What is the treatment approach for a 7-year-old child with an 8th relapse of nephrotic syndrome, hypoalbuminemia (low albumin level), and no prior renal biopsy?

Treatment for a 7-Year-Old Child with Frequent Relapse Nephrotic Syndrome

For a 7-year-old child with an 8th relapse of nephrotic syndrome and albumin of 1.5 g/dL, rituximab is recommended as an effective steroid-sparing agent, administered as a single dose of 375 mg/m² intravenously, with potential for a second dose if needed based on B-cell recovery and clinical response.

Initial Management of Current Relapse

• First, treat the current relapse with oral prednisone at 60 mg/m² per day (maximum 60 mg) daily until remission (urine dipstick trace/negative for at least 3 consecutive days) 1
• Once remission is achieved, decrease prednisone to 40 mg/m² per day on alternate days for 1 week, then taper by 10 mg/m² per week to complete a total of 4 weeks 1
• Consider albumin infusion only if there are clinical indicators of hypovolemia (tachycardia, hypotension, oliguria, prolonged capillary refill time) rather than based solely on the low albumin level 2
• If albumin infusion is necessary, administer furosemide (0.5-2 mg/kg) at the end of the infusion to enhance diuresis 2

Long-term Management Strategy

Rituximab Administration Protocol

• Administer rituximab as a single intravenous infusion of 375 mg/m² 1
• Prior to infusion:
  • Premedicate with acetaminophen and an antihistamine to reduce infusion reactions 1
  • Ensure B-cell counts (CD19/CD20) are measured before administration to establish baseline 1
• Monitor for infusion reactions during administration (fever, chills, rash) 1
• Consider a second dose after 1-3 months if B-cell recovery occurs with early signs of relapse 1

Rationale for Rituximab

• The child has had 8 relapses, qualifying as frequently relapsing/steroid-dependent nephrotic syndrome, which warrants steroid-sparing therapy 1
• Rituximab has shown effectiveness in both frequently relapsing and steroid-dependent forms of nephrotic syndrome 1
• The KDIGO 2021 guidelines specifically recommend rituximab as an appropriate steroid-sparing agent for children with steroid-dependent nephrotic syndrome 1
• The low albumin level (1.5 g/dL) indicates severe disease activity requiring aggressive management 3

Additional Management Considerations

• A kidney biopsy should be considered at this point given the frequent relapses and severe hypoalbuminemia, as this may help guide further therapy 1
• Monitor for potential complications:
  • Thromboembolism risk is increased with severe hypoalbuminemia; consider prophylactic anticoagulation if immobilized or with central venous access 4
  • Infection risk is elevated; ensure appropriate vaccinations are up to date 5
  • Monitor growth and development, as frequent steroid courses can affect linear growth 6

Alternative Therapies if Rituximab is Unavailable

If rituximab is not available or contraindicated, consider these alternatives in order of preference:

1. Calcineurin inhibitors (cyclosporine or tacrolimus) 1, 7
2. Mycophenolate mofetil 1, 7
3. Cyclophosphamide (2 mg/kg/day for 12 weeks, maximum cumulative dose 168 mg/kg) 1
4. Levamisole (if available, 2.5 mg/kg on alternate days) 1

Follow-up and Monitoring

• Monitor urine protein regularly to detect early relapse 7
• After rituximab administration, check CD19/CD20 B-cell counts every 1-3 months 1
• Monitor serum albumin, renal function, and lipid profile regularly 7
• Assess for steroid-related side effects and growth parameters at each visit 6

Important Caveats

• The absence of a previous biopsy is concerning after multiple relapses; histological confirmation should be considered to rule out other glomerular pathologies 1
• Children with frequent relapses before age 6 years and those with delayed response to initial steroid therapy are at higher risk for continued relapses 3
• Rituximab can cause infusion reactions and increases infection risk; careful monitoring during and after administration is essential 1