Rapidly Progressive Glomerulonephritis

Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome of rapid loss of renal function (50% decline in GFR within days to 3 months) with active urinary sediment, usually with crescents in over 50% of glomeruli.

• Type I (anti-GBM disease, 10 to 15%): linear IgG along the GBM.
• Type II (immune complex, 25 to 45%): IgA nephropathy and vasculitis, lupus nephritis, post-infectious GN, cryoglobulinaemia, MPGN.
• Type III (pauci-immune, 50%): ANCA-associated vasculitis (MPA, GPA, EGPA), renal-limited vasculitis.
• Double-positive anti-GBM and ANCA in 10 to 40% of anti-GBM disease.
• Other: drug-induced (hydralazine, propylthiouracil, penicillamine), infection.
• Incidence 7 per million; prognosis depends on creatinine at presentation and percentage crescents; untreated, most progress to ESKD in weeks.

• Oliguria, haematuria (often macroscopic), oedema, hypertension, fatigue, nausea.
• Pulmonary-renal syndrome (haemoptysis, dyspnoea): anti-GBM, ANCA vasculitis, lupus.
• Systemic vasculitis: sinusitis, purpura, mononeuritis multiplex, arthralgia, fever.
• Preceding infection (streptococcal, staphylococcal), drug exposure.

• Urgent investigations: creatinine, potassium, urinalysis with microscopy (dysmorphic red cells, red cell casts, proteinuria), CBC, CRP.
• Serology: ANCA (MPO, PR3), anti-GBM, ANA, anti-dsDNA, complement C3/C4, cryoglobulins, ASO and anti-DNase B, hepatitis B/C, HIV, blood cultures.
• Chest imaging for pulmonary haemorrhage.
• Renal biopsy as soon as possible: crescents (cellular, fibrocellular, fibrous), immunofluorescence pattern (linear, granular, pauci-immune), activity and chronicity scoring.
• Do not delay therapy for biopsy if anti-GBM or ANCA is strongly positive with severe disease.

• Pulse methylprednisolone 500 to 1000 mg IV daily for 3 days, then prednisolone 1 mg/kg (maximum 60 to 80 mg), tapered to 5 mg by 6 months (reduced-dose regimens preferred).
• Anti-GBM disease: plasma exchange daily or on alternate days for 14 days (4 L exchanges), cyclophosphamide 2 mg/kg orally (or 15 mg/kg IV) for 2 to 3 months, imlifidase in dialysis-dependent disease.
• ANCA vasculitis: rituximab 375 mg/m2 weekly for 4 doses (or 1 g on days 1 and 15) or cyclophosphamide 15 mg/kg IV every 2 to 3 weeks (3 to 6 pulses), avacopan 30 mg twice daily as steroid-sparing agent. Plasma exchange (7 exchanges) for creatinine over 300 µmol/L or pulmonary haemorrhage. Maintenance with rituximab 500 mg every 6 months or azathioprine 2 mg/kg for 18 to 24 months.
• Immune complex RPGN: treat the cause (lupus: cyclophosphamide, mycophenolate, belimumab; post-infectious: antibiotics and supportive; cryoglobulinaemia: rituximab).
• Supportive: dialysis for uraemia, hyperkalaemia, volume overload; blood pressure control; Pneumocystis prophylaxis (co-trimoxazole 960 mg three times weekly); gastric and bone protection; vaccination.
• Dialysis-dependent patients with 100% crescents or fibrous crescents may not benefit from aggressive therapy.
• Monitor creatinine, urine sediment, ANCA/anti-GBM titres, and relapses.