What is the treatment for prerenal failure in a child with Steroid-Resistant Nephrotic Syndrome (SRNS)?

Treatment of Prerenal Failure in Children with Steroid-Resistant Nephrotic Syndrome

Immediate volume restoration with albumin infusion followed by diuretics is the cornerstone of treating prerenal failure in children with SRNS, while simultaneously continuing or initiating calcineurin inhibitor therapy for the underlying nephrotic syndrome. 1, 2

Immediate Stabilization and Volume Management

The priority is restoring effective circulating volume while managing fluid overload:

• Administer 20% albumin 0.5-1 g/kg IV over 2-4 hours immediately before each diuretic dose to enhance intravascular volume and improve renal perfusion in severely hypoalbuminemic patients 1
• Resume or initiate furosemide at appropriate doses (typically starting at 1-2 mg/kg/dose, up to 5.5 mg/kg/day in divided doses for severe cases) after albumin administration 1
• Restrict fluid intake to insensible losses plus urine output to prevent worsening volume overload while addressing prerenal azotemia 1, 2
• Monitor strict intake/output, daily weights, serum creatinine, and electrolytes to assess response and detect acute kidney injury 1, 2

Critical distinction: Prerenal failure in SRNS represents a paradox—these children are simultaneously volume overloaded (total body fluid) yet intravascularly depleted (effective circulating volume) due to severe hypoalbuminemia. Never use diuretics alone without albumin supplementation, as efficacy is markedly reduced and may worsen prerenal azotemia. 1

Immunosuppressive Management for Underlying SRNS

While managing prerenal failure, continue or initiate definitive treatment for SRNS:

• Calcineurin inhibitors (CNIs) are the first-line immunosuppressive therapy after steroid failure: cyclosporine 4-5 mg/kg/day or tacrolimus 0.1 mg/kg/day 3, 2
• Continue CNI for minimum 6 months; if partial or complete remission is achieved by 6 months, continue for at least 12 months 3, 2
• Add low-dose corticosteroid therapy (not high-dose) combined with CNI therapy 3
• Initiate ACE inhibitor or ARB for antiproteinuric effect and renal protection 3, 2

Monitoring Renal Function During Treatment

Distinguish between prerenal azotemia (reversible) and intrinsic acute kidney injury:

• Check serum creatinine and electrolytes immediately when oliguria develops 2
• Monitor urine output closely—improvement in urine flow after albumin-diuretic therapy suggests prerenal etiology 4
• If urine flow was >0.3 mL/minute before intervention, prognosis is more favorable 4
• Assess for signs of adequate perfusion: reversal of mental status changes, improved capillary refill, increased toe temperature 4

Second-Line Therapies if CNI Fails

If no partial or complete remission after 6 months of CNI therapy:

• Consider mycophenolate mofetil at appropriate dosing: 1200 mg/m²/day in two divided doses 3, 1, 2
• High-dose corticosteroids or combination therapy may be considered 3
• Rituximab (375 mg/m² per dose for 3-4 doses) is an option for CNI-resistant SRNS, though efficacy is more established in steroid-sensitive disease 3, 1
• Avoid cyclophosphamide in SRNS—it is not effective per guidelines 3, 2

Essential Diagnostic Workup

These should be completed if not already done:

• Kidney biopsy is required to define the cause of SRNS and guide therapy (most commonly shows focal segmental glomerulosclerosis) 3, 1
• Genetic testing is strongly recommended, especially in children <5 years old, as monogenic SRNS (due to podocyte gene mutations) will not respond to immunosuppression 3, 1, 5
• Evaluation of kidney function by GFR or eGFR and quantitation of urine protein excretion 3

Critical Pitfalls to Avoid

• Never give diuretics without albumin in severely hypoalbuminemic patients—this worsens effective circulating volume and prerenal failure 1
• Avoid excessive diuresis that could precipitate thrombotic complications (nephrotic syndrome is a hypercoagulable state) 1
• Do not delay CNI initiation—early aggressive treatment improves remission rates 6, 7
• Stop CNI therapy only if no partial or complete remission is achieved by 6 months; otherwise continue for at least 12 months 3, 2
• Monitor for CNI nephrotoxicity with regular serum creatinine and drug levels 7, 8
• Rule out infection before administering rituximab or other intensive immunosuppression 1

Expected Outcomes and Prognosis

• Approximately 50-65% of children with SRNS achieve partial or complete remission with CNI therapy 7, 8
• Patients whose physiological parameters have not undergone extreme deterioration respond better—shorter time between symptom onset and treatment initiation improves prognosis 4
• Without achieving remission, significant proportion progress to end-stage renal disease 6, 5, 8
• Children with genetic forms of SRNS have lower risk of recurrence after kidney transplantation compared to immune-mediated forms 5