About Focal Segmental Glomerulosclerosis (FSGS)

What is FSGS?

Focal segmental glomerulosclerosis [gloh-MAIR-yoo-loh-skluh-ROH-sis] (FSGS) is a kidney condition characterized by the scarring of tiny filters called glomeruli, which clean the blood inside the kidneys. FSGS gets its name from two key features:

Focal: Only some of the millions of glomeruli in the kidneys are affected by scarring
Segmental: Only a portion of each affected glomerulus is scarred

FSGS is a rare condition that can lead to serious kidney problems if left untreated. It is important to understand the causes, symptoms, diagnosis, treatment, and prevention strategies for FSGS.

FSGS Causes and Risk Factors

Focal segmental glomerulosclerosis (FSGS) can have various causes, including genetic factors and underlying health conditions. Here are the causes and risk factors of FSGS:

Types and Causes of FSGS:

Primary FSGS, sometimes called idiopathic FSGS, is diagnosed when a specific underlying cause cannot be identified. Researchers suspect that circulating factors in the blood may injure podocytes, which are specialized cells in the glomeruli. Podocyte injury can allow protein to leak into the urine.
Secondary (adaptive) FSGS: In this type, doctors can identify a distinct cause for FSGS. Conditions that increase blood flow to the kidneys can put excessive stress on the glomeruli, leading to FSGS. Examples of conditions that may lead to secondary FSGS include obesity, diabetes, sickle cell anemia, sleep apnea, and other kidney diseases. Secondary FSGS can also be associated with infections such as HIV, medications or drugs, and conditions such as sickle cell disease and sleep apnea.
Genetic (familial) FSGS: Genetic anomalies are a rare cause of FSGS. Doctors may suspect genetic FSGS when multiple family members have the condition.

Risk factors for FSGS include inherited factors, kidney structure or function differences, certain health conditions, infections, and some medications or drug exposures. Some risk factors can be managed or treated, while others cannot be changed.

Inherited risk factors: Some people may have a higher risk of FSGS because of inherited gene variants. A family history of FSGS can increase the likelihood of a genetic form, but genetic risk can also be present without a known family history. Some people with certain inherited APOL1 gene variants have a higher risk of developing FSGS, especially when other kidney stressors are present. Having a genetic risk factor does not mean a person will definitely develop FSGS.
Associated conditions and exposures: Conditions such as obesity, diabetes, sickle cell disease, and sleep apnea have been associated with secondary FSGS. Treating or managing these conditions may help reduce kidney stress, but not all of these risk factors can be fully changed.
Kidney structure or function differences: Some people have reduced kidney filtering capacity because of congenital kidney differences, prior kidney injury, reflux nephropathy, or surgical removal of kidney tissue. These conditions can increase pressure on the remaining kidney filters and may contribute to secondary FSGS.
Viral infections: Some infections, especially HIV, have been associated with FSGS. Other viral infections have also been reported in association with FSGS, but the strength of the association varies.

FSGS Symptoms

FSGS may not cause noticeable symptoms in the early stages. In some people, the first sign is an abnormal urine test showing increased protein in the urine. When symptoms do occur, they often reflect protein loss in the urine, fluid buildup, high blood pressure, or declining kidney function.

FSGS can cause nephrotic syndrome, a group of findings that may include:

High levels of protein in the urine, also called proteinuria
Swelling, also called edema, especially around the eyes, ankles, feet, legs, or abdomen
Foamy or bubbly urine, which may be a sign of protein in the urine
Weight gain from fluid buildup
Low levels of albumin, a protein in the blood
High cholesterol or triglyceride levels
Increased risk of blood clots

Some people with FSGS may also have:

High blood pressure
Fatigue
Loss of appetite
Nausea
Blood in the urine, which may be microscopic and found only on a urine test

If FSGS worsens and kidney function declines, symptoms may include:

Decreased urination or changes in urination
Nausea or vomiting
Trouble concentrating, confusion, or drowsiness
Muscle cramps
Shortness of breath or worsening swelling from fluid buildup
General weakness or feeling unwell

How Is FSGS Diagnosed?

FSGS is usually suspected when urine tests show increased protein in the urine, especially if swelling, high blood pressure, or reduced kidney function is also present. A healthcare provider may use several tests to evaluate kidney health and look for possible causes of proteinuria.

