Management of Secondary Steroid-Resistant Nephrotic Syndrome

Immediate Stabilization

The American Academy of Pediatrics recommends continuing oxygen support to maintain SpO2 >92% and considering escalation to CPAP or mechanical ventilation if work of breathing worsens 2
The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest performing therapeutic pleural tap if respiratory distress worsens 2
Monitoring for pulmonary edema with serial chest examinations and considering chest X-ray if clinical deterioration occurs is recommended 2
The European Society of Pediatric Nephrology recommends resuming furosemide at 5.5 mg/kg/day in divided doses given the recurrent edema and respiratory compromise 2
Administering 20% albumin 0.5-1 g/kg IV over 2-4 hours immediately before each furosemide dose to enhance diuretic response in severely hypoalbuminemic patients is suggested 2
Restricting fluid intake to insensible losses plus urine output to prevent further volume overload is recommended 2
Monitoring strict intake/output, daily weights, and abdominal girth measurements is advised 2
Completing the septic workup immediately (blood culture, urine culture) given the new fever and prior history of fever with abdominal pain is necessary 2
Holding rituximab dose until infection is ruled out, as immunosuppression increases infection risk, is recommended 1

Proceeding with the 3rd dose of rituximab once infection is excluded, as this is the appropriate first-line steroid-sparing agent for SRNS after CNI failure, is suggested 1, 3
Planning for a 4th dose if edema persists after the 3rd dose, as some children require the full 4-dose course (375 mg/m² per dose), is recommended 1, 3
Continuing hydrocortisone stress dosing during acute illness rather than prednisolone is advised 1
Considering low-dose alternate-day prednisone (0.3-0.5 mg/kg on alternate days) as adjunctive therapy, though avoiding high-dose steroids given the 2-month failure initially, is suggested 1, 4

Monitoring urine protein daily with dipstick looking for trace/negative proteinuria for 3 consecutive days to define remission is recommended 4, 2
Measuring spot urine protein/creatinine ratio weekly to quantify response (partial remission = 50% reduction in proteinuria; complete remission = protein/creatinine <0.2) is advised 1, 2
Checking serum albumin weekly to assess for improvement is suggested 2
Assessing response to rituximab at 3-6 months after completing the course, as B-cell depletion takes time to translate into clinical improvement, is recommended 1, 3

Not giving rituximab during active infection - this child's fever and respiratory symptoms must be fully evaluated first, is recommended 3
Monitoring for opportunistic infections given the multiple immunosuppressive agents is advised 3
Not using diuretics alone without albumin supplementation in severely hypoalbuminemic patients, as efficacy is markedly reduced, is suggested 2
Avoiding excessive diuresis that could precipitate acute kidney injury or thrombotic complications is recommended 2
Avoiding restarting high-dose daily steroids given the prior 2-month failure and significant steroid-related complications is advised 1, 4
Not stopping rituximab after 2 doses - complete at least 3-4 doses before assessing efficacy, is recommended 1, 3

Considering mycophenolate mofetil dose escalation to 1200 mg/m²/day in divided doses (currently underdosed at 750 mg total daily) if rituximab fails, is suggested 1, 3
Pursuing genetic testing urgently if not already done, as monogenic SRNS (likely given age <5 years and steroid resistance) won't respond to immunosuppression, is recommended 1
Referring for consideration of novel therapies or clinical trials is advised 1, 3
Kidney biopsy should have been performed at diagnosis of steroid resistance (after 8 weeks of steroid failure) to guide therapy and assess for FSGS vs. other pathology, is recommended 1, 4