Progressive peritoneal fibrosis and the loss of peritoneal function often emerged in patients undergoing long-term peritoneal dialysis (PD), resulting in PD therapy failure. Varieties of cell-cell communications among peritoneal cells play a significant role in peritoneal fibrogenesis. Extracellular vesicles (EVs) have been confirmed to involve in intercellular communication by transmitting proteins, nucleic acids or lipids. However, their roles and functional mechanisms in peritoneal fibrosis remain to be determined. Using integrative analysis of EV proteomics and single-cell RNA sequencing, we characterized the EVs isolated from PD patient's effluent and revealed that mesothelial cells are the main source of EVs in PD effluent. We demonstrated that transforming growth factor-β1 (TGF-β1) can substitute for PD fluid to stimulate mesothelial cells releasing EVs, which in turn promoted fibroblast activation and peritoneal fibrogenesis. Blockade of EVs secretion by GW4869 or Rab27a knockdown markedly suppressed PD-induced fibroblast activation and peritoneal fibrosis. Mechanistically, injured mesothelial cells produced EVs containing high level of integrin-linked kinase (ILK), which was delivered to fibroblast and activated them via p38 MAPK signalling pathway. Clinically, the expression of ILK was up-regulated in fibrotic peritoneum of patients undergoing long-term PD. The percentage of ILK positive EVs in PD effluent correlated with peritoneal dysfunction and the degree of peritoneal damage. Our study highlights that peritoneal EVs mediate communications between mesothelial cells and fibroblasts to initiate peritoneal fibrogenesis. Targeting EVs or ILK could provide a novel therapeutic strategy to combat peritoneal fibrosis.

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Background: Home blood pressure monitoring helps patients with chronic kidney disease to improve blood pressure control and can predict cardiovascular events, renal function progress, and risk of death. Few instruments are available to assess patient adherence to home blood pressure monitoring. Objective: The aim of the study was to develop an instrument to evaluate home blood pressure monitoring adherence in patients with chronic kidney disease and test its reliability and validity. Methods: An item pool was formed for the Home Blood Pressure Monitoring Adherence Scale by literature review. Patients with chronic kidney disease (n = 436) were surveyed to assess item selection and examine item reliability and validity. Scale reliability was evaluated using internal, split-half, and test-retest reliability, while validity was assessed according to content, construct, and criterion validity. Results: The scale comprising eight items was formed from the item pool and item selection. Cronbach's α was 0.906, split-half reliability was 0.947, and test-retest reliability was 0.716. Item-level and scale-level (both universal agreement and average) content validity indices were 1.00. According to the Self-Efficacy for Managing Chronic Disease 6-item Scale, criterion validity for our scale was 0.251. Exploratory factor analysis extracted one factor and the cumulative variance contribution rate was 61.568%. Confirmatory factor analysis showed the model fit well (Χ 2 =50.125, df=17, Χ 2 /df=2.949, root mean square error of approximation=0.095, confirmatory fit index=0.970). Conclusion: The scale has good reliability and validity for patients with chronic kidney disease, representing an efficient instrument for clinical assessment of home blood pressure monitoring adherence.

Peritoneal fibrosis progression is regarded as a significant cause of the loss of peritoneal function, markedly limiting the application of peritoneal dialysis (PD). However, the pathogenesis of peritoneal fibrosis remains to be elucidated. Tissue-derived extracellular vesicles (EVs) change their molecular cargos to adapt the environment alteration, mediating intercellular communications and play a significant role in organ fibrosis. Hence, we performed, for the first time, four-dimensional label-free quantitative liquid chromatography–tandem mass spectrometry proteomic analyses on EVs from normal peritoneal tissues and PD-induced fibrotic peritoneum in mice. We demonstrated the alterations of EV concentration and protein composition between normal control and PD groups. A total of 2339 proteins containing 967 differentially expressed proteins were identified. Notably, upregulated proteins in PD EVs were enriched in processes including response to wounding and leukocyte migration, which participated in the development of fibrosis. In addition, EV proteins of the PD group exhibited unique metabolic signature compared with those of the control group. The glycolysis-related proteins increased in PD EVs, while oxidative phosphorylation and fatty acid metabolism-related proteins decreased. We also evaluated the effect of cell-type specificity on EV proteins, suggesting that mesothelial cells mainly cause the alterations in the molecular composition of EVs. Our study provided a useful resource for further validation of the key regulator or therapeutic target of peritoneal fibrosis.

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