Covadonga Hevia

Stability of the Peritoneal Membrane in Long-Term Peritoneal Dialysis Patients

One of main challenges of peritoneal dialysis (PD) is the functional and vital long-term stability of the peritoneal membrane. Few longitudinal and controlled studies on peritoneal function have been published, and the results are somewhat contradictory. We have performed a longitudinal study with 90 patients. The overall analysis has shown that creatinine mass transfer coefficient (MTC) significantly increases and ultrafiltration (UF) capacity decreases over time. Nevertheless, urea MTC remained unaltered and MTC ratios significantly decreased after the third year. Subsequently, we examined the clinical outcomes and identified 19 patients who required peritoneal resting periods for Type I UF failure and 71 patients who did not require such a procedure. The latter patients did not show any significant functional change over time, whereas the former 19 patients showed an increase of peritoneal creatinine transport and a loss of UF capacity. These data corroborate changes in long-term peritoneal function in approximately 20% of PD patients. These changes consist of an increase in effective exchange area, peritoneal permeability, or both, accompanied by signs suggestive of mesothelial regenerative capacity loss. Infectious peritoneal injuries, especially appearing during late PD periods, are deleterious to the peritoneum. The remainder of the functional-structural changes are related to the effects of currently used dialysate. Early diagnosis, preemptive, and therapeutic measures should permit better management of long-term PD patients. The particular response to these injuries has individual characteristics that when addressed permit PD to be used long-term.

Myofibroblastic differentiation in simple peritoneal sclerosis

Objective 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. Methods 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 α-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. Results 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. Conclusions 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.