What is the initial treatment for nephrotic syndrome?

Initial Treatment of Nephrotic Syndrome

The initial treatment for nephrotic syndrome should begin with supportive management including sodium restriction (<2.0 g/day), loop diuretics for edema, and ACE inhibitors or ARBs at maximally tolerated doses, while immunosuppressive therapy with corticosteroids (prednisone 1 mg/kg/day, maximum 80 mg) is reserved for specific indications based on the underlying pathology. 1, 2

Immediate Supportive Management (All Patients)

Dietary and Fluid Management:

• Restrict dietary sodium to <2.0 g/day to reduce edema and proteinuria 1, 2
• Avoid intravenous fluids and saline, which worsen edema 3, 2
• Concentrate oral fluid intake if necessary 3

Edema Control:

• Administer loop diuretics (furosemide) as first-line agents for managing edema and anasarca 1, 2
• Avoid routine intravenous albumin infusions; use only when clinical indicators of hypovolemia are present (hypotension, tachycardia, prolonged capillary refill time, oliguria, acute kidney injury), not based on serum albumin levels alone 3, 2

Antiproteinuric Therapy:

• Initiate ACE inhibitors (lisinopril) or ARBs (losartan) at maximally tolerated doses for proteinuria reduction and blood pressure control 1, 2, 4, 5
• Target systolic blood pressure <120 mmHg using standardized office measurement 1
• These agents reduce glomerular protein loss via dose-dependent mechanisms 3

Corticosteroid Therapy (Disease-Specific)

Adults with Primary Nephrotic Syndrome:

• Administer prednisone 1 mg/kg/day (maximum 80 mg) as a single daily dose, or alternate-day dosing at 2 mg/kg (maximum 120 mg) 1, 2
• Continue high-dose therapy for a minimum of 4 weeks and up to 16 weeks as tolerated or until complete remission is achieved 1, 2
• After achieving complete remission, taper corticosteroids slowly over 6 months 3
• Do not declare steroid resistance until at least 8 weeks of adequate therapy has been completed 2

Children with Nephrotic Syndrome:

• Administer prednisone 60 mg/m²/day (maximum 60 mg) as a single daily dose for 4-6 weeks 2
• Follow with alternate-day dosing at 40 mg/m² per dose (maximum 40 mg on alternate days) for 2-5 months with gradual tapering 2
• Total initial treatment duration should be at least 12 weeks, with evidence supporting up to 6 months for reduced relapse rates 2
• In children with typical presentation, kidney biopsy may be deferred if there is response to initial steroid therapy 1

Alternative First-Line Therapy (Steroid Contraindications)

Calcineurin Inhibitors (CNIs):

• Consider CNIs as first-line therapy for patients with contraindications to high-dose corticosteroids, including uncontrolled diabetes mellitus, severe psychiatric conditions, severe osteoporosis, or morbid obesity with elevated HbA1c 2
• Cyclosporine: 3-5 mg/kg/day divided into 2 doses 3, 2
• Tacrolimus: 0.1-0.2 mg/kg/day divided into 2 doses (children) or 0.05-0.1 mg/kg/day (adults) 3, 2
• Critical caveat: CNIs must be used with caution in patients with significant vascular or interstitial disease on renal biopsy and in those with decreased eGFR 3

Disease-Specific Treatment Thresholds

Membranous Nephropathy:

• Start initial immunosuppressive therapy only when urinary protein excretion persistently exceeds 4 g/day AND remains >50% of baseline despite 6 months of conservative therapy with ACE inhibitors/ARBs and sodium restriction 3, 1
• Alternative indications: severe, disabling, or life-threatening symptoms related to nephrotic syndrome, or serum creatinine risen by 30% or more within 6-12 months (with eGFR not less than 25-30 mL/min/1.73 m²) 3
• When indicated, administer a 6-month course of alternating monthly cycles of oral and intravenous corticosteroids with oral alkylating agents 3

Focal Segmental Glomerulosclerosis (FSGS):

• Confirm idiopathic FSGS before initiating immunosuppressive therapy 1
• For steroid-resistant FSGS, the combination of 12-month MMF with high-dose dexamethasone induces 33% combined partial and complete remission 3

Minimal Change Disease:

• Oral prednisone/prednisolone at 1 mg/kg/day (maximum 80 mg) or alternate-day dose of 2 mg/kg (maximum 120 mg) 1

Infection Prevention (Critical During Immunosuppression)

• Administer pneumococcal vaccination (23-valent or conjugate vaccine) before or early in immunosuppressive therapy 1, 2
• Give annual influenza vaccination to patients and household contacts 1, 2
• Consider prophylactic trimethoprim-sulfamethoxazole for patients receiving high-dose immunosuppression 1

Monitoring Treatment Response

• Monitor urine protein daily using dipstick or spot urine protein-to-creatinine ratio 1, 2
• Define complete remission as urine protein <200 mg/g (<20 mg/mmol) or trace/negative on dipstick for 3 consecutive days 2
• Regularly assess kidney function (serum creatinine, eGFR) to evaluate treatment response 1
• Monitor for medication side effects, particularly with long-term immunosuppressive therapy 1

Special Populations

Congenital Nephrotic Syndrome:

• Refer immediately to specialized pediatric nephrology units due to disease complexity 3, 1
• Use albumin infusions based on clinical indicators of hypovolemia (oliguria, acute kidney injury, prolonged capillary refill time, tachycardia, hypotension), not serum albumin levels 3
• Consider ambulatory management when possible to improve quality of life and reduce nosocomial infection risk 3

Secondary Causes:

• Perform investigations to exclude secondary causes in all cases, including diabetes mellitus, systemic lupus erythematosus, infections, and medication review 1
• Kidney biopsy is typically indicated for diagnosis in adults, except in patients with positive serum anti-phospholipase A2 receptor antibodies (diagnostic of membranous nephropathy) 6

Common Pitfalls to Avoid

• Do not stop therapy prematurely if partial response is occurring; continue up to 16 weeks in appropriate patients 2
• Avoid declaring treatment failure before at least 6 months following completion of initial immunosuppressive regimen, unless kidney function is deteriorating or severe symptoms are present 3
• Do not routinely use intravenous albumin based solely on low serum albumin levels 3, 2
• Avoid central venous lines when possible due to high thrombosis risk; if required, administer prophylactic anticoagulation for the duration of line placement 3