Peritoneal dialysis (PD) is an established renal replacement therapy for renal disease. It is based on the capacity of the peritoneum to act as a semipermeable membrane for the exchange of toxic solutes and water, which is called ultrafiltration capacity. Peritoneal membrane (PM) is lined by a monolayer of mesothelial cells (MCs), which lay on an extracellular matrix bed where other cell types and blood and lymphatic vessels can be found. Long-term exposure to hyperosmotic PD fluids (PDFs), peritonitis or hemoperitoneum causes peritoneal injury by the generation of an inflammatory state. Inflammatory cells and their mediators initiate a cascade of reactions promoting alterations in peritoneal cells, loss of MCs, fibrosis, vasculopathy, and angiogenesis, leading to ultrafiltration failure. Recent studies support that the so-called “mesothelial to mesenchymal transition” process of the MCs runs parallel to the anatomical and functional ridging of PM, which suggests that its inhibition might slow down or stop the PM damage. The fight against PM damage begins with the improvement in PDF biocompatibility. Complementary to this, an alternative approach to preserve the PM might be the use of pharmacological agents or molecular strategies. Here, we explain the existing research models for the development of new therapies and analyze several therapeutic options tested with them.
Part of the book: Some Special Problems in Peritoneal Dialysis
The ultrafiltration failure during peritoneal dialysis (PD) is related to inflammatory responses induced by bio-incompatible PD fluids, which may lead to deterioration of peritoneal membrane (PM) function. Mesothelial cells, lymphocytes, macrophages and other cell types present in the peritoneal cavity are stimulated to produce cytokines and growth factors that promote pathological processes. Due to these factors, blood and lymphatic vessels proliferate and could be responsible for hyperfiltration and PM failure type III and IV. Vessels proliferation may be related to fibrosis, being the cause and/or effect of the mesenchymal conversion of different cell types such as mesothelial (MMT), bone marrow-derived (fibrocytes) or endothelial (vascular- and lymph-endo-MT) cells. Lymphangiogenesis in PD is a poorly analysed process; however, its contribution to peritoneal function disorders has been recently recognized. VEGF production is associated with blood and lymphatic vessels proliferation, while specifically lymphangiogenesis is mainly regulated by VEGF-C and VEGF-D. Excessive lymphatic fluid drainage from the abdominal cavity may be related with macromolecule and isosmotic solutions reuptake and convective reabsorption of solutes that were cleared from plasma by diffusion. Some drugs have been shown to modulate tissue fibrosis, MMT, EndoMT, angiogenesis and lymphangiogenesis and could represent interesting therapeutic strategies to protect the PM.
Part of the book: Aspects in Dialysis