What is the initial workup and treatment for nephrotic syndrome?

Initial Workup and Treatment for Nephrotic Syndrome

The initial workup for nephrotic syndrome should include investigations to exclude secondary causes, followed by supportive management with sodium restriction, diuretics, and ACE inhibitors/ARBs, while immunosuppressive therapy should be tailored based on the underlying pathology identified through kidney biopsy.1, 2

Definition and Diagnosis

• Nephrotic syndrome is characterized by proteinuria (>3.5g/day), hypoalbuminemia (<3.0g/dL), peripheral edema, and often hyperlipidemia 3, 4
• In children, nephrotic syndrome is defined as proteinuria (UPCR ≥2 g/g) with serum albumin ≤2.5 g/dL 1

Initial Diagnostic Workup

• Confirm nephrotic-range proteinuria with 24-hour urine collection or spot urine protein-to-creatinine ratio 1, 4
• Measure serum albumin, lipid profile, and kidney function (serum creatinine, eGFR) 3, 4
• Perform investigations to exclude secondary causes in all cases 1:
  • Diabetes mellitus (HbA1c, fasting glucose)
  • Systemic lupus erythematosus (ANA, anti-dsDNA, complement levels)
  • Infections (hepatitis B, hepatitis C, HIV, syphilis screening)
  • Medications review (NSAIDs, gold, penicillamine)
  • Malignancy screening when clinically indicated 2, 4

Kidney Biopsy Indications

• In adults, kidney biopsy is generally recommended to determine the underlying pathology 3, 4
• In children with typical presentation, biopsy may be deferred if there is response to initial steroid therapy 1
• Biopsy is indicated in steroid-resistant nephrotic syndrome in children 1
• Consider biopsy when there is:
  • Rapidly deteriorating kidney function
  • Suspicion of secondary causes
  • Atypical presentation (hematuria, hypertension) 1

Initial Supportive Management

• Restrict dietary sodium to <2.0 g/day to reduce edema and help manage proteinuria 2
• Use loop diuretics as first-line agents for edema management 2, 3
• Initiate ACE inhibitors or ARBs at maximally tolerated doses for proteinuria and blood pressure control 2, 3
• Target systolic blood pressure <120 mmHg in adults using standardized office BP measurement 2
• Adjust protein intake based on degree of proteinuria and kidney function:
  • For nephrotic-range proteinuria: 0.8-1 g/kg/day with additional protein to compensate for losses (up to 5 g/day) 2
  • For eGFR <60 ml/min/1.73 m² with nephrotic-range proteinuria: limit to 0.8 g/kg/day 2

Specific Treatment Based on Underlying Pathology

Minimal Change Disease (MCD)

• In children: Oral prednisone/prednisolone at 1 mg/kg/day (max 80 mg) or alternate-day dose of 2 mg/kg (max 120 mg) 1
• Treatment duration: 8 weeks (4 weeks daily + 4 weeks alternate-day) or 12 weeks (6 weeks daily + 6 weeks alternate-day) 1
• In adults: Similar corticosteroid regimen for initial treatment, maintained for at least 4 weeks if complete remission is achieved, and up to 16 weeks if not 1
• Taper corticosteroids slowly over 6 months after achieving remission 1

Focal Segmental Glomerulosclerosis (FSGS)

• Confirm idiopathic FSGS before initiating immunosuppressive therapy 1
• For steroid-resistant FSGS, cyclosporine at 3-5 mg/kg/day in divided doses for at least 4-6 months 1
• If partial or complete remission occurs, continue cyclosporine for at least 12 months, followed by slow taper 1
• For patients who don't tolerate cyclosporine, consider mycophenolate mofetil (MMF) with high-dose dexamethasone 1

Membranous Nephropathy (MN)

• Initial therapy should be started only when:
  • Urinary protein persistently exceeds 4 g/day and remains >50% of baseline despite 6 months of conservative therapy, or
  • Severe, disabling symptoms are present, or
  • Serum creatinine has risen by ≥30% within 6-12 months 1
• Recommended initial therapy: 6-month course of alternating monthly cycles of oral and IV corticosteroids with oral alkylating agents (cyclophosphamide preferred over chlorambucil) 1
• For patients who cannot tolerate this regimen, consider cyclosporine or tacrolimus for at least 6 months 1, 2

Monitoring and Complications Management

• Monitor for thromboembolism, which is a significant risk in nephrotic syndrome 5, 4
• Consider prophylactic anticoagulation for high-risk patients, particularly those with membranous nephropathy 4
• Administer pneumococcal and influenza vaccines to prevent infections 2
• Consider prophylactic trimethoprim-sulfamethoxazole for patients receiving high-dose immunosuppression 2
• Regularly assess proteinuria and kidney function to evaluate treatment response 2
• Monitor for side effects of medications, particularly with long-term immunosuppressive therapy 2

Special Considerations for Congenital Nephrotic Syndrome

• Refer children with congenital nephrotic syndrome to specialized pediatric nephrology units 1
• Avoid intravenous fluids and saline; concentrate oral fluid intake if necessary 1
• Use albumin infusions based on clinical indicators of hypovolaemia, not serum albumin levels 1
• Consider ambulatory management when possible to improve quality of life and reduce infection risk 1