Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 22-14: Nephritic Spectrum Glomerular Diseases + Key Features Download Section PDF Listen +++ ++ Pauci-immune necrotizing glomerulonephritis is caused by Granulomatosis with polyangiitis Microscopic polyangiitis Eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome) Antineutrophil cytoplasmic antibody (ANCA)–associated glomerulonephritis can also present as a primary renal lesion without systemic involvement Circulating ANCAs bind to antigens and activate a neutrophil respiratory burst with consequent vascular damage; primed neutrophils also appear to activate the alternative complement pathway Renal involvement classically presents as a rapid progressive glomerulonephritis, but more indolent presentations can be seen as well Putative environmental exposures that may incite the initial response include Staphylococcus aureus and silica Immunofluorescence of kidney biopsy specimens do not reveal any evidence of immunoglobulin or complement deposition, hence the term "pauci-immune" + Clinical Findings Download Section PDF Listen +++ ++ Fever, malaise, and weight loss may be present and usually precede initial presentation by several months Hematuria and proteinuria from glomerular inflammation Purpura from dermal capillary involvement and mononeuritis multiplex from nerve arteriolar involvement seen in some patients Ninety percent of patients who have granulomatosis with polyangiitis have upper (especially sinus) or lower respiratory tract symptoms with nodular lesions that can cavitate and bleed Hemoptysis is a concerning sign and usually warrants hospitalization and aggressive immunosuppression + Diagnosis Download Section PDF Listen +++ ++ ANCA subtype analysis is done to determine whether antiproteinase-3 antibodies (PR3-ANCA) or antimyeloperoxidase antibodies (MPO-ANCA) are present Most patients with granulomatosis with polyangiitis are PR3 positive; the remainder are MPO positive or, rarely, do not demonstrate circulating ANCA Microscopic angiitis is generally associated with MPO ANCA Kidney biopsy demonstrates necrotizing lesions and crescents on light microscopy Immunofluorescence is negative for immune complex deposition ("pauci-immune") + Treatment Download Section PDF Listen +++ ++ Institute treatment early if aggressive disease is present; prognosis depends mainly on extent of renal involvement before treatment is started High-dose corticosteroids (methylprednisolone, 1–2 g/day intravenously for 3 days, followed by prednisone, 1 mg/kg orally for 1 mo, with a slow taper over the next 6 mo) and cytotoxic agents (cyclophosphamide, 0.5–1.0 g/m2 intravenously per month or 1.5–2 mg/kg orally for 3–6 months is followed by long-term azathioprine or mycophenolate mofetil) Patients receiving cyclophosphamide should receive prophylaxis for Pneumocystis jirovecii, such as double-strength trimethoprim-sulfamethoxazole orally 3 days per week Rituximab Shown to be noninferior to cyclophosphamide for induction Also used in refractory or relapsing cases and as an alternative to azathioprine for maintenance of remission Plasma exchange Has been used in conjunction with induction therapy in particularly severe cases and especially those involving pulmonary hemorrhage However, its efficacy not supported by large trial Monitor ANCA levels to help determine efficacy of treatment