Intraperitoneal Inflammation Research Articles

Profiling cytokines in peritoneal effluent through a targeted multiplex cytokine panel provides novel insight into the localized proinflammatory processes in patients undergoing peritoneal dialysis.

The number of relevant markers indicating local intraperitoneal inflammation in patients undergoing peritoneal dialysis (PD) is limited. Therefore, this study aimed to evaluate the compatibility of peritoneal effluent (PE) for proteomic analysis and assess its potential utility in immunoprofiling studies. This pilot study included six PD patients from the Peritoneal Dialysis Center, Department of Nephrology, Transplantology, and Internal Medicine in Szczecin, Poland. All patients were clinically stable, with no signs of infections or malignancy at the time of study. PE samples were collected during routine surveillance visits at the Peritoneal Dialysis Center. Proteomic analysis of the samples was conducted using the Olink® (Olink Proteomics AB, Uppsala, Sweden) Target 48 Cytokine panel. PE samples were successfully analyzed, with 28 out of 45 proteins found within the limit of quantitation (LOQ) and 32 out of 45 proteins detected above the limit of detection (LOD). No significant interference from the matrix was observed in the assay. Biomarkers associated with low-grade inflammation showed varied levels, and the observed patterns were comparable across all patients. This study suggests that utilizing a cytokine panel with relative quantification is a promising method for PE immunoprofiling.

Osteoprotegerin and Inflammation in Incident Peritoneal Dialysis Patients.

Objectives: Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor family involved in processes in many inflammatory states. OPG concentration is enhanced in the majority of chronic kidney disease (CKD) patients and those undergoing renal replacement therapy. The aim of the study was to assess the relation of OPG and chronic inflammation in peritoneal dialysis (PD) patients and to evaluate whether OPG concentrations in plasma and dialysate were related to plasma and dialysate levels of proinflammatory mediators (interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), interleukin 33 (IL-33) and interleukin 1 receptor-like 1IL-1RL1 (IL-1RL1, sST2)). Methods: The study included 37 patients of the Peritoneal Dialysis Center, Department of Nephrology, Transplantology and Internal Medicine, Szczecin, Poland, 4-6 weeks after the onset of peritoneal dialysis therapy. During a peritoneal equilibration test, plasma (at 2 h) and dialysate (at 4 h) OPG, IL-33, 1IL-1RL1 (sST2), IL-6 and hsCRP concentrations were determined. Results: Plasma concentration of OPG did not correlate with dialysate OPG level (Rs = 0.04, p = 0.8). There was a strong positive correlation between plasma OPG concentrations and plasma IL-1RL1 (sST2) (Rs = 0.41; p = 0.01), plasma IL-6 (Rs = 0.38; p = 0.01) and plasma hsCRP (Rs = 0.35; p = 0.02). Dialysate OPG concentrations were positively associated with dialysate IL-1RL1 (sST2) (Rs = 0.37; p = 0.02) and dialysate IL-6 levels (Rs = 0.44; p = 0.005). Multivariate analysis showed that higher IL-1RL1 (sST2) (ß = +0.38, p = 0.006), higher plasma hsCRP (ß = +0.32, p = 0.02) and older age (ß = +0.35, p = 0.01) were independent determinants of higher plasma OPG concentration and that higher concentrations of dialysate IL-6 (ß = +0.37, p = 0.02) were independent determinants of higher dialysate OPG concentration. Conclusions: Both plasma and dialysate OPG levels are associated with the severity of systemic and local inflammation illustrated by the plasma and dialysate concentrations of IL-1RL1 (sST2), hsCRP and IL-6, suggesting that OPG might have a pivotal role in explaining the milieu of systemic and intraperitoneal inflammation.

Multiple site inflammation and acute kidney injury in crush syndrome.

Crush syndrome, which frequently occurs in earthquake disasters, often leads to rhabdomyolysis induced acute kidney injury (RIAKI). Recent findings indicate that systemic inflammatory response syndrome (SIRS) exacerbates muscle collapse, contributing to RIAKI. The purpose of this study is to investigate the involvement of multiple site inflammation, including intraperitoneal, in crush syndrome. In a mouse model of RIAKI, elevated levels of inflammatory mediators such as TNFα, IL-6, myoglobin, and dsDNA were observed in serum and the peritoneal cavity, peaking earlier in the intraperitoneal cavity than in serum or urine. Our previously developed novel peptide inhibiting leukocyte extracellular traps was administered intraperitoneally and blocked all of these mediators in the intraperitoneal cavity and serum, ameliorating muscle damage and consequent RIAKI. Although further studies are needed to determine whether intraperitoneal inflammation associated with muscle collapse can lead to systemic inflammation, resulting in more severe and prolonged muscle damage and renal injury, early suppression of multiple site inflammation, including intraperitoneal, might be an effective therapeutic target.

