Pauci-Immune Crescentic Glomerulonephritis

Following two witnessed tonic-clonic seizures, a 65-year-old woman with a history of chronic obstructive pulmonary disease was admitted to the hospital. Results of laboratory studies included serum creatinine level, 2 mg/dL; blood urea nitrogen level, 28 mg/dL; and erythrocyte sedimentation rate, 61 mm/h. The patient's antinuclear antibody (ANA) titer was 1:40 with a speckled pattern, and creatinine clearance was 17 mL/min. An ultrasonogram revealed bilateral small kidneys. CT and MRI of the head revealed no abnormalities.

Workup continued on an outpatient basis, and the patient was readmitted a month later because of worsening kidney function (serum creatinine level of 4.5 mg/dL) and a diffuse purpuric rash on her legs. Examination of a skin biopsy specimen (A) showed a leukocytoclastic vasculitis (infiltration of the blood vessel wall with polymorphonuclear cells). The patient's ANA titer was now 1:640, speckled pattern; perinuclear antineutrophil cytoplasmic antibody (ANCA) titer, 1:160; and antimyeloperoxidase (anti-MPO) level, 3,465 U/mL. A kidney biopsy was carried out, and specimens showed focal segmental glomerulonephritis with fibrosis and crescents (B, C). Immunofluorescence staining was positive only for fibrinogen.

Positive MPO and ANCA titers, usually with a perinuclear ANCA pattern, are associated mainly with microscopic polyangiitis, a necrotizing vasculitis with few or no immune deposits (ie, pauci-immune) that involves capillaries, venules, and arterioles. Necrotizing crescentic glomerulonephritis is very common among patients thus affected, and an associated pulmonary capillaritis may also be present.

The patient was treated with cyclophosphamide and prednisone. Dr Chris Derk of Bala-Cynwyd, Pa, writes that these agents stabilized her creatinine clearance and 24-hour clearance. The patient's seizures were believed to be secondary to CNS vasculitis, but this was not established by biopsy.