Glomerulonephritis, Pauci-Immune

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

Diagnosis

• 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

• 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 is likely helpful in conjunction with induction therapy for cases complicated by pulmonary hemorrhage

• Monitor ANCA levels to help determine efficacy of treatment

• Trials using the complement inhibitor avacopan in place of glucocorticoids in cyclophosphamide- or rituximab-based regimens are ongoing and appear promising