Key Facts

RPGN is a nephrological emergency requiring urgent investigation and treatment. The key is to identify the underlying cause (anti-GBM, immune complex, or ANCA-associated) to guide specific therapy.

Epidemiology

• Rare; overall incidence ~7 per million/year
• ANCA-associated is the most common cause (55-60%)
• Anti-GBM disease: 0.5-1 per million/year
• Peak incidence: bimodal – young adults (20-30) and elderly (60-70)

Aetiology

Pathophysiology

• Severe glomerular injury → fibrin deposition in Bowman's space
• Proliferation of parietal epithelial cells and macrophages forms crescents
• Crescents compress glomerular tuft → loss of filtration
• Irreversible fibrotic crescents develop within 1-2 weeks if untreated
• Tubulointerstitial inflammation accelerates damage

Presentation

• Rapidly declining renal function (days to weeks)
• Haematuria (macroscopic or microscopic with red cell casts)
• Proteinuria (usually subnephrotic)
• Oliguria/anuria in advanced cases
• Constitutional symptoms: malaise, fever, weight loss, arthralgia

Type-Specific Features

• Anti-GBM: haemoptysis (Goodpasture syndrome), young males or elderly
• Immune complex: features of underlying disease (SLE, IgA nephropathy)
• ANCA-associated: upper/lower respiratory tract involvement, purpura, neuropathy

Red Flags

• Haemoptysis + renal failure → anti-GBM disease or ANCA vasculitis (pulmonary-renal syndrome)
• Rapidly rising creatinine with active sediment → do not delay treatment
• Anuria → urgent dialysis + biopsy

Urgent Investigations

• Urinalysis: haematuria with red cell casts (nephritic sediment), proteinuria
• U&Es: rapidly rising creatinine
• Immunology (urgent):
  • ANCA: c-ANCA/PR3 (GPA), p-ANCA/MPO (MPA)
  • Anti-GBM antibodies: positive in type I
  • ANA, dsDNA, C3/C4: lupus screen
  • Immunoglobulins, complement: immune complex disease
• FBC: anaemia, thrombocytopenia (TMA), eosinophilia (EGPA)
• CRP/ESR: elevated
• Blood film: fragmentation if TMA
• Chest X-ray: pulmonary haemorrhage

Renal Biopsy

• Urgent (within 24-48 hours)
• LM: crescents in >50% of glomeruli
• IF: linear IgG (anti-GBM), granular (immune complex), pauci-immune/negative (ANCA)
• Proportion of fibrous vs cellular crescents guides treatment (fibrous = irreversible)

Emergency Management

• Start treatment empirically if high clinical suspicion – do not wait for biopsy
• IV methylprednisolone 500mg-1g daily for 3 days, then oral prednisolone 1mg/kg/day tapering

Anti-GBM Disease (Type I)

• Plasma exchange (daily for 14 days or until antibodies clear) – removes circulating anti-GBM antibodies
• Cyclophosphamide 2-3mg/kg/day PO for 3 months
• Prednisolone 1mg/kg/day tapering over 6 months
• Prognosis: if dialysis-dependent at presentation, renal recovery is unlikely (<10%)

ANCA-Associated (Type III)

• Cyclophosphamide (IV pulses 15mg/kg every 2 weeks × 3, then every 3 weeks × 3-6) OR rituximab 375mg/m² weekly × 4 (RAVE trial showed non-inferiority)
• Prednisolone 1mg/kg/day tapering; consider avacopan (complement C5a receptor inhibitor, ADVOCATE trial) as steroid-sparing
• Plasma exchange: consider if creatinine >500 µmol/L or pulmonary haemorrhage (PEXIVAS trial showed no overall benefit for renal outcomes but may help in severe pulmonary haemorrhage)
• Maintenance: azathioprine or rituximab for 18-24 months minimum

Immune Complex (Type II)

• Treat underlying cause (SLE, infection)
• Immunosuppression as per specific disease

Referral Criteria

• All cases → urgent nephrology (same day)
• Pulmonary haemorrhage → ICU
• Dialysis-dependent → renal team for RRT

• Untreated: almost 100% progress to ESRD within weeks
• Anti-GBM: renal survival ~30-40% overall; <10% if dialysis-dependent at presentation
• ANCA-associated: 60-80% renal survival at 5 years with treatment
• Creatinine at presentation is the strongest predictor of renal outcome
• Proportion of fibrous crescents: higher = worse prognosis
• Relapse rate: anti-GBM <5%, ANCA-associated 30-50% (PR3 > MPO)

Classification of Crescentic GN

Pulmonary-Renal Syndromes