Development and validation of a nomogram for predicting refractory peritoneal dialysis related peritonitis.

OBJECTIVE: To identify the risk factors of refractory peritoneal dialysis related peritonitis (PDRP) and construct a nomogram to predict the occurrence of refractory PDRP. METHODS: Refractory peritonitis was defined as the peritonitis episode with persistently cloudy bags or persistent dialysis effluent leukocyte count >100 × 109/L after 5 days of appropriate antibiotic therapy. The study dataset was randomly divided into a 70% training set and a 30% validation set. Univariate logistic analysis, LASSO regression analysis, and random forest algorithms were utilized to identify the potential risk factors for refractory peritonitis. Independent risk factors identified using multivariate logistic analysis were used to construct a nomogram. The discriminative ability, calibrating ability, and clinical practicality of the nomogram were evaluated using the receiver operating characteristic curve, Hosmer-Lemeshow test, calibration curve, and decision curve analysis. RESULTS: A total of 294 peritonitis episodes in 178 patients treated with peritoneal dialysis (PD) were enrolled, of which 93 were refractory peritonitis. C-reactive protein, serum albumin, diabetes mellitus, PD duration, and type of causative organisms were independent risk factors for refractory peritonitis. The nomogram model exhibited excellent discrimination with an area under the curve (AUC) of 0.781 (95% CI: 0.716-0.847) in the training set and 0.741 (95% CI: 0.627-0.855) in the validation set. The Hosmer-Lemeshow test and calibration curve indicated satisfactory calibration ability of the predictive model. Decision curve analysis revealed that the nomogram model had good clinical utility in predicting refractory peritonitis. CONCLUSION: This nomogram can accurately predict refractory peritonitis in patients treated with PD.

Effect of different exit-site care dressings on preventing peritoneal dialysis related infection from nontropical area: a systematic review and network meta-analysis.

OBJECT: This study aims to conduct a systematic review and network meta-analysis to comprehensively evaluate the efficacy of various dressings in preventing exit-site infection (ESI) and peritonitis. METHODS: We searched PubMed, Embase, Web of Science, CINAHL Plus with Full Text (EBSCO), Sino Med, Wan Fang Data, China National Knowledge Infrastructure (CNKI) from 1 January 1999 to 10 July 2023. The language restrictions were Chinese and English. Randomized controlled trials, non-randomized controlled trials, and self-controlled trials were included in this study. We used ROB 2 tool to evaluate the quality of the included literature. Two authors independently extracted the data according to the Cochrane Handbook. A Frequentist network meta-analysis was performed using Stata17.0 according to PRISAMA with a random effects model. RESULTS: From 2092 potentially eligible studies, thirteen studies were selected for analysis, including nine randomized controlled studies, three quasi-experimental studies and one self-controlled trial. A total of 1229 patients were included to compare five types of exit site care dressings, named disinfection dressings, antibacterial dressings, non-antibacterial occlusive dressings, sterile gauze, and no-particular dressings. The outcome of prevention ESI is antibacterial dressings (SUCRA = 97.6) >non-antibacterial occlusive dressings (SUCRA = 68.3) >disinfection dressings (SUCRA = 50.6) >no-particular dressings (SUCRA = 23.9) >sterile gauze (SUCRA = 9.5). The antibacterial dressings were more effective than sterile gauze (OR = 0.13, 95%CI 0.04∼0.44), and no-particular dressing (OR = 0.18, 95%CI 0.07∼0.50) in preventing ESI; the non-antibacterial occlusive dressings were effective than sterile gauze (OR:0.30, 95%CI 0.16∼0.57). There is no statistical significance between no-particular dressings and other types of dressings in preventing the mature ESI. There is no statistical significance in the effectiveness of five types of dressings in preventing peritonitis. CONCLUSIONS: The no-particular dressings maybe more cost-effective for preventing mature ESI. None of the dressings was more effective than another in preventing peritonitis. Then, none of the different types of dressing is strongly recommended for preventing ESI or peritonitis.RegistrationCRD42022366756.

Peritoneal dialysis-related peritonitis caused by Stephanoascus ciferrii: A Case Report.

