7 Key Symptoms of Focal Segmental Glomerulosclerosis (FSGS)

Focal segmental glomerulosclerosis (FSGS) is a serious kidney disease that causes scarring in the glomeruli—the tiny filtering units within the kidneys. This condition disrupts the kidney’s ability to filter waste and excess fluids from the blood, leading to protein loss in the urine and progressive kidney damage. FSGS is one of the leading causes of nephrotic syndrome in adults and can eventually lead to kidney failure if left untreated.

Understanding the symptoms of FSGS is crucial for early detection and intervention. Many people with FSGS may not notice symptoms in the early stages, making regular health check-ups important, especially for those at higher risk. Below, we outline the key symptoms associated with this condition to help you recognize potential warning signs.

1. Proteinuria (Protein in Urine)

Proteinuria is the hallmark symptom of FSGS and often the first sign that something is wrong with kidney function. When the glomeruli become scarred and damaged, they can no longer effectively prevent protein from leaking into the urine.

In healthy kidneys, proteins such as albumin remain in the bloodstream because they’re too large to pass through the glomerular filters. However, with FSGS, the damaged filters allow significant amounts of protein to escape. This protein loss can be substantial—sometimes exceeding 3.5 grams per day, which defines nephrotic-range proteinuria.

Key characteristics:

• Usually detected through routine urine tests
• May not cause noticeable symptoms initially
• Can lead to foamy or frothy urine when protein levels are high
• Often discovered during routine medical examinations

2. Edema (Swelling)

Edema, or swelling, is one of the most visible and troublesome symptoms of FSGS. This occurs as a direct result of protein loss through the urine. When albumin levels in the blood drop significantly, the body’s ability to maintain proper fluid balance is compromised.

Albumin helps keep fluid inside blood vessels through osmotic pressure. When albumin levels decrease, fluid leaks from blood vessels into surrounding tissues, causing swelling. This swelling typically follows a characteristic pattern in FSGS patients.

Common areas affected by edema:

• Lower extremities: Feet, ankles, and legs are usually affected first, with swelling often worsening throughout the day
• Face and eyes: Particularly noticeable in the morning, with puffiness around the eyelids
• Hands and arms: May experience tightness in rings or difficulty making a fist
• Abdomen: Fluid accumulation in the abdominal cavity (ascites) can occur in severe cases
• Lungs: In advanced cases, fluid may accumulate around the lungs (pleural effusion), causing breathing difficulties

3. Foamy or Frothy Urine

Many people with FSGS notice that their urine appears unusually foamy or frothy, especially when urinating into the toilet. This distinctive appearance is a direct visual indicator of excessive protein in the urine.

The foam is created when protein interacts with water and air during urination, similar to how egg whites foam when whisked. While occasional foam in urine can be normal—especially if urinating forcefully or if the urine is concentrated—persistent foamy urine is a red flag that warrants medical evaluation.

Characteristics of protein-related foamy urine:

• Foam persists for several minutes rather than dissipating quickly
• Appears consistently across multiple bathroom visits
• Bubbles are typically small and numerous
• May have a different texture compared to occasional foam from normal urine

4. Fatigue and Weakness

Persistent fatigue and generalized weakness are common but often overlooked symptoms of FSGS. These symptoms can significantly impact daily activities and quality of life, yet many patients attribute them to stress, aging, or lack of sleep rather than kidney disease.

The fatigue associated with FSGS has multiple underlying causes:

Contributing factors to fatigue:

• Anemia: Damaged kidneys produce less erythropoietin, a hormone that stimulates red blood cell production, leading to anemia
• Protein loss: Loss of essential proteins through urine can result in nutritional deficiencies and muscle weakness
• Toxin accumulation: As kidney function declines, waste products and toxins build up in the bloodstream, causing lethargy
• Poor sleep quality: Fluid retention and other symptoms may disrupt sleep patterns
• Metabolic changes: Altered metabolism due to kidney dysfunction affects energy levels

Patients often describe this fatigue as overwhelming and different from normal tiredness, persisting even after adequate rest.

