Treatment for Rapidly Progressive Glomerulonephritis (RPGN)
Treatment for RPGN should include prompt initiation of induction therapy with glucocorticoids plus either cyclophosphamide or rituximab, without waiting for kidney biopsy results if clinical suspicion is high and serologies are positive for ANCA or anti-GBM antibodies. 1
Classification and Diagnosis
RPGN is a severe clinical syndrome characterized by rapid decline in kidney function over days to weeks that can lead to irreversible kidney failure if not promptly diagnosed and treated 1. It can be classified into three major immunopathological categories:
- Type I: Anti-GBM antibody disease
- Type II: Immune complex-mediated
- Type III: Pauci-immune (most common form, >50% of cases) 1
Early diagnosis is critical and should be pursued when patients present with:
- "Flu-like syndrome" with "glomerular" hematuria (tea-colored urine)
- Proteinuria
- RBC casts and deformed RBCs in urine
- Rapidly declining kidney function 1, 2
Diagnostic Workup
Initial laboratory evaluation should include:
- Complete blood count with platelets
- Serum creatinine and eGFR
- Urinalysis with microscopy
- 24-hour urine protein or protein-to-creatinine ratio
- Serum complement levels (C3 and C4)
- ANCA panel (anti-MPO and anti-PR3)
- Anti-GBM antibodies
- Antinuclear antibody, anti-double stranded DNA
- Hepatitis B and C serologies, HIV testing
- Serum protein electrophoresis
- Cryoglobulins and rheumatoid factor 1
Kidney biopsy remains the gold standard for definitive diagnosis but treatment should not be delayed while awaiting biopsy results if clinical suspicion is high 1.
Treatment Algorithm
1. Induction Therapy
- Glucocorticoids: IV pulse methylprednisolone 500-1000 mg daily for 3 days, followed by oral prednisone (1 mg/kg/day, maximum 60-80 mg) 1
- PLUS either:
- Cyclophosphamide OR
- Rituximab 1
2. Plasmapheresis
- Should be considered for patients with:
- Anti-GBM disease
- Severe renal dysfunction
- Pulmonary hemorrhage 3
3. Maintenance Therapy
- Continue for at least 18 months with:
- Rituximab OR azathioprine
- Low-dose glucocorticoids 1
Special Considerations
Elderly Patients
- Elderly patients can respond to immunosuppressive therapy similar to younger patients
- However, they are at higher risk for adverse events and require careful monitoring
- Treatment must be individualized with consideration of comorbidities 4
Timing of Treatment
- Early treatment is crucial for favorable outcomes
- Treatment should be initiated promptly when RPGN is suspected, even before kidney biopsy results are available if serologies are positive 1, 2
- Delaying treatment can lead to irreversible kidney damage and poor outcomes 1
Monitoring
Regular assessment should include:
- Kidney function tests
- Urinalysis to monitor disease activity
- Complete blood count to monitor for treatment toxicity
- ANCA titers (though treatment decisions should not be based solely on ANCA titers) 1
Prognosis
Prognosis depends on several factors:
- Severity of kidney dysfunction at presentation
- Percentage of crescents on biopsy
- Underlying cause of RPGN
- Promptness of treatment initiation 1
Without treatment, RPGN leads to renal or patient death in approximately 90% of cases, highlighting the importance of early diagnosis and aggressive management 2.