Focal Segmental Glomerulosclerosis: Causes, Symptoms & Treatment

What is Focal Segmental Glomerulosclerosis (FSGS)?

Focal Segmental Glomerulosclerosis (FSGS) is a kidney disorder that causes scarring (sclerosis) in parts of the glomeruli—the tiny filtering units within the kidneys that remove waste and excess fluid from the blood.

According to the National Institutes of Health (NIH), the term “focal segmental” means that only some (focal) of the glomeruli are affected, and within those, only a portion (segmental) is scarred.

This condition can lead to protein leakage in urine (proteinuria), swelling (oedema), and eventually chronic kidney disease (CKD) or kidney failure if untreated. FSGS can occur in both adults and children and is one of the most common causes of adult-onset primary nephrotic syndrome.

Types of Focal Segmental Glomerulosclerosis (FSGS)

FSGS includes several related disorders that scar parts of the kidney’s glomeruli. Identifying the type helps guide treatment and predict outcomes.

1. Primary (Idiopathic) FSGS:
   Occurs without a known cause, likely due to circulating permeability factors or immune-mediated podocyte injury.
2. Secondary FSGS:
   Triggered by conditions such as obesity, hypertension, reduced nephron mass, chronic infections, or drug toxicity. Managing the underlying cause is key.
3. Genetic or Familial FSGS:
   Results from inherited mutations affecting podocytes, often resistant to steroids and seen early in life.
4. Adaptive (Maladaptive) FSGS:
   Develops when remaining glomeruli overwork due to reduced kidney mass, obesity, or high blood pressure. Managed by reducing hyperfiltration and kidney strain.
5. Collapsing Variant FSGS:
   An aggressive subtype often linked to viral infections (especially HIV, SARS-CoV-2, or parvovirus B19), autoimmune diseases, or APOL1 gene variants, leading to rapidly progressive kidney failure.

Primary vs. Secondary Focal Segmental Glomerulosclerosis (FSGS)

Symptoms of Focal Segmental Glomerulosclerosis (FSGS)

FSGS symptoms appear gradually as kidney function declines and may resemble other kidney disorders. Early detection is vital for effective treatment.

• Swelling (oedema): Puffiness in legs, ankles, or around the eyes due to fluid buildup.
• Foamy urine: Indicates excess protein loss (proteinuria).
• Unexplained weight gain: Caused by fluid retention.
• Fatigue and poor appetite: Toxin buildup leads to weakness and reduced appetite.
• High blood pressure: Kidneys fail to balance salt and fluid levels.
• Changes in urination: Either reduced urine output or frequent nighttime urination.

Causes and Risk Factors

The causes of Focal Segmental Glomerulosclerosis (FSGS) depend largely on the underlying type—primary or secondary. While primary FSGS often occurs without a known trigger, secondary forms are associated with other health conditions or external factors that strain or damage the kidneys over time.

Primary FSGS:

The exact cause remains uncertain, but it is believed to result from an autoimmune reaction that damages the glomeruli (kidney filters). This immune dysfunction increases the permeability of the glomerular membrane, allowing proteins to leak into the urine.

Secondary FSGS:

Develops as a consequence of prolonged kidney stress or injury caused by other conditions, including:

• Obesity and metabolic stress: Increased body weight raises filtration pressure on the kidneys.
• Hypertension (high blood pressure): Constant pressure damages glomeruli and reduces blood flow to kidney tissues.
• Viral infections: Especially HIV, Hepatitis B, or Parvovirus B19, which directly injure kidney cells.
• Toxic drug exposure: Long-term use of medications such as lithium or pamidronate may harm kidney function.
• Genetic mutations: Changes in genes controlling podocyte (filtering cell) integrity can predispose individuals to FSGS.

Risk Factors:

Certain factors increase the likelihood of developing FSGS, including:

• African ancestry, due to the presence of specific APOL1 gene variants linked to podocyte injury.
• Family history of kidney disease.
• Male sex and middle age, where incidence rates are slightly higher.
• Prolonged hypertension, obesity, or diabetes, which heighten kidney workload and damage risk.

How Focal Segmental Glomerulosclerosis (FSGS) Affects the Kidneys?

