Treatment of Acute Glomerulonephritis in Children with Hypercholesterolemia
In children with acute glomerulonephritis presenting with hypercholesterolemia (indicating nephrotic syndrome), treatment should focus on supportive care with diuretics, antihypertensives, and fluid/sodium restriction, while reserving immunosuppression only for severe crescentic disease with deteriorating renal function. 1, 2
Understanding the Clinical Context
Hypercholesterolemia in acute glomerulonephritis indicates nephrotic syndrome, which occurs when significant proteinuria leads to hypoalbuminemia and compensatory hepatic lipoprotein synthesis. 1 The specific etiology of the glomerulonephritis determines the treatment approach:
Post-Streptococcal Glomerulonephritis (Most Common)
Post-streptococcal glomerulonephritis requires only supportive management in the vast majority of cases, as it is self-limited with excellent prognosis. 1, 2
- Treat with penicillin (or erythromycin if penicillin-allergic) even without persistent infection to decrease antigenic load 1
- Manage nephritic syndrome with diuretics, antihypertensives, and supportive care 1, 2
- Most children recover completely within 2-4 weeks without immunosuppression 2
- Corticosteroids should only be considered for severe crescentic glomerulonephritis based on anecdotal evidence 1
- Evidence shows no advantage of immunosuppressants over supportive therapy alone for crescentic post-streptococcal glomerulonephritis 3
Membranoproliferative Glomerulonephritis (MPGN)
If biopsy reveals MPGN with nephrotic syndrome and progressive renal decline:
Consider alternate-day prednisone 40 mg/m² for 6-12 months (potentially longer with clear clinical response) as first-line therapy. 1
- Level 1 evidence shows renal survival at 130 months was 61% with prednisone versus 12% with placebo (P=0.07) 4
- Treatment duration of 38 months in one series showed decreased glomerular inflammatory activity in 88% of patients 5
- Important caveat: Hypercholesterolemia is associated with reduced therapeutic effect of cyclosporin 1, making this relevant if second-line therapy is needed
- For patients failing steroids with nephrotic syndrome AND progressive decline, consider oral cyclophosphamide or mycophenolate mofetil plus low-dose corticosteroids for less than 6 months 1
Henoch-Schönlein Purpura (HSP) Nephritis
For HSP with nephrotic-range proteinuria:
- Start with ACE inhibitors or ARBs for persistent significant proteinuria 1
- Reserve corticosteroids only for nephrotic-range proteinuria that has not improved after trial of angiotensin blockade 1
- For crescentic HSP with nephrotic syndrome and/or deteriorating function, use high-dose intravenous methylprednisolone 1
- Cyclophosphamide (2 mg/kg/day for 12 weeks) plus corticosteroids showed significant reduction in proteinuria in one retrospective series 6
Critical Management Principles
Supportive Care (All Types)
- Fluid and sodium restriction 2
- Antihypertensive therapy (ACE inhibitors/ARBs preferred for proteinuria reduction) 1
- Monitor for complications including acute kidney injury requiring dialysis 1
When to Avoid Immunosuppression
Do not use immunosuppression in patients with: 1
- Advanced chronic kidney disease
- Severe tubulointerstitial fibrosis
- Small kidney size
- Findings consistent with chronic inactive disease
- Normal eGFR with non-nephrotic-range proteinuria (good long-term outcome with conservative management)
Common Pitfalls
- Do not routinely use corticosteroids for post-streptococcal glomerulonephritis - the disease is self-limited and evidence shows no benefit except in severe crescentic disease 1, 3
- Recognize that hypercholesterolemia reduces cyclosporin efficacy 1 - this is critical if considering calcineurin inhibitors for steroid-resistant disease
- Ensure kidney biopsy before initiating immunosuppression to distinguish between disease types, as treatment differs significantly 1
- Monitor for hypertension development - it occurred in 10/12 patients in one HSP treatment series and requires aggressive control 6
- The approach must be highly individualized based on biopsy findings, as most trials lumped disease subtypes together before understanding pathogenic processes 1