can no longer keep up with the demands of the body. As a result, the body retains dangerous amounts of waste, electrolytes and fluids. People with kidney failure require dialysis or an organ transplant to stay alive.It is estimated that 10% to 15% of children who develop kidney failure have FSGS.

However, there are treatments available for some forms of FSGS that can help prevent disease progression and lower the risk of kidney failure. For some, complete or partial remission from FSGS is possible.

There are four types of FSGS — primary, secondary, genetic and unknown. Understanding the type and cause of FSGS is critical because that determines the best treatment strategies moving forward, Dr. Fervenza says.

Also called idiopathic FSGS, this type is thought to be caused by certain circulating molecules that damage and dysregulate podocytes — the specialized kidney cells that line the surface of the glomeruli. Although researchers are still working to identify the exact molecules responsible, primary FSGS may be associated with certain proteins, including antibodies and chemical messengers called cytokines. Often, people with primary FSGS experience a sudden onset of nephrotic syndrome, low serum albumin in the blood, edema and proteinuria.

This type of FSGS can have a number of causes, including drug toxicity and misuse, chronic conditions such as sickle cell anemia and diabetes, or even other kidney conditions. Certain infections, such as HIV, hepatitis B, hepatitis C and COVID-19, can cause FSGS. Usually, people with secondary FSGS develop proteinuria and hypertension over time.

But Dr. Fervenza adds that children born with a single kidney, those with a low birth weight or those who have been diagnosed with reflux nephropathy have a higher risk of secondary FSGS.

Also called familial FSGS, this type is caused by genetic variances that affect the podocytes or glomerular membrane proteins. The genetic variances can be passed down from parent to child. Symptoms of genetic FSGS may be present at birth or develop at an early age, and children often develop severe nephrotic syndrome. Dr. Fervenza recommends that parents seek out genetic analysis for their child with FSGS — especially if the child has nephrotic syndrome and doesn’t respond to immunosuppressive therapies.

Sometimes it may not be possible to determine the cause of FSGS even after testing and evaluation. In these situations, FSGS is considered to be of an indeterminate cause.A guide for parents — What to ask your care team about focal segmental glomerulosclerosisAs your family navigates an FSGS diagnosis, consider connecting with reputable organizations such as the National Kidney Foundation, NephCure and the American Association of Kidney Patients. They can offer free educational guides, support groups and practical resources.

Your care team also can help you understand your options and refer you to resources. Dr. Fervenza recommends discussing the following with your care team:

• What is causing FSGS?
• Should I seek care from a pediatric kidney disease center?
• Are there genetic factors at play? Does my child need genetic analysis?
• What is the prognosis for my child? How likely is it that FSGS will progress? How quickly do you expect it to progress?
• What are the pros, cons and side effects of each treatment option?
• Are there any lifestyle or diet changes that can support kidney health?
• Are there other specialists or supportive care experts you can refer me to?
• What resources, websites, support groups or services can you refer me to?