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Frontiers in Immunology 2022Extracellular vesicles (EVs) from peritoneal dialysis effluent (PDE), containing molecules such as proteins and microRNAs (miRNAs), may be potential biological markers...
BACKGROUND
Extracellular vesicles (EVs) from peritoneal dialysis effluent (PDE), containing molecules such as proteins and microRNAs (miRNAs), may be potential biological markers to monitor peritoneal function or injury. Peritoneal inflammation is an important determinant of peritoneal solute transport rate (PSTR). Thus, the aim of this study is to determine whether the specific proteins capable of evaluating the PSTR could be found in PDE-EVs, and explore the underlying mechanism for the association between PSTR and peritoneal inflammation.
METHODS
Sixty patients undergoing peritoneal dialysis (PD) were divided into two groups: high/high average transport (H/A) group (PET >0.65) and low/low average transport (L/A) group (PET <0.65). EVs derived from PDE (PDE-EVs) were isolated by ultracentrifugation. Proteomic analysis was performed to explore the differentially expressed proteins and identify the potential biomarkers in PDE-EVs from the two groups, and we focused on glycoprotein 96 (GP96) as it could be involved in the inflammatory process. The expression of GP96 in PDE-EVs and inflammatory cytokines was quantified by real-time PCR and enzyme-linked immunosorbent assay. The infiltration of macrophages and neutrophils into the peritoneum was detected using immunohistochemistry in a PD rat model.
RESULTS
The expression of PDE-EVs-GP96 was significantly higher in the H/A group, and was positively correlated with the PSTR and the level of the inflammatory factor interleukin (IL)-6. GP96-enriched EVs enhanced the secretion of proinflammatory cytokines IL-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-8 in macrophages, which was reversed by a pharmacological GP96-specific inhibitor (PU-WS13). The GP96 inhibitor also reduced local peritoneal inflammation by decreasing the infiltration of inflammatory cells and levels of proinflammatory cytokines (IL-6 and TNF-α) and chemokines (CCL2, CXCL1, and CXCL2) in a PD rat model.
CONCLUSIONS
PDE-EVs-GP96 is a new promising tool to evaluate the status of peritoneal inflammation and PSTR, and the mechanism may be related to affecting the inflammatory properties of macrophages.
Topics: Animals; Biomarkers; Cytokines; Extracellular Vesicles; Glycoproteins; Humans; Inflammation; Interleukin-6; Peritoneal Dialysis; Peritoneum; Peritonitis; Proteomics; Rats
PubMed: 35222405
DOI: 10.3389/fimmu.2022.824278 -
International Journal of Molecular... May 2023In peritoneal dialysis (PD) patients, fungi and are considered important causative microorganisms for peritonitis with poor prognosis. Our objective was to explore...
In peritoneal dialysis (PD) patients, fungi and are considered important causative microorganisms for peritonitis with poor prognosis. Our objective was to explore expressions of membrane complement (C) regulators (CRegs) and tissue injuries in the peritoneum of patients with PD-related peritonitis, including fungal and peritonitis. In peritoneal biopsy tissues obtained at PD catheter removal, we investigated the severity of peritonitis-associated peritoneal injuries and the expression of CRegs, CD46, CD55, and CD59 against peritoneal tissues without any episode of peritonitis. In addition, we evaluated peritoneal injuries among fungal and -peritonitis (P1) and Gram-positive bacterial peritonitis (P2). We also observed deposition of C activation products such as activated C and C5b-9 and measured sC5b-9 in the PD fluid of patients. As a result, the severity of peritoneal injuries correlated inversely with the expression of peritoneal CRegs. Peritoneal CReg expression in peritonitis was significantly reduced compared to no peritonitis. Peritoneal injuries were more severe in P1 than in P2. CReg expression was further decreased and C5b-9 further increased in P1 than in P2. In conclusion, severe peritoneal injuries due to fungal and -peritonitis decreased CReg expression and increased deposition of activated C3 and C5b-9 in the peritoneum, suggesting that peritonitis, particularly fungal and -peritonitis, might induce susceptibility to further peritoneal injuries due to excessive C activation.
Topics: Humans; Peritoneum; Complement Membrane Attack Complex; Complement Activation; Peritoneal Dialysis; Peritonitis; Immunologic Factors
PubMed: 37298097
DOI: 10.3390/ijms24119146 -
Scientific Reports Apr 2020The role of intra-peritoneal mediators in the regulation peritoneal transport is not completely understood. We investigate the relation between longitudinal changes in...
