Antineutrophil cytoplasmic autoantibody--associated glomerulonephritis: potentially reversible disease

Renal vasculitis frequently presents itself as rapidly progressive glomerulonephritis, but its diagnosis may be hampered by the difficulty in demonstrating classic vasculitic lesions in renal biopsy specimens. Early diagnosis of renal vasculitis has been greatly enhanced by the advent of antineutrophil cytoplasmic autoantibodies (ANCA). On indirect immunofluorescence microscopy, cytoplasmic ANCA (C-ANCA) show cytoplasmic staining of alcohol-fixed neutrophils and are directed against proteinase 3 in the primary granules of neutrophils. Perinuclear ANCA (P-ANCA) show perinuclear staining due to redistribution of granular antigens, and are specific for myeloperoxidase in the primary granules of the vasculitic patients. C-ANCA are most frequently associated with Wegener's granulomatosis and P-ANCA, with "idiopathic" necrotizing and crescentic glomerulonephritis (renal-limited disease). Patients with microscopic polyarteritis may be associated with either P-ANCA or C-ANCA and there is a considerable overlap between Wegener's granulomatosis and microscopic polyarteritis in both clinical features and serologic patterns. ANCA are not only the markers for vasculitis but may also play a role in the pathogenesis by activating the neutrophils to attack target blood vessels. There is also a crude correlation between ANCA titer and the activity of vasculitis. ANCA-associated vasculitis responds well to steroid and/or cyclophosphamide therapy. Renal failure in these patients is frequently reversible if treated early. Long-term patient and kidney survival rates are good with proper treatment and are far better than those of the other causes of rapidly progressive glomerulonephritis. Potential morbidity of steroid and immunosuppressive therapy should be reduced by the use of low effective doses and by close clinical observation and management.