Crescentic
glomerulonephritis (GN) in a renal biopsy is a widely accepted "critical diagnosis" in Anatomic Pathology practice. Prompt biopsy evaluation and notification of the referring physician is essential to facilitate rapid therapeutic intervention. The differential diagnostic categories of crescentic GN include pauci-immune GN, anti-glomerular basement membrane (GBM)
nephritis and
immune complex-mediated GN, distinguished from one another by immunofluorescence and electron microscopic study of the renal biopsy.
Immune complex-mediated GN is characterized by abundant glomerular deposits and encompasses several diseases including but not limited to
lupus nephritis, cryoglobulinemic GN and
immunoglobulin A nephropathy. Pauci-immune GN, with paucity of deposits, correlates closely with
antineutrophil cytoplasmic antibody disease due to the identifiable circulating pathogenic
antineutrophil cytoplasmic antibody in most patients. Recent studies have identified other
antibodies in pauci-immune GN and implicated infectious organisms in triggering autoimmunity in a susceptible host by molecular mimicry of host
antigens.
Anti-GBM nephritis is a rare but potentially life-threatening
autoimmune disease with circulating
antibodies against GBM
epitopes in α3 chain of
type IV collagen. It is characterized by a linear
immunoglobulin G deposition along GBM on immunofluorescence microscopy. Environmental triggers including
infections and
solvent exposure seem to change the tertiary structure of the
type IV collagen α345 hexamer in GBM, expose neoepitopes, and initiate autoimmunity. Even in light of advances in understanding of pathophysiology and serologic testing, renal biopsy remains the mainstay of diagnosis of crescentic GN.