The role of intra-peritoneal mediators in the regulation peritoneal transport is not completely understood. We investigate the relation between longitudinal changes in dialysis effluent level of nuclear factor kappa-B (NF-κB) downstream mediators and the change in peritoneal transport over 1 year. We studied 46 incident PD patients. Their peritoneal transport characteristics were determined after starting PD and then one year later. Concomitant dialysis effluent levels of interleukin-6 (IL-6), cyclo-oxygenase-2 (COX-2) and hepatocyte growth factor (HGF) are determined. There were significant correlations between baseline and one-year dialysis effluent IL-6 and COX-2 levels with the corresponding dialysate-to-plasma creatinine level at 4 hours (D/P4) and mass transfer area coefficient of creatinine (MTAC). After one year, patients who had peritonitis had higher dialysis effluent IL-6 (26.6 ± 17.4 vs 15.1 ± 12.3 pg/ml, p = 0.037) and COX-2 levels (4.97 ± 6.25 vs 1.60 ± 1.53 ng/ml, p = 0.007) than those without peritonitis, and the number of peritonitis episode significantly correlated with the IL-6 and COX-2 levels after one year. In contrast, dialysis effluent HGF level did not correlate with peritoneal transport. There was no difference in any mediator level between patients receiving conventional and low glucose degradation product solutions. Dialysis effluent IL-6 and COX-2 levels correlate with the concomitant D/P4 and MTAC of creatinine. IL-6 and COX-2 may contribute to the short-term regulation of peritoneal transport.
Topics: Aged; Creatinine; Cyclooxygenase 2; Dialysis Solutions; Female; Follow-Up Studies; Hepatocyte Growth Factor; Humans; Interleukin-6; Kidney Failure, Chronic; Longitudinal Studies; Male; Middle Aged; NF-kappa B; Peritoneal Dialysis; Peritoneum; Peritonitis
PubMed: 32296091
DOI: 10.1038/s41598-020-63258-3 -
American Journal of Physiology. Renal... Mar 2005The peritoneal cavity is important in clinical medicine because of its use as a portal of entry for drugs utilized in regional chemotherapy and as a means of dialysis... (Review)
Review
The peritoneal cavity is important in clinical medicine because of its use as a portal of entry for drugs utilized in regional chemotherapy and as a means of dialysis for anephric patients. The barrier between the therapeutic solution in the cavity and the plasma does not correspond to the classic semipermeable membrane but instead is a complex structure of cells, extracellular matrix, and blood microvessels in the surrounding tissue. New research on the nature of the capillary barrier and on the orderly array of extracellular matrix molecules has provided insights into the physiological basis of osmosis and the alterations in transport that result from infusion of large volumes of fluid. The anatomic peritoneum is highly permeable to water, small solutes, and proteins and therefore is not a physical barrier. However, the cells of the mesothelium play an essential role in the immune response in the cavity and produce cytokines and chemokines in response to contact with noncompatible solutions. The process of inflammation, which depends on the interaction of mesothelial, interstitial, and endothelial cells, ultimately leads to angiogenesis and fibrosis and the functional alteration of the barrier. New animal models, such as the transgenic mouse, will accelerate the discovery of methods to preserve the functional peritoneal barrier.
Topics: Animals; Antineoplastic Agents; Aquaporins; Biological Transport; Humans; Injections, Intraperitoneal; Peritoneal Cavity; Peritoneal Dialysis; Peritoneum; Peritonitis; Water-Electrolyte Balance
PubMed: 15692055
DOI: 10.1152/ajprenal.00313.2004 -
Kidney International May 2017Peritonitis remains the major obstacle for the maintenance of long-term peritoneal dialysis and dysregulated host peritoneal immune responses may compromise local...
Peritonitis remains the major obstacle for the maintenance of long-term peritoneal dialysis and dysregulated host peritoneal immune responses may compromise local anti-infectious defense, leading to treatment failure. Whilst, tissue mononuclear phagocytes, comprising macrophages and dendritic cells, are central to a host response to pathogens and the development of adaptive immune responses, they are poorly characterized in the human peritoneum. Combining flow cytometry with global transcriptome analysis, the phenotypic features and lineage identity of the major CD14 macrophage and CD1c dendritic cell subsets in dialysis effluent were defined. Their functional specialization was reflected in cytokine generation, phagocytosis, and antigen processing/presentation. By analyzing acute bacterial peritonitis, stable (infection-free) and new-starter patients receiving peritoneal dialysis, we identified a skewed distribution of macrophage to dendritic cell subsets (increasing ratio) that associated with adverse peritonitis outcomes, history of multiple peritonitis episodes, and early catheter failure, respectively. Intriguingly, we also noted significant alterations of macrophage heterogeneity, indicative of different maturation and activation states that were associated with different peritoneal dialysis outcomes. Thus, our studies delineate peritoneal dendritic cells from macrophages within dialysate, and define cellular characteristics associated with peritoneal dialysis treatment failure. These are the first steps to unravelling the detrimental adaptive immune responses occurring as a consequence of peritonitis.
