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.

Dynamic contrast-enhanced MRI for advanced esophageal cancer response assessment after concurrent chemoradiotherapy.

PURPOSE: We aimed to evaluate the treatment response of patients with esophageal cancer after concurrent chemoradiation therapy (CRT) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: This retrospective study included 59 patients with histologically confirmed esophageal squamous cell carcinoma. The patients underwent DCE-MRI before and 4 weeks after CRT. Patients with complete response were defined as the CR group; partial response, stable disease, and progressive disease patients were defined as the non-CR group. DCE-MRI parameters (Ktrans, Ve, and Kep) were measured and compared between pre- and post-CRT in the CR and non-CR groups, respectively. Pre-CRT and post-CRT parameters were used to calculate the absolute change and the ratio of change. DCE-MRI parameters were compared between the CR and non-CR groups. Receiver operating characteristic (ROC) curves were used to verify diagnostic performance. RESULTS: Patients with higher T-stage esophageal cancer might present with poorer response. After CRT, the Ktrans and Kep values significantly decreased in the CR group, whereas only Kep value decreased in the non-CR group. The post-Ktrans and post-Kep values were observed to be significantly lower in the CR group than in the non-CR group. The absolute change and ratio of change of both Ktrans and Kep were higher in the CR group than in the non-CR group. Based on ROC analysis, the ratio of change in Ktrans was the best parameter to assess treatment response (AUC= 0.840). CONCLUSION: DCE-MRI parameters are valuable in predicting and assessing concurrent CRT response for advanced esophageal cancer.