A review of research progress on mechanisms of peritoneal fibrosis related to peritoneal dialysis.

Peritoneal dialysis (PD) is an effective alternative treatment for patients with end-stage renal disease (ESRD) and is increasingly being adopted and promoted worldwide. However, as the duration of peritoneal dialysis extends, it can expose problems with dialysis inadequacy and ultrafiltration failure. The exact mechanism and aetiology of ultrafiltration failure have been of great concern, with triggers such as biological incompatibility of peritoneal dialysis solutions, uraemia toxins, and recurrent intraperitoneal inflammation initiating multiple pathways that regulate the release of various cytokines, promote the transcription of fibrosis-related genes, and deposit extracellular matrix. As a result, peritoneal fibrosis occurs. Exploring the pathogenic factors and molecular mechanisms can help us prevent peritoneal fibrosis and prolong the duration of Peritoneal dialysis.

High intraperitoneal interleukin-6 levels predict ultrafiltration (UF) insufficiency in peritoneal dialysis patients: A prospective cohort study.

IntroductionUF insufficiency is a major limitation in PD efficiency and sustainability. Our study object to investigate the efficacy of intraperitoneal inflammation marker, IL-6 level as a predictor of UF insufficiency in continuous ambulatory peritoneal dialysis (CAPD) patients.MethodsStable prevalent CAPD patients were enrolled in this prospective study. IL-6 concentration in the overnight effluent was determined and expressed as the IL-6 appearance rate (IL-6 AR). Patients were divided into two groups according to the median of IL-6 AR and prospectively followed up until death, transfer to permanent HD, recovery of renal function, kidney transplantation, transfer to other centers, lost to follow-up or to the end of study (January 31, 2021). Factors associated with UF capacity as well as dialysate IL-6 AR were assessed by multivariable linear regression. Cox proportional hazards model was used to examine the association between dialysate IL-6 AR and UF insufficiency.ResultsA total of 291 PD patients were enrolled, including 148 males (51%) with a mean age of 56.6 ± 14.1 years and a median PD duration of 33.4 (12.7–57.5) months. No correlation was found between dialysate IL-6 AR and UF capacity at baseline. PD duration was found positively correlated with baseline dialysate IL-6 AR, while 24h urine volume was negatively correlated with baseline dialysate IL-6 AR (P < 0.05). By the end of study, UF insufficiency was observed in 56 (19.2%) patients. Patients in the high IL-6 AR group showed a significantly inferior UF insufficiency-free survival when compared with their counterparts in the low IL-6 AR group (P = 0.001). In the multivariate Cox regression analysis, after adjusting for DM, previous peritonitis episode and 24h urine volume, higher baseline dialysate IL-6 AR (HR 3.639, 95% CI 1.776–7.456, P = 0.002) were associated with an increased risk of UF insufficiency. The area under the ROC curve (AUC) for baseline IL-6 AR to predict UF insufficiency was 0.663 (95% CI, 0.580–0.746; P < 0.001).ConclusionOur study suggested that the dialysate IL-6 AR could be a potential predictor of UF insufficiency in patients undergoing PD.

MO682: Serum Total Indoxyl Sulfate is Associated with Intraperitoneal Inflammation and High Peritonitis Episodes in Peritoneal Dialysis Patients