Stephanoascus ciferrii, a conditional pathogenic fungus prevalent in nature, is more frequently encountered in patients with compromised immunity. However, the literature rarely reports infections caused by Stephanoascus ciferrii in peritoneal dialysis patients. Here, we detail the case of a 66-year-old female suffering from renal failure who experienced catheter-related infection during peritoneal dialysis. Dialysate turbidity prompted the detection of Stephanoascus ciferrii in both peritoneal dialysate and tubes through microbiological cultures. Subsequent treatment involved antifungal drugs and a transition to hemodialysis, resulting in the disappearance of peritonitis symptoms and the patient's discharge. In recent years, fungal infections, particularly dialysis-related infections, are on the rise. This marks the first reported case of catheter-related peritonitis infection caused by Stephanoascus ciferrii. Compared to bacterial infections, fungal infections pose challenges due to limited drug options, significant side effects, and prolonged treatment durations. Hence, prompt pathogen diagnosis and drug sensitivity testing are crucial for effective clinical treatment. In essence, this scientific case report underscores the uncommon occurrence of catheter-related peritonitis attributed to Stephanoascus ciferrii in a peritoneal dialysis patient with renal failure, emphasizing the distinctive management challenges and underscoring the critical significance of prompt diagnosis and suitable intervention in such instances.

Protective effect of Cyclo(His-Pro) on peritoneal fibrosis through regulation of HDAC3 expression.

Peritoneal dialysis is a common treatment for end-stage renal disease, but complications often force its discontinuation. Preventive treatments for peritoneal inflammation and fibrosis are currently lacking. Cyclo(His-Pro) (CHP), a naturally occurring cyclic dipeptide, has demonstrated protective effects in various fibrotic diseases, yet its potential role in peritoneal fibrosis (PF) remains uncertain. In a mouse model of induced PF, CHP was administered, and quantitative proteomic analysis using liquid chromatography-tandem mass spectrometry was employed to identify PF-related protein signaling pathways. The results were further validated using human primary cultured mesothelial cells. This analysis revealed the involvement of histone deacetylase 3 (HDAC3) in the PF signaling pathway. CHP administration effectively mitigated PF in both peritoneal tissue and human primary cultured mesothelial cells, concurrently regulating fibrosis-related markers and HDAC3 expression. Moreover, CHP enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) while suppressing forkhead box protein M1 (FOXM1), known to inhibit Nrf2 transcription through its interaction with HDAC3. CHP also displayed an impact on spleen myeloid-derived suppressor cells, suggesting an immunomodulatory effect. Notably, CHP improved mitochondrial function in peritoneal tissue, resulting in increased mitochondrial membrane potential and adenosine triphosphate production. This study suggests that CHP can significantly prevent PF in peritoneal dialysis patients by modulating HDAC3 expression and associated signaling pathways, reducing fibrosis and inflammation markers, and improving mitochondrial function.

Peritoneal Dialysis Aggravates and Accelerates Atherosclerosis in Uremic ApoE-/- Mice.

BACKGROUND: Atherosclerosis is highly prevalent in people with chronic kidney disease (CKD), including those receiving peritoneal dialysis (PD). Although it is lifesaving, PD induces profound systemic inflammation, which may aggravate atherosclerosis. Therefore, the hypothesis is that this PD-induced inflammation aggravates atherosclerosis via immune cell activation. METHODS AND RESULTS: ApoE-/- mice were subjected to a 5/6 nephrectomy to induce CKD. Three weeks later, mice were fed a high-cholesterol diet. Half of the nephrectomized mice then received daily peritoneal infusions of 3.86% Physioneal for 67 further days (CKD+PD) until the end of the experiment, and were compared with mice without CKD. Sham operated and PD-only mice were additional controls. CKD+PD mice displayed more severe atherosclerotic disease than control mice. Plaque area increased, and plaques were more advanced with a vulnerable phenotype typified by decreased collagen content and decreased fibrous cap thickness. Increased CD3+ T-cell numbers were present in plaques and perivascular adipose tissue of CKD and CKD+PD mice. Plaques of CKD+PD mice contained more iNOS+ immune cells. Spleens of CKD+PD mice showed more CD4+ central memory, terminally differentiated type 1 T-helper (Th1), Th17, and CX3C motif chemokine receptor 1+ (CX3CR1) CD4+ T-cells with less regulatory and effector T-cells. CONCLUSIONS: PD-fluid exposure in uremic mice potentiates systemic and vascular T-cell-driven inflammation and aggravates atherosclerosis. PD polarized CD4+ T-cells toward an inflammatory Th1/Th17 phenotype, and increased CX3CR1+ CD4+ T-cells, which are associated with vascular homing in CKD-associated atherosclerosis. Targeting CD4+ T-cell activation and CX3CR1+ polarization has the potential to attenuate atherosclerosis in PD patients.

