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-ß (TGF-ß) 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.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Glomerulonephritis/immunology , Kidney Glomerulus/pathology , Signal Transduction/immunology , TOR Serine-Threonine Kinases/metabolism , Adult , Aged , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology , Autoantibodies/immunology , Autoantibodies/isolation & purification , Biopsy , Disease Progression , Female , Glomerulonephritis/drug therapy , Glomerulonephritis/pathology , Humans , Immunohistochemistry , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/therapeutic use , Kidney Glomerulus/blood supply , Kidney Glomerulus/immunology , Male , Middle Aged , PTEN Phosphohydrolase/immunology , PTEN Phosphohydrolase/metabolism , Retrospective Studies , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/antagonists & inhibitors , TOR Serine-Threonine Kinases/immunology , Transforming Growth Factor beta/immunology , Transforming Growth Factor beta/metabolismABSTRACT
Coeliac disease is an autoimmune enteropathy characterised by chronic inflammation of the small intestinal mucosa and the presence of typical autoantibodies. Coeliac disease may be a risk factor for renal disease. Immunoglobulin A (IgA) nephropathy is reported in the majority of these cases. Only one adult patient had been reported with membranoproliferative glomerulonephritis (MPGN) and coeliac disease. Here, we report a case in a 12-year-old girl with coeliac disease who presented with severe anaemia and later developed nephrotic syndrome. Renal biopsy of the patient was consistent with MPGN type 1, which has not been previously reported in children with coeliac disease. A gluten-free diet was started. After 6 months of this diet, her nephrotic syndrome resolved completely. This case is presented to draw attention to the rare association of coeliac disease and MPGN type 1.
Subject(s)
Celiac Disease/complications , Celiac Disease/pathology , Glomerulonephritis, Membranoproliferative/complications , Glomerulonephritis, Membranoproliferative/pathology , Nephrotic Syndrome/complications , Biopsy , Celiac Disease/immunology , Child , Diet, Gluten-Free , Female , Fluoresceins/metabolism , Fluorescent Antibody Technique, Indirect , Fluorescent Dyes/metabolism , Follow-Up Studies , Glomerular Mesangium/immunology , Glomerular Mesangium/pathology , Glomerular Mesangium/ultrastructure , Humans , Immunoglobulin G/immunology , Immunoglobulin G/metabolism , Kidney/surgery , Nephrotic Syndrome/pathology , Time Factors , Treatment OutcomeABSTRACT
Schimke immuno-osseous dysplasia is a rare autosomal recessive multi-system disorder, with clinical features of growth retardation, spondylo-epiphyseal dysplasia, nephrotic syndrome and immunodeficiency beginning in childhood. Here, we report a new case, in a 10-year-old boy with characteristic symptoms of Schimke immuno-osseous dysplasia. The patient presented with short stature and, later, developed nephrotic syndrome and peritonitis. In addition, he had perinuclear anti-neutrophilic cytoplasmic antibody (p-ANCA)-positive arthritis. Renal pathology of the patients with this disease usually show focal segmental glomerulonephritis, whereas our patient had membranous nephropathy, which has not previously been reported.
