Write a short note on rapidly progressive glomerulonephritis.

Definition

Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome of glomerulonephritis with rapid loss of renal function — typically a 50% or greater fall in GFR over days to weeks — accompanied on biopsy by CRESCENT formation in more than 50% of glomeruli.

It is a nephrological emergency. Without prompt diagnosis and treatment it progresses to irreversible end-stage renal failure within weeks, and much of the mortality and morbidity arises from delay in recognition rather than from lack of effective therapy.

Pathology — WHY Crescents Form

Severe glomerular capillary wall injury causes rupture of the capillary basement membrane, allowing fibrin and inflammatory cells (macrophages) to leak into Bowman's space. These, together with proliferating parietal epithelial cells, form the crescent — a cellular mass that compresses the glomerular tuft and destroys filtration. Cellular crescents are potentially reversible with prompt immunosuppression; fibrous crescents are not — which is precisely why time matters.

CLASSIFICATION — the three immunofluorescence patterns

This classification determines investigation and treatment, and is the core of any answer.

Type III (pauci-immune, ANCA-associated) is the commonest, particularly in older adults.

Clinical Features

• Nephritic syndrome with rapid deterioration: haematuria (often macroscopic), red cell casts, proteinuria, hypertension, oedema and OLIGURIA with rapidly rising creatinine.
• Constitutional symptoms — fever, malaise, weight loss, arthralgia — reflecting the systemic nature of many causes.
• PULMONARY–RENAL SYNDROME — the combination of haemoptysis or pulmonary haemorrhage with glomerulonephritis, which is the presentation that must never be missed. Causes: anti-GBM (Goodpasture's) disease, granulomatosis with polyangiitis, microscopic polyangiitis, and severe lupus.
• Features of the underlying systemic disease: sinusitis, epistaxis and nasal crusting with saddle-nose deformity (GPA); asthma and eosinophilia (EGPA); malar rash, arthritis and serositis (SLE); palpable purpura (vasculitis, HSP); mononeuritis multiplex.

Investigations

These must be sent urgently and in parallel — not sequentially.

• Urinalysis and microscopy — dysmorphic red cells and RED CELL CASTS confirm glomerular bleeding; proteinuria.
• Renal function — serial creatinine to document the rate of decline.
• THE URGENT SEROLOGICAL TRIAD: ANCA (with PR3 and MPO), anti-GBM antibody, and ANA with anti-dsDNA and complement (C3, C4). These three tests, sent together, classify most cases.
• CBC (anaemia, eosinophilia in EGPA), CRP and ESR, blood cultures (to exclude endocarditis), hepatitis B and C, HIV, cryoglobulins, and serum and urine electrophoresis.
• Chest X-ray and CT chest — pulmonary infiltrates, haemorrhage, cavitating nodules; transfer factor (KCO) is characteristically RAISED in alveolar haemorrhage — a useful and counterintuitive finding.
• RENAL BIOPSY — URGENT AND ESSENTIAL. It confirms crescents, quantifies the proportion of glomeruli involved and the ratio of cellular to fibrous crescents (which determines reversibility), and defines the immunofluorescence pattern. The biopsy should be arranged within hours to a day, not electively.

Management

Treatment must begin on clinical and serological suspicion, without waiting for the biopsy result if the delay would be significant.

1. Remission induction

• High-dose corticosteroids — intravenous methylprednisolone pulses followed by oral prednisolone.
• Cyclophosphamide or rituximab — both effective for ANCA-associated disease; rituximab is preferred in younger patients (preserving fertility) and in relapsing disease; cyclophosphamide requires mesna and hydration to prevent haemorrhagic cystitis, with monitoring for marrow suppression and later malignancy.
• PLASMA EXCHANGE (plasmapheresis) — essential and urgent in anti-GBM disease, where it removes the pathogenic antibody and is the difference between recovery and dialysis dependence. Its role in ANCA-associated vasculitis has been narrowed by recent trial evidence, and is now largely reserved for severe renal failure or diffuse alveolar haemorrhage.

2. Disease-specific therapy

• Anti-GBM disease: plasma exchange PLUS cyclophosphamide and steroids, started immediately — outcome depends almost entirely on the creatinine at presentation. Patients presenting dialysis-dependent with a high proportion of fibrous crescents rarely recover renal function, though treatment is still given to protect the lungs.
• Lupus nephritis: corticosteroids with mycophenolate mofetil or cyclophosphamide, guided by class.
• Post-infectious: treat the infection; usually supportive.

3. Maintenance and supportive care

• Maintenance immunosuppression for at least 2 years — azathioprine, rituximab or mycophenolate — since relapse is common.
• *Pneumocystis* prophylaxis with co-trimoxazole during intensive immunosuppression; bone protection; vaccination; and screening for latent tuberculosis and hepatitis B, which is essential in India.
• Blood pressure control and ACE inhibitor/ARB once stable.
• Dialysis for established renal failure; transplantation after the disease has been in remission (with anti-GBM antibodies undetectable for at least 6 months before transplantation, to prevent recurrence).