Nephrotic syndrome

Pathophysiology - Leaky Kidney Chaos

• Primary Insult: Damage to glomerular basement membrane (GBM) & podocyte foot processes.
• Core Defect: Loss of negative charge & size barrier → massive leakage of plasma proteins.

• Consequences:
  • Edema: Periorbital, pitting, can lead to anasarca.
  • Hyperlipidemia: ↑ liver production of lipids.
    • Lipiduria: Oval fat bodies in urine (Maltese cross sign).
  • Thrombosis Risk: ↑ loss of Antithrombin III in urine.

⭐ The hypercoagulable state, particularly renal vein thrombosis, is a classic and dangerous complication due to urinary loss of anticoagulant factors.

Etiology - The Usual Suspects

• Primary Glomerular Disease (Idiopathic)

  • Minimal Change Disease (MCD): Most common cause in children.
  • Focal Segmental Glomerulosclerosis (FSGS): Most common cause in adults of African ancestry; associated with HIV, heroin use, obesity.
  • Membranous Nephropathy: Most common cause in Caucasian adults.
  • Membranoproliferative Glomerulonephritis (MPGN): Mixed nephrotic-nephritic picture.

• Secondary Causes

  • Systemic Disease: Diabetes Mellitus (most common secondary cause), SLE, Amyloidosis.
  • Infection: Hepatitis B & C, HIV.
  • Drugs: NSAIDs, penicillamine, gold salts.
  • Malignancy: Lymphoma (MCD), solid tumors (Membranous).

⭐ In an older patient (>60 yrs) with new-onset nephrotic syndrome, suspect Membranous Nephropathy and screen for an underlying solid tumor (e.g., lung, colon).

Diagnosis - Puffy Patient Puzzle

• Urinalysis: Initial screen shows proteinuria. Key finding is heavy proteinuria: >3.5 g/24h or urine protein/creatinine ratio (UPCR) >3.5.
• Blood Tests:
  • Hypoalbuminemia: Serum albumin <3 g/dL.
  • Hyperlipidemia: ↑ LDL, ↑ cholesterol.
• Microscopy: Lipiduria with oval fat bodies.

⭐ Under polarized light, oval fat bodies containing cholesterol esters appear as classic “Maltese crosses.”

• Kidney Biopsy: Gold standard to identify the specific underlying glomerular disease (e.g., MCD, FSGS, MN).

Management & Complications - Damage Control Duty

• General Management

  • Diet: Salt restriction (<2 g/day), fluid restriction.
  • Proteinuria: ACE inhibitors or ARBs.

• Specific Therapy

  • Edema: Loop diuretics (furosemide).
  • Hyperlipidemia: HMG-CoA reductase inhibitors (statins).
  • Thrombosis Prophylaxis: Consider anticoagulation if albumin is <2.5 g/dL or with other risk factors.

• Key Complications

  • Thromboembolism: Due to loss of antithrombin III. Most common is renal vein thrombosis.
  • Infection: Loss of immunoglobulins (IgG) increases risk from encapsulated bacteria (e.g., S. pneumoniae).

⭐ In a patient with nephrotic syndrome, the sudden onset of flank pain, hematuria, and fever should raise high suspicion for renal vein thrombosis.

• Nephrotic syndrome is defined by massive proteinuria (>3.5 g/day), hypoalbuminemia, generalized edema, and hyperlipidemia/lipiduria.
• The core pathology is podocyte injury, which compromises the glomerular filtration barrier, leading to protein loss.
• Minimal Change Disease is the most common cause in children and shows effacement of foot processes on EM.
• Membranous Nephropathy is the most common primary cause in white adults.
• FSGS is the most frequent cause in African American and Hispanic adults.
• Major complications include thromboembolism and increased susceptibility to infections.