Abstract
Cardiorenal syndrome (CRS) is described as primary dysfunction in the heart culminating in renal injury or vice versa. CRS can be classified into five groups, and uremic toxin (UT) accumulation is observed in all types of CRS. Protein-bound uremic toxin (PBUT) accumulation is responsible for permanent damage to the renal tissue, and mainly occurs in CRS types 3 and 4, thus compromising renal function directly leading to a reduction in the glomerular filtration rate (GFR) and/or subsequent proteinuria. With this decrease in GFR, patients may need renal replacement therapy (RRT), such as peritoneal dialysis (PD). PD is a high-quality and home-based dialysis therapy for patients with end-stage renal disease (ESRD) and is based on the semi-permeable characteristics of the peritoneum. These patients are exposed to factors which may cause several modifications on the peritoneal membrane. The presence of UT may harm the peritoneum membrane, which in turn can lead to the formation of extracellular vesicles (EVs). EVs are released by almost all cell types and contain lipids, nucleic acids, metabolites, membrane proteins, and cytosolic components from their cell origin. Our research group previously demonstrated that the EVs can be related to endothelial dysfunction and are formed when UTs are in contact with the endothelial monolayer. In this scenario, this review explores the mechanisms of EV formation in CRS, uremia, the peritoneum, and as potential biomarkers in peritoneal dialysis.
Highlights
Extracellular vesicles (EVs) have been widely investigated for their role in intercellular communication and as potential biomarkers, in inflammatory pathological conditions
Key Contribution: Extracellular vesicles (EVs) have been widely investigated for their role in intercellular communication and as potential biomarkers; and could be a promising tool to improve the quality of care in kidney disease patients
FT-Raman spectroscopy has been explored in several diagnostic experiments [194], including cancer diagnosis, neurological problems, diabetes, atherosclerosis, red blood cells infected with malaria, and monitoring osteoarthritis and rheumatoid arthritis in different experimental models, and in renocardiac syndrome induced by renal ischemia and reperfusion [197]
Summary
Extracellular vesicles (EVs) have been widely investigated for their role in intercellular communication and as potential biomarkers, in inflammatory pathological conditions. Cardiorenal syndrome results from interrelated heart and kidney injuries, which leads to an accumulation of uremic toxins in the body, especially with the progression of chronic kidney disease (CKD) [1,2,3]. The participation of EVs in CRS has not been fully elucidated. Clinical and in vitro studies have shown that uremic toxins induce the formation of EVs [4,5,6,7,8]. We address the role of EVs in CRS, especially their relationship with uremic toxins and kidney dysfunction. EVs from the peritoneal membrane in ESRD patients undergoing peritoneal dialysis are potential biomarkers. We discuss the classification of EVs and the main methods for isolating and characterizing EVs, including electron microscopy, proteomics, lipidomics, transcriptome and metabolomics analyses, Fourier transform infrared (FTIR), and Raman spectroscopies, as well as possible use of EVs as biomarkers of cell injury and the therapeutic strategies to avoid their formation
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