Caused by three major categories of disease: anti–GBM disease in approximately 10% of cases, pauci-immune crescentic glomerulonephritis in approximately 60%, and immune-complex glomerulonephritis in approximately 30%.
Characterized by severe immune mediated glomerular injury.
A syndrome of the kidney that is characterized by a rapid loss of renal function, usually a 50% decline in the glomerular filtration rate (GFR) within 3 months, with glomerular crescent formation seen in at least 50% or 75% of glomeruli seen on kidney biopsies.
Untreated, it rapidly progresses into acute renal failure and death within months.
In 50% of cases it is associated with an underlying disease such as Goodpasture syndrome, systemic lupus erythematosus, or Wegener granulomatosis and the remaining cases are idiopathic.
Involves severe injury to the kidneys’ glomeruli, with many of the glomeruli containing characteristic glomerular crescents (crescent-shaped scars).
Microscopic feature of RPGN is called crescentic glomerulonephritis.
Patients with RPGN have hematuria, proteinuria, and occasionally hypertension and edema.
The process is consistent with nephritic syndrome, although the degree of proteinuria may occasionally exceed 3 g/24 h, a range associated with nephrotic syndrome.
Treatment depends on the underlying disease.
Plasmapheresis, corticosteroids, and cytotoxic drugs may promote recovery in Goodpasture syndrome, a cause of type I RPGN.
Many patients with RPGN may ultimately require dialysis and ultimately renal transplant.
Classified into 3 types, based upon the immunofluorescence patterns.
Type I RPGN, which accounts for approximately 20% of RPGN cases.
Type I injury is caused by antibodies directed against the glomerular basement membrane.
Type I RPGN is also called anti-GBM glomerulonephritis.
The antibodies In type I RPGN are directed against a particular protein found in the GBM, type IV collagen, specifically the noncollagenous region of its α3 chain.
Some cases of type I RPGN are also associated with antibodies directed against the basement membrane of lung alveoli, producing Goodpasture syndrome.
The majority of type I disease cases have anti-GBM antibodies alone, and are idiopathic.
Type II RPGN accounts for roughly 25% of RPGN cases and is characterized by the deposition of immune complexes in the glomerulus.
A immune complex disease that involves the glomerulus may progress to RPGN if severe enough, and include systemic lupus erythematosus, acute proliferative glomerulonephritis, Henoch-Schönlein purpura, and IgA nephropathy.
The remainder of RPGN cases are type III, or pauci-immune RPGN.
Type III features antibodies directed against neutrophils (anti-neutrophil cytoplasmic antibodies, ANCA).
Type III RPGN accounts for 55% of RPGN and has neither immune complex deposition nor anti-GBM antibodies.
In Type III RPGN glomeruli are damaged through the activation of neutrophils in response to anti-neutrophil cytoplasmic antibodies (ANCA).
Type III RPGN may be isolated to the glomerulus or associated with a systemic disease such as Wegener granulomatosis, microscopic polyangiitis, or Churg-Strauss syndrome.
Secondary type III RPGN may represent a spectrum of the same disease process.
A punctate or granular pattern on immuno florescence is evidence of lupus nephritis.
A linear autoantibody deposition along the glomerular basement membrane is pathognomonic for anti-GBM disease.
A negative or pauci-immune pattern is associated with the ANCA-associated vasculitis syndrome of granulomatosis angiitis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis
The ANCA associated disease may have a more favorable response to treatment than other types.
Rapidly progressive glomerulonephritis with coexistent ANCA’s and anti-GBM antibodies is referred to as double antibody-positive disease.
Up to 1/3 of patients with anti-GBM antibodies also have ANCAs.
Approximately 5% of patients initially positive for ANCA are found to have anti-GBM antibodies.
ANCAs and anti–GBM antibodies do not react with one another and do not interact with typeIV collagen..
A Type IV process may be included in the classification, called “double-antibody” positive disease, has features of type I and III.
Anti-GBM is a pulmonary-renal disease which often manifests with both glomerulonephritis and alveolar hemorrhage.
The autoantibody is expressed against the non-collagenous domain 1 of the alpha-3 chain of type IV collagen specific to specialize basement membranes of the glomeruli and alveoli.
Most cases are characterized by severe and rapid loss of kidney function featuring severe hematuria, red blood cell casts in the urine, and proteinuria.
Proteinuria sometimes may exceed 3 g protein/24 h, and be associated with nephrotic syndrome.
Some patients experience hypertension and edema.
Severe disease is characterized by oliguria or anuria, with a poor prognosis.
The presence of anti-GBM antibodies suggests type I RPGN.
Antinuclear antibodies (ANA) may support a diagnosis of systemic lupus erythematosus and type II RPGN.
Type III and idiopathic RPGN are frequently associated with ANCA-positive serum.
All types of RPGN are characterized by glomeruluar injury and the formation of crescents.
Glomerular basement membrane injury and rupture leads to the leakage of plasma proteins through the GBM.
Fibrin protein is thought to contribute most strongly to crescent formation, by stimulating epithelial cells lining the Bowman capsule to respond and proliferate.
Infiltrating white blood cells such as monocytes and macrophages proliferate and surround and compress the glomerulus, forming a crescent-shaped scar that is readily visible on light microscopy of a renal biopsy.
Light microscopy of renal biopsy usually shows glomerular inflammation, necrosis, and crescent formation.
Direct immunofluorescence narrows the differential diagnosis.