FSGS scars the glomeruli—the kidney’s filters—reducing their ability to remove waste and maintain fluid balance.

This leads to several complications:

• Proteinuria: Damaged filters let proteins like albumin leak into urine, causing swelling and fluid imbalance.
• Edema: Low blood protein causes fluid buildup in legs, ankles, and around the eyes.
• Hypertension: Impaired sodium regulation increases blood volume and blood pressure.
• Kidney damage: Waste buildup from poor filtration gradually weakens kidney function.

How Focal Segmental Glomerulosclerosis (FSGS) is Diagnosed?

Diagnosing Focal Segmental Glomerulosclerosis (FSGS) involves medical history, physical examination, lab tests, and kidney biopsy. Because symptoms mimic other kidney diseases, precise diagnosis is crucial for proper treatment.

Diagnosis typically involves:

1. Medical history and physical examination:
   The doctor reviews symptoms such as swelling, foamy urine, fatigue, and blood pressure levels while assessing risk factors like obesity, diabetes, infections, or drug exposure.
2. Blood and urine tests:
   These tests help identify abnormalities in kidney function and detect protein leakage or other markers of kidney injury.

Blood and Urine Tests

• Urinalysis: Detects the presence of protein, blood, and other substances that indicate kidney damage.
• Serum creatinine and estimated Glomerular Filtration Rate (eGFR): Measure kidney filtration efficiency and help determine the stage of chronic kidney disease (CKD).
• Albumin-to-Creatinine Ratio (ACR): Quantifies the level of protein leakage in urine — a key indicator of glomerular damage.
• Lipid Profile: Assesses cholesterol and triglyceride levels, which are often elevated in patients with nephrotic syndrome due to FSGS.

Kidney Biopsy

A kidney biopsy is the key test for diagnosing FSGS. A small tissue sample is taken with a fine needle and examined under a microscope for segmental glomerular scarring.

The results help distinguish FSGS from other kidney diseases and, combined with clinical findings, guide nephrologists in identifying the type and planning appropriate treatment.

Treatment Options for Focal Segmental Glomerulosclerosis (FSGS)

The aim of FSGS treatment is to lower proteinuria, control blood pressure, relieve symptoms, and slow progression to kidney failure. Treatment depends on the cause and patient’s response.

Medications

• Corticosteroids (Prednisone): First-line therapy for primary FSGS; reduce inflammation and protein loss. Long-term use requires careful monitoring for side effects.
• Immunosuppressants (Cyclosporine, Tacrolimus, Mycophenolate): Used when steroids fail; stabilize podocytes and limit kidney damage.
• ACE Inhibitors / ARBs: Lower blood pressure and reduce proteinuria, protecting kidney function.
• Diuretics: Control swelling and fluid buildup.
• Statins: Reduce cholesterol and triglycerides in nephrotic syndrome.
• Anticoagulants: Used in patients at high risk of blood clots.

Dialysis and Transplant

When kidney function declines severely and medications can no longer maintain adequate filtration, renal replacement therapy becomes necessary:

• Dialysis: Removes waste and excess fluid when kidneys fail; supports patients until transplant.
• Kidney Transplant: The most effective long-term option, though FSGS may recur in approximately 30–40% of cases. Continuous follow-up and immunosuppression are essential to protect graft health.

Lifestyle and Home Care Tips

Managing Focal Segmental Glomerulosclerosis (FSGS) extends beyond medications—adopting the right lifestyle habits plays a crucial role in protecting kidney function and improving long-term health outcomes.

• Follow a low-sodium, low-protein diet: Helps control blood pressure, fluid retention, and kidney strain.
• Maintain healthy weight and blood pressure: Regular exercise and balanced nutrition slow disease progression.
• Avoid NSAIDs and harmful drugs: Painkillers like ibuprofen or naproxen can worsen kidney damage.
• Stay adequately hydrated and quit smoking: Supports kidney function and improves overall vascular health.
• Schedule regular tests: Monitor creatinine, eGFR, and urine protein for timely treatment adjustments.

