The association between self-management ability and malnutrition-inflammation-atherosclerosis syndrome in peritoneal dialysis patients: a cross-sectional study.

BACKGROUND: The relationship between malnutrition-inflammation-atherosclerosis syndrome (MIAS) and self-management ability has not been previously revealed even though both play an important role in the management of peritoneal dialysis (PD) patients. METHODS: In total, 93 patients were enrolled in this study. A self-management questionnaire was used for the evaluation of self-management ability. The identification of MIAS was based on one or more of the following three conditions: C-reactive protein (CRP)≥10 mg/L, malnutrition-inflammation score (MIS)> 7, and the presence of atherosclerosis-related medical records. The possible association between different self-management abilities and MIAS was analyzed with a Spearman correlation analysis. RESULTS: There were 40 (43.0%) patients in the atherosclerosis group, and 38 (40.9%), 38 (40.9%), 10 (10.8%), and 7 (7.5%) patients in the MIAS0, MIAS1, MIAS2, and MIAS3 groups, respectively. The group with a score above the mean score of the Dialysis Effect Evaluation and Monitoring dimension had a fewer number of hospitalizations, higher albumin levels, lower MIS scores, a lower level of IL-6, and a lower number of MIAS factors. The Pearson and Spearman correlation analyses also revealed that this dimension was negatively correlated with the MIAS, MIS, IL-6, BNP, number of hospitalizations, and age and positively associated with albumin and prealbumin. CONCLUSION: The Dialysis Effect Evaluation and Monitoring dimension of the self-management scale for PD patients is closely linked to the MIAS, and a better dialysis effect evaluation and monitoring capacity results in a decreased likelihood of exposure to malnutrition and inflammation. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000035525 ( http://www.chictr.org.cn/showproj.aspx?proj=58110 ), registered August 13, 2020.

Glycoprotein 96 in Peritoneal Dialysis Effluent-Derived Extracellular Vesicles: A Tool for Evaluating Peritoneal Transport Properties and Inflammatory Status.

Background: Extracellular vesicles (EVs) from peritoneal dialysis effluent (PDE), containing molecules such as proteins and microRNAs (miRNAs), may be potential biological markers to monitor peritoneal function or injury. Peritoneal inflammation is an important determinant of peritoneal solute transport rate (PSTR). Thus, the aim of this study is to determine whether the specific proteins capable of evaluating the PSTR could be found in PDE-EVs, and explore the underlying mechanism for the association between PSTR and peritoneal inflammation. Methods: Sixty patients undergoing peritoneal dialysis (PD) were divided into two groups: high/high average transport (H/A) group (PET >0.65) and low/low average transport (L/A) group (PET <0.65). EVs derived from PDE (PDE-EVs) were isolated by ultracentrifugation. Proteomic analysis was performed to explore the differentially expressed proteins and identify the potential biomarkers in PDE-EVs from the two groups, and we focused on glycoprotein 96 (GP96) as it could be involved in the inflammatory process. The expression of GP96 in PDE-EVs and inflammatory cytokines was quantified by real-time PCR and enzyme-linked immunosorbent assay. The infiltration of macrophages and neutrophils into the peritoneum was detected using immunohistochemistry in a PD rat model. Results: The expression of PDE-EVs-GP96 was significantly higher in the H/A group, and was positively correlated with the PSTR and the level of the inflammatory factor interleukin (IL)-6. GP96-enriched EVs enhanced the secretion of proinflammatory cytokines IL-1ß, IL-6, tumor necrosis factor (TNF)-α, and IL-8 in macrophages, which was reversed by a pharmacological GP96-specific inhibitor (PU-WS13). The GP96 inhibitor also reduced local peritoneal inflammation by decreasing the infiltration of inflammatory cells and levels of proinflammatory cytokines (IL-6 and TNF-α) and chemokines (CCL2, CXCL1, and CXCL2) in a PD rat model. Conclusions: PDE-EVs-GP96 is a new promising tool to evaluate the status of peritoneal inflammation and PSTR, and the mechanism may be related to affecting the inflammatory properties of macrophages.

Peritoneal dialysis effluent-derived exosomal miR-432-5p: an assessment tool for peritoneal dialysis efficacy.

Background: Ultrafiltration (UF) volume and peritoneal solute transport rate (PSTR) are common parameters used to evaluate the efficacy of peritoneal dialysis (PD) on individual patients. It is unclear whether the level of exosomal microRNA (miRNA) in peritoneal dialysis effluent (PDE) can predict UF or PSTR. This study was designed to investigate if there is a correlation between PDE exosomal miRNA (miR-432-5p) levels and various UF volumes and PSTRs in PD patients. It also aimed to explore the underlying mechanism of water and dialytic sodium removal (DSR). Methods: The PSTR was quantified using the 4-hour (4 h) 3.86% dialysate to plasma creatinine ratio. The PDE exosomes (PDE-exo) were isolated by ultracentrifugation. An miRNA assay was used to identify the different miRNA in the PDE-exo of patients in a high (H; PSTR >0.65, n=5) and low (L; PSTR <0.65, n=5) group. We focused on miR-432-5p as bioinformatic analysis had shown that it could be involved in sodium transport. We used mimic/inhibitor transfection and dual luciferase reporter assay to verify the target genes of miR-432-5p. We used PKH-67 stained PDE-exo to observe their interaction with human MeT-5A mesothelial cells. Results: Our results showed that the PDE-exo-miR-432-5p level was higher in group H than in group L. The levels of PDE-exo-miR-432-5p were positively correlated with PSTR (r=0.391; P<0.05; n=40) and negatively correlated with the 4 h UF volume (r=-0.376; P<0.05; n=40) and 4 h DSR (r=-0.535; P<0.01; n=24). Epithelial sodium channel α subunit (α-ENaC) was revealed as a direct target gene of miR-432-5p and expressed on both human peritoneum and MeT-5A cells. Furthermore, we found the PKH67 labeled-PDE-exo could be internalized into MeT-5A cells. Conclusions: A high PDE-exo-miR-432-5p level was associated with poor UF volume and DSR. It may be that PDE-exo-miR-432-5p affects DSR through downregulating α-ENaC expression.