Abstract BACKGROUND AND AIMS The accumulating evidence presented thus far supports the idea that indoxyl sulfate (IS) is a trigger of chronic inflammation in end-stage kidney disease patients. However, although serum IS is one of the most extensively studied uremic toxins, no single study exists which has investigated the association between serum IS and intraperitoneal inflammation in peritoneal dialysis (PD) patients. The present study was undertaken to evaluate the association between serum total IS (tIS) concentration and the pro-inflammatory markers in peritoneal dialysis effluent (PDE) and peritonitis episodes in PD patients. METHOD In this observational cross-sectional study, we analysed serum tIS concentration and 24-h PDE levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein -1 (MCP-1) in 74 PD patients with an average age of 55 (38–64) years and dialysis vintage of 36 (30–58) months. All patients had been undergoing continuous ambulatory PD and had no PD-associated infectious complications for more than 3 months. Serum concentrations of tIS were determined using the spectrophotometry method. The concentrations of IL-6, TNF-α and MCP-1 in PDE were analysed using ELISA. For the statistical analysis, we stratified this PD patient cohort into two groups depending on experienced peritonitis: the peritonitis group (n = 48) and the peritonitis-free group (n = 26). The data were presented as the median and the interquartile ranges [Me (Q25–Q75)] and compared using the Kruskal–Wallis test. The Spearmen correlation test was performed to assess the association between IS and the pro-inflammatory markers. RESULTS Significant differences were found in serum concentrations of tIS and PDE levels of IL-6 between the peritonitis and the peritonitis-free PD patients (Table 1). In addition, serum tIS was significantly associated with number of experienced peritonitis episodes (r = 0.26, P = 0.022). Although PDE levels of TNF-a and MCP-1 did not differ between the peritonitis and the peritonitis-free groups in our cohort, they had a direct association with serum tIS similar to those of IL-6 (Fig. 1, 2). Moreover, serum tIS was statistically higher in the anuric PD patients compared with the non-anuric patients [33.6 (13.9–74) versus 20.2 (9.3–46) μg/mL, P = 0.043], had a negative association with residual renal function (r = −0.39, P = 0.0017) and, accordingly, total weekly Kt/V (r = −0.27, P = 0.026). CONCLUSION Serum tIS concentration has a significant direct association with PDE levels of the pro-inflammatory markers, high peritonitis episodes and their outcomes in PD patients. Further well-designed studies are required to establish the effect of serum tIS concentration on intraperitoneal inflammation and clinical outcomes in PD patients.

Peritoneal calprotectin level in peritoneal dialysis patients.

Calprotectin is an important molecule in the initiation and progression of the inflammatory process. Systemic and local intraperitoneal inflammation are distinct processes and consequences in peritoneal dialysis (PD). We aimed to evaluate dialysate calprotectin levels and its associations with peritonitis and dialysis adequacy in PD patients. Forty-four PD patients were included in this prospective study. Calprotectin concentration was evaluated in 24-h peritoneal drainage fluid. Patients were followed-up for 1 year, and peritonitis episodes were recorded. Dialysate calprotectin levels were compared to dialysis adequacy parameters and peritonitis frequency. The mean age of patients was 54.9±12.7 years. Median PD duration was 54 (23-76) months. Seventeen patients (38.6%) had previous peritonitis episodes. During follow-up, 15 of 44 patients (34.1%) had peritonitis. The median calprotectin concentration was 79.5 (75.2-86.3) ng/ml. The patients were divided into low and high calprotectin groups according to median value. In the high calprotectin group, BMI was found higher (p = 0.04). There was no significant relationship between calprotectin concentration and peritonitis during follow-up (p = 0.29). However, the patients that have had previous peritonitis had higher calprotectin concentrations (p = 0.02). The patients who had higher erythrocyte sedimentation rate (ESR) levels also had higher calprotectin concentrations (p = 0.01). Peritoneal calprotectin concentrations were correlated with higher BMI and ESR, and it was higher in patients with previous peritonitis episodes. To our knowledge, this is the first study to examine the peritoneal calprotectin levels in PD patients. Further studies are needed to determine the use of peritoneal calprotectin as an inflammatory marker in PD.

Pleiotropic effects of atorvastatin in peritoneal dialysis patients: A retrospective-prospective observational cohort study

