SP140ANCA NEGATIVE PAUCI-IMMUNE GLOMERULONEPHRITIS

Abstract

INTRODUCTION AND AIMS: Pauci-immune crescentic necrotizing glomerulonephritis (GN) is defined clinically by rapidly progressive glomerulonephritis and histologically by the presence of focal glomerular necrosis and extracapillary proliferation in the absence of significant glomerular immune deposits. It is usually associated with anti-neutrophil cytoplasmic antibodies (ANCAs). However, ANCA's are absent in up to 10% of cases, which constitutes a rarely studied variant of renal vasculitis. The objective of our study is to collect the main clinical, biological, immunological and histological data. METHODS: This retrospective study identified 14 patients who presented between 2000 and 2016 in our department with a pauci-immune crescentic necrotizing GN and in whom no evidence for circulating ANCAs was found by immunofluorescence (IF) testing. In each patient, a renal biopsy had been performed at the time of diagnosis. RESULTS: Fourteen patients were identified (10 males and 4 females) with a median age of 46 years at presentation (range 16-78 years). All patients presented with acute renal injury. Nine of them showed acute renal failure with a creatinine >500μmol/l; three required short-term hemodialysis at diagnosis. Median serum creatinine at presentation was 1043,93 μmol/l (range 202-3600μmol/l). Nephrotic syndrome was present in four cases (28,6%). Hypertensive was showed in two cases (14, 3 %). Sinusitis or rhinitis or both was noted in two cases (14,3%). Pulmonary involvement was seen in three cases (21, 5 %) without intra alveolar hemorrhage. Both Anti-nuclear antibodies and anti-DNA antibodies were not detected in any of the patients. Anti-GBM antibodies were negative in all cases. Renal biopsy showed pauci immune state with cellular crescents in all the cases. Glomeruli showed focal proliferative lesions with neutrophilic infiltrates. However necrotic lesions in the glomeruli were rare (14,29%) . Interstitial fibrosis was present in 73,7 % of biopsies and it was scored as severe in half of these cases. Interstitial infiltrates were seen in 85,7 % of all biopsies, being moderate or intense in 57,2 %. Vascular disease was showed in 14,3 % of cases. IF studies showed the absence of significant immune deposits in all cases. 85,7 % received a primary immunosuppressive protocol with oral and with intravenous steroids, and cyclophosphamide pulse therapy. No Patient had plasma exchange. Five patients (35,7 %) progressed to end-stage renal failure. Relapse of disease requiring the reintroduction or an increase of immunosuppressive therapy occurred in 28 % of all patients. CONCLUSIONS: The histological findings and prognosis in ANCA-negative renal vasculitis are comparable with those of ANCA-positive disease. Our data underline the importance of the exact diagnosis in an active vasculitic disease process even in the absence of ANCAs.