Topics: Adaptive Immunity; Antigens, CD1; Bacterial Infections; Cytokines; Dendritic Cells; Dialysis Solutions; Flow Cytometry; Glycoproteins; Humans; Lipopolysaccharide Receptors; Macrophages, Peritoneal; Male; Middle Aged; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Peritoneum; Peritonitis; Transcriptome
PubMed: 28065517
DOI: 10.1016/j.kint.2016.10.030 -
Molecules (Basel, Switzerland) Mar 2018Acute inflammation is a protective response of the host to physical injury and invading infection. Timely treatment of acute inflammatory reactions is essential to...
Acute inflammation is a protective response of the host to physical injury and invading infection. Timely treatment of acute inflammatory reactions is essential to prevent damage to organisms that can eventually lead to chronic inflammation. Forsythoside A (FTA), an active constituent of , has been reported to have anti-inflammatory, antioxidant, and antibacterial properties. Despite increasing knowledge of its anti-inflammatory effects, the mechanism and the effects on acute inflammation are poorly understood. This study is aimed at exploring the pro-resolving effects of FTA on zymosan-induced acute peritonitis. FTA significantly alleviated peritonitis as evidenced by the decreased number of neutrophils and levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) in the peritoneal cavity, without interfering with interleukin-10 (IL-10). FTA showed marked regulation of inflammatory cytokines and chemokine levels in zymosan-stimulated RAW 264.7 macrophages. Moreover, FTA could suppress the activation of NF-κB. In conclusion, FTA alleviated zymosan-induced acute peritonitis through inhibition of NF-κB activation.
Topics: Animals; Anti-Inflammatory Agents; Cytokines; Glycosides; Inflammation Mediators; Mice; NF-kappa B; Neutrophils; Peritoneal Cavity; Peritonitis; RAW 264.7 Cells; Zymosan
PubMed: 29509714
DOI: 10.3390/molecules23030593 -
Internal Medicine (Tokyo, Japan) Feb 2024
Topics: Humans; Female; Ascites; Peritoneum; Tuberculosis; Ovarian Neoplasms; Peritonitis, Tuberculous
PubMed: 37344427
DOI: 10.2169/internalmedicine.2013-23 -
Srpski Arhiv Za Celokupno Lekarstvo 2005Peritonitis is a serious clinical complication in patients with terminal chronic renal failure (CRF) on peritoneal dialysis (PD). The incidence of peritonitis varies... (Review)
Review
Peritonitis is a serious clinical complication in patients with terminal chronic renal failure (CRF) on peritoneal dialysis (PD). The incidence of peritonitis varies from center to center, and during the last decade it occurs approximately in one patient during 24-60 therapeutical months, which is the result of good education of patients, but also of employing the new systems for PD. Fungi as well as Mycobacterium tuberculosis are rare causes of peritonitis in patients on PD therapy. The incidence of peritonitis with these two causes varies: 1-15% and 0.7-3%, respectively. The most frequent causes of fungal peritonitis are yeasts (Candida species 70-100%, with most frequent C. parapsilosis), but rarely filamentous fungi such as: Aspergillus, Paecilomyces, Penicillium, Zygomycetes, etc. Gram stains are helpful for diagnosis, as well as the culture of peritoneal effluent. There are various kinds of treatment protocols: withdrawal of peritoneal catheters and application of antimicotic drugs such as amphotericin B (which has recently been abandoned), oral flucytosine, oral or intraperitoneal fluconazole (imidazol) or itraconazol in the case of resistance. Although clinical signs disappear, most of these patients cannot continue with peritoneal dialysis therapy because of peritoneal adhesions, abscesses, fibrosis or progressive sclerosing peritonitis. Percentage of death is 12-44%. The incidence of tuberculosis is higher in patients with CRF in comparison with the entire population, and tuberculous peritonitis can develop in patients who had infection with Mycobacterium tuberculosis which was not treated adequately. Diagnosis can be made by detecting mycobacterium in peritoneal effluent (cultivation for 6 weeks) and/or acidophilic bacillus or typical granuloma in peritoneal biopsy. Therapy consists of removing the peritoneal catheter and long lasting antituberculotic therapy: izoniazid, rifampicin, pyrazinamide, pyridoxin (6-12 months). Streptomycin and ethambutol are to be avoided because of side effects in these patients. In spite of therapy, possible consequences are: ultrafiltration loss, obstruction of intestines because of adhesions, abdominal abscesses, fistulae, ending PD therapy, and even death.
