Rapidly Progressive Glomerulonephritis (RPGN)

Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome characterized by an acute nephritic illness and a rapid, progressive loss of kidney function occurring over a period of days to weeks.
The histopathological hallmark of RPGN is crescentic glomerulonephritis (CGN), which is defined by the presence of epithelial crescents involving 50% or more of the glomeruli on a kidney biopsy.
Crescents form within Bowman's space primarily due to the proliferation of parietal epithelial cells, accompanied by infiltrating macrophages, which subsequently compress the glomerular capillary tuft.
Over time, early active cellular crescents are invaded by connective tissue, evolving into fibrocellular crescents and ultimately into fibrous crescents, leading to glomerular obsolescence and irreversible chronic renal failure.

RPGN is broadly classified into three main categories based on the immunofluorescence patterns observed on kidney biopsy:
Immune Complex-Mediated Crescentic GN: Characterized by granular deposits of immunoglobulins (such as IgG or IgA) and complement (C3). This category includes severe presentations of acute postinfectious glomerulonephritis, IgA nephropathy, IgA vasculitis (Henoch-Schönlein purpura nephritis), and lupus nephritis.
Pauci-Immune Crescentic GN: Characterized by a paucity or complete absence of immune deposits on immunofluorescence and electron microscopy. This form is typically associated with small-vessel systemic vasculitides and positive antineutrophil cytoplasmic antibodies (ANCA), encompassing conditions like microscopic polyangiitis and granulomatosis with polyangiitis.
Anti-Glomerular Basement Membrane (GBM) GN: Characterized by continuous, linear deposition of IgG along the GBM due to pathogenic autoantibodies targeting type IV collagen. When accompanied by pulmonary hemorrhage, this condition is recognized as Goodpasture syndrome.

Children typically present with severe features of acute nephritis, including macroscopic or microscopic hematuria, marked hypertension, and varying degrees of renal insufficiency.
Concomitant proteinuria is a common finding, frequently reaching the nephrotic range and manifesting with severe edema or anasarca.
Some patients may present late in the disease course with profound oliguria or anuric renal failure.
Extrarenal manifestations are critical for identifying underlying systemic etiologies; these may include pulmonary hemorrhage (seen in Goodpasture syndrome or ANCA vasculitis), purpuric rash and arthritis (indicative of IgA vasculitis or systemic lupus erythematosus), or respiratory tract granulomas (suggestive of granulomatosis with polyangiitis).

A prompt kidney biopsy is the gold standard for diagnosing RPGN, as it allows for the quantification of crescents and identifies the specific underlying immunopathological pattern.
Comprehensive serological testing is essential and must include serum complement levels (C3, C4), antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA), ANCA titers, and anti-GBM antibodies.
If the patient lacks extrarenal manifestations, has negative serological markers, and shows no immune deposits on renal biopsy, the diagnosis is confirmed as idiopathic pauci-immune crescentic glomerulonephritis.

The natural history of untreated RPGN involves a rapid progression to end-stage kidney disease (ESKD) within weeks to months; therefore, immediate and aggressive therapy is mandatory.
The presence of predominantly fibrous crescents on the initial biopsy portends a poor prognosis, as it signifies advanced and irreversible kidney damage.
Induction therapy generally consists of intravenous methylprednisolone pulses administered for 3 days, followed by a regimen of high-dose oral corticosteroids and intravenous cyclophosphamide.
Following successful induction, maintenance immunosuppression is typically continued for 2 to 3 years, utilizing agents such as low-dose oral prednisone combined with azathioprine or mycophenolate mofetil.
Prompt initiation of plasmapheresis (plasma exchange) is strongly recommended for patients diagnosed with anti-GBM disease.
Plasmapheresis is also indicated for patients with ANCA-associated crescentic GN who present with dialysis dependence or life-threatening pulmonary hemorrhage.
Rituximab, a monoclonal anti-CD20 antibody, is increasingly utilized as an adjunctive immunosuppressive agent, particularly in patients with ANCA-associated small vessel vasculitis.