Medical history and physical exam: A healthcare provider may ask about symptoms, family history of kidney disease, medications, infections, and other health conditions. During the exam, they may check for swelling, blood pressure changes, or other signs of kidney disease.
Urine tests: Urine testing can measure how much protein is in the urine and check for blood or other abnormalities. A urine albumin-to-creatinine ratio or protein-to-creatinine ratio may be used to estimate protein loss.
Blood tests: Blood tests can measure kidney function, including creatinine and estimated glomerular filtration rate, or eGFR. They may also check albumin, cholesterol, and other markers that can be abnormal in nephrotic syndrome.
Tests for underlying causes: Depending on the person’s history and symptoms, additional blood or urine tests may be done to look for infections, autoimmune conditions, diabetes, or other causes of kidney disease.
Kidney imaging: Ultrasound or other imaging may be used to look at kidney size, structure, or other abnormalities. Imaging cannot diagnose FSGS by itself.
Kidney biopsy: A kidney biopsy is usually needed to confirm FSGS. During a biopsy, a small sample of kidney tissue is examined under a microscope to look for the characteristic pattern of scarring.
Genetic testing: Genetic testing may be considered when FSGS begins in childhood or young adulthood, occurs in more than one family member, does not respond as expected to standard treatment, or when an inherited form is suspected.

FSGS Treatment Options

Treatment for FSGS depends on the suspected type, the amount of protein in the urine, kidney function, blood pressure, symptoms, and whether an underlying cause can be identified. The main goals are to reduce protein loss in the urine, control blood pressure, manage swelling and other complications, and slow loss of kidney function.

Supportive kidney-protective care: Many people with FSGS are treated with medicines that lower blood pressure and reduce protein in the urine, such as angiotensin-converting enzyme inhibitors, called ACE inhibitors, or angiotensin II receptor blockers, called ARBs. These medicines may be used even when blood pressure is not very high, if appropriate.
Diet and lifestyle changes: A healthcare provider may recommend limiting sodium to help control swelling and blood pressure. Weight management, regular physical activity, and treatment of related conditions such as diabetes or sleep apnea may also be recommended.
Diuretics: Diuretics, sometimes called water pills, may be used to help reduce swelling caused by fluid buildup.
Cholesterol-lowering treatment: Some people with nephrotic syndrome may need medicines to help manage high cholesterol or triglyceride levels.
Medicines that affect the immune system: Corticosteroids or other immunosuppressive medicines may be considered for some people with primary FSGS, especially when nephrotic syndrome is present. These medicines are not appropriate for all types of FSGS and are usually not the main treatment for secondary FSGS.
Treatment of an underlying cause: If FSGS is secondary to another condition or exposure, treatment focuses on managing that cause, such as treating HIV, reducing kidney stress related to obesity or reduced kidney mass, stopping an offending medication or drug when possible, or managing sleep apnea or diabetes.
Blood clot prevention or treatment: People with nephrotic syndrome may have an increased risk of blood clots. Blood thinners may be used in selected cases based on individual risk and clinician judgment.
Dialysis or kidney transplant: If FSGS progresses to kidney failure, dialysis or kidney transplant may be needed. FSGS can recur after kidney transplant, especially in some people with primary FSGS, so ongoing monitoring is important.

FSGS Complications

FSGS can lead to complications related to protein loss in the urine, nephrotic syndrome, high blood pressure, and declining kidney function. The risk and severity of complications vary from person to person.

Nephrotic syndrome: FSGS can cause nephrotic syndrome, which may include high levels of protein in the urine, low blood albumin, swelling, and high cholesterol or triglyceride levels.
Swelling and fluid buildup: Loss of protein in the urine can lead to fluid retention, causing swelling in the legs, feet, ankles, around the eyes, or abdomen.
High blood pressure: FSGS can cause or worsen high blood pressure, which can further damage the kidneys.
Declining kidney function: In some people, FSGS can gradually reduce kidney function and may lead to chronic kidney disease.
Kidney failure: If kidney function becomes severely reduced, dialysis or kidney transplant may be needed.
Blood clots: People with nephrotic syndrome may have a higher risk of blood clots.
Infections: Low levels of certain proteins in the blood and some immune-suppressing treatments may increase infection risk.
High cholesterol or triglycerides: Nephrotic syndrome can raise cholesterol and triglyceride levels, which may require monitoring or treatment.
Recurrence after kidney transplant: FSGS can come back after a kidney transplant, especially in some people with primary FSGS.

Regular follow-up with a healthcare provider is important to monitor kidney function, urine protein levels, blood pressure, and complications.