What is the treatment for acute kidney injury (AKI) stage 4 in children with Glomerulonephritis with crescents (GNAPS)?

Treatment of Acute Kidney Injury Stage 4 in Children with Glomerulonephritis with Crescents (GNAPS)

For children with rapidly progressive crescentic glomerulonephritis (GNAPS), high-dose glucocorticoids combined with cyclophosphamide is the recommended treatment approach to address acute kidney injury stage 4. 1

Initial Management

• Begin high-dose glucocorticoids with intravenous pulse methylprednisolone followed by oral prednisone, similar to the regimen used for ANCA-associated vasculitis 1
• Add cyclophosphamide as the primary immunosuppressive agent for crescentic glomerulonephritis with rapidly progressive renal deterioration 1
• Consider rituximab as an alternative to cyclophosphamide in patients with contraindications to cyclophosphamide 1
• Perform kidney biopsy during episodes of macroscopic hematuria if kidney function does not improve within 5 days of onset 1

Supportive Care for AKI

• Implement meticulous fluid management to prevent both dehydration and fluid overload 2, 3
• Monitor and correct electrolyte abnormalities, particularly potassium, which should be limited in children at risk of hyperkalemia 1, 4
• Maintain acid-base balance, treating metabolic acidosis if serum bicarbonate is <22 mmol/l 1
• Provide nutritional support tailored to the child's metabolic needs 2, 3

Renal Replacement Therapy

• Initiate renal replacement therapy when there are metabolic or clinical complications of AKI that cannot be managed conservatively 3
• Consider peritoneal dialysis as the preferred initial modality for hemodynamically unstable children, especially in resource-limited settings 5, 3
• Hemodialysis or continuous renal replacement therapy may be more appropriate for children with severe fluid overload or those who are critically ill 2, 6
• The timing of renal replacement therapy initiation should be based on the presence of uremia, fluid overload, electrolyte disturbances, and acid-base abnormalities rather than arbitrary laboratory values 7, 3

Blood Pressure Management

• Use angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) at maximally tolerated doses for controlling hypertension and proteinuria 1, 8
• Target 24-hour mean arterial pressure in children at ≤50th percentile for age, sex, and height by ambulatory blood pressure monitoring 1
• Consider temporarily holding RAS inhibitors during acute illness with risk of volume depletion 1
• Add diuretics if blood pressure remains elevated despite RAS blockade 1

Special Considerations

• For children with Henoch-Schönlein purpura nephritis with crescents and deteriorating kidney function, use the same approach as for crescentic IgA nephropathy 8
• In children with persistent proteinuria >1 g/day/1.73m² despite ACEi/ARB therapy, consider a 6-month course of corticosteroids 8
• Avoid nephrotoxic medications, particularly NSAIDs, which can worsen kidney injury 4, 8
• Screen for latent infections prior to initiating immunosuppression 1

Monitoring and Follow-up

• Regularly assess kidney function, electrolytes, and acid-base status 2, 3
• Monitor for complications of immunosuppressive therapy, including infections and malignancies 1
• Ensure appropriate vaccination status prior to immunosuppression when possible 1
• Arrange long-term follow-up as children who experience AKI are at risk for late development of chronic kidney disease 2, 3

Treatment Algorithm Based on Clinical Presentation

1. For crescentic GNAPS with rapidly progressive deterioration:

   • High-dose glucocorticoids + cyclophosphamide 1

2. For GNAPS with nephrotic syndrome without rapid progression:

   • Glucocorticoids with consideration of steroid-sparing agents 1, 8

3. For GNAPS with eGFR <30 ml/min/1.73m² without active inflammation:

   • Focus on supportive care unless there is evidence of active inflammation 1

4. For GNAPS with AKI and macroscopic hematuria:

   • Supportive care initially, with kidney biopsy if no improvement within 5 days 1