Μηχανισμοί εξέλιξης της σπειραματικής βλάβης προς χρόνια νεφρική ανεπάρκεια

Abstract

The evolution of an acute glomerular injury towards chronic renal failure is characterized by an inflammatory process that is initially localized in the glomeruli and then in the tubulointerstitial area and vessels of the kidney. The deposition of immune complexes in the glomeruli is the main cause of this process that leads to the development of glomerular sclerosis, interstitial fibrosis and tubular atrophy. In this process various cytokines [interleukins (IL), (IL-1, IL-2, IL-6)] and growth factors [Transforming Growth Factor-β (TGF-β), Epidermal Growth Factor (EGF) and Insulin Growth Factor (IGF-1)] are involved. The phenomenon of cellular apoptosis is implicated in the development of renal scarring. Apoptosis represents the programmed cellular death that is in balance with the generation of cells. The rate of cellular apoptosis is responsible for the preservation of homeostasis in each organism. Various genes and proteins are involved in the regulation of apoptosis within kidney. Bax and bcl-2 proteins represent markers of the apoptotic process since bax is related to an enhanced apoptotic rate whereas bcl-2 provides a survival advantage to renal cells. The aim of this study is to investigate the expression of growth factors (TGF-β1, EGF, IGF-1) and apoptotic markers (bax and bcl-2 proteins) in the renal tissue of patients with various types of glomerulonephritis and to identify any correlation of this expression with the severity of histological injury and with the course of renal function. Seventy six patients (44 males and 32 females) were included in the study. The histological diagnoses were: idiopathic membranous nephropathy (n=26), IgA nephropathy (n=15), minimal changes disease (n=12), rapidly progressive glomerulonephritis (n=11), focal segmental glomerulosclerosis (n=7) and lupus nephritis (n=5). The mean follow-up period was 4 years. The expression of growth factors, apoptotic markers and myofibroblasts (cells that are involved in the development of scarring) in the renal tissue was investigated by immunohistochemical technique and quantitated by morphometric analysis. In the renal tissue of patients with glomerulonephritis presence of growth factors, myofibroblasts and apoptotic markers was identified in the glomeruli and in the tubulointerstitial area. The expression of TGF-β1, myofibroblasts and bax, bcl-2 proteins was particularly severe in patients with glomerular sclerosis, interstitial fibrosis and tubular atrophy. The severity of this expression was related to the degree of histological damage (r=0.444, p<0.05) and that of renal impairment (r=0.454, p<0.05) whereas it was not related to the type of glomerulonephritis. In conclusion, it was found that: 1. Growth factors and myofibroblasts are localized in the glomeruli and in the tubulointerstitial area of patients with glomerulonephritis. 2. The severity of growth factors and in particular that of TGF-β1 expression is related to the degree of renal function impairment and to the severity of histological involvement. 3. The rate of cellular apoptosis in the kidney of patients with glomerulonephritis is also related to the severity of histological involvement and to the degree of renal function imparment.