Abstract. Recent studies demonstrate a large number of non-lipid modifiable effects of statins in various diseases. However, although atherogenic dyslipidemia is a common feature in peritoneal dialysis (PD) patients, statins use is supported by limited data and there is a general lack of research on their pleiotropic effects in this patients’ cohort. The present study aimed to evaluate the possible pleiotropic effects of atorvastatin in PD patients.&#x0D; Methods. A total of 114 PD patients with an average age of 55 (48-65) years and a dialysis vintage of 31 (14-50) months were included in this combined retrospective and prospective multicentre cohort study. PD patients (n = 54) who had started receiving atorvastatin before or after dialysis initiation and been treated with atorvastatin no less than 12 months were included in the Atorvastatin Group. PD patients (n = 60) who have never taken statins consisted of Atorvastatin-free Group.&#x0D; In addition to routine clinical and PD adequacy tests, concentrations of interleukins -6, -10, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 in PD effluent (PDE) were evaluated in all study participants at the start of the follow-up period. The primary outcomes were the 3-year PD technique survival and the all-cause mortality of PD patients during the follow-up period.&#x0D; Results. Atorvastatin users had lower serum phosphate and parathyroid hormone concentrations, higher weekly creatinine clearance, peritoneal weekly Kt/V urea, and, accordingly, total weekly Kt/V compared to the Atorvastatin-free Group. PDE cytokines assessment demonstrated significantly lower concentrations of all studied cytokines in the Atorvastatin Group compared with the Atorvastatin-free Group. In the Cox regression models, atorvastatin use was significantly associated with better PD technique survival (HR = 0.28 (95% CI 0.15; 0.54), p = 0.003) and mortality reduction in the PD patients regardless of their age, diabetes, anuric status, albumin and C-reactive protein levels, and history of PD peritonitis (HR = 0.24 (95% CI 0.15; 0.44), p &lt; 0.0001).&#x0D; Conclusions. Atorvastatin treatment was associated with the normalization of phosphate-calcium metabolism, low intraperitoneal inflammation and incidence of PD-associated peritonitis, and better dialysis adequacy in our cohort of PD patients. These pleiotropic effects of atorvastatin may be one of the reasons for the lower all‐cause mortality in PD patients. Further studies are needed to determine the necessity of statins prescribing in PD patients.

Effect of platelet-rich plasma on postoperative peritoneal inflammation and adhesions.

IntroductionPostoperative peritoneal adhesion is an important complication of abdominopelvic surgery. The aim of this study is to reveal the effect of platelet-rich plasma (PRP) on postoperative intraperitoneal inflammation and adhesions.Material and methodsTwenty-four Wistar albino rats were divided into three groups. Cecal incision and suturation was carried out for the experimental model. Intraperitoneally, 3 ml of 0.9% NaCl, 3 ml of PRP, and nothing were applied, and called as saline, PRP, and control groups, respectively. Four subjects in each group were sacrificed at the 3rd and 7th days postoperatively. Adhesion formations and giant cell, lymphocyte/plasmocyte, neutrophil, and histiocyte counts were assessed and hydroxyproline levels were measured in all groups and statistical comparisons were performed.ResultsExcept giant cell 3rd day scores, PRP had the lowest adhesion, neutrophil, lymphocyte, plasmocyte, histiocyte and fibrosis scores. Both 3rd and 7th days scores of giant cell, neutrophil, lymphocyte, plasmocyte, but only 7th days scores of histiocyte reaction and fibrosis were statistically significant (p < 0.05). Hydroxyproline levels were lower in the saline group at the 3rd day. However, at the 7th day, the levels were lower in the PRP group and no statistically significant difference was found compared to the saline group 3rd day levels (p > 0.05).ConclusionsPlatelet-rich plasma has a reducing effect on the postoperative peritoneal adhesions with separation of the damaged tissues, affecting the inflammation, matrix metalloproteinase, plasminogen activation or the other stages of adhesion formation.

Effluent Osteopontin levels reflect the peritoneal solute transport rate.

Long-term peritoneal dialysis (PD) is accompanied by low-grade intraperitoneal inflammation and may eventually lead to peritoneal membrane injury with a high solute transport rate and ultrafiltration failure. Osteopontin (OPN) is highly expressed through the stimulation of pro-inflammatory cytokines in many cell types. This study aimed to investigate the potential of OPN as a new indicator of peritoneal deterioration. One hundred nine continuous ambulatory PD patients were analyzed. The levels of OPN and IL-6 in peritoneal effluents or serum were analyzed by ELISA kits. The mean effluent OPN concentration was 2.39 ± 1.87 ng/mL. The OPN levels in drained dialysate were correlated with D/P Cr (p < 0.0001, R = 0.54) and D/D0 glucose (p < 0.0001, R = 0.39). Logistic regression analysis showed that the OPN levels in peritoneal effluents were an independent predictive factor for the increased peritoneal solute transport rate (PSTR) obtained by the peritoneal equilibration test (p < 0.001). The area under the receiver operating characteristic curve of OPN was 0.84 (95% CI: 0.75–0.92) in predicting the increased PSTR with a sensitivity of 86% and a specificity of 67%. The joint utilization of effluent OPN with age, effluent IL-6, and serum albumin further increased the specificity (81%). Thus, OPN may be a useful indicator of peritoneal deterioration in patients with PD.

