What is the treatment for nephrotic syndrome?

Treatment of Nephrotic Syndrome

The treatment of nephrotic syndrome requires rapid referral to a specialized nephrology unit and includes disease-specific therapy targeting the underlying cause, along with supportive measures to manage symptoms and prevent complications. 1

Diagnosis and Classification

Nephrotic syndrome is characterized by:

• Heavy proteinuria (>3.5g/24h or urine protein:creatinine ratio >300-350 mg/mmol)
• Hypoalbuminemia (<3.0g/dL)
• Edema
• Hyperlipidemia 1

Classification:

• Congenital/infantile
• Primary/idiopathic (most common in adults: focal segmental glomerulosclerosis and membranous nephropathy)
• Secondary (due to diabetes, lupus, infections, etc.) 1, 2

Treatment Algorithm

1. Initial Management

• Fluid and sodium restriction

  • Restrict oral fluid intake to avoid marked edema
  • Avoid intravenous fluids and saline 3, 1

• Diuretics

  • Furosemide (0.5-2 mg/kg per dose, up to six times daily; maximum 10 mg/kg per day)
  • Administer at the end of albumin infusions unless marked hypovolemia is present 3
  • Consider combination therapy with thiazide or potassium-sparing diuretics for severe cases 1

• Antiproteinuric therapy

  • ACE inhibitors or ARBs to reduce proteinuria 1, 2
  • Monitor for hypotension and acute kidney injury

2. Disease-Specific Treatment

For Primary/Idiopathic Nephrotic Syndrome:

• Corticosteroids

  • High-dose oral prednisone (1mg/kg/day) for 4-16 weeks 1
  • Monitor for side effects, especially in pediatric patients (growth velocity, blood pressure, weight, intraocular pressure) 4

• For steroid-resistant cases:

  • Calcineurin inhibitors (cyclosporine, tacrolimus)
  • Mycophenolate mofetil
  • Anti-CD20 monoclonal antibodies (rituximab)
  • Cyclophosphamide 1, 5

For Genetic Forms:

• Avoid immunosuppressive agents as they are typically ineffective 3
• Consider genetic testing, especially in congenital/infantile cases 1

For Infection-Associated Nephrotic Syndrome:

• Treat with specific antimicrobial agents 3
• Screen for congenital infections 3

3. Management of Complications

• Thromboprophylaxis

  • Consider prophylactic anticoagulation in high-risk patients
  • Recommended when central venous access is required 3, 1

• Hyperlipidemia

  • Statins for persistent hyperlipidemia 1

• Edema management

  • Albumin infusions based on clinical indicators of hypovolemia (oliguria, acute kidney injury, prolonged capillary refill time, tachycardia, hypotension)
  • Do not administer albumin based solely on serum albumin levels 3

• Infection prevention

  • Monitor for signs of infection, especially in immunosuppressed patients 1

4. Special Considerations for Children

• Monitor growth velocity
• Consider growth hormone substitution in children with growth issues 3, 1
• Home administration of albumin infusions may be feasible after proper training 3

5. Monitoring and Follow-up

• Regular assessment of:

  • Renal function
  • Proteinuria
  • Blood pressure
  • Edema
  • Growth velocity in children 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

When to Consider Kidney Biopsy

• Adults with nephrotic syndrome without clear etiology
• Suspected underlying systemic disease (e.g., lupus)
• Steroid-resistant nephrotic syndrome
• Atypical presentation or course 1, 2

When to Consider Nephrectomy (for Congenital Nephrotic Syndrome)

• Persistent hypovolemia
• Thrombosis
• Failure to thrive despite optimal management 3

Common Pitfalls and How to Avoid Them

1. Treating based on serum albumin levels alone

   • Use clinical indicators of hypovolemia instead 3

2. Overreliance on immunosuppression for genetic forms

   • Perform genetic testing before initiating immunosuppression 3, 1

3. Fluid overload due to excessive fluid administration

   • Restrict sodium and fluid intake based on volume status assessment 1

4. Inadequate thromboprophylaxis

   • Consider anticoagulation in high-risk patients 3, 1

5. Failure to monitor for complications

   • Regular assessment for infections, thrombosis, and growth issues in children 1, 4

6. Delaying referral to specialists

   • Early referral to nephrology and transplant units when appropriate 3, 1