Clinical and preclinical studies of mesenchymal stem cells to alleviate peritoneal fibrosis.

Peritoneal dialysis is an important part of end-stage kidney disease replacement therapy. However, prolonged peritoneal dialysis can result in peritoneal fibrosis and ultrafiltration failure, forcing patients to withdraw from peritoneal dialysis treatment. Therefore, there is an urgent need for some effective measures to alleviate the occurrence and progression of peritoneal fibrosis. Mesenchymal stem cells play a crucial role in immunomodulation and antifibrosis. Numerous studies have investigated the fact that mesenchymal stem cells can ameliorate peritoneal fibrosis mainly through the paracrine pathway. It has been discovered that mesenchymal stem cells participate in the improvement of peritoneal fibrosis involving the following signaling pathways: TGF-ß/Smad signaling pathway, AKT/FOXO signaling pathway, Wnt/ß-catenin signaling pathway, TLR/NF-κB signaling pathway. Additionally, in vitro experiments, mesenchymal stem cells have been shown to decrease mesothelial cell death and promote proliferation. In animal models, mesenchymal stem cells can enhance peritoneal function by reducing inflammation, neovascularization, and peritoneal thickness. Mesenchymal stem cell therapy has been demonstrated in clinical trials to improve peritoneal function and reduce peritoneal fibrosis, thus improving the life quality of peritoneal dialysis patients.

Value of DUSP6 in peripheral blood mononuclear cells in predicting adverse cardiovascular events after peritoneal dialysis in diabetic nephropathy. / å¤–å‘¨è¡€å•ä¸ªæ ¸ç»†èƒžä¸­DUSP6é¢„è­¦ç³–å°¿ç— è‚¾ç— è ¹è†œé€æžåŽä¸è‰¯å¿ƒè¡€ç®¡äº‹ä»¶çš„ä»·å€¼.

OBJECTIVES: Adverse cardiovascular events are the leading cause of death in peritoneal dialysis patients. Identifying indicators that can predict adverse cardiovascular events in these patients is crucial for prognosis. This study aims to assess the value of dual-specificity phosphatase 6 (DUSP6) in peripheral blood mononuclear cells as a predictor of adverse cardiovascular events after peritoneal dialysis in diabetic nephropathy patients. METHODS: A total of 124 diabetic nephropathy patients underwent peritoneal dialysis treatment at the Department of Nephrology of the First Affiliated Hospital of Hebei North University from June to September 2022 were selected as study subjects. The levels of DUSP6 in peripheral blood mononuclear cells were determined using Western blotting. Patients were categorized into high-level and low-level DUSP6 groups based on the median DUSP6 level. Differences in body mass index, serum albumin, high-sensitivity C-reactive protein, and dialysis duration were compared between the 2 groups. Pearson, Spearman, and multiple linear regression analyses were performed to examine factors related to DUSP6. Patients were followed up to monitor the occurrence of adverse cardiovascular events, and risk factors for adverse cardiovascular events after peritoneal dialysis were analyzed using Kaplan-Meier and Cox regression. RESULTS: By the end of the follow-up, 33 (26.61%) patients had experienced at least one adverse cardiovascular event. The high-level DUSP6 group had higher body mass index, longer dialysis duration, and higher high-sensitivity C-reactive protein, but lower serum albumin levels compared to the low-level DUSP6 group (all P<0.05). DUSP6 was negatively correlated with serum albumin levels (r=-0.271, P=0.002) and positively correlated with dialysis duration (rs=0.406, P<0.001) and high-sensitivity C-reactive protein (rs=0.367, P<0.001). Multiple linear regression analysis revealed that dialysis duration and high-sensitivity C-reactive protein were independently correlated with DUSP6 levels (both P<0.05). The cumulative incidence of adverse cardiovascular events was higher in the high-level DUSP6 group than in the low-level DUSP6 group (46.67% vs 7.81%, P<0.001). Cox regression analysis indicated that low serum albumin levels (HR=0.836, 95% CI 0.778 to 0.899), high high-sensitivity C-reactive protein (HR=1.409, 95% CI 1.208 to 1.644), and high DUSP6 (HR=6.631, 95% CI 2.352 to 18.693) were independent risk factors for adverse cardiovascular events in peritoneal dialysis patients. CONCLUSIONS: Dialysis duration and high-sensitivity C-reactive protein are independently associated with DUSP6 levels in peripheral blood mononuclear cells of diabetic nephropathy patients undergoing peritoneal dialysis. High DUSP6 levels indicate a higher risk of adverse cardiovascular events.

