What are the causes of rapidly progressive renal failure (RPRF)?

Causes of Rapidly Progressive Renal Failure (RPRF)

Primary Etiologic Categories

Rapidly progressive renal failure is most commonly caused by three major categories of rapidly progressive glomerulonephritis (RPGN): pauci-immune disease (ANCA-associated vasculitis), anti-GBM antibody disease, and immune complex-mediated glomerulonephritis. 1

Pauci-Immune RPGN (50-60% of cases)

• ANCA-associated vasculitis is the most common cause of rapidly progressive kidney failure, accounting for approximately 50-60% of RPGN cases 1, 2
• Specific subtypes include:
  • Granulomatosis with polyangiitis (GPA) 1
  • Microscopic polyangiitis (MPA) 1
• Approximately 90% of patients with pauci-immune RPGN have detectable ANCA antibodies (MPO or PR3), though ANCA negativity does not exclude the diagnosis 1

Anti-GBM Antibody Disease (20% of cases)

• Anti-GBM disease (Goodpasture's Syndrome) accounts for approximately 20% of RPGN cases 1, 3
• Often presents with pulmonary-renal syndrome (simultaneous lung and kidney injury) 1, 3
• Approximately 10% of anti-GBM disease cases may have falsely negative circulating antibodies, requiring kidney biopsy showing linear IgG staining on GBM by immunofluorescence for diagnosis 3

Immune Complex-Mediated RPGN (20-25% of cases)

• Accounts for approximately 20-25% of RPGN cases 1
• Common causes include:
  • IgA nephropathy with extensive crescent formation 1
  • Lupus nephritis presenting with nephrotic-range proteinuria and crescentic changes 1
  • Post-infectious glomerulonephritis (PIGN) 4
  • Idiopathic membranoproliferative glomerulonephritis (MPGN) with nephrotic syndrome and progressive decline 1

Secondary Causes and Precipitating Factors

Infection-Related

• Hepatitis C-associated cryoglobulinemic vasculitis can cause RPGN with severe/rapidly progressive renal involvement 5
• Post-infectious glomerulonephritis, particularly in children 4
• Infective endocarditis 5

Drug-Induced

• Acute interstitial nephritis from medications 6
• NSAIDs and certain antibiotics causing nephrotoxicity 5

Systemic Diseases

• Systemic lupus erythematosus is an important differential diagnosis for RPRF 6
• Multiple myeloma 6
• Thrombotic microangiopathy 6

Critical Diagnostic Distinction

True RPGN requires BOTH histologic crescents (usually >50% of glomeruli) AND rapid deterioration of kidney function over days to weeks. 1 The presence of crescents alone on kidney biopsy without a concomitant rapid decline in GFR does not constitute RPGN 1.

Prerenal and Postrenal Causes (Less Common)

While prerenal and postrenal etiologies account for <3% of acute kidney injury cases, they must be excluded 5:

Prerenal Factors

• Hypotension, hypovolemia, decreased cardiac output 5
• Renal artery occlusion 5
• Volume overload, right heart failure, and renal venous congestion 5

Postrenal Obstruction

• Ureteral, bladder, or urethral obstruction 5
• Prostatic obstruction 5

Common Clinical Pitfall

Do not delay immunosuppressive therapy while waiting for kidney biopsy results if clinical presentation is compatible with small-vessel vasculitis and MPO- or PR3-ANCA serology is positive, especially in rapidly deteriorating patients. 1, 7 The only absolute requirement before starting treatment is excluding infection with as much certainty as possible 7.