Predictors of outcome in idiopathic rapidly progressive glomerulonephritis (IRPGN)

BACKGROUND: Small vessel vasculitides are known to follow a devastating course towards end-stage renal disease, unless treated with immunosuppressive regiments. We investigated the value of clinical, histological and immunohistochemical parameters as predictors of outcome at diagnosis in patients with pauci immune necrotizing glomerulonephritis. METHODS: In 34 patients the percentage and evolution stage of crescents, the presence of glomerular necrosis, the degree or severity of arteriosclerosis, as well as the extent of tubulointerstitial infiltration, interstial fibrosis and tubular atrophy were assessed. Monoclonal antibodies were used to identify infiltrating macrophages, α-SMA(+) and PCNA(+) cells, the expression of integrins α3β1 and LFA-1β, the adhesion molecule ICAM-1, the growth factor TGF-β1 and the terminal complement component C5b-9. RESULTS: 24 pts (70.6%) showed a complete or partial response to the treatment. The follow-up period was 20 ± 22 months. At multivariate analysis, serum CRP (p = 0.024), the intensity of tubular expression of C5b-9 (p < 0.0001) as well as the extent of glomerular and tubular expression of α3β1 integrin (p = 0.001 and 0.008 respectively) independently predicted the response to treatment. The response rate was better in ANCA(+) pts (p = 0.008). The extent of interstitial infiltrate (p < 0.0001), the severity of tubulointerstitial fibrosis (p < 0.0001) and the severity of tubular TGF-β1 expression (p < 0.0001) were independent predictors of long term outcome of renal function. CONCLUSION: Patients with ANCA-associated renal vasculitis seem to respond better to the treatment. Acute phase reactants, such as CRP, implying a more intense parenchymal inflammatory reaction, as well as the intensity of the de novo expression of C5b-9 and the glomerular and tubular expression of α3β1 integrin predict the response to therapy. The severity of TIN lesions and of the tubulo-interstitial TGF-β1 and C5b-9 expression predict an unfavourable outcome