Effluent decoy receptor 2 as a novel biomarker of peritoneal fibrosis in peritoneal dialysis patients

Abstract

Background: Peritoneal fibrosis (PF) is a common complication of peritoneal dialysis (PD), but a specific and sensitive biomarker for PF is lacking. The present study aimed to determine the use of effluent decoy receptor 2 (eDcR2) as a biomarker for PF in PD patients. Methods: PD patients ( n = 248) were recruited, and peritoneal specimens were collected at PD initiation ( n = 30) and cessation ( n = 33). Enzyme-linked immunoassay was used to measure eDcR2 and the eDcR2 appearance rate (eDcR2-AR) was calculated. The levels of DcR2 mRNA and protein were determined. The correlation of eDcR2 level with peritoneal function, histological parameters and DcR2 expression were analysed. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic performance of eDcR2 for PF, which was defined as a submesothelial thickness 150 µm or more. Co-localisation of DcR2 with a mesothelial marker, fibroblast markers and fibrotic markers were determined. Results: The eDcR2-AR level correlated with PD duration, D/P Cr values, peritoneal Kt/V and peritoneal injury scores, especially submesothelial thickness ( r = 0.638, p < 0.001). DcR2 was primarily expressed in peritoneal fibroblasts, and co-localised with α-SMA, vimentin, collagen I and fibronectin, but not with E-cadherin. Peritoneal DcR2 expression had a positive correlation with eDcR2-AR. ROC analysis indicated eDcR2 had an area under the curve of 0.907 for detection of PF (sensitivity: 78.6%, specificity: 100%) and the best cut-off value was 392.5 pg/min. Conclusion: The eDcR2-AR level is a potential biomarker for assessing PF in PD patients. Effluent DcR2 was mainly derived from peritoneal fibroblasts and DcR2-positive cells may accelerate PF, suggesting that it may be a potential therapeutic target.

Preventive effect of culture supernatant of epithelial-like peritoneal mesothelial cells on peritoneal fibrosis

“…The pathogenesis of PF involves multiple factors, including uremic state, high levels of glucose and glucose degradation products, high osmolality, infection and acidic pH. 12,13 Using neutral dialysis fluid and avoiding high-glucose dialysate does not completely prevent peritoneal deterioration. One of the central findings of this study is PF prevention by CS-P-Epi, similarly to the previous report, where PMC transplantation was applied, 6 suggesting that paracrine effect is predominant in therapeutic mechanisms of PMC therapy.…”

Current Insights into Cellular Determinants of Peritoneal Fibrosis in Peritoneal Dialysis: A Narrative Review

“…Another study documented the potential of effluent decoy receptor 2 (eDcR2) as a biomarker of peritoneal fibrosis in PD patients. DcR2 is mainly expressed in peritoneal fibroblasts and co-localized with α-smooth muscle antigen (α-SMA), vimentin, collagen I, and fibronectin [ 42 ]. In addition to eDcR2, serum α-Klotho below 742 pg/mL is also associated with the sub-mesothelial thickness of the peritoneal membrane, whereas galectin-3 uremic levels are associated with PD failure and time to PD failure [ 43 ].…”