What is the treatment for nephrotic syndrome?

Treatment of Nephrotic Syndrome

Begin treatment with prednisone 60 mg/m²/day (or 2 mg/kg/day, maximum 60 mg) as a single daily dose for 6 weeks, followed by alternate-day prednisone 40 mg/m² for at least 6 additional weeks, with total treatment duration of at least 12 weeks. 1

Initial Corticosteroid Therapy

For Children:

• Start prednisone at 60 mg/m²/day or 2 mg/kg/day (maximum 60 mg/day) as a single daily dose 1, 2
• Continue daily dosing for 6 weeks to maximize initial response 1
• After initial response, transition to alternate-day prednisone at 40 mg/m² or 1.5 mg/kg (maximum 40 mg on alternate days) 1, 2
• Total treatment duration should be at least 12 weeks, with evidence supporting up to 6 months for reduced relapse rates 1
• Monitor urine protein daily using dipstick or spot urine protein-to-creatinine ratio 1
• Complete remission is defined as urine protein <200 mg/g or trace/negative on dipstick for 3 consecutive days 1

For Adults:

• Initial dose is 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
• Adults require longer treatment duration (>16 weeks) to achieve remission rates of 80% compared to 50-60% with shorter courses 1
• Do not stop therapy prematurely if partial response is occurring; continue up to 16 weeks 1

Immediate Supportive Management

Edema Control:

• Restrict dietary sodium to <2.0 g/day as first-line intervention 1, 3
• Administer loop diuretics (furosemide 0.5-2 mg/kg per dose) only in patients with intravascular volume overload and preserved renal function 1, 3, 4
• Critical pitfall: Do not give diuretics to patients with evidence of intravascular hypovolemia (prolonged capillary refill time, tachycardia, hypotension) despite low serum albumin—this worsens intravascular depletion 4, 2
• Furosemide can be given up to 6 times daily (maximum 10 mg/kg per day) based on edema severity 2, 3
• If albumin infusions are administered, give furosemide 0.5-2 mg/kg at the end of each infusion unless marked hypovolemia or hyponatremia is present 3, 2

Albumin Administration:

• Avoid routine intravenous albumin infusions; use only if clinical indicators of hypovolemia are present (hypotension, tachycardia, poor perfusion, oliguria, acute kidney injury) 1, 4, 2
• Do not administer albumin based solely on serum albumin levels 4, 2
• Avoid intravenous saline administration, which can worsen edema 1

Proteinuria and Blood Pressure Management

• Initiate ACE inhibitors or ARBs as first-line therapy for proteinuria reduction and blood pressure control 4, 2
• Target proteinuria <1 g/day when feasible 4
• Target blood pressure <130/80 mmHg in most patients 4
• Monitor electrolytes and creatinine frequently after starting RAS inhibitors 4
• For congenital nephrotic syndrome, combined ACE inhibitor therapy reduces glomerular protein loss via dose-dependent mechanisms 2

Management of Relapses

• Treat relapses with prednisone 60 mg/m²/day or 2 mg/kg (maximum 60 mg/day) until remission for at least 3 days 1
• After achieving remission, switch to alternate-day prednisone (40 mg/m² or 1.5 mg/kg) for at least 4 weeks 1
• Relapse is defined as ≥3+ protein on urine dipstick for 3 consecutive days or uPCR ≥2000 mg/g 1
• Approximately 80% of children will experience at least one relapse, and 50% will have frequent relapses or become steroid-dependent 1
• During upper respiratory tract infections in children with frequent relapses, daily prednisone at 0.5 mg/kg/day for 5-7 days may reduce relapse risk 1

Steroid-Sparing Agents for Frequent Relapses or Steroid-Dependent Disease

For frequent relapses (≥2 relapses in 6 months) or steroid-dependent disease, consider:

• Cyclophosphamide: 2 mg/kg/day for 8-12 weeks (maximum cumulative dose <200 mg/kg to minimize gonadal toxicity) 2, 1
• Cyclosporine: 3-5 mg/kg/day in divided doses, with target trough levels 50-100 ng/ml 2, 1
• Tacrolimus: 0.1-0.2 mg/kg/day in divided doses for children; 0.05-0.1 mg/kg/day for adults 2, 1
• Levamisole: 2.5 mg/kg on alternate days for 12-24 months 2
• Mycophenolate mofetil or rituximab as alternative options 1

Alternative First-Line Therapy

• For patients with contraindications to high-dose corticosteroids, consider calcineurin inhibitors as first-line therapy 1
• Cyclosporine produces complete remissions in 85% of children and 79% of adults with steroid dependence 5

Prevention of Complications

Thromboembolism:

• Prophylactic anticoagulation should be employed when thromboembolism risk exceeds bleeding risk, specifically when serum albumin <20-25 g/L plus other risk factors 4, 3
• Use low-molecular-weight heparin or unfractionated heparin 5000 U subcutaneously twice daily for prophylaxis during high-risk periods 4
• If central venous access is required, administer prophylactic anticoagulation for as long as the line is in place 2

Infection Prevention:

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

Metabolic Complications:

• Supplement with vitamin D (colecalciferol) or 25-OH-D3 (calcifediol) and calcium (250-500 mg/day) when 25-OH-D3 is low, ionized calcium is low, or PTH is elevated 3, 4
• Consider statin therapy for persistent hyperlipidemia, particularly in patients with additional cardiovascular risk factors 3, 4
• Monitor and treat iron deficiency; administer erythropoietin in patients with anemia despite iron supplementation 3

Special Populations

Children Under 1 Year:

• Do not treat with standard regimen without further evaluation, as they are more likely to have genetically definable causes requiring different management 1
• Refer rapidly to specialized pediatric nephrology centers for multidisciplinary management 4, 2
• Pursue stepwise approach with prolonged conservative management; avoid routine early nephrectomies 4, 2
• Do not use immunosuppressive agents for genetic forms of nephrotic syndrome as they are unlikely to respond 4, 2

Elderly Patients:

• Elderly patients are at particular risk of hip osteonecrosis with prolonged glucocorticoid therapy, especially post-menopausal women 1, 6
• Start at the low end of the dosing range, reflecting greater frequency of decreased hepatic, renal, or cardiac function 6
• Consider increased risk of diabetes mellitus, fluid retention, and hypertension 6

Critical Pitfalls to Avoid

• Do not discontinue steroids too rapidly, as this increases relapse risk 1
• Do not administer diuretics to hypovolemic patients despite low serum albumin—this worsens intravascular depletion 4, 2
• Do not give albumin infusions based solely on serum albumin levels—only for clinical hypovolemia 4, 2
• Do not stop therapy prematurely if partial response is occurring; continue up to 16 weeks 1
• Avoid central venous lines when possible due to high risk of thrombosis 2

Monitoring During Treatment

• Monitor urine protein daily using dipstick or spot urine protein-to-creatinine ratio to assess treatment response 1
• Carefully observe with frequent measurements of blood pressure, weight, height, intraocular pressure, and clinical evaluation for infection, psychosocial disturbances, thromboembolism, peptic ulcers, cataracts, and osteoporosis 6
• Monitor linear growth in pediatric patients, as growth velocity may be a more sensitive indicator of systemic corticosteroid exposure than HPA axis function tests 6