Hyaluronan reduces colitis-induced intraperitoneal inflammation during peritoneal dialysis.

Peritoneal dialysis induces the inflammatory response within the peritoneal cavity, which contributes to the progressive damage of the peritoneum. Due to close contact of the peritoneal cavity and the intestines, there is the possibility that the visceral disorders can affect the intraperitoneal inflammation during peritoneal dialysis. Study of the effect of acute colitis on the intraperitoneal inflammation in conditions of peritoneal dialysis and evaluation of the protective effect of hyaluronan in that scenario. In rats with the dextran sulphate-induced colitis, 6-h peritoneal dialysis was performed with dianeal 2.5% +/- hyaluronan 10 mg/dL. In the control group, rats without colitis were studied. Peritoneal permeability and dialysate inflammation were studied at the end of the dialysate exchange. In rats with colitis, intraperitoneal inflammatory reaction was increased as compared with the control group and reflected by the following studied parameters: dialysate cell count (+26%, p < 0.01), number of neutrophils (+75%, p < 0.01), generation of free radicals in the leukocytes (+70%, p < 0.05), dialysate level of elastase (+102%, p < 0.01), tumor necrosis factor α (+48%, p < 0.01) and monocyte chemoattractant protein-1 (+42%, p < 0.01). Drained dialysate volume was lower (-21%, p < 0.01) and peritoneal permeability increased in rats with colitis (+55%, p < 0.01). In animals with the hyaluronan supplemented dialysis fluids, the intensity of the intraperitoneal inflammation was reduced. Visceral inflammation during colitis induces the inflammatory reaction within the peritoneal cavity that may accelerate damage to the peritoneum. Supplementation of the dialysis fluid with hyaluronan reduces the intensity of that effect.

N-acetylcysteine modulates effect of the iron isomaltoside on peritoneal mesothelial cells.

Intravenous (i.v.) iron supplementation is used in patients on chronic peritoneal dialysis (pd). Iron induced intraperitoneal inflammation observed in our previous studies with iron sucrose may deteriorate the function of the peritoneum as the dialysis membrane. We evaluated effect iron compound, iron-isomaltoside-100 (IIS) on the peritoneal mesothelial cells (MC). We studied the effect of iv treatment with IIS ± N-acetylcysteine (NAC) on the dialysate parameters and function of MC. In 7 uremic pd patients IIS 200 mg was infused i.v. ± NAC 600 mg. Afterward, a 4 hours exchange was performed with Dianeal 1.5%. As a control dialysate exchange preceding IIS treatment was used. Inflammatory parameters of the drained dialysates as well as the dialysates and IIS effects on MC were evaluated in ex vivo experiments. Intravenous infusion of IIS resulted in an increase of the dialysate Fe (+147%, P < 0.01). Concentrations of the dialysates inflammatory mediators were increased: interleukin-6 (IL-6) +39%, P < 0.02, monocyte chemoattractant protein-1(MCP1) +50%, P < 0.02, and hyaluronan (HA) +64%, P < 0.02. Simultaneous i.v. infusion of NAC prevented increase of the dialysate inflammatory mediators. Dialysates collected after IIS treatment induced oxidative stress in MC (+29%, P < 0.05) and stimulated IL-6 synthesis (+64%, P < 0.05) in MC; no such effect was seen in dialysates obtained after simultaneous IIS and NAC i.v. treatment. IIS used as the additive to culture medium stimulated synthesis in MC of IL6 (+76%, P < 0.001) and plasminogen activator inhibitor-1 (PAI-1) (28%, P < 0.001) whereas synthesis of tissue plasminogen activator (t-PA) was reduced (-16%, P < 0.001). These changes were prevented in the presence of NAC 1 mmol/L. Intravenous administration of IIS results in the mild stimulation of intraperitoneal inflammation. IIS changes MC phenotype to the inflammatory one with reduced fibrinolytic activity. These effects are prevented by NAC.

