P1146ENHANCED EXPRESSION OF THIOREDOXIN-INTERACTING-PROTEIN (TXNIP) MAY REGULATE OXIDATIVE DAMAGE IN PERITONEAL DIALYSIS PATIENTS

Abstract

Abstract Background and Aims Glucose-based solutions used as peritoneal dialysis fluids influence the peritoneal membrane. Exposure to high glucose-based peritoneal dialysis solutions induces reactive oxygen species (ROS) production due to upregulation of TXNIP as shown by several studies in rats as well as in human primary cells. Enhanced expression of TXINP also regulates oxidative damage. Therefore the aim of this study was to investigate the expression of TXNIP and the extent of oxidative damage in human peritoneal biopsies. Method Human peritoneal biopsies of healthy controls, PD patients and patients with EPS were collected. TXNIP and thioredoxin-1 (TRX) mRNA expression was determined by qPCR. Protein expression and the extent of oxidative damage were examined by immunohistochemistry. Results Biopsies from the peritoneum of 7 healthy controls, 36 patients on PD without signs of EPS as well as of 12 patients with EPS were collected. The age of the healthy controls was higher (median 64.00 years, IQR: 53.00-70.00) than in the other subgroups (PD: median 60.50 years, IQR: 46.00-69.00 and EPS: median 51.00 years, IQR: 38.00-58.75). Furthermore, compared to the PD- (39 %) and EPS-group (33 %), there were more female participants in the control-group (86 %). Time on PD was longer in EPS patients (median 70.00 months) than in PD patients (median 33.50 months). In a preliminary study, exposure to high glucose-based peritoneal dialysis solutions did not markedly influence the mRNA expression of TXNIP and TRX. However, on protein level a significant glucose-related upregulation of TXNIP could be observed especially in PD patients. Interestingly, there was no glucose-related change in protein expression of its interacting partner and cellular anti-oxidant TRX. To study the effect of TXNIP expression on the generation of oxidative damage, pH2AX positive nuclei were counted on peritoneal membrane sections. A slight increase of pH2AX positive nuclei upon exposure to dialysis solutions could be observed in the cohort analysed. Conclusion Here, we show for the first time a clear tendency for upregulation TXNIP in human peritoneal tissue after exposure to high glucose-based peritoneal dialysis solutions especially in PD patients. This increase in TXNIP expression may correlate with the accumulation of oxidative damage of macromolecules. Therefore, manipulation of TXNIP expression may be a promising therapeutic target to improve peritoneal membrane function.