Peritoneal injury induced by dialysis fluids

Peritoneal dialysis (PD) is used to treat end-stage renal disease (ESRD). PD requires the instillation and periodical renovation of PD fluid (PDF) into the peritoneal cavity. PDFs are hyperosmotic solutions generally based on glucose. An osmotic agent is needed to create a gradient that allows a negative fluid balance. However, PDFs may injure the peritoneal membrane in the long term, causing mesothelial cell loss, inflammation, vasodilatation, epithelial–mesenchymal transition (EMT) of mesothelial cells and angiogenesis that lead to fibrosis and ultrafiltration failure. Factors contributing to the bioincompatibility of PDFs include high glucose or glucose degradation product (GDPs) concentrations, low pH and lactate buffer [1]. Bioincompatibility may be reduced by using alternative osmotic agents and glucose-based PDFs with a more physiological pH, lower GDPs concentrations or bicarbonate buffer. Low-GDP PDFs better preserve peritoneal morphology [2, 3]. However, a completely biocompatible PDF will be difficult to achieve, glucose-based PDFs are still needed, and more biocompatible PDFs are expensive so many potential users cannot afford them.

Pharmacological modulation: is it an option?

An alternative approach to preserve the peritoneal membrane, complementary to the efforts aimed at improving PDFs biocompatibility, is the use of pharmacological agents protecting the mesothelium or targeting inflammation and fibrosis. The feasibility of two chronic pharmacological intervention approaches has been tested in experimental PD. One was the addition of pharmacological agents to the PDFs. This approach has been useful for proof-of-concept studies. Industrial addition of therapeutic agents as another component of PDF could be interesting for the future. However, incorporation of new components of PDFs requires major changes from a regulatory point of view and will increase the cost of PD. Self administration of a therapeutic agent into the PDF by the patient will also increase the cost of PD and has a potential risk of PDF contamination. The other approach, the …

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