P1215INVERSE ASSOCIATION BETWEEN DIALYSATE OXALATE REMOVAL AND INTRAPERITONEAL INFLAMMATION IN PERITONEAL DIALYSIS PATIENTS

Abstract Background and Aims Due to inadequate oxalate removal, hyperoxalemia is a well-established feature in end-stage renal disease (ESRD) patients. Considering the fact that oxalate is primarily removed by kidneys in healthy individuals, we hypothesized that oxalate elimination in peritoneal dialysis (PD) patients could be compensated by PD effluent (PDE). In addition, its dialysate concentration could be associated with intraperitoneal inflammation. In the present study, we investigated oxalate excretion in PDE and its association with intraperitoneal inflammation in PD patients. Method We performed a cross-sectional single-center observational study involving 30 PD patients (17 women and 13 men). The average age was 48.3 ± 9.2 years. Among them, there were 11 (37%) diabetics and 19 (63%) non-diabetic patients. The mean time on PD was 32 [18.5-47] months. Parameters of dialysis adequacy, cytokines concentration and oxalate removal levels with PDE were determined. The spectrophotometric method was performed for determining oxalate concentration in PDE using oxalate oxidase/peroxidase reagent (BioSystems, Spain). The ELISA method was used for the determination of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) measurements in dialysate. For the statistical analysis, we used Kruskal-Wallis’s t-test and Spearman's rank correlation test. The median (Me) and interquartile ranges [Q25 - Q75] were calculated according to abnormal distribution. All statistical analyses were performed using MedCalc. Results No differences in peritoneal oxalate, IL-6, and MCP-1 excretion between diabetics and non-diabetic patients were observed (Table 1). However, the higher dialysate oxalate concentration was, the lower residual renal function was observed (r = - 0.69; p &amp;lt; 0.0001). Surprisingly, increased dialysate oxalate level was associated with low IL-6 (r = - 0.54; p = 0.002) (Fig. 1) and MCP-1 (r = - 0.7; p &amp;lt; 0.0001) (Fig. 2) concentrations in PDE. Conclusion To the best of our knowledge, the association between PDE oxalate excretion and proinflammatory mediators’ concentrations in PD patients has never been reported before. We suppose that peritoneal oxalate excretion might be involved in the intraperitoneal inflammation process. Further studies are needed to determine the possible pathogenetic role of dialysate oxalate removal in the conditions of intraperitoneal inflammation in PD patients.

Measurement of innate immune response biomarkers in peritoneal dialysis effluent using a rapid diagnostic point-of-care device as a diagnostic indicator of peritonitis

Peritonitis is the commonest complication of peritoneal dialysis and a major reason for treatment failure. Current diagnosis is based on clinical symptoms, cloudy effluent and a dialysate white cell count (over 100 cells/μl). A rapid point-of-care diagnostic test would accelerate diagnosis and potentially improve outcomes from infection. Here, in a clinical audit project, we used PERiPLEX®, a point-of-care device which detects when levels of matrix metalloproteinase-8 and interleukin-6 are elevated above a threshold within minutes in dialysis effluent, to assess whether it could confirm or exclude peritonitis in 107 patients undergoing peritoneal dialysis. Mean patient age was 64.6 years with a median duration of peritoneal dialysis of 13.3 months (interquartile range 6.3 - 33.5 months). Presence of peritonitis was confirmed by clinical criteria. There were 49 positive tests of which 41 patients had peritonitis, three had other causes of intra-peritoneal inflammation, three had severe urosepsis and two patients required no treatment. Fifty-eight tests were negative with one patient having a false negative result. The positive predictive value of the test was 83.7% (95% confidence interval 72.8 - 90.8) and the negative predictive value was 98.3% (89.1 - 99.8). Sensitivity and specificity were 97.6% (87.4 - 99.9) and 87.7% (77.2 - 94.5) respectively. Thus, PERiPLEX® could be used as a rapid point-of-care test that can aid the diagnosis or exclusion of peritonitis with a high negative predictive value.

Application value of CT/MRI examination in clinical diagnosis and treatment of Crohn′s disease

Accurate evaluation of Crohn′s disease is critical for determination of a therapeutic plan. Computed tomography (CT)/magnetic resonance imaging (MRI) can not only display the intraluminal and intraperitoneal inflammation objectively, but also reveal accurately the affected mesentery and related complications comprehensively, which attracted more and more attention in recent years. This review discussed the choice of CT/MRI examination methods, their roles in determining the severity of intestinal and mesenteric inflammation, the nature of intestinal stenosis, the extent of fistula, abscess and cellulitis, and the value in diagnosing postoperative complications, in order to investigate the application value of CT/MRI examination in clinical diagnosis and treatment of Crohn′s disease. Key words: Crohn′s disease; Computed tomography; Magnetic resonance imaging; Clinical diagnosis; Clinical treatment

Expression of XBP1s in peritoneal mesothelial cells is critical for inflammation-induced peritoneal fibrosis

