Nephrotic Syndrome Lecture Notes

Introduction to Nephrotic Syndrome

• Nephrotic syndrome is a type of glomerulonephritis.
• Commonly brings fear and anxiety among students.
• Aim is to provide a clear understanding of the topic.

Importance of Glomerular Filtration Barrier (GFB)

• GFB Structure: Three layers comprise the GFB:
  • Fenestrated Capillaries: Porous capillaries allowing selective movement of substances from blood to Bowman space.
  • Glomerular Basement Membrane (GBM): Negatively charged, repels large negatively charged proteins.
  • Podocytes: Specialized cells with foot processes and filtration slits controlling permeability.

Function of the GFB

• Regulates the filtration of:
  • Allowed: Sodium, water, electrolytes, nutrients.
  • Blocked: Red blood cells, white blood cells, proteins.
• Damage to GFB leads to loss of control over filtration.

Mechanism of Nephrotic Syndrome

• Pathophysiology:
  • Injury primarily to podocytes results in podocyte effacement.
• Outcome of podocyte injury:
  • Massive Protein Loss: Loss of proteins, especially albumin, leads to proteinuria.
  • Proteinuria is defined as greater than or equal to 3.5 grams of protein lost per day.

Clinical Features of Nephrotic Syndrome

• Hypoalbuminemia: Low albumin levels in blood due to protein loss.
• Edema: Due to decreased oncotic pressure, leading to fluid retention in tissues.
  • Types of edema include peripheral, pulmonary, ascites, and periorbital edema.
• Hyperlipidemia: Increased lipid levels due to compensatory mechanisms from low albumin.
  • Increased production of VLDL and LDL, causing lipiduria and fat oval bodies in urine.
• Increased Risk of Clots: Loss of antithrombin III leads to hypercoagulability, resulting in DVTs, PEs, and renal vein thrombosis.
• Increased Infection Risk: Decreased immunoglobulins lead to susceptibility to infections, especially with Streptococcus pneumoniae.

Types of Nephrotic Syndromes

Primary Nephrotic Syndromes

1. Minimal Change Disease:
   • Most common in children, often idiopathic.
   • Associated with infections, Hodgkin's lymphoma, NSAIDs.
2. Membranous Nephropathy:
   • Can be primary (anti-PLA2 receptor antibody) or secondary (associated with infections like hepatitis).
3. Focal Segmental Glomerulosclerosis (FSGS):
   • Can be primary (usually idiopathic) or secondary (associated with HIV, heroin use, etc.).

Secondary Nephrotic Syndromes

• Caused by systemic diseases like diabetes or amyloidosis.
• Diabetic Nephropathy: Most common cause of nephrotic syndrome and chronic kidney disease.
• Amyloidosis: Associated with chronic inflammatory conditions.

Diagnosis of Nephrotic Syndrome

• Urinalysis and Microscopy:
  • Nephrotic syndrome shows heavy proteinuria and lipiduria (fat oval bodies).
  • Differentiation from nephritic syndrome based on presence of hematuria and pyuria.
• 24-hour Urine Collection or Urine Albumin-Creatinine Ratio: Confirms proteinuria.
• Serum Tests: Check albumin levels, lipid panels for hyperlipidemia.

Treatment of Nephrotic Syndrome

1. Symptomatic Treatment:

   • Edema management: Fluid and sodium restriction, diuretics (e.g., loop diuretics).
   • Hyperlipidemia: Diet changes, statins.
   • Anticoagulation for hypercoagulable states.
   • Vaccinations against Streptococcus pneumoniae.

2. Treating the Underlying Cause:

   • Steroids for primary nephrotic syndromes (minimal change disease, membranous nephropathy, FSGS).
   • Other treatments specific to secondary causes (e.g., managing diabetes).

3. Immunosuppressive Therapy:

   • If steroids are ineffective, switch to long-term immunosuppressants (e.g., cyclophosphamide, tacrolimus).
   • Monitor for chronic kidney disease progression.

Conclusion

• Nephrotic syndrome results from podocyte damage leading to significant proteinuria and various complications.
• Understanding mechanisms, types, and treatment approaches are essential for effective patient management.