Possible Complications

If Focal Segmental Glomerulosclerosis (FSGS) is not diagnosed and managed early, it can lead to several serious complications due to progressive kidney damage and loss of filtration capacity. Common complications include:

• Chronic Kidney Disease (CKD):
  Gradual scarring of the glomeruli leads to declining kidney function over time, potentially progressing to end-stage renal disease.
• Nephrotic Syndrome:
  Severe protein loss through urine causes swelling, fatigue, and increased risk of infections and blood clots.
• Severe Hypertension:
  Damaged kidneys struggle to regulate blood pressure, leading to persistent high blood pressure that further accelerates kidney injury.
• High Cholesterol and Triglycerides:
  Protein loss and metabolic changes in nephrotic syndrome result in elevated lipid levels, increasing the risk of cardiovascular disease.
• Blood Clots (Thrombosis):
  Low albumin levels and changes in blood composition increase the risk of clot formation, especially in veins.
• Kidney Failure:
  In advanced stages, the kidneys may lose nearly all function, requiring dialysis or kidney transplantation for survival.

Living with Focal Segmental Glomerulosclerosis (FSGS)

Living with FSGS requires continuous care, medical supervision, and lifestyle changes to protect kidney function. Regular nephrologist visits help track progress, adjust treatment, and prevent complications.

Adhering to prescribed medications, blood pressure control, and dietary guidelines is crucial for slowing disease progression. Emotional support from family or patient groups also helps manage stress and maintain positivity.

With proactive care and a healthy lifestyle, individuals with FSGS can live fulfilling lives while reducing the risk of kidney failure.

Prognosis and Long-term Outlook

The prognosis of Focal Segmental Glomerulosclerosis (FSGS) varies by type, kidney damage severity, and treatment response. Early diagnosis and effective therapy can lead to remission and stable kidney function for years. However, in some cases, kidney performance gradually declines, leading to chronic kidney disease or kidney failure requiring dialysis or transplant.

Strict blood pressure control with ACE inhibitors or ARBs, healthy lifestyle habits, and regular nephrologist follow-ups are vital for reducing proteinuria, slowing disease progression, and preserving kidney function long term.

When to See a Doctor

It’s important to seek medical attention promptly if you notice any signs that could indicate kidney damage or declining kidney function. Early evaluation helps prevent complications and allows timely management of Focal Segmental Glomerulosclerosis (FSGS) or other related kidney disorders.

You should see a doctor if you experience:

• Persistent swelling in the legs, ankles, feet, or around the eyes that doesn’t subside.
• Foamy urine or reduced urine output, which may suggest protein loss or impaired kidney filtration.
• Uncontrolled or high blood pressure despite lifestyle changes or medication.
• Fatigue, weakness, or loss of appetite, which can occur as toxins build up in the blood.
• A family history of kidney disease or known genetic predisposition to renal disorders.

Conclusion

Focal Segmental Glomerulosclerosis (FSGS) is a complex but manageable kidney disorder when detected early. Understanding its causes, symptoms, and treatment options helps patients take proactive steps to preserve kidney health.

For precise diagnosis and monitoring, Metropolis Healthcare offers over 4000 diagnostic tests, including kidney function panels, urine protein analysis, and nephrotic syndrome profiles, with home sample collection, quick turnaround, and nationwide availability across 10,000+ touchpoints.

Stay proactive — early detection can make all the difference.

FAQs

Can FSGS be prevented?

There’s no guaranteed way to prevent FSGS, but managing risk factors—such as high blood pressure, diabetes, and obesity—can reduce the likelihood of developing secondary forms.

Is FSGS the same as chronic kidney disease?

No. FSGS is a specific cause of kidney damage that can lead to chronic kidney disease over time if not treated effectively.

What is the life expectancy with FSGS?

With early diagnosis, proper treatment, and lifestyle management, many patients can live for decades without requiring dialysis or a transplant.

Can FSGS go into remission?

Yes. Many patients achieve partial or complete remission through corticosteroid therapy and blood pressure management.

How serious is FSGS?

FSGS is a serious condition that can lead to chronic kidney failure if untreated. However, with ongoing medical supervision and adherence to treatment, its progression can often be slowed or controlled.