Rapidly progressive glomerulonephritis (RPGN) is an inflammatory disease of the kidneys characterized by rapid destruction of the renal glomeruli that often leads to end-stage renal disease. There are three different pathophysiological mechanisms that can result in RPGN: anti-glomerular basement membrane antibody disease (Goodpasture syndrome), immune complex glomerulonephritis (e.g., lupus nephritis), and glomerulonephritis associated with vasculitis (e.g., granulomatosis with polyangiitis). Patients may present with mild symptoms such as flank pain, edema, and decreased urine output. Laboratory tests show a sudden rise in serum BUN and creatinine as well as RBC casts and dysmorphic red blood cells on urinalysis. If the patient presents with hemoptysis, pulmonary-renal syndrome should be suspected. RPGN requires rapid diagnosis and immediate initiation of immunosuppressive therapy to prevent irreversible kidney damage.
- Type I: anti-GBM glomerulonephritis: ()
Type II: immune complex-mediated glomerulonephritis
- HSP) (
- Type III: glomerulonephritis associated with vasculitis (pauci-immune GN, ANCA-associated)
- Breaks in the glomerular capillary wall and dysfunction of the glomerular basement membrane (GBM) → leakage of plasma proteins (e.g., coagulation factors) and passage of inflammatory cells (macrophages, T cells) into Bowman space
- Release of inflammatory cytokines → damage to the membrane of Bowman space and passage of cells from the interstitium into Bowman space
- This causes the formation of fibrin clots and proliferation of cells (e.g., macrophages, fibroblasts, neutrophils, epithelial cells) → crescent moon formation → compression of the glomerulus → renal dysfunction
- Decrease in urine output within days to weeks → possibly anuria
- Pulmonary symptoms (e.g., hemoptysis) may occur (see “”).
|Characteristics of RPGN|
|Anti-GBM disease||Immune complex-mediated glomerulonephritis||Glomerulonephritis associated with vasculitis (pauci-immune GN)|
If serum creatinine rises rapidly due to renal damage, always suspect RPGN and initiate testing immediately. If urinalysis shows nephritic sediment, a renal biopsy is vital for quick diagnosis and initiation of appropriate treatment.
|Differential diagnosis of pulmonary-renal syndromes|
|Clinical findings|| |
|Nephritis|| || || |
| || |
The differential diagnoses listed here are not exhaustive.
- Glucocorticoids and cyclophosphamide
- Goodpasture syndrome: plasmapheresis in addition to immunosuppression
- RPGN due to ANCA-associated vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis): combination therapy with glucocorticoids and rituximab is an effective alternative
- If therapy is initiated early: full recovery of renal function in > 50% of cases
- Without proper treatment, the prognosis is unfavorable: rapid progression to end-stage renal disease and high mortality