İMMÜNGLOBULİN A NEFROPATİLİ HASTALARDA C4d, ADAM10 VE WT1 EKSPRESYONUNUN ARAŞTIRILMASI VE PROGNOZ ÜZERİNE ETKİSİ

Abstract

Immunoglobulin A (IgA) nephropathy is the most common chronic glomerular disease in the world. It has variable clinical, morphologic and prognostic features. It is important to define new parameters to better understand the pathogenesis of the disease, predict prognosis at earlier stages and to pave the path for new treatment modalities. We thus aimed to investigate the immunhistochemical expression of C4d, ADAM10 and WT-1 in kidney biopsies of IgA nephropathy patients and correlate the findings with clinical, laboratory and histopathologic features. In this study we compiled paraffine embedded kidney core biopsy samples of patients who had recieved a diagnosis of IgA nephropathy between the years of 2001 and 2018 at the Pathology Department of Hacettepe University Faculty of Medicine. The sections were immunhistochemically treated with C4d and ADAM10 / WT-1 dual stain. Perimesangial/mesangial localization was accepted as positive staning. Biopsies were evaluated according to parameters of the Oxford classification, epidemiologic features (age, gender), laboratory findings at presentation(daily proteinuria, serum creatinine and estimated glomerular filtration rate) and clinical follow up (type of treatment and kidney function tests’ status). Renal survival analyses was carried out by recording the follow up times and whether or not the patients progressed to end stage renal disease. We detected that C4d positive patients were statistical significanty older, had higher proteinuria values at presentation and had a higher rate of progression to end stage renal disease. The renal survival time of C4d positive patients were statistical significantly shorter than negative ones. In the biopsies of C4d positive patients there were statistically significantly more >25% segmental sclerosis and more >25% cellular/fibrocellular cresents. In accordance with the literature mesangial/perimesangial C4d positivity, which is the indicator of activation of the mannose binding lectine pathway, was related to bad prognosis. There wasn’t any statistical significant correlation between ADAM10 staning results and clinical or pathologic parameters. It is known that WT-1 protein regulates protein expression at the transcriptional level and there is nuclear expression of this protein. It was later found out that WT-1 regulates protein expression not only at the transcriptional level but also at the posttranscriptional level, due to its relationship with active proteosomes, disclosing a possible explanation for the cytoplasmic expression of this protein. In our series, podocytes in some biopsies showed cytoplasmic expression with WT-1. The patients with cytoplasmic WT-1 expression had statistically marginally higher positivity rates of progression to end stage renal disease. It was not related to any clinical and morphologic parameters like proteinuria or segmental sclerosis.