Rapidly progressive glomerulonephritis

Last updated: March 23, 2022

Summary

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.

Etiology

Type I: anti-GBM glomerulonephritis: anti-glomerular basement membrane antibody disease (Goodpasture syndrome)
Type II: immune complex-mediated glomerulonephritis
Type III: glomerulonephritis associated with vasculitis (pauci-immune GN, ANCA-associated)

References:^[1]

Pathophysiology

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

References:^[2]

Clinical features

Nephritic syndrome
Decrease in urine output within days to weeks → possibly anuria
Fatigue
Pulmonary symptoms (e.g., hemoptysis) may occur (see “Differential diagnosis of pulmonary-renal syndromes”).

References:^[1]^[3]

Diagnostics

Characteristics of RPGN
	Anti-GBM disease	Immune complex-mediated glomerulonephritis	Glomerulonephritis associated with vasculitis (pauci-immune GN)
Laboratory findings	Nephritic sediment Microhematuria (acanthocytes, RBC casts) Non-selective glomerular proteinuria Pyuria Rapid rise of BUN and creatinine
Serology	Anti-glomerular basement membrane antibodies	↓ C3 complement Lupus nephritis: anti-dsDNA antibodies Poststreptococcal GN: ASO/ADB	Granulomatosis with polyangiitis: c-ANCA Microscopic polyangiitis: p-ANCA
Biopsy findings	Crescent-moon shape: extracapillary cell proliferation that displaces the glomerulus
Biopsy findings	Linear pattern on immunofluorescence microscopy: linear IgG deposits along the glomerular basal membrane	“Humps”: granular pattern on immunofluorescence microscopy (antigen-antibody complexes between the capillary endothelium and the basal membrane)	Negative on immunofluorescence microscopy (few immunologic findings)

Red blood cell (RBC) casts in urine sediment Acanthocytes Crescent formation in rapidly progressive glomerulonephritis (RPGN)

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 diagnoses

Differential diagnosis of pulmonary-renal syndromes
	Goodpasture syndrome	Granulomatosis with polyangiitis	Churg-Strauss syndrome	Microscopic polyangiitis	Systemic lupus erythematosus
Pathophysiology	Auto-antibodies against collagen type IV in the renal and pulmonary capillary basement membrane Possibly triggered by viral infections, lymphoma	Granulomatous vasculitis		Necrotizing vasculitis (no granulomas)	Connective tissue disease
Clinical findings	Hemoptysis Cough Dyspnea	Chronic sinusitis Nasal ulcers Perforation of the nasal septum	Palpable purpura		Pleuritis Malar rash Joint pain Anemia
	Hemoptysis Cough Dyspnea		Peripheral neuropathy Asthma, rhinitis	Mild respiratory symptoms	Pleuritis Malar rash Joint pain Anemia
	Nephritic syndrome
Nephritis	Proliferative glomerulonephritis	Segmental necrotizing glomerulonephritis	Focal segmental necrotizing glomerulonephritis	Pauci-immune glomerulonephritis	Diffuse proliferative glomerulonephritis
Laboratory findings	Anti-GBM antibodies	c-ANCA	p-ANCA Peripheral eosinophilia	p-ANCA	Anti-dsDNA antibodies Low complement

Elevated renal function parameters and hemoptysis are a red flag for RPGN.

References:^[1]

The differential diagnoses listed here are not exhaustive.

Treatment

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

References:^[1]

References

Goldman L, Schafer AI. Goldman-Cecil Medicine, 25th Edition. Elsevier ; 2016
Kumar V, Abbas AK, Aster JC. Robbins & Cotran Pathologic Basis of Disease. Elsevier Saunders ; 2015
Longo D, Fauci A, Kasper D, Hauser S, Jameson J, Loscalzo J. Harrisons's Principles of Internal Medicine, 18th Edition, 2011. McGraw-Hill Medical ; 2011

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