Treatment of Type 2 (Immune Complex-Mediated) RPGN
For type 2 RPGN with crescentic presentation and rapidly progressive disease, treat immediately with high-dose glucocorticoids combined with cyclophosphamide (or rituximab as alternative), using the same aggressive regimen as ANCA-associated vasculitis. 1
Immediate Treatment Initiation
- Start immunosuppression before biopsy confirmation if clinical presentation is compatible with RPGN, as waiting for histologic confirmation can result in irreversible kidney damage within days to weeks 1, 2
- The only absolute requirement before starting treatment is excluding infection with as much certainty as possible 3, 1
- Obtain kidney biopsy when feasible for diagnosis confirmation and prognosis, but do not delay treatment waiting for results 1
Standard Immunosuppressive Regimen
Induction therapy consists of:
- Pulse IV methylprednisolone 500-1000 mg daily for 3 consecutive days, followed by oral prednisone starting at 1 mg/kg/day with gradual taper over at least 6 months 1
- Cyclophosphamide as the preferred cytotoxic agent for immune complex-mediated RPGN with crescentic presentation 1
- Rituximab may be considered as an alternative to cyclophosphamide, particularly when there are concerns about cyclophosphamide toxicity 1
Disease-Specific Considerations
The treatment approach varies based on the underlying cause of immune complex deposition:
- For IgA nephropathy with rapidly progressive course: Use cyclophosphamide and glucocorticoids according to ANCA-associated vasculitis protocols 4
- For HCV-associated cryoglobulinemic RPGN: Treat with both direct-acting antivirals AND immunosuppressive agents, with or without plasma exchange 5, 4
- For lupus nephritis presenting with RPGN: Follow standard lupus nephritis treatment protocols with mycophenolate mofetate or cyclophosphamide plus corticosteroids 5
Critical Treatment Contraindications
Withhold immunosuppression ONLY if ALL of the following are present: 1
- eGFR <30 mL/min/1.73 m²
- Kidney biopsy shows high degree of interstitial fibrosis and tubular atrophy
- Extensive glomerulosclerosis present
- Absence of active necrotizing or crescentic lesions
However, treat aggressively if there is:
- Active necrotizing or crescentic GN on biopsy, regardless of eGFR 1
- Preserved renal parenchyma with acute tubular necrosis 1
Plasma Exchange Considerations
- Plasma exchange is NOT routinely recommended for immune complex-mediated RPGN based on current evidence 3, 1
- Consider plasma exchange for severe cases with pulmonary hemorrhage or when RPGN overlaps with anti-GBM antibody disease 1
- Some older observational data suggest potential benefit when combined with immunosuppression, but controlled trial evidence is limited 6, 7
Common Pitfalls to Avoid
- Never use calcineurin inhibitors (tacrolimus, cyclosporine) for immune complex RPGN, as these cause immune complex-negative angiopathy and thrombotic microangiopathy 1
- Do not delay treatment while waiting for biopsy results when clinical presentation and serologies are compatible with RPGN 1, 2
- Do not assume all patients with low eGFR should not be treated—the decision must be based on biopsy findings showing renal viability, not eGFR alone 1
- Do not treat patients with advanced chronic kidney disease and extensive fibrosis on biopsy, as they will not benefit and face only toxicity risk 1
Special Exception: Infection-Associated RPGN
- If RPGN appears after an infectious disease, this represents a distinct entity with excellent prognosis that may require only antibiotic therapy without immunosuppression 8
- Exclude active infection before starting immunosuppression, including hepatitis B and C serologies 5
Monitoring and Maintenance
- The treatment approach is determined by the underlying pathology and biopsy findings, not by whether the patient initially presented with nephritic versus nephrotic features 5
- For idiopathic immune complex GN (ICGN), the 2021 KDIGO guideline recommends a more nuanced approach that tailors therapy to severity of disease presentation and histology, with restraint in treating patients aggressively 3