Peritoneal dialysis-induced senescence contributes to treatment failure in long-term PD

Abstract Peritoneal dialysis (PD) is an effective method of kidney replacement therapy. It offers patients a high degree of autonomy. However, long-term PD remains problematic. Continuous exposure of the peritoneal membrane to high-glucose solutions causes structural changes over time. This can ultimately result in a failure of ultrafiltration. It is known that PD patients exhibit elevated levels of oxidative stress, which can trigger senescence. However, it remains unclear, whether senescence occurs in the peritoneal membrane of PD patients. In this study, we demonstrate that senescent cells are mainly localized in the mesothelium. They are rarely found in adipose tissue or the vascular endothelium. After initiation of PD, senescent cells are more frequently detected in the submesothelium. We also found increased expression of the senescence markers p16 and p21 in biopsy samples from PD patients. LaminB1 showed a decreasing trend in PD samples compared to uremic samples and healthy controls. These results suggest the need for further in vitro studies using primary mesothelial cells. These studies should investigate the mechanisms of action of various senolytic agents.