What is the management of Rapidly Progressive Glomerulonephritis (RPGN)?

Management of Rapidly Progressive Glomerulonephritis (RPGN)

Start aggressive immunosuppression immediately with high-dose corticosteroids combined with either cyclophosphamide or rituximab without waiting for biopsy confirmation if clinical presentation and serologies suggest RPGN. 1

Immediate Actions Before Treatment

• Exclude active infection as thoroughly as possible—this is the only absolute requirement before initiating immunosuppression 1
• Send urgent serologies: ANCA (MPO and PR3), anti-GBM antibodies, ANA, complement levels (C3, C4) 2
• Obtain urinalysis showing glomerular hematuria (dysmorphic RBCs, RBC casts) and proteinuria 2
• Pursue kidney biopsy when feasible for diagnosis and prognosis, but do not delay treatment waiting for biopsy results 1

Initial Immunosuppressive Regimen

Corticosteroid Therapy (All Patients)

• IV methylprednisolone pulse: 500-1000 mg daily for 3 consecutive days 1
• Follow with oral prednisone 1 mg/kg/day, tapering gradually over at least 6 months 1

Choice of Second Agent: Cyclophosphamide vs. Rituximab

The selection between these agents depends on disease severity and patient factors:

• Cyclophosphamide is preferred when severe kidney dysfunction is present (higher creatinine, dialysis-dependent) 1
• Rituximab is preferred when kidney dysfunction is less severe or when cyclophosphamide toxicity is a concern (fertility preservation, malignancy risk, hemorrhagic cystitis risk) 1
• Both agents combined with corticosteroids are equally effective for ANCA-associated vasculitis 3, 1

Disease-Specific Considerations

ANCA-Associated Vasculitis (Most Common Cause)

• Initiate treatment based on positive MPO or PR3 ANCA serology combined with compatible clinical presentation, even before biopsy confirmation 3
• Use cyclophosphamide or rituximab plus high-dose corticosteroids as described above 3, 1
• Plasma exchange is NOT routinely recommended based on the PEXIVAS trial 1

Anti-GBM Antibody Disease

• Add plasmapheresis to cyclophosphamide and glucocorticoids for all patients except those with 100% crescents, >50% global glomerulosclerosis, dialysis-dependent without pulmonary hemorrhage 3
• Treat aggressively even without alveolar hemorrhage if there is potential renal viability 3
• Patients presenting on dialysis have >90% chance of remaining dialysis-dependent, so treatment should be reserved for those with pulmonary hemorrhage or recent dialysis initiation 3

Immune Complex-Mediated RPGN (Including Idiopathic ICGN/MPGN)

For crescentic presentation with rapidly progressive disease:

• Treat with high-dose glucocorticoids and cyclophosphamide, similar to ANCA-associated vasculitis regimen 3
• Use pulse IV methylprednisolone followed by oral prednisone as described above 3
• Consider rituximab as alternative to cyclophosphamide 3

Critical Contraindications to Immunosuppression

Withhold immunosuppression in patients with eGFR <30 mL/min/1.73 m² ONLY if kidney biopsy shows:

• High degree of interstitial fibrosis and tubular atrophy 3
• Extensive glomerulosclerosis 3
• Absence of active necrotizing or crescentic lesions 3

DO treat patients with eGFR <30 if they have:

• Active necrotizing or crescentic GN on biopsy 3, 1
• Preserved renal parenchyma with acute tubular necrosis 3, 1
• No significant chronic fibrosis or atrophy 3

The decision should be based on overall renal viability assessed by biopsy findings, not eGFR alone 3.

Plasmapheresis Indications

• Recommended for anti-GBM disease (except futile cases as described above) 3, 1
• Recommended for dual-positive disease (ANCA + anti-GBM overlap) 1
• NOT routinely recommended for isolated ANCA vasculitis 1

Common Pitfalls to Avoid

• Delaying treatment while waiting for biopsy results—the combination of compatible clinical presentation and positive serology is sufficient to begin therapy 3, 1
• Treating patients with advanced chronic kidney disease and extensive fibrosis on biopsy—these patients will not benefit and face only toxicity risk 3
• Using calcineurin inhibitors (tacrolimus, cyclosporine) for immune complex RPGN—these cause immune complex-negative angiopathy and thrombotic microangiopathy 3
• Assuming all patients with low eGFR should not be treated—active crescentic disease warrants treatment regardless of eGFR 3, 1