Targeting STING in experimental peritoneal damage: a novel approach in peritoneal dialysis therapy DOI Open Access
Vanessa Marchant, Jorge García‐Giménez, Guadalupe Tirma González-Mateo

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 21, 2024

Abstract Peritoneal dialysis (PD) is a widely used kidney replacement therapy for end-stage disease (ESKD) patients. However, long-term exposure to PD fluids (PDF) can lead peritoneal membrane (PM) damage, causing ultrafiltration failure and thus discontinuation. Investigating the molecular mechanisms underlying this damage crucial identifying new therapeutic targets mitigate deterioration in Therefore, work we study role of STING inflammation fibrosis. To aim, performed different preclinical mouse models inflammation, fibrosis, adhesions. In chlorhexidine gluconate (CHX)-induced model, found changes transcriptomic profile, cytosolic DNA-sensing signaling was one most enriched KEGG pathways. STING, as conspicuous member pathway, upregulated CHX-and PDF-exposed mice, biopsies from genetic deficiency diminished by downregulating inflammatory gene expression, preventing NF-κB pathway activation, decreasing cell infiltration, early (10 days) advanced (30 stages CHX model. absence also decreased PM thickness fibrosis reduced adhesion scores post-surgical intra-abdominal an S. epidermidis -induced peritonitis Furthermore, pharmacological inhibition with C-176 macrophage-mediated mesothelial-to-mesenchymal transition cultured mesothelial cells, CHX-induced mice. Altogether, these findings highlight key mediator suggest it may be novel target PD-associated deterioration.

Language: Английский

Development and validation of a nomogram for predicting refractory peritoneal dialysis related peritonitis DOI Creative Commons
Qiqi Yan,

Guiling Liu,

Ruifeng Wang

et al.

Renal Failure, Journal Year: 2024, Volume and Issue: 46(2)

Published: July 3, 2024

Objective To identify the risk factors of refractory peritoneal dialysis related peritonitis (PDRP) and construct a nomogram to predict occurrence PDRP.

Language: Английский

Citations

2
Effects of Molecular Hydrogen in the Pathophysiology and Management of Metabolic and Non-communicable Diseases DOI
Ram B. Singh, Alex Tarnava, Ján Fedačko

et al.

Advances in biochemistry in health and disease, Journal Year: 2024, Volume and Issue: unknown, P. 287 - 317

Published: Jan. 1, 2024

Language: Английский

Citations

1
BET Protein Inhibitor JQ1 Ameliorates Experimental Peritoneal Damage by Inhibition of Inflammation and Oxidative Stress DOI Creative Commons
Vanessa Marchant, Flavia Trionfetti, Lucía Tejedor-Santamaría

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(12), P. 2055 - 2055

Published: Nov. 29, 2023

Peritoneal dialysis (PD) is a current replacement therapy for end-stage kidney diseases (ESKDs). However, long-term exposure to PD fluids may lead damage of the peritoneal membrane (PM) through mechanisms involving activation inflammatory response and mesothelial-to-mesenchymal transition (MMT), leading filtration failure. depends on complex interaction among external stimuli, intrinsic properties PM, subsequent activities local innate–adaptive immune system. Epigenetic drugs targeting bromodomain extra-terminal domain (BET) proteins have shown beneficial effects different experimental preclinical diseases, mainly by inhibiting proliferative responses. However effect BET inhibition has not been studied. To this aim, we evaluated treatment with inhibitor JQ1 in mouse model induced chlorhexidine gluconate (CHX). We found that ameliorated CHX-induced PM thickness cell infiltration. Moreover, decreased gene overexpression proinflammatory profibrotic markers, together an nuclear factor-κB (NF-κB) pathway. Additionally, blocked factor erythroid 2-related 2 (NRF2) restored changes mRNA expression levels NADPH oxidases (NOX1 NOX4) NRF2/target antioxidant genes. corroborate vivo findings, patients’ effluent-derived primary mesothelial cells MeT-5A line. inhibited tumor necrosis factor-α (TNF-α)-induced upregulation MMT phenotype changes, downmodulation oxidative stress. Taken together, these results suggest inhibitors be potential therapeutic option ameliorate damage.

Language: Английский

Citations

3
Postoperative Outcomes After Gastrointestinal Surgery in Patients Receiving Chronic Kidney Replacement Therapy DOI Open Access
Dharmenaan Palamuthusingam, Carmel M. Hawley, Elaine M. Pascoe

et al.

