Reduced Peritoneal NRF2 Immunoreactivity in Encapsulating Peritoneal Sclerosis and Its Implications for Redox Homeostasis

Peritoneal dialysis (PD) is an effective modality of renal replacement therapy that provides patients with a high degree of autonomy. However, its long-term use is limited by the detrimental effects of PD fluids on the structure and function of the peritoneal membrane, ultimately leading to a loss of dialysis efficacy. Disruption of redox homeostasis plays a central role in these pathological changes, highlighting the importance of endogenous defense mechanisms in maintaining membrane integrity. Nuclear factor erythroid 2–related factor 2 (NRF2) is a key transcription factor regulating cellular antioxidant and cytoprotective responses. However, its immunoreactivity and localization in the peritoneal tissue of PD patients and patients with encapsulating peritoneal sclerosis (EPS) have not been well characterized. Therefore, we analyzed peritoneal biopsies from healthy controls, pre-dialysis patients, PD patients, and EPS patients. Immunohistochemical analysis demonstrated significantly reduced NRF2 immunoreactivity in patients with EPS compared with all other study groups. In contrast, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) immunoreactivity was increased in PD and EPS patients. These results suggest that dysregulation of the NRF2–NFκB axis may be involved in peritoneal membrane injury, which warrants its further investigation as a potential target for preserving peritoneal membrane integrity during long-term PD.