Nephrotic Syndrome is a collection of symptoms that indicate kidney damage, specifically to the tiny filtering units called glomeruli. When these filters are damaged, they allow large amounts of protein, primarily albumin, to leak from the blood into the urine. This significant protein loss leads to a cascade of problems throughout the body, affecting fluid balance, cholesterol levels, and increasing the risk of complications.

What is Nephrotic Syndrome?

Nephrotic Syndrome is characterized by four main features:

• Heavy Proteinuria: Very high levels of protein in the urine (typically more than 3.5 grams per 24 hours in adults).
• Hypoalbuminemia: Low levels of albumin in the blood due to its loss in urine.
• Edema: Significant swelling, especially around the eyes, in the legs, ankles, feet, and sometimes the abdomen (ascites), caused by fluid retention due to low blood albumin.
• Hyperlipidemia: High levels of cholesterol and triglycerides in the blood.

It can affect people of all ages, including children, and can be a primary kidney disorder or a complication of other systemic diseases.

Causes of Nephrotic Syndrome

Nephrotic Syndrome is not a disease itself, but a syndrome caused by various underlying conditions that damage the kidney's filtering units (glomeruli). These causes can be primary (originating in the kidney) or secondary (due to other diseases affecting the body):

Primary Kidney Diseases:

• Minimal Change Disease (MCD): The most common cause of nephrotic syndrome in children, and also seen in adults. The glomeruli appear normal under a light microscope, but changes are visible under an electron microscope. It often responds well to steroids.
• Focal Segmental Glomerulosclerosis (FSGS): Characterized by scarring in specific parts of some glomeruli. It can be primary (idiopathic), genetic, or secondary to other conditions like obesity, HIV, or certain medications. FSGS can lead to kidney failure.
• Membranous Nephropathy (MN): The most common cause of nephrotic syndrome in adults. It involves thickening of the glomerular basement membrane due to immune complex deposits. It can be primary (often related to anti-PLA2R antibodies) or secondary to autoimmune diseases, infections (e.g., Hepatitis B), or certain drugs.
• Membranoproliferative Glomerulonephritis (MPGN): Involves changes in the structure of the glomeruli, often associated with autoimmune diseases or chronic infections.

Secondary Causes:

• Diabetic Nephropathy: Kidney damage caused by long-standing diabetes, a very common cause of proteinuria and, in advanced stages, nephrotic syndrome.
• Systemic Lupus Erythematosus (SLE) / Lupus Nephritis: An autoimmune disease that can cause inflammation and damage to various organs, including the kidneys.
• Amyloidosis: A rare condition where abnormal proteins (amyloid) build up in organs, including the kidneys.
• Certain Infections: Such as Hepatitis B, Hepatitis C, HIV, and malaria.
• Certain Medications: Nonsteroidal anti-inflammatory drugs (NSAIDs), gold salts, and some antibiotics.
• Cancer: Rarely, certain cancers can cause nephrotic syndrome.

Symptoms of Nephrotic Syndrome

The primary symptoms are related to the massive loss of protein and fluid retention:

• Severe Edema: Swelling, especially prominent around the eyes (periorbital edema) in the morning, and later in the legs, ankles, feet, and sometimes hands. Fluid can also accumulate in the abdomen (ascites) or around the lungs (pleural effusion).
• Foamy or Frothy Urine: Due to the high concentration of protein.
• Weight Gain: Due to fluid retention.
• Fatigue and weakness.
• Loss of appetite.
• Increased susceptibility to infections (due to loss of antibodies in urine).
• Increased risk of blood clots (due to loss of anticoagulant proteins).

Diagnosis of Nephrotic Syndrome

Diagnosis involves a thorough evaluation:

• Urine Tests:
  • Urinalysis: To detect high levels of protein.
  • 24-Hour Urine Collection: The gold standard for measuring the exact amount of protein lost in urine over a day.
  • Urine protein-to-creatinine ratio (UPCR) can also be used.
• Blood Tests:
  • Serum Albumin: To confirm low levels of albumin in the blood.
  • Kidney Function Tests (Creatinine, eGFR): To assess how well the kidneys are filtering.
  • Lipid Panel: To check cholesterol and triglyceride levels.
  • Tests for underlying causes: Blood sugar (for diabetes), ANA (for lupus), Hepatitis B/C serology, complement levels, anti-PLA2R antibodies (for membranous nephropathy).
• Kidney Biopsy: Often essential to determine the specific underlying cause of Nephrotic Syndrome. A small tissue sample is examined under a microscope to identify the type of glomerular damage, which guides specific treatment.

Treatment and Management

Treatment for Nephrotic Syndrome aims to reduce protein in the urine, manage symptoms, prevent complications, and treat the underlying cause. The approach is highly individualized:

• Treating the Underlying Cause:
  • Corticosteroids: (e.g., prednisone) Often the first-line treatment, especially for Minimal Change Disease, to reduce inflammation and protein leakage.
  • Immunosuppressants: (e.g., cyclophosphamide, calcineurin inhibitors like cyclosporine or tacrolimus, mycophenolate mofetil, rituximab) Used for specific types of GN (like FSGS, Membranous Nephropathy, Lupus Nephritis) that are steroid-resistant or relapsing.
  • Diabetes Management: Strict blood sugar and blood pressure control for diabetic nephropathy.
• Symptomatic Management:
  • Diuretics: To reduce swelling and fluid retention.
  • Blood Pressure Medications: ACE inhibitors or ARBs are crucial, as they not only lower blood pressure but also help reduce protein loss in the urine.
  • Statins: To manage high cholesterol levels.
  • Anticoagulants: Blood thinners may be prescribed to prevent blood clots in high-risk patients.
• Dietary Modifications:
  • Low Sodium Diet: To control swelling and blood pressure.
  • Moderate Protein Intake: As advised by a renal dietitian.
• Monitoring: Regular follow-up with a nephrologist to monitor kidney function, protein levels, and medication effectiveness.