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For further information, see CMDT Part 22-14: Nephritic Spectrum Glomerular Diseases

Key Features

  • 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

  • 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


  • 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")


  • 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

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