Annals of Surgery, Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 12, 2023

Objective: This study evaluated the postoperative mortality and morbidity outcomes following different subtypes of gastrointestinal (GI) surgery over a 15-year period. Background: Patients receiving chronic kidney replacement therapy (KRT) experience higher rates general compared to other types. Contemporary data on types surgeries their are lacking. KRT was defined as patients requring dialysis (haemodialysis or peritoneal dilaysis) having fucntioning transplant long-term. Methods: All incident prevalent aged greater than 18 years identified in Australia New Zealand Dialysis Transplant (ANZDATA) Registry were linked with jurisdictional hospital admission datasets between January 1 2000 until December 31 2015. categorised by modality (hemodialysis [HD], [PD], home hemodialysis [HHD] [KT]). GI categorised: Upper (UGI), bowel (small large bowel), anorectal, hernia surgery, cholecystectomy appendicectomy. The primary outcome surgeries, estimated using Poisson models. Secondary risks 30-day/in-hospital risk non-fatal logistic regression. Independent predictors 30-day-mortality examined comorbidity-adjusted Cox Results: Overall, 46,779 datasets, 9,116 undergone 14,540 combined follow-up 76,593 years. PD had highest (8 per 100-patient years), being most frequent. also 30-day more 2-fold after emergency elective procedures. Infective complications common cardiac complications. observed U-shaped association body mass index (BMI) mortality, nadir 30-35 kg/m 2 group. Conclusions: have high morbidity, particularly those who receive PD, older either underweight moderately obese.

Language: Английский

Citations

1
Diagnostic Accuracy of MMP-8 and IL-6-Based Point-of-Care Testing to Detect Peritoneal Dialysis-Related Peritonitis: A Single-Center Experience DOI Creative Commons
Rania Ibrahim, Mido Max Hijazi,

Fadwa Al‐Ali

et al.

Diagnostics, Journal Year: 2024, Volume and Issue: 14(11), P. 1113 - 1113

Published: May 27, 2024

Background: Peritoneal dialysis-related peritonitis (PDRP) is the most common complication of peritoneal dialysis (PD), which can lead to poor outcomes if not diagnosed and treated early. We aimed investigate diagnostic accuracy MMP-8 IL-6-based point-of-care tests (POCTs) in diagnosing PDRP PD patients. Methods: This retrospective chart review study was conducted at a comprehensive kidney center Qatar. It involved all adult patients who underwent from July 2018 October 2019 for whom POCTs were used diagnose presumptive peritonitis. Measures computed. fluid effluent analysis reference standard. Results: included 120 (68 [56.7%] females, ages 55.6 ± 15.6 years, treatment duration 39.5 30.4 months [range: 5–142 months]). In this population, yielded 100% dimensions (sensitivity, specificity, positive negative predictive values). Conclusions: might be helpful early detection PDRP. monocentric observation requires further confirmation prospective multicentric setting.

Language: Английский

Citations

0
Targeting STING in experimental peritoneal damage: a novel approach in peritoneal dialysis therapy DOI Open Access
Vanessa Marchant, Jorge García‐Giménez, Guadalupe Tirma González-Mateo

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 21, 2024

Abstract Peritoneal dialysis (PD) is a widely used kidney replacement therapy for end-stage disease (ESKD) patients. However, long-term exposure to PD fluids (PDF) can lead peritoneal membrane (PM) damage, causing ultrafiltration failure and thus discontinuation. Investigating the molecular mechanisms underlying this damage crucial identifying new therapeutic targets mitigate deterioration in Therefore, work we study role of STING inflammation fibrosis. To aim, performed different preclinical mouse models inflammation, fibrosis, adhesions. In chlorhexidine gluconate (CHX)-induced model, found changes transcriptomic profile, cytosolic DNA-sensing signaling was one most enriched KEGG pathways. STING, as conspicuous member pathway, upregulated CHX-and PDF-exposed mice, biopsies from genetic deficiency diminished by downregulating inflammatory gene expression, preventing NF-κB pathway activation, decreasing cell infiltration, early (10 days) advanced (30 stages CHX model. absence also decreased PM thickness fibrosis reduced adhesion scores post-surgical intra-abdominal an S. epidermidis -induced peritonitis Furthermore, pharmacological inhibition with C-176 macrophage-mediated mesothelial-to-mesenchymal transition cultured mesothelial cells, CHX-induced mice. Altogether, these findings highlight key mediator suggest it may be novel target PD-associated deterioration.

Language: Английский

Citations

0