Peritoneal aging during PD: implication of RAGE, the receptor for AGEs

Area of Science:

• Nephrology
• Cell Biology
• Biomaterials Science

Background:

• Long-term peritoneal dialysis (PD) is increasing, leading to complications like sclerosing syndromes and membrane failure.
• Conventional PD fluids (PDFs) exhibit poor biocompatibility, causing chemical peritonitis and accelerated peritoneal aging.
• Key factors in PD fluids, including non-physiological pH, high glucose, and glucose degradation products (GDPs), contribute to peritoneal damage.

Purpose of the Study:

• To summarize in vitro findings on the role of mesothelial receptor for advanced glycation end-products (RAGE) in peritoneal membrane aging.
• To elucidate the mechanisms by which conventional PDFs induce peritoneal membrane alterations.
• To differentiate early and late stages of peritoneal aging in response to PD fluid exposure.

Main Methods:

• In vitro studies focusing on human peritoneal mesothelial cells (HPMCs).
• Investigation of the implication of RAGE in HPMC activation and peritoneal aging.
• Analysis of the effects of glucose, GDPs, and advanced glycation end-products (AGEs) on peritoneal cells.

Main Results:

• Exposure to conventional PDFs accelerates peritoneal aging, characterized by mesothelial cell activation and loss.
• Advanced glycation end-products (AGEs), formed from GDPs during PDF sterilization, activate HPMCs via RAGE.
• Two distinct aging phases were observed: early mesothelial cell changes and late submesothelial fibrosis and neovascularization.

Conclusions:

• Mesothelial RAGE plays a critical role in the aging of the peritoneal membrane during long-term PD.
• Poorly biocompatible PDFs contribute significantly to peritoneal membrane failure and aging through AGEs formation and RAGE activation.
• Understanding these mechanisms is crucial for developing improved PD fluids and strategies to mitigate long-term PD complications.