Is Rapidly Progressive Glomerulonephritis (RPGN) a form of acute glomerulonephritis?

Is RPGN Acute Glomerulonephritis?

Yes, rapidly progressive glomerulonephritis (RPGN) is a severe, acute form of glomerulonephritis characterized by rapid decline in kidney function over days to weeks, typically with extensive crescent formation (usually >50% of glomeruli) on kidney biopsy. 1

Clinical Definition and Presentation

RPGN represents a clinical syndrome rather than a single disease entity, defined by:

• Rapid deterioration of kidney function occurring over days to weeks, distinguishing it from chronic glomerulonephritis 2, 3
• Histopathologic hallmark of crescentic glomerulonephritis with crescents in at least 50-75% of glomeruli, often with glomerular necrosis 2, 4
• Clinical manifestations including proteinuria, hematuria (glomerular), oliguria, hypertension, and edema 3

The term "acute" applies because RPGN develops acutely and represents a medical emergency requiring immediate diagnosis and treatment to prevent irreversible kidney failure and death, which occurs in approximately 90% of untreated cases 2.

Diagnostic Approach

When RPGN is suspected based on rapid kidney function decline, the diagnostic workup must proceed urgently:

• Urinalysis showing urine dipstick positive for protein and blood, with sediment demonstrating glomerular hematuria and/or pyuria without infection 1
• Autoimmune serologies including ANCA, ANA, anti-GBM antibodies, and complement levels 1
• Kidney biopsy when feasible to confirm diagnosis and assess disease activity versus chronicity 1, 3

Critical caveat: If clinical presentation is compatible with small-vessel vasculitis and MPO- or PR3-ANCA serology is positive, immunosuppressive therapy should not be delayed while waiting for kidney biopsy results 1. The same applies for suspected anti-GBM antibody GN or lupus nephritis presenting as RPGN 1.

Major Etiologic Categories

RPGN encompasses three main pathophysiologic types:

1. ANCA-associated vasculitis (AAV) - the most common cause of rapidly progressive kidney failure 1
2. Anti-GBM antibody glomerulonephritis 1
3. Immune complex-mediated diseases including lupus nephritis and IgA nephropathy with extensive crescents 1, 3

Relationship to Other Forms of Acute Glomerulonephritis

Important distinction: The presence of crescents on kidney biopsy without concomitant decline in GFR does not constitute RPGN, even though crescents may be present 1. These patients require close monitoring but do not meet criteria for the RPGN syndrome.

RPGN differs from other acute glomerulonephritides (such as post-infectious glomerulonephritis) in its:

• Tempo of progression - much more rapid decline in kidney function 2, 3
• Histologic severity - extensive crescent formation (>50% of glomeruli) 2, 4
• Prognosis without treatment - nearly 90% progress to kidney failure or death if untreated 2

Clinical Significance

The potentially reversible nature of RPGN makes early recognition critical. 2 Favorable outcomes depend on:

• Early diagnosis before irreversible kidney damage occurs 2, 5
• Prompt initiation of immunosuppressive therapy - induction with cyclophosphamide or rituximab plus glucocorticoids for AAV 1, 6
• Exclusion of infection before starting significant immunosuppression 1

Patients presenting with seemingly nonspecific manifestations such as "flu-like syndrome" associated with glomerular hematuria should prompt consideration of RPGN among diagnostic possibilities, as these may be detectable before obvious kidney function deterioration 2.