Abstract
Background: The characteristic lesion of pauci-immune glomerulonephritis is focal necrotizing and crescentic glomerulonephritis. The underlying mechanisms in the formation or progression of crescent formation need further investigations. Therefore, we aimed to evaluate the role of mammalian target of rapamycin (mTOR), which might be a potential therapeutic target, in kidney biopsies of patients with pauci-immune glomerulonephritis.Methods: The patients diagnosed as pauci-immune glomerulonephritis at an outpatient nephrology clinic were retrospectively reviewed and those patients who had a kidney biopsy before receiving an immunosuppressive treatment were included in the study. Kidney biopsy specimens were immunohistochemically stained with mTOR, antibodies of 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 pauci-immune glomerulonephritis (28 [52%] female) were included. According to the histopathologic examination, 22% of our cases were classified as focal, 33% crescentic, 22% mixed, and 22% as sclerotic. The mTOR was expressed in substantial percentages of glomeruli of patients with pauci-immune glomerulonephritis. 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. Serum creatinine level or response to treatment was not found to be associated with mTOR pathway expression.Conclusion: Our results suggest that mTOR pathway may play role in the pathogenesis of pauci-immune glomerulonephritis, besides targeting this signaling may be an alternative option for those patients.
Highlights
Pauci-immune glomerulonephritis is the most common form of rapidly progressive glomerulonephritis in adults
Mammalian target of rapamycin is a serine/ threonine kinase and plays role in the regulation of cell growth and proliferation. It regulates cell survival and is stimulated by growth factors, nutrients, stress signals, phosphatidylinositol-4,5-bisphosphate 3kinase(PI3K), mitogen-activated protein kinase(MAPK), 5’ adenosine monophosphate(AMP), and 5’ adenosine monophosphate-activated protein kinase (AMPK). mammalian target of rapamycin (mTOR) complex includes two multiprotein complexes; mTOR complex 1 and mTOR complex 2 [3]. mTORC1 activates a number of substrates like ribosomal subunit-6 kinase-1 (S6K1) and eucaryotic initiation factor 4E binding protein-1 (4EBP1), which are responsible for mRNA translation [4]. mTORC2 regulates actin cytoskeleton and activates protein kinase C-a (PKC-a) and AKT
Rune Bjørneklett’s study showed that there was no difference in the classification of patients with pauciimmune glomerulonephritis between 10 and over glomeruli in renal biopsies and those with between 3 and 9 glomeruli [17], so we examined pauci-immune glomerulonephritis patients with at least 3 and over glomeruli in renal biopsies we included in the study
Summary
Pauci-immune glomerulonephritis is the most common form of rapidly progressive glomerulonephritis in adults. The characteristic lesion of the disease is focal necrotizing and crescentic glomerulonephritis. It may be a component of systemic small vessel vasculitis or kidney-limited disease [1]. Mammalian target of rapamycin (mTOR) is a serine/ threonine kinase and plays role in the regulation of cell growth and proliferation. The characteristic lesion of pauci-immune glomerulonephritis is focal necrotizing and crescentic glomerulonephritis. We aimed to evaluate the role of mammalian target of rapamycin (mTOR), which might be a potential therapeutic target, in kidney biopsies of patients with pauci-immune glomerulonephritis. The mTOR was expressed in substantial percentages of glomeruli of patients with pauci-immune glomerulonephritis. Conclusion: Our results suggest that mTOR pathway may play role in the pathogenesis of pauciimmune glomerulonephritis, besides targeting this signaling may be an alternative option for those patients
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