Fibrosis of Peritoneal Membrane as Target of New Therapies in Peritoneal Dialysis

Abstract

Peritoneal dialysis (PD) is an efficient renal replacement therapy for patients with end-stage renal disease. Even if it ensures an outcome equivalent to hemodialysis and a better quality of life, in the long-term, PD is associated with the development of peritoneal fibrosis and the consequents patient morbidity and PD technique failure. This unfavorable effect is mostly due to the bio-incompatibility of PD solution (mainly based on high glucose concentration). In the present review, we described the mechanisms and the signaling pathway that governs peritoneal fibrosis, epithelial to mesenchymal transition of mesothelial cells, and angiogenesis. Lastly, we summarize the present and future strategies for developing more biocompatible PD solutions.

Proteome-Wide Differential Effects of Peritoneal Dialysis Fluid Properties in an In Vitro Human Endothelial Cell Model

“…Other molecular pathways enriched by all PD fluids included acute phase response, integrin signaling, senescence, and fibrosis-related pathways. All of them—but especially fibrosis—are well-described pathomechanisms of the peritoneal membrane exposed to PD [ 7 , 37 , 38 , 39 , 40 , 41 ]. Different combinations of exogenous stressors (osmotic agent, pH, buffer system, toxic GDPs) which characterize the individual PD fluid properties also trigger more specific pathways.…”

“…The high amounts of glucose itself have been shown to induce oxidative stress responses in mesothelial cells [ 40 , 42 , 43 , 44 ]. In addition, increased systemic oxidative stress arises already in early stages of chronic kidney disease, posing an important pathophysiological condition in PD patients [ 39 , 45 , 46 , 47 ].…”

Mechanisms of Peritoneal Mesothelial Cells in Peritoneal Adhesion

“…PMCs have epithelial and mesenchymal features and can transform under physiological and pathological conditions [ 6 ]. The peritoneum is a naturally semipermeable membrane under physiological conditions [ 31 , 32 , 33 ], but after repeated peritoneal dialysis, PMCs undergo mesothelial–mesenchymal transformation (MMT), which can lead to peritoneal fibrosis [ 34 , 35 , 36 , 37 ]. In addition, PMCs can capture bacteria, chemical molecules, and other substances to play a protective barrier role [ 21 ].…”

“…This transformation is manifested by the loss of the apical–basolateral polarity of PMCs and E-cadherin expression, as well as overexpression of α-smooth muscle actin (α-SMA) and vimentin. The PMCs eventually transform into fibroblast-like cells with enhanced migratory ability and production of ECM to promote PA formation [ 30 , 33 , 82 ].…”

Peritoneal dialysis and peritoneal fibrosis: molecular mechanisms, risk factors and prospects for prevention

“…1b) [3,4,7,8]. Реактивні зміни та/або втрата мезотеліальних клітин супроводжуються збільшенням товщини субмезотеліальної компактної зони, що може бути опосередковано безліччю молекулярних механізмів, включаючи активацію ренін-ангіотензин-альдостерон системи та індукцію чисельних медіаторів запалення [1,8,9]. Збільшення товщини перитонеальної мембрани до понад 700 мкм (за фізіологічних умов товщина перитонеуму складає приблизно 50 мкм) також опосередковано мезотеліальними клітинами, які набувають фібробластоподібний вигляд, що сприяє утворенню колагену та накопиченню позаклітинного матриксу [1,6,8].…”