Topics: Humans; Mycoses; Peritoneal Dialysis; Peritonitis; Peritonitis, Tuberculous
PubMed: 16206710
DOI: No ID Found -
Journal of Nephrology Sep 2023Peritoneal dialysis- (PD) related infections continue to be a major cause of morbidity and mortality in patients on renal replacement therapy via PD. However, despite... (Review)
Review
Peritoneal dialysis- (PD) related infections continue to be a major cause of morbidity and mortality in patients on renal replacement therapy via PD. However, despite the great efforts in the prevention of PD-related infectious episodes, approximately one third of technical failures are still caused by peritonitis. Recent studies support the theory that ascribes to exit-site and tunnel infections a direct role in causing peritonitis. Hence, prompt exit site infection/tunnel infection diagnosis would allow the timely start of the most appropriate treatment, thereby decreasing the potential complications and enhancing technique survival. Ultrasound examination is a simple, rapid, non-invasive and widely available procedure for tunnel evaluation in PD catheter-related infections. In case of an exit site infection, ultrasound examination has greater sensitivity in diagnosing simultaneous tunnel infection compared to the physical exam alone. This allows distinguishing the exit site infection, which will likely respond to antibiotic therapy, from infections that are likely to be refractory to medical therapy. In case of a tunnel infection, the ultrasound allows localizing the catheter portion involved in the infectious process, thus providing significant prognostic information. In addition, ultrasound performed after two weeks of antibiotic administration allows monitoring patient response to therapy. However, there is no evidence of the usefulness of ultrasound examination as a screening tool for the early diagnosis of tunnel infections in asymptomatic PD patients.
Topics: Humans; Catheter-Related Infections; Catheters, Indwelling; Peritoneal Dialysis; Anti-Bacterial Agents; Peritonitis
PubMed: 36939999
DOI: 10.1007/s40620-023-01589-w -
Kidney International Oct 2017Peritoneal dialysis (PD) therapy substantially requires biomarkers as tools to identify patients who are at the highest risk for PD-related complications and to guide... (Review)
Review
Peritoneal dialysis (PD) therapy substantially requires biomarkers as tools to identify patients who are at the highest risk for PD-related complications and to guide personalized interventions that may improve clinical outcome in the individual patient. In this consensus article, members of the European Training and Research in Peritoneal Dialysis Network (EuTRiPD) review the current status of biomarker research in PD and suggest a selection of biomarkers that can be relevant to the care of PD patients and that are directly accessible in PD effluents. Currently used biomarkers such as interleukin-6, interleukin-8, ex vivo-stimulated interleukin-6 release, cancer antigen-125, and advanced oxidation protein products that were collected through a Delphi procedure were first triaged for inclusion as surrogate endpoints in a clinical trial. Next, novel biomarkers were selected as promising candidates for proof-of-concept studies and were differentiated into inflammation signatures (including interleukin-17, M/M macrophages, and regulatory T cell/T helper 17), mesothelial-to-mesenchymal transition signatures (including microRNA-21 and microRNA-31), and signatures for senescence and inadequate cellular stress responses. Finally, the need for defining pathogen-specific immune fingerprints and phenotype-associated molecular signatures utilizing effluents from the clinical cohorts of PD patients and "omics" technologies and bioinformatics-biostatistics in future joint-research efforts was expressed. Biomarker research in PD offers the potential to develop valuable tools for improving patient management. However, for all biomarkers discussed in this consensus article, the association of biological rationales with relevant clinical outcomes remains to be rigorously validated in adequately powered, prospective, independent clinical studies.
Topics: Biomarkers; Biomedical Research; Consensus; Dialysis Solutions; Humans; Kidney Failure, Chronic; Nephrologists; Peritoneal Dialysis; Peritoneum; Peritonitis; Practice Guidelines as Topic; Precision Medicine; Proteomics
PubMed: 28797473
DOI: 10.1016/j.kint.2017.02.037