Pressure induces peritoneal fibrosis and inflammation through CD44 signaling.

Peritoneal dialysis (PD) is a widely used sustainable kidney replacement therapy. Prolonged use of PD fluids is associated with mesothelial-mesenchymal transition, peritoneal fibrosis, and eventual ultrafiltration (UF) failure. However, the impact of pressure on the peritoneum remains unclear. In the present study, we hypothesized increased pressure is a potential contributing factor to peritoneal fibrosis and investigated the possible mechanisms. In vitro experiments found that pressurization led to a mesenchymal phenotype, the expression of fibrotic markers and inflammatory factors in human mesothelial MeT-5A cells. Pressure also increased cell proliferation and augmented cell migration potential in MeT-5A cells. The mouse PD model and human peritoneum equilibrium test (PET) data both showed a positive association between higher pressure and increased small solute transport, along with decreased net UF. Mechanistically, we found that significant upregulation of CD44 in mesothelial cells upon pressurization. Notably, the treatment of CD44 neutralizing antibodies prevented pressure-induced phenotypic changes in mesothelial cells, while a CD44 inhibitor oligo-fucoidan ameliorated pressure-induced peritoneal thickening, fibrosis, and inflammation in PD mice. To conclude, intraperitoneal pressure results in peritoneal fibrosis in PD via CD44-mediated mesothelial changes and inflammation. CD44 blockage can be utilized as a novel preventive approach for PD-related peritoneal fibrosis and UF failure.

Prognostic Factors of Peritonitis in Patients on Peritoneal Dialysis: a Retrospective Observational Study.

Background/Objectives. Peritoneal dialysis stands as an established form of renal replacement therapy; yet peritonitis remains a major complication associated with it. This study, analyzing two decades of data from the Nephrology, Dialysis, and Hypertension Division of the University-Hospital IRCCS in Bologna, aimed to identify prognostic factors linked to peritonitis events. It also sought to evaluate the suitability of different peritoneal dialysis techniques, with a focus on Automated Peritoneal Dialysis (APD) and Continuous Ambulatory Peritoneal Dialysis (CAPD). Additionally, the study assessed the impact of an educational program introduced in 2005 on peritonitis frequency. Methods. Conducting an observational, retrospective, single-center study, 323 patients were included in the analysis, categorized based on their use of APD or CAPD. Results. Despite widespread APD usage, no significant correlation was found between the dialysis technique (APD or CAPD) and peritonitis onset. The analysis of the educational program's impact revealed no significant differences in peritonitis occurrence. However, a clear relationship emerged between regular patient monitoring at the reference center and the duration of peritoneal dialysis. Conclusions. Despite the absence of a distinct association between peritonitis onset and dialysis technique, regular patient monitoring at the reference center significantly correlated with prolonged peritoneal dialysis duration.

Establishing an animal model for peritoneal catheter malfunction caused by omental wrapping using negative pressure suction: in vitro and in vivo exploration.

