Acute Post-Streptococcal Glomerulonephritis (APSGN): A Detailed Management Approach

1. Introduction

Acute Post-Streptococcal Glomerulonephritis (APSGN) is a renal disorder that arises as a sequela to an infection with Group A Streptococcus (GAS), typically following pharyngitis or impetigo. It is an immune-mediated condition that predominantly affects children between the ages of 5 and 12 years. APSGN is a significant cause of acute nephritic syndrome and, although generally self-limited, requires careful management to prevent complications.

2. Pathophysiology

APSGN is characterized by the deposition of immune complexes in the glomeruli, which trigger an inflammatory response leading to glomerular damage. The sequence of events includes:

• Streptococcal Infection: The primary infection occurs in the throat (pharyngitis) or skin (impetigo) caused by nephritogenic strains of Group A Streptococcus (GAS), particularly serotypes 1, 4, 12, and 49.

• Immune Response: The body generates antibodies against streptococcal antigens. These antigens, particularly the streptococcal pyrogenic exotoxin B (SpeB) and nephritis-associated plasmin receptor, circulate and form immune complexes.

• Glomerular Deposition: These immune complexes deposit in the glomerular basement membrane and mesangium, leading to complement activation (especially the alternative pathway) and a cascade of inflammatory responses.

• Glomerular Damage: Inflammation results in capillary wall thickening, mesangial proliferation, and glomerular basement membrane damage, manifesting clinically as hematuria, proteinuria, and reduced glomerular filtration rate (GFR).
  

3. Clinical Presentation

Children with APSGN typically present 1-2 weeks after a streptococcal throat infection or 3-6 weeks following a skin infection with the following features:

• Hematuria: Gross hematuria is common, often described as "tea-colored" or "cola-colored" urine.

• Edema: Facial puffiness, especially periorbital edema, is a hallmark. Generalized edema may also occur.

• Hypertension: Elevated blood pressure is a frequent finding, secondary to fluid retention and increased renin-angiotensin-aldosterone system (RAAS) activity.

• Oliguria: Decreased urine output may indicate significant glomerular injury.

• Proteinuria: Usually mild to moderate, but significant proteinuria can occur.

• Systemic Symptoms: These may include malaise, lethargy, and occasionally low-grade fever.
  

4. Diagnosis

The diagnosis of APSGN is clinical but supported by several laboratory findings:

• Urinalysis:

  • Hematuria: Dysmorphic red blood cells and red blood cell casts.

  • Proteinuria: Mild to moderate levels.

• Serum Complement Levels: Low C3 (due to activation of the alternative complement pathway), typically normal C4.

• Streptococcal Serology:

  • Anti-streptolysin O (ASO) Titer: Elevated, especially following pharyngitis.

  • Anti-DNase B: Often elevated following skin infections.

• Renal Function Tests: BUN and creatinine levels may be elevated depending on the severity of renal impairment.

• Imaging: Generally not required unless there is a concern for complications or atypical presentation.

• Renal Biopsy: Rarely needed, but when performed, it shows diffuse proliferative glomerulonephritis with immune complex deposition.
  

5. Management

Definitive Treatment

• Antibiotic Therapy:

  • Indication: Although the acute nephritis is not due to ongoing infection, antibiotics are necessary to eradicate any residual streptococcal bacteria and prevent further transmission.

  • Drug of Choice:

    • Penicillin V: 250 mg orally twice daily for 10 days for children.

    • Amoxicillin: 50 mg/kg/day in divided doses every 8 hours for 10 days. Maximum daily dose is 3 grams.

  • For Penicillin-Allergic Patients:

    • Erythromycin: 40 mg/kg/day in divided doses every 6-8 hours for 10 days (maximum 1 gram per day).

• Antihypertensive Therapy:

  • First-line Agents:

    • Nifedipine (oral): 0.25-0.5 mg/kg/dose every 8 hours for short-term control, particularly for hypertensive emergencies.

    • Amlodipine (oral): 0.1-0.2 mg/kg/day once daily. Adjust as needed, with a maximum dose of 5 mg/day for children.

  • If Severe Hypertension Persists:

    • Intravenous (IV) Medications:

      • Labetalol IV: 0.2-1 mg/kg/hour as a continuous infusion. Titrate as needed.

      • Hydralazine IV: 0.1-0.2 mg/kg/dose every 4-6 hours, particularly if there is a concern for labetalol contraindications.

Supportive Treatment

• Diuretic Therapy:

  • Indication: To manage edema and control hypertension.

  • Furosemide (IV or oral): 1-2 mg/kg/dose every 12 hours. The maximum dose is 6 mg/kg/day.

  • Monitoring: Monitor electrolytes (especially potassium) and kidney function closely.

• Fluid Management:

  • Fluid Restriction: Usually restricted to insensible losses plus urine output (calculated based on the child’s size and urine production).

  • Sodium Restriction: Typically limited to 1-2 mEq/kg/day to reduce edema and hypertension.

• Dietary Management:

  • Protein Restriction: Mild restriction may be recommended if the child has significant azotemia (BUN > 80 mg/dL).

  • Potassium Restriction: If hyperkalemia is present or if there is significant oliguria.
    

6. Monitoring and Follow-Up

• In-Hospital Monitoring:

  • Daily Monitoring:

    • Blood Pressure: Measure at least every 4-6 hours initially, more frequently if hypertensive.

    • Weight: Monitor daily for changes indicating fluid retention or loss.

    • Urine Output: Hourly monitoring initially; watch for signs of improvement in oliguria.

    • Electrolytes, BUN, and Creatinine: Daily or every other day depending on severity.

    • C3 Levels: Can be rechecked weekly; normalization usually occurs within 6-8 weeks.

• Post-Discharge Follow-Up:

  • First Visit: 1-2 weeks post-discharge. Check BP, urinalysis, and renal function.

  • Subsequent Visits: Every 2-4 weeks initially, then space out to every 3-6 months.

  • Long-Term Monitoring:

    • Blood Pressure: To ensure no long-term hypertension.

    • Urinalysis: To monitor for persistent hematuria or proteinuria.

    • Renal Function: Repeat serum creatinine and BUN to monitor for resolution.
      

7. Complications to Monitor:

• Hypertensive Encephalopathy: Presents with headache, vomiting, visual disturbances, seizures. Requires urgent management.

• Acute Kidney Injury (AKI): Monitor for worsening oliguria or increasing creatinine.

• Heart Failure: Secondary to severe hypertension; watch for dyspnea, tachypnea, or new-onset murmur.

• Chronic Kidney Disease (CKD): Though rare, some children may develop progressive CKD requiring long-term nephrology follow-up.
  

8. Long-Term Prognosis

• Prognosis: Generally excellent in children, with complete recovery in most cases.

• Chronic Hematuria: Some children may have persistent microscopic hematuria for months, which usually resolves over time.

• Renal Scarring: Rare but can be a cause of long-term hypertension or CKD; hence the importance of follow-up.