THU0458 Investigation of the role of m-tor pathway in kidney needle biopsies of patients with antineutrophil cytoplasmic autoantibody-associated vasculitis

Background Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) frequently affect the kidneys and renal involvement is an important factor regarding morbidity and mortality. Kidney lesion in AAV is characterised by necrotizing and crescentic glomerulonephritis by little or no immune deposition, and hence it was called pauci-immune glomerulonephritis (PIGN). The underlying mechanisms in the formation or progression of crescent formation need further investigations. Mammalian target of rapamycin (mTOR) is a serine/threonine kinase and plays role in the regulation of cell growth and proliferation. Objectives We aimed to evaluate the role of mTOR, which might be a potential therapeutic target, in kidney biopsies of patients with AAV. Methods The patients diagnosed as PIGN at an outpatient nephrology clinics of a tertiary hospital, between May 2009 and June 2016, were retrospectively reviewed and those patients who had a renal biopsy before receiving an immunosuppressive treatment were included in the study. Renal biopsy specimens were immunohistochemically stained with antibodies of mTOR, phosphatase and tensin homolog (PTEN) and transforming growth factor- β (TGF-β) and scored by an experienced renal pathologist. Results In total 54 patients with AAV ([52%] female) were included in the study. Twenty-five (46%) patients were diagnosed as granulomatosis with polyangiitis, 6 (11%) patients as microscopic polyangiitis, 16 (30%) patients as renal-limited disease, one (2%) patient as eosinophilic granulomatosis with polyangiitis. Six (11%) patients with PIGN could not be classified definitely. According to the histopathologic examination; 22% of the biopsies were classified as focal, 33% crescentic, 22% mixed and 22% as sclerotic. The mTOR was expressed in substantial percentages of glomeruli of patients with PIGN. However we observed PTEN expression in all samples and mTOR in all tubulointerstitial areas. mTOR expression was found to be related with the presence of crescentic and sclerotic changes observed in glomeruli and the degree of fibrosis in interstitial areas. In our study serum creatinine level or response to treatment were not found to be associated with mTOR pathway expression Conclusions Our study showed that glomerular or interstitial expression of PI3K/Akt/mTOR pathway may play a role in the pathogenesis of PIGN and mTORC1 inhibitors might provide a viable alternative for this disease. Disclosure of Interest None declared