BACKGROUND: This study aims to establish a simplified and effective animal model of catheter malfunction caused by omental wrapped using negative pressure suction. METHOD: The peritoneal dialysis catheter outlet was linked to a negative-pressure (0-75mmHg) suction pump to intensify the negative pressure. Different negative pressures were tested for model construction in vitro. In vivo, a model of peritoneal catheter malfunction caused by omental wrapped was constructed in five beagles after catheter placement. Catheter drainage conditions and related complications were monitored before and after the model establishment. RESULTS: In the vitro experiment, the overall success rate of constructed models was 90% (36/40). The total malfunction rate was higher in 62.5 mmHg (10/10) and 75 mmHg (10/10) than in 12.5 mmHg (8/10) and 37.5 mmHg (8/10). The outflow velocity of dialysate at 62.5 mmHg was significantly lower than that at 12.5 mmHg and 37.5 mmHg, without a statistically significant difference compared to 75 mmHg. In the in vivo experiment, catheter outflow velocity increased, and residual fluid volume decreased after omental wrapped (99.6 ± 6.7 ml/min vs. 32.6 ± 4.6 ml/min at initial five minutes, p < 0.0001; 69.2 ± 16.3 ml vs. 581.0 ± 109.4 ml, p < 0.001). And the outflow velocity was finally below 2 ml/min. No severe related complications (such as infection, organ damage, or bleeding) were observed through laparoscopic examination and dialysate tests seven days post-operation. CONCLUSION: Utilizing negative pressure suction to increase negative pressure around catheter tip is a simple, safe, and effective method for establishing an animal model of omental wrapped leading to catheter malfunction.

Exploring symptom clusters in Chinese patients with peritoneal dialysis: a network analysis.

BACKGROUND: In recent years, the research on symptom management in peritoneal dialysis (PD) patients has shifted from a single symptom to symptom clusters and network analysis. This study collected and evaluated unpleasant symptoms in PD patients and explored groups of symptoms that may affect PD patients with a view to higher symptom management. METHODS: The symptoms of PD patients were measured using the modified Dialysis Symptom Index. The symptom network and node characteristics were assessed by network analysis, and symptom clusters were explored by factor analysis. RESULTS: In this study of 602 PD patients (mean age 47.8 ± 16.8 years, 47.34% male), most had less than 2 years of dialysis experience. Five symptom clusters were obtained from factor analysis, which were body symptom cluster, gastrointestinal symptom cluster, mood symptom cluster, sexual disorder symptom cluster, and skin-sleep symptom cluster. Itching and decreased interest in sex may be sentinel symptoms, and being tired or lack of energy and feeling anxious are core symptoms in PD patients. CONCLUSIONS: This study emphasizes the importance of recognizing symptom clusters in PD patients for better symptom management. Five clusters were identified, with key symptoms including itching, decreased interest in sex, fatigue, and anxiety. Early intervention focused on these symptom clusters in PD patients holds promise for alleviating the burden of symptoms.

[Acquired cystic kidney hemorrhage in peritoneal dialysis patients: A report of three cases].

Spontaneous renal cyst hemorrhage is one of the clinical emergencies in peritoneal dialysis (PD) patients and is potentially life-threatening. The main complaints are sudden low back pain, paleness, and hypotensive shock with or without vomiting or fever. In contrast to inherited polycystic kidney disease, acquired cystic kidney disease (ACKD) secondary to chronic kidney disease is easily overlooked or delayed in clinical diagnosis and treatment, leading to severe clinical outcomes. We report three patients with spontaneous hemorrhage of ACKD in the peritoneal dialysis center at Peking University First Hospital. The common features are as follows, long history of dialysis, mild to severe low back pain, decrease in hemoglobulin, negative PD solutions, diagnosis established through computed tomography (CT), and continuing PD during treatment of ACKD hemorrhage. Treatments vary from conservative to unilaterally selective renal artery embolization. In this study, ACKD morbidity was investigated in PD patients. A total of 316 patients who had an abdominal ultrasound, CT, or magnetic resonance imaging (MRI) in the past 1 year were enrolled. Among them, 103 cases (32.9%) met the diagnostic criteria of ACKD. The morbidity rates were 27.5%, 37.8%, 43.8%, 59.1%, and 88.6%, when the dialysis history ranged from ≤3, >3 & ≤5, >5 & ≤7, >7 & ≤9, >9 years, respectively, showing a increasing trend. Most ACKD hemorrhages could be healed and got an acceptable prognosis after treatment, including rest, blood transfusion, selective renal artery embolization, or nephrectomy. We summarize the risk factors, including a long history of dialysis, anticoagulation or antiplatelet, and inflammation or stones of the urinary system, but with no difference in initial kidney diseases and gender. ACKD hemorrhage mainly includes intracapsular hemorrhage, cyst rupture, and spontaneous retroperitoneal hemorrhage. In addition, we also recommend an adaptive process for spontaneous kidney hemorrhage of diagnosis and treatment in peritoneal dialysis patients. The significance of these cases lies in the fact that patients with ACKD are potentially associated with complications such as cyst hemorrhage and malignancy. Thus, peritoneal dialysis physicians should place great importance on the surveillance of ACKD.