Intraperitoneal inflammation is the most important determinant of peritoneal fibrosis in patients with long-term peritoneal dialysis (PD). Spliced x-box binding protein-1 (XBP1s), a major proximal effector of unfolded protein response (UPR) signaling, plays an indispensable role in inflammation. Our study demonstrated that the inflammatory factor interleukin-1β (IL-1β) dose- and time-dependently induced XBP1s upregulation and interleukin-6 (IL-6) secretion, as well as the expression of the fibrotic marker fibronectin. However, these effects were prevented by the IRE1 endonuclease inhibitor STF083010 since it time-dependently reduced IL-1β-induced Xbp1 mRNA splicing, XBP1s protein expression, inflammatory factor IL-6 secretion and the expression of the fibrotic marker fibronectin in human peritoneal mesothelial cells (HPMCs). The overexpression and knockdown of XBP1s in HPMCs had a similar effect on fibronectin expression. In a rat model of peritoneal inflammation, STF083010 significantly attenuated chlorhexidine digluconate-induced XBP1s and α-smooth muscle actin expression, as well as fibrotic tissue proliferation, in the peritoneum. Our results suggest that XBP1s is a strong pathogenic factor that mediates inflammation-induced peritoneal fibrosis in peritoneal dialysis.

Dyslipidemia and Intraperitoneal Inflammation Axis in Peritoneal Dialysis Patients: A Cross-Sectional Pilot Study

Background: We have hypothesized that the problem of dyslipidemia in peritoneal dialysis (PD) patients lies beyond certain levels of plasma lipoprotein and involves cardiovascular risk, but can also influence the development of chronic intraperitoneal inflammation. Objectives: The aim of our work was to define whether the association of dyslipidemia with intraperitoneal inflammation really exists and if it could it be used in a prospective cohort of PD patients. Patients and Methods: We performed a cross-sectional, single-center, pilot study involving 40 nondiabetic PD patients (27 men and 13 women with an average age of 49.3 ± 12.2 years). The median time on PD was 29 (18.5–37) months. The parameters dialysis adequacy, blood lipid profile, and the concentrations of tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-10 in peritoneal dialysate effluent (PDE) were determined. Cohen’s d effect size was computed post hoc to determine the differences between groups in the concentrations of pro- and anti-inflammatory mediators. Results: PD patients with atherogenic dyslipidemia had significantly high levels of MCP-1 compared with dyslipidemia-free patients (Cohen’s d = 1.32). A reduced high-density lipoprotein cholesterol level was associated with a high intraperitoneal production of the proinflammatory mediator TNF-α (p < 0.0001) and anti-inflammatory IL-10 (p < 0.0001). Atherogenic index of plasma was directly correlated with MCP-1 (p < 0.0001) and TNF-α (p < 0.0001). In multiple regression analysis, MCP-1 appeared to predict PD inadequacy (R² = 0.58; F ratio = 9.4; p = 0.006) independently of age and blood C-reactive protein level. Effect size was 1.38 with α = 0.05, n = 40, and 3 predictors. Conclusions: Our cross-sectional pilot study first demonstrated a close interaction between the atherogenic lipid profile and a high concentration of MCP-1 in PDE; this might be a prognostic marker for PD inadequacy. The potential significance of our finding is that it provides useful preliminary information necessary for further research into this area.

Dialysate copeptin and peritoneal transport in incident peritoneal dialysis patients

PurposeSystemic and intraperitoneal inflammation are characteristic features of patients with end-stage renal disease undergoing chronic peritoneal dialysis (PD). Arginine vasopressin (AVP) and its surrogate marker copeptin play important roles in many pathophysiological processes in chronic kidney disease. The aim of this study was to assess if copeptin concentrations in plasma and dialysate were related to peritoneal transport parameters and residual renal function (RRF) in incident PD patients.MethodsIn 37 clinically stable incident PD patients (mean age 50 years, 68% women, 32% diabetes), a 4 h peritoneal equilibration test (PET) was performed 4–6 weeks after the onset of PD. Plasma (at 2 h of PET) and dialysate (at 4 h) concentrations of copeptin, high-sensitivity C-reactive protein and interleukin-6 (IL-6) were determined.ResultsPlasma (80.7 ± 37.3 pg/mL) and dialysate (33.2 ± 18.0 pg/mL) concentrations of copeptin were correlated (Rs = 0.52, p = 0.001). Plasma and dialysate copeptin concentrations were negatively correlated with renal function as assessed by renal Kt/V (Rs = − 0.38; p = 0.021 and Rs = − 0.33; p = 0.047, respectively). At PET, dialysate copeptin negatively correlated with D/P creatinine (Rs = − 0.35, p = 0.033), and positively with D/D0 glucose (Rs = 0.33, p = 0.045) and ultrafiltration (Rs = 0.37, p = 0.024). Multivariate analysis showed that low dialysate copeptin (β = –0.30, p = 0.049) and high dialysate IL-6 (β = + 0.40, p = 0.012) were independent determinants of higher D/P creatinine.ConclusionsDialysate copeptin was negatively associated with D/P creatinine in incident PD patients suggesting a potential influence of copeptin or AVP on peritoneal solute transport rate that might involve vasoactive mechanisms.

