Osteopontin levels in the drained dialysate reflect the peritoneal solute transport rate

Abstract Background and objectives: Long-term peritoneal dialysis (PD) is accompanied by low-grade intraperitoneal inflammation, may eventually lead to peritoneal membrane injury with high solute transport rate and ultrafiltration failure. Osteopontin(OPN) is highly expressed with the pro-inflammatory cytokines stimulation in many cell types, and evolves in the process of tissue fibrosis. This study aimed to investigate the potential of OPN as a new indicator of peritoneal injury. Methods: We analyzed a total of 125 PD patients with end-stage renal disease, including 16 patients with continuous ambulatory PD(CAPD)-related peritonitis and 109 patients without peritonitis in a single renal center. The OPN levels in the overnight peritoneal effluents or in serum were analyzed using ELISA. In HMrSV5 cells, The OPN and fibronectin(FN) protein expression were identified using western blot analysis. Results: The OPN levels in overnight drained dialysate were significantly correlated with D/P Cr (P < 0.0001, R =0.54) and D/D0 glucose (P < 0.0001 R=-0.39). Logistical regression analysis showed that the OPN levels in peritoneal effluents was an independent predictive factor for the increased peritoneal solute transport rate (PSTR) (p < 0.001). The area under the receiver operating characteristic (ROC) curve of the OPN-PSTR model for identifying PSTR was 0.88, with 95% confidence interval (CI):0.81-0.95. The OPN was more abundant in peritoneal effluents of the CAPD-related peritonitis group compared with the patients without peritonitis (18.64±13.04 vs. 2.23±1.63 ng/ml, p<0.001). In the in vitro experiment, lipopolysaccharides(LPS) increased the OPN expression in HMrSV5 cells, whereas downregulation of OPN suppressed FN induction with transforming growth factor-β1(TGF-β1)stimulation. Conclusions: The OPN levels in drained dialysate were independently correlated with peritoneal transport status in accordance with the PET results. OPN was highly expressed in effluents in patients with CAPD-related peritonitis. Peritoneal mesothelial cells displayed a high expression of OPN under inflammatory stimuli and OPN was likely to be implicated in the progression of peritoneal fibrosis. Thus, OPN may be a useful indicator of peritoneal injury in patients with PD. Keywords: peritoneal dialysis, osteopontin, peritoneal injury, peritoneal solute transport rate