Rare Pathogens in Peritoneal Dialysis-Associated Peritonitis: A Comprehensive Case Study and Guideline Review.

BACKGROUND Peritoneal dialysis (PD) serves as a critical renal replacement therapy for individuals with end-stage renal disease (ESRD), leveraging the peritoneum for fluid and substance exchange. Despite its effectiveness, PD is marred by complications such as peritonitis, which significantly impacts patient outcomes. The novelty of our report lies in the presentation of a rare case of PD-associated peritonitis caused by 2 unusual pathogens, emphasizing the importance of rigorous infection control measures. CASE REPORT We report on an 80-year-old African-American female patient with ESRD undergoing PD, who was admitted twice within 8 months for non-recurring episodes of peritonitis. These episodes were attributed to the rare pathogens Achromobacter denitrificans/xylosoxidans and Carbapenem-resistant Acinetobacter baumannii. Despite presenting with similar symptoms during each episode, such as abdominal pain and turbid dialysis effluent, the presence of these uncommon bacteria highlights the intricate challenges in managing infections associated with PD. The treatment strategy encompassed targeted antibiotic therapy, determined through susceptibility testing. Notably, the decision to remove the PD catheter followed extensive patient education, ensuring the patient comprehended the rationale behind this approach. This crucial step, along with the subsequent shift to hemodialysis, was pivotal in resolving the infection, illustrating the importance of patient involvement in the management of complex PD-related infections. CONCLUSIONS This case underscores the complexities of managing PD-associated peritonitis, particularly with uncommon and resistant bacteria. It emphasizes the importance of rigorous infection control measures, the need to consider atypical pathogens, and the critical role of patient involvement in treatment decisions. Our insights advocate for a more informed approach to handling such infections, aiming to reduce morbidity and improve patient outcomes. The examination of the literature on recurrent peritonitis and treatment strategies provides key perspectives for navigating these challenging cases effectively.

A rare case of successful treatment of peritoneal dialysis patient with Serratia marcescens peritonitis without catheter removal: case report and literature review.

Serratia marcescens, as a Gram-negative opportunistic pathogen, is a rare cause of peritonitis and has worse clinical outcomes than Gram-positive peritonitis. In this case report, we describe a case of Serratia marcescens associated peritonitis that was successfully cured without catheter removal. A 40-year-old male patient with peritoneal dialysis who worked in the catering industry was admitted to the hospital for 16 hours after the discovery of cloudy peritoneal dialysate and abdominal pain. Ceftazidime and cefazolin sodium were immediately given intravenously as an empirical antibiotic regimen. After detecting Serratia marcescens in the peritoneal diasate culture, the treatment was switched to ceftazidime and levofloxacin. The routine examination of peritoneal dialysate showed a significant decrease in white blood cells, the peritoneal dialysate became clear, and the peritoneal dialysis catheter was retained. The patient was treated for 2 weeks and treated with oral antibiotics for 1 week. It is necessary to further strengthen the hygiene of work environment to prevent Serratia marcescens infection in peritoneal dialysis patients. We recommend that patients with Serratia marcescens associated peritonitis should be treated with a combination of antibiotics as early as possible empirically, and at the same time, the peritoneal dialysis fluid culture should be improved, and the antibiotic regimen should be timely adjusted according to the drug sensitivity results. For patients with clinical symptoms for more than 3 days, considering the strong virulence of Serratia marcescens, whether to use meropenem directly or not can provide a reference for clinical decision-making. Further clinical studies are needed to achieve more precise anti-infective treatment.

Oxidative stress reduction by icodextrin-based glucose-free solutions in peritoneal dialysis: Support for new promising approaches.