Dialysate cell-free mitochondrial DNA fragments as a marker of intraperitoneal inflammation and peritoneal solute transport rate in peritoneal dialysis

BackgroundMitochondrial DNA (mtDNA) released into extracellular subsequent to cell injury and death can promote inflammation in patients and animal models. However, the effects of peritoneal dialysate cell-free mtDNA on intraperitoneal inflammation and peritoneal solute transport rate (PSTR) in peritoneal dialysis (PD) patients remain unclear.MethodsWe select the incident patients who began PD therapy between January 1, 2009, and December 30, 2010. Peritoneal dialysate was collected at the time of peritoneal equilibration test. The cell-free mtDNA, IL-6, IL-17A, TNF-α and IFN-γ were measured. All patients were followed till December 2017. The results were compared with PSTR and patient survival.ResultsOne hundred and eighty-nine patients were included in the study. The average age was 47.1 ± 13.5 years, 55.6% of the patients were males. The average PSTR was 0.66 ± 0.12, the median dialysate mtDNA levels were 4325 copies/ul. The median concentrations of IL-6, IL-17A, TNF-α and IFN-γ were 25.9, 10.8, 25.8 and 17.9 pg/ml, respectively. We found that dialysate mtDNA was significantly correlated with PSTR (r = 0.461, P < 0.001), IL-6 (r = 0.568, P < 0.001), TNF-α (r = 0.454, P < 0.001) and IFN-γ (r = 0.203, P = 0.005). After adjustment for multiple covariates, dialysate mtDNA levels were independently correlated with IL-6 and PSTR. Dialysate mtDNA levels were not associated with patient survival.ConclusionsWe found that dialysate mtDNA levels correlated with the degree of intraperitoneal inflammatory status in PD patients. Peritoneal effluent mtDNA was an independent determinant of PSTR but did not affect patient survival.

Low-Fiber Intake Is Associated With High Production of Intraperitoneal Inflammation Biomarkers

Fiber intake influences disturbances in the gastrointestinal tract and is associated with systemic inflammation in the general population. Systemic and intraperitoneal inflammation play an important role in defining outcomes in peritoneal dialysis (PD), but the relationship between dietary fiber intake and inflammatory biomarkers has not yet been reported in the population on PD. The objective of the present study is to analyze whether or not fiber intake in patients on PD is associated with serum and intraperitoneal levels of inflammatory biomarkers. Adult and clinically stable PD patients were included in this observational and cross-sectional study. Fiber intake was assessed by means of a dietary survey and calculated using the DietPro program 5.6i. The population was divided into two groups according to the median fiber intake. We investigated interleukin (IL)-1β, IL-6, tumor necrosis factor-α, monocyte chemoattractant protein-1 (MCP-1), B-cell-activating factor, and plasminogen-activator inhibitor-1 in both serum and peritoneal fluid. The latter was determined after a dwell time of 4 hours. Fifty-two patients (42% men; aged 53±14years, 36% diabetics) were evaluated. Low intake of dietary fiber was found in 90% of patients, with a median of 12.2g per day (3.4-33.3). The group with the highest fiber intake presented lower intraperitoneal levels of IL-6, IL-8, and MCP-1. In contrast, only MCP-1 was lower in the serum of those who consumed more fiber. All the associations remained significant after adjustment for confounders with plasminogen-activator inhibitor-1 included. Patients on PD frequently present inadequate dietary fiber intake, which appears to have an association with the inflammatory response, particularly in the intraperitoneal component. Further prospective studies, evaluating whether or not a dietetic intervention with a focus on fiber intake affects these biomarkers and clinical outcomes, are essential to determine causality and clinical relevance.