What are the symptoms and treatment of nephrotic syndrome?

Symptoms of Nephrotic Syndrome

Nephrotic syndrome is characterized by a classic tetrad of heavy proteinuria (>3.5g/24h), hypoalbuminemia (<3.0g/dL), edema, and hyperlipidemia. 1

Clinical Presentation

Primary Symptoms

• Edema

  • Periorbital edema (most noticeable in the morning)
  • Dependent pitting edema (more common later in the day)
  • Generalized fluid accumulation

• Laboratory Findings

  • Proteinuria >3.5g/24h or urine protein:creatinine ratio (PCR) >300-350 mg/mmol
  • Hypoalbuminemia (<3.0g/dL)
  • Hyperlipidemia (elevated cholesterol and triglycerides)
  • Lipiduria

Associated Complications

1. Thrombotic Complications 2

   • Renal vein thrombosis (29%)
   • Pulmonary embolism (17-28%)
   • Deep vein thrombosis (11%)

2. Cardiovascular Complications

   • Accelerated coronary heart disease (4x greater risk than age/sex-matched controls) 2
   • Hypertension

3. Infection Risk

   • Increased susceptibility to bacterial infections
   • Particularly cellulitis and spontaneous bacterial peritonitis in children 2

4. Renal Complications

   • Progressive renal scarring
   • Risk of end-stage renal disease (35% risk within 2 years for patients with proteinuria >3.8g/day) 2

Management Approach

Fluid and Edema Management

• Sodium restriction
• Fluid restriction to avoid marked edema 1
• Diuretic therapy
  • Furosemide as first-line treatment
  • For resistant cases, combination therapy with thiazide or potassium-sparing diuretics 1

Antiproteinuric Therapy

• ACE inhibitors or ARBs to reduce proteinuria 1
• Hold these medications during periods of volume depletion (diarrhea, vomiting, excessive sweating) 2
• Avoid dihydropyridine calcium channel blockers (amlodipine, nifedipine) as they may exacerbate edema and increase proteinuria 2

Hyperlipidemia Management

• Statin therapy 1

Thromboprophylaxis

• Consider prophylactic anticoagulation in high-risk patients 1
• Unfractionated or low-molecular-weight heparin or warfarin are preferred agents 2
• Factor Xa inhibitors and direct thrombin inhibitors are not recommended due to significant albumin binding and urinary loss 2

Infection Prevention

• Vaccination against encapsulated organisms 2
• Trimethoprim-sulfamethoxazole prophylaxis when using prednisone ≥20mg daily or other immunosuppressants 2
• Screening for latent infections (tuberculosis, hepatitis B/C, HIV, syphilis) 2

Disease-Specific Therapy

• Primary FSGS: High-dose oral glucocorticoids as first-line therapy 2
  • Continue until complete remission or maximum of 16 weeks
  • Maintain treatment for ≥6 months in responders

Common Pitfalls to Avoid

• Treating based on serum albumin levels alone rather than clinical indicators of hypovolemia 1
• Overreliance on immunosuppression for genetic forms of nephrotic syndrome 1
• Fluid overload due to excessive fluid administration 1
• Inadequate thromboprophylaxis in high-risk patients 1
• Failure to monitor for and prevent infections in immunosuppressed patients 1

Monitoring

• Regular assessment of renal function, proteinuria, blood pressure, and edema 1
• In children, monitor growth velocity 1
• Response assessment:
  • Complete response: return of serum creatinine to baseline and decline in UPCR to <500-700 mg/g
  • Partial response: stabilization or improvement of serum creatinine but UPCR still >500-700 mg/g 1