Pathology of the ANCA-associated vasculitides

The international guidelines emphasize the crucial role of renal biopsy in the diagnosis of Anti-Neutrophil Cytoplasmic Autoantibody (ANCA)- associated glomerulonephritis (Microscopic Polyangiitis, Granulomatosis with Polyangiitis and Eosinophilic Granulomatosis with Polyangiitis). 1) According to the recent 2012 Chapel Hill Consensus Conference, ANCA- associated vasculitides are classified in the group of small vessel vasculitis. 2) Pauci-immune necrotizing crescentic glomerulonephritis is the morphological hallmark of ANCA-associated vasculitis. The lesion can vary widely in severity and extent of the damage, from segmental tuft necrosis to massive circumferential crescents and frequent peri-glomerular granulomatous reaction. 3) The ANCA test is highly specific for these types of autoimmune vasculitides but renal biopsy still remains the gold standard for final diagnosis, prognostic evaluation and therapeutic intervention, although discrepancy between clinical and morphological features is frequently found. 4) Crescentic damage of the glomerular tuft is characterized by monocyte.- macrophage accumulation through Vascular Cell Adhesion Molecule-1 (VCAM-1) activation. Activated macrophages are considered to have a key role in the chronic progression of renal damage due to their ability to produce substances directly involved in matrix remodelling (Tumor Growth Factor b). 5) Diffuse and marked interstitial infiltration of T, B lymphocytes and monocyte- macrophages is another frequent morphological feature with aspects of tubulitis recently being considered important markers for a worse prognosis. 6) Unfortunately, repeat biopsies are infrequently performed in these disorders and long-term renal changes have remained largely unidentified. 7) Despite the formulation of standardized scoring for renal biopsies, definitive histopathologic classification is still lacking. The European Vasculitis Study (EUVAS) group has proposed a classification system based on glomerular pathology as assessed by light microscopy which is, in turn, divided into four categories: focal, crescentic, sclerotic and mixed. A preliminary correlation with clinical features in 100 cases of ANCA-associated vasculitis has demonstrated that renal biopsy categories were the only independent predictors for the estimated glomerular flow rate (eGFR). The international study currently way is being evaluated by EUVAS for possible confirmation of the classification