Date: Monday, June 3, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Peritoneal fibrosis (PF) is an intractable complication which leads to peritoneal membrane failure in peritoneal dialysis (PD). The aim of this study was to investigate the role of suppression of tumorigenicity-2 (ST2) involved in PF.
*Methods: Samples of dialysate and clinical data were prospectively collected from 54 patients at Seoul National University Hospital between 2010 and 2016. Dialysate soluble ST2 (sST2) levels were measured after 1 month of PD initiation (baseline) using the enzyme-linked immunoabsorbant assay (ELISA) technique. Fibrosis was induced by TGF-β and high concentration of glucose in primary cultured human peritoneal mesothelial cells (HPMCs) and anti-ST2 monoclonal antibody (mAb) was treated to evaluate the neutralizing effect of ST2 on PF. Immunohistochemistry (IHC) stain of ST2 was performed in peritoneum tissue samples of chlorhexidine gluconate (CG)-induced PF mice and control.
*Results: Baseline dialysate sST2 (sST2-b) levels were 2063.4 ± 2457.8 pg/mL and mean duration of follow-up periods was 53.4 ± 18.8 months. We observed that patients who changed dialysis modality to hemodialysis due to PD failure had high sST2-b levels in peritoneal effluent compared with others (1576.2 ± 199.9 versus 4143.1 ± 1107.3, P = 0.03). High sST2-b was associated with a hazard ratio (HR) for PD failure of 7.72 (95% CI 1.10-54.3, P = 0.04) in a fully adjusted model. sST2-b showed a good performance in predicting PD failure; the area under the ROC curve was 0.780 (P = 0.001). We found that in primary cultured HPMCs, TGF-β treatment increased protein expressions of ST2, fibronectin, β-galactosidase, snail and decreased expression of E-cadherin in a dose-dependent manner. Protein expression of ST2 and fibronectin were decreased after anti-ST2 Ab administration. High concentration of glucose (100mmol/L) also induced fibrosis in HPMCs and fibrosis was ameliorated after ST2 blockade. ST2 was found in fibroblasts and mesothelial cells within the underlying submesothelial zones of CG-induced PF mice.
*Conclusions: An elevated dialysate levels of ST2 appears to play a role in fibrosis and inflammation during peritoneal injury. Targeting ST2 pathway may be an effective strategy to prevent peritoneal fibrosis.
To cite this abstract in AMA style:Kim Y, Lee S, Yu M, Lee H, Kim Y, Lee C, Cha R, Yang S. Initial Peritoneal sST2 Levels Are Associated with Peritoneal Failure and ST2 Blockade Mitigates TGF-β and High Glucose-Induced Peritoneal Fibrosis [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/initial-peritoneal-sst2-levels-are-associated-with-peritoneal-failure-and-st2-blockade-mitigates-tgf-%ce%b2-and-high-glucose-induced-peritoneal-fibrosis/. Accessed September 27, 2021.
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