Characteristics and outcome of crescentic glomerulonephritis in patients with both antineutrophil cytoplasmic antibody and anti-glomerular basement membrane antibody

Abstract

A subset of patients with crescentic glomerulonephritis (CGN) is characterized serologically by the presence of antineutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane antibody (anti-GBM) called "double positive" disease. The clinical significance of the occurrence of both antibodies is not clear. This study aims to describe the clinical and histologic characteristics and outcomes of CGN in a US cohort of double positive (DP) patients and compare them to patients with anti-GBM disease only or ANCA only (ANCA-associated vasculitis (AAV)). Renal biopsies with a diagnosis of CGN with either pauci-immune or linear immunofluorescence were selected and classified as AAV, anti-GBM disease, or DP based on serologic testing at the time of biopsy. Data on demographics, clinical presentation, treatment, and outcome were obtained by chart review. Six patients with anti-GBM disease, 9 with DP disease, and 18 AAV patients matched for year of diagnosis with DP were identified. Extrarenal disease manifestations were more prominent in the DP patients. The DP patients had severe renal dysfunction at presentation with eight of nine patients requiring dialysis at presentation. Renal biopsy findings of DP patients were similar to anti-GBM disease with majority of glomeruli showing cellular crescents. Eighty-nine percent of patients were treated with immunosuppressive therapy and 78% with plasmapheresis. At 1year, all nine DP patients reached end-stage renal disease. We conclude that the DP patients share extrarenal manifestations similar to AAV patients while the renal manifestations resemble anti-GBM patients clinically and histologically. The renal prognosis of DP patients remains poor despite treatment.