What is the initial workup and treatment for a patient presenting with nephrotic syndrome?

Initial Workup and Treatment for Nephrotic Syndrome

The initial workup for nephrotic syndrome should include confirmation of nephrotic-range proteinuria, investigations to exclude secondary causes, and 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

Diagnostic Workup

• Confirm nephrotic syndrome diagnosis with 24-hour urine collection or spot urine protein-to-creatinine ratio 1
• Refer patients to specialized teams in tertiary nephrology centers for multidisciplinary management, as this condition requires expertise 1, 2
• Perform comprehensive investigations to exclude secondary causes including:
  • Diabetes mellitus
  • Systemic lupus erythematosus
  • Infections
  • Medication review 1
• Consider genetic testing as a first-line diagnostic measure, especially in congenital or early-onset cases, using massively parallel sequencing or whole-exome sequencing 3, 2
• Extended diagnostic workup should identify non-kidney manifestations of hereditary forms (neurological status, sight, hearing, dysmorphic features) 3

Kidney Biopsy Indications

• In children with typical presentation, biopsy may be deferred if there is response to initial steroid therapy 1
• Biopsy is indicated in the following scenarios:
  • Steroid-resistant nephrotic syndrome in children
  • Adult patients with nephrotic syndrome
  • Atypical presentations (hematuria, hypertension, renal insufficiency)
  • Suspicion of secondary causes 1

Initial Treatment Approach

• Restrict dietary sodium to <2.0 g/day to reduce edema and help manage proteinuria 1
• Use loop diuretics as first-line agents for edema management 1
• Initiate ACE inhibitors or ARBs at maximally tolerated doses for proteinuria and blood pressure control 1
• Target systolic blood pressure <120 mmHg in adults using standardized office BP measurement 1
• Avoid intravenous fluids and saline when possible; concentrate oral fluid intake if necessary 2
• Administer albumin infusions only based on clinical indicators of hypovolemia, not based solely on serum albumin levels 1, 2

Specific Treatment Based on Histology

• For minimal change disease:
  • Administer oral prednisone/prednisolone at 1 mg/kg/day (max 80 mg) or alternate-day dose of 2 mg/kg (max 120 mg) 1
  • In children, administer prednisone at 60 mg/m² per day (maximum 80 mg/day) or 2 mg/kg/day for 4-6 weeks 1
  • Continue high-dose corticosteroids for a minimum of 4 weeks and up to 16 weeks as tolerated or until complete remission 1
• For focal segmental glomerulosclerosis:
  • Confirm idiopathic FSGS before initiating immunosuppressive therapy 1
  • Consider calcineurin inhibitors as first-line therapy for patients with contraindications to corticosteroids 1
• For membranous nephropathy:
  • Initiate therapy only when urinary protein persistently exceeds 4 g/day and remains >50% of baseline despite 6 months of conservative therapy, or when severe symptoms are present 1

Monitoring and Complications Management

• Administer pneumococcal and influenza vaccines to prevent infections 1, 4
• Consider prophylactic trimethoprim-sulfamethoxazole for patients receiving high-dose immunosuppression 1
• Monitor for potential complications:
  • Infections (peritonitis, sepsis, cellulitis)
  • Thromboembolism (venous thrombosis, pulmonary embolism)
  • Hypovolemic crisis
  • Cardiovascular problems (hyperlipidemia)
  • Acute renal failure
  • Anemia 4, 5
• Regularly assess proteinuria and kidney function to evaluate treatment response 1
• Monitor for side effects of medications, particularly with long-term immunosuppressive therapy 1, 6
• In pediatric patients, carefully monitor growth velocity as it may be affected by corticosteroid therapy 6

Special Considerations

• For congenital nephrotic syndrome (onset within first 3 months of life), refer to specialized pediatric nephrology units 3, 1
• Consider early referral to transplant center for patients with progressive disease to minimize time on dialysis 3
• For frequently relapsing nephrotic syndrome, consider steroid-sparing agents such as rituximab, calcineurin inhibitors, mycophenolate mofetil, cyclophosphamide, or levamisole 2, 7
• When stable, transition to ambulatory management to increase quality of life, decrease risk of nosocomial infections, and reduce treatment costs 2