5. High Blood Pressure (Hypertension)

Elevated blood pressure is both a symptom and a complication of FSGS, creating a dangerous cycle that can accelerate kidney damage. Studies show that up to 30-50% of FSGS patients develop hypertension during the course of their disease.

The relationship between FSGS and high blood pressure is complex and bidirectional:

Why FSGS causes high blood pressure:

• Fluid retention: Damaged kidneys struggle to eliminate excess sodium and water, increasing blood volume and pressure
• Hormonal imbalances: Kidney disease disrupts the renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure
• Reduced kidney function: As the kidneys lose their ability to regulate blood pressure, hypertension develops
• Vascular changes: The disease process itself may affect blood vessel function

High blood pressure in FSGS patients requires careful monitoring and management, as uncontrolled hypertension can further damage the kidneys and increase the risk of cardiovascular complications.

6. Changes in Urination Patterns

Many individuals with FSGS experience various changes in their urination habits, though these symptoms may be subtle and develop gradually over time. These changes reflect the kidneys’ declining ability to properly filter blood and regulate fluid balance.

Common urination changes include:

• Decreased urine output: Some patients produce less urine than normal (oliguria), particularly as kidney function declines
• Color changes: Urine may appear darker or more concentrated due to reduced kidney function
• Increased nighttime urination: Nocturia, or frequent urination at night, disrupts sleep and may indicate fluid redistribution
• Blood in urine: While less common in FSGS than in some other kidney diseases, microscopic or visible blood (hematuria) can occasionally occur

These urinary changes may be accompanied by the foamy appearance mentioned earlier, providing multiple clues to underlying kidney problems.

7. Unexplained Weight Gain

Sudden or gradual weight gain without changes in diet or exercise habits is a significant symptom of FSGS that often correlates with fluid retention. This weight gain is not due to increased fat or muscle mass but rather to the accumulation of excess fluid in the body’s tissues.

Characteristics of FSGS-related weight gain:

• Rapid onset: Weight may increase by several pounds within days or weeks
• Corresponds with edema: Weight gain typically accompanies visible swelling in the legs, face, or abdomen
• Fluctuations: Weight may vary depending on fluid retention levels
• Clothing fit: Shoes, rings, and clothes may feel tighter than usual
• Scale patterns: Daily weighing may reveal consistent upward trends

In severe cases, patients can gain 10-20 pounds or more due to fluid accumulation. This weight gain may also be accompanied by a feeling of heaviness, bloating, or discomfort, particularly in the abdomen and lower extremities.

What Causes Focal Segmental Glomerulosclerosis?

FSGS can be classified into two main categories based on its underlying cause: primary (idiopathic) and secondary FSGS. Understanding the potential causes helps healthcare providers determine the best approach to management.

Primary (Idiopathic) FSGS

In many cases, the exact cause of FSGS remains unknown. Primary FSGS is believed to result from immune system dysfunction that damages the glomeruli, though the specific mechanisms are not fully understood. Genetic factors may play a role in some individuals, with certain gene mutations increasing susceptibility to the disease.

Secondary FSGS

Secondary FSGS develops as a consequence of other conditions or factors that stress or damage the kidneys:

• Viral infections: HIV, parvovirus B19, and hepatitis B or C can trigger FSGS
• Medications and toxins: Certain drugs, including heroin, anabolic steroids, and some prescription medications, can cause kidney damage leading to FSGS
• Genetic mutations: Inherited genetic defects affecting podocytes (specialized kidney cells) can cause familial forms of FSGS
• Obesity: Excess body weight puts increased strain on the kidneys, potentially leading to obesity-related FSGS
• Reduced kidney mass: Having only one kidney, kidney surgery, or congenital kidney abnormalities forces remaining kidney tissue to work harder, increasing risk
• Reflux nephropathy: Chronic urine backflow from the bladder to the kidneys can cause scarring
• Sickle cell disease: This blood disorder can damage kidney structures over time
• Hypertension: Long-standing high blood pressure can damage glomeruli

Genetic Forms

Research has identified several genetic mutations associated with FSGS, including mutations in genes such as NPHS1, NPHS2, ACTN4, TRPC6, and INF2. Genetic testing may be recommended for patients with a family history of kidney disease or early-onset FSGS.

