• Clinical science

Rapidly progressive glomerulonephritis

Abstract

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

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 → passage of cells from the interstitium into Bowman space → formation of fibrin clot 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:[3][1][4]

Diagnostics

Characteristics of RPGN
Anti-GBM disease Immune complex glomerulonephritis Glomerulonephritis associated with vasculitis
  • Anti-glomerular basement membrane antibodies
  • Biopsy: linear IgG deposits along the glomerular basal membrane

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!

References:[5][6][7][8][9]

Differential diagnoses

Differential diagnosis of pulmonary-renal syndromes

Goodpasture syndrome
Granulomatosis with polyangiitis (Wegener) Churg-Strauss syndrome Microscopic polyangiitis Systemic lupus erythematodes
Pathophysiology
Clinical findings
  • Mild respiratory symptoms
  • Palpable purpura
Nephritis
  • Diffuse proliferative glomerulonephritis

Laboratory findings


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

References:[3][10][1][1][11]

The differential diagnoses listed here are not exhaustive.

Treatment

References:[1][12][6]