Abstract
Preservation of peritoneal cavity homeostasis and peritoneal membrane function is critical for long-term peritoneal dialysis (PD) treatment. Several microRNAs (miRNAs) have been implicated in the regulation of key molecular pathways driving peritoneal membrane alterations leading to PD failure. miRNAs regulate the expression of the majority of protein coding genes in the human genome, thereby affecting most biochemical pathways implicated in cellular homeostasis. In this review, we report published findings on miRNAs and PD therapy, with emphasis on evidence for changes in peritoneal miRNA expression during long-term PD treatment. Recent work indicates that PD effluent- (PDE-) derived cells change their miRNA expression throughout the course of PD therapy, contributing to the loss of peritoneal cavity homeostasis and peritoneal membrane function. Changes in miRNA expression profiles will alter regulation of key molecular pathways, with the potential to cause profound effects on peritoneal cavity homeostasis during PD treatment. However, research to date has mainly adopted a literature-based miRNA-candidate methodology drawing conclusions from modest numbers of patient-derived samples. Therefore, the study of miRNA expression during PD therapy remains a promising field of research to understand the mechanisms involved in basic peritoneal cell homeostasis and PD failure.
Highlights
Peritoneal dialysis (PD) therapy involves constant exposure of the peritoneal membrane to bioincompatible peritoneal dialysis (PD) solutions and a high basal inflammatory state
Further research to identify PD effluent- (PDE-)miRNAs as biomarkers may contribute to individualizing PD therapy by indicating the adequacy of switching therapy, interrogating and discriminating clinical trials competence, and guiding the development of therapy innovations
Peritoneal therapy may require multiple biomarkers to achieve the degree of accuracy needed and different biomarkers may be required to address distinct specific questions. In this respect miRNAs are convenient as biomarkers due to easy, cost-effective, multiple-detection methods that have been recently developed. These studies suggest that miRNAs are likely to be important in the regulation of mesothelial cell phenotype and homeostasis in the peritoneal cavity during PD therapy
Summary
Peritoneal dialysis (PD) therapy involves constant exposure of the peritoneal membrane to bioincompatible PD solutions and a high basal inflammatory state. This results in an alteration of the peritoneal cavity homeostasis characterized by progressive fibrosis, angiogenesis, and ultrafiltration failure [1]. PD failure has been largely associated with the conversion of MCs to myofibroblasts, via mesothelial-to-mesenchymal transition (MMT) and mesothelial cell loss [2]. This phenotypic conversion leads to increased synthesis of extracellular matrix components and release of proinflammatory and proangiogenic factors [3] (Figure 1(b)).
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