Frequently Asked Questions About FSGS

Can FSGS be cured?

Currently, there is no definitive cure for FSGS. However, early detection and appropriate management can slow disease progression and help preserve kidney function. Some patients achieve remission, where proteinuria decreases significantly or disappears, but the underlying condition may still require ongoing monitoring. Treatment focuses on managing symptoms, reducing protein loss, and preventing complications. Anyone diagnosed with FSGS should work closely with a nephrologist to develop an individualized management plan.

How is FSGS diagnosed?

FSGS is definitively diagnosed through a kidney biopsy, where a small sample of kidney tissue is examined under a microscope. Prior to biopsy, doctors typically perform blood tests, urine tests, and imaging studies. The biopsy reveals the characteristic scarring pattern in some but not all glomeruli (focal) affecting only parts of each damaged glomerulus (segmental). Blood tests check kidney function, protein levels, and cholesterol, while urine tests measure protein and blood in the urine.

Is FSGS hereditary?

FSGS can be hereditary in some cases, particularly in familial forms caused by specific genetic mutations. However, most cases of FSGS are not inherited. If you have a family member with FSGS, your risk may be slightly elevated, but it doesn’t mean you will definitely develop the condition. Genetic testing and counseling may be recommended for families with multiple affected members or for patients diagnosed at a young age.

How quickly does FSGS progress?

The progression of FSGS varies significantly among individuals. Some people experience rapid decline in kidney function within months to a few years, while others maintain stable kidney function for many years or even decades. Factors affecting progression include the amount of protein in urine, blood pressure control, response to treatment, the underlying cause, and genetic factors. Regular monitoring by a nephrologist is essential to track disease progression and adjust management strategies accordingly.

Can lifestyle changes help with FSGS?

Yes, lifestyle modifications play an important supportive role in managing FSGS. Key recommendations include following a kidney-friendly diet with controlled protein, sodium, and potassium intake; maintaining a healthy weight; engaging in regular, moderate exercise as tolerated; avoiding nephrotoxic substances including NSAIDs and certain herbal supplements; managing stress; avoiding smoking; and limiting alcohol consumption. These changes should be made in consultation with your healthcare team, as individual needs vary based on disease stage and other health conditions.

What is the difference between FSGS and minimal change disease?

Both FSGS and minimal change disease (MCD) cause nephrotic syndrome and can present with similar symptoms, but they differ in several important ways. Under a microscope, MCD shows no visible scarring in the glomeruli with standard light microscopy (changes are only visible with electron microscopy), while FSGS shows characteristic scarring in parts of some glomeruli. MCD typically responds well to corticosteroid treatment with high remission rates, whereas FSGS is often more treatment-resistant. MCD is more common in children, while FSGS affects both children and adults. Additionally, FSGS generally has a higher risk of progressing to kidney failure compared to MCD.

Should I see a specialist if I have symptoms of FSGS?

Yes, if you experience symptoms such as persistent foamy urine, unexplained swelling, significant fatigue, or sudden weight gain, you should see your primary care doctor promptly. If initial tests suggest kidney disease or proteinuria, your doctor will likely refer you to a nephrologist—a kidney specialist. Early evaluation and diagnosis are crucial, as timely intervention can significantly impact long-term outcomes. Don’t delay seeking medical attention if you notice concerning symptoms, especially if you have risk factors such as a family history of kidney disease, obesity, or viral infections.

References:

• National Kidney Foundation – Focal Segmental Glomerulosclerosis (FSGS)
• National Institute of Diabetes and Digestive and Kidney Diseases – FSGS
• Mayo Clinic – Nephrotic Syndrome
• Johns Hopkins Medicine – Focal Segmental Glomerulosclerosis
• StatPearls – Focal Segmental Glomerulosclerosis