Myofibroblastic Differentiation in Simple Peritoneal Sclerosis

Abstract

To analyze the presence of myofibroblasts in a series of peritoneal dialysis (PD) patients with simple sclerosis and non-PD, uremic patients. Since there is a close correlation between active fibrosis and myofibroblastic differentiation we wanted to test if myofibroblasts are present in uremic, non-PD peritoneal samples. To determine if there are correlations between myofibroblastic presence and other functional and morphologic peritoneal parameters. Biopsies were collected from three patient groups: 1) Normal control samples (n = 15) of parietal and visceral peritoneum 2) non-PD uremic patients (n = 16); and 3) uremic patients on PD (n = 32). Peritoneal morphologic and functional parameters and immunohistochemical expression of alfa-smooth muscle actin was analyzed in each case. Vascular endothelial growth factor (VEGF), bcl-2 anti-apoptotic protein, and progesterone receptor was evaluated in a subset of cases. Myofibroblasts were present in 56.3% of the patients with PD-related simple sclerosis. In most cases they were distributed in the upper submesothelial area. None of the biopsies from normal controls and uremic, non-PD patients showed myofibroblasts. Within the group of PD patients, myofibroblasts showed no correlation with time on dialysis, urea/creatinine MTAC, episodes of peritonitis, submesothelial thickening, hyalinizing vasculopathy or mesothelial status. In a subset of PD patients VEGF expression was observed in submesothelial fibroblastic cells. No expression of progesterone receptor or bcl-2 was observed. Myofibroblasts are a reliable and simple indicator of fibrosis since they appear in early stages of PD treatment and in patients with minor morphologic anomalies. They are not exclusive of patients with sclerosing peritonitis, ultrafiltration loss or long standing treatment. Their absence in non-PD, uremic patients suggest that uremia-related fibrosis takes place without a significant participation of myofibroblasts.