BACKGROUND: Oxidative stress (OxSt) and inflammation are common in CKD and are known CV and mortality risk factors. In peritoneal dialysis (PD) OxSt and Inflammation even increase due to the use of glucose-based solutions. PATIENTS AND METHODS: This study analyzed in 15 PD patients the effect of 3 and 6 months of treatment with icodextrin-based glucose-free solutions on OxSt and inflammation, evaluating p22phox protein expression (Western blot), NADPH oxidase subunit, essential for OxSt activation, MYPT-1 phosphorylation state, marker of RhoA/Rho kinase pathway (ROCK) activity, involved in the induction of OxSt (Western blot) and Malondialdehyde (MDA) production (fluorimetric assay). Interleukin (IL)-6 blood level (chemiluminescence assay) has been measured and used as a marker of inflammation. RESULTS: p22phox protein expression, MYPT 1 phosphorylation, and MDA were reduced after 3 months from the start of icodextrin (1.28 ± 0.18 d.u. vs. 1.50 ± 0.19, p = 0.049; 0.89 ± 0.03 vs. 0.98 ± 0.03, p = 0.004; 4.20 ± 0.18 nmol/mL vs. 4.84 ± 0.32 nmol/mL, p = 0.045, respectively). In a subgroup of 9 patients who continued the treatment up to 6 months, MYPT-1 phosphorylation was further reduced at 6 months compared to baseline (0.84 ± 0.06 vs. 0.99 ± 0.04, p = 0.043), while p22phox protein expression was reduced only at 6 months versus baseline (1.03 ± 0.05 vs. 1.68 ± 0.22, p = 0.021). In this subgroup, MDA was reduced at 6 months versus baseline (4.03 ± 0.24 nmol/mL vs. 4.68 ± 0,32, p = 0.024) and also versus 3 months (4.03 ± 0.24 vs. 4.35 ± 0.21, p = 0.008). IL-6 level although reduced both at 3 and 6 months, did not reach statistical significance. CONCLUSIONS: The reduction of OxSt with icodextrin-based PD solutions, although obtained in a small patients cohort and in a limited time duration study, strongly supports the rationale of using osmo-metabolic agents-based fluids replacing glucose-based fluids. Ongoing studies with these agents will provide information regarding preservation of peritoneal membrane integrity, residual renal function, and reduction of CVD risk factors such as OxSt and inflammation.

Surgical Treatment of Medically Refractory Encapsulating Peritoneal Sclerosis in a Patient After Kidney Transplant.

Encapsulating peritoneal sclerosis is a rare but highly morbid disease process in patients with end-stage kidney disease on peritoneal dialysis. Surgical management has been described in patients with encapsulation of bowel causing obstruction. Here, we describe a case of surgical management in a patient following kidney transplant with medically refractory ascites and lower extremity edema.

The role of macrophage-derived Exosomes in reversing peritoneal fibrosis: Insights from Astragaloside IV.

BACKGROUND: Peritoneal dialysis (PD) is a successful renal replacement therapy for end-stage renal disease. Long-term PD causes mesothelial-mesenchymal transition (MMT) of peritoneal mesothelial cells (PMCs), leading to peritoneal fibrosis (PF), which reduces the efficiency of PD. Macrophages are thought to play a role in the onset and perpetuation of peritoneal injury. However, the mechanisms by which macrophages-PMCs communication regulates peritoneal fibrosis are not fully understood resulting in a lack of disease-modifying drugs. Astragaloside IV (AS-IV) possessed anti-fibrotic effect towards PF in PD whereas the mechanistic effect of AS-IV in PD is unknown. METHODS: The primary macrophages were extracted and treated with LPS or AS-IV, then co-cultured with primary PMCs in transwell plates. The macrophage-derived exosomes were extracted and purified by differential centrifugation, then co-cultured with primary PMCs. Small RNA-seq was used to detect differential miRNAs in exosomes, and then KEGG analysis and q-PCR were performed for validation. In vivo PD rat models were established by inducing with high-glucose peritoneal dialysis fluid and different concentrations of AS-IV and exosomes were intraperitoneal injection. Through qRT-PCR, western blotting, and luciferase reporting, candidate proteins and pathways were validated in vivo and in vitro. The functions of the validated pathways were further investigated using the mimic or inhibition strategy. PF and inflammatory situations were assessed. RESULTS: We found AS-IV reversed the MMT of PMCs caused by LPS-stimulated macrophages and the improving effect was mediated by macrophage-derived exosomes in vitro. We also demonstrated that AS-IV significantly reduced the MMT of PMCs in vitro or PF in a rat PD model via regulating exosome-contained miR-204-5p which targets Foxc1/ß-catenin signaling pathway. CONCLUSION: AS-IV attenuates macrophage-derived exosomes induced fibrosis in PD through the miR-204-5p/Foxc1 pathway.