ANCA-associated glomerulonephritis (pauci-immune crescentic glomerulonephritis) accounts for more than half of all RPGN cases and has a particularly high prevalence in patients >65 years of age presenting with AKI and active urinary sediment. ANCA are autoantibodies that target proteins within neutrophil granules and monocyte lysosomes. There are two types of vasculitis-associated ANCA: p-ANCA (perinuclear) is directed against the neutrophil enzyme myeloperoxidase (MPO), and c-ANCA (cytoplasmic) is directed against the neutrophil proteinase 3 (PR3).
Most patients with ANCA-associated glomerulonephritis report a vasculitic prodrome of malaise, arthralgia, myalgia, and flu-like symptoms that can include fever. Kidney involvement can produce dark brown (tea-colored) urine, and laboratory studies will confirm the presence of hematuria, proteinuria, and AKI. Lung and sinus involvement often occurs in ANCA-associated glomerulonephritis, with patients reporting hemoptysis and/or epistaxis.
Serologic testing for ANCA using enzyme-linked immunosorbent assay is usually performed at the time of presentation if RPGN is suspected. Light microscopy of the kidney biopsy shows a crescentic glomerulonephritis, but immunofluorescence shows a paucity or absence of immune-type deposits. Foci of necrosis or cellular crescents are highlighted by immunofluorescence staining for fibrinogen.
The initial treatment of organ-threatening disease is an area of ongoing controversy. Typical induction therapy consists of glucocorticoids combined with either cyclophosphamide or rituximab. Plasmapheresis is reserved for patients with evidence of alveolar hemorrhage or severe kidney failure. Other induction options include cyclophosphamide or rituximab-based therapies. After remission is induced, maintenance therapy is usually continued for at least 12 to 24 months using rituximab, azathioprine, or mycophenolate mofetil.
Patients with c-ANCA/anti-PR3 have a significantly higher rate of relapse than patients with p-ANCA/anti-MPO, particularly if there is a history of lung or sinus involvement. ANCA-associated glomerulonephritis is associated with an approximately 20% mortality rate within the first year of diagnosis and results in ESKD in up to 25% of surviving patients within the first 4 years after diagnosis.