Peritoneal Dialysis Effluent Research Articles

Pet-related Pasteurella multocida induced peritonitis in peritoneal dialysis: a case report and review of the literatures

BackgroundP. multocida (Pasteurella multocida) is animal-sourced gram-negative coccobacillus which can be transmitted to human through many animals including household pets. P. multocida induced peritoneal dialysis-related peritonitis has rarely been reported. In recent years, there has been an increase in the incidence of P. multocida induced peritoneal dialysis-related peritonitis, for the reason that patients with PD at home bred household pets. In this study, we present a case of a P. multocida induced peritoneal dialysis-related peritonitis, which is suspected to be caused through intimate contact with a household cat and we have reviewed 28 cases reported before and give suggestions for treatment and the way of prevention.Case presentationA 75-year-old man with end-stage renal disease (ESRD) for nearly 5 years on continuous ambulatory peritoneal dialysis (CAPD) was admitted to the nephrology department with a 1-week history of abdominal pain and a cloudy peritoneal dialysis effluent. Based on the history, physical examination and laboratory results with the findings in the peritoneal dialysis fluid, a diagnosis of peritoneal dialysis-related peritonitis was confirmed. The final culture of initial peritoneal effluent results indicated the organism was P. multocida. After a 12-day antibiotic treatment, the condition of patient was not improved. The patient was switched to ampicillin/sulbactam (3 g intravenously) twice every day and the condition was improved significantly. On further inquiring, the patient reported that he had had a cat at home and when the patient did CAPD, the cat was usually playing with the tubing or contacting the patient during CAPD.ConclusionIn our case and reviewed cases, P. multocida induced peritoneal dialysis-related peritonitis could be cured by proper antibiotic treatment. If individuals keep the pet away from the PD process, the infection route may be severed. P. multocida induced peritoneal dialysis-related peritonitis does not need catheter removal and exchange with hemodialysis except long-time intractable peritonitis.

Clostridioides difficile associated peritonitis in peritoneal dialysis patients \u2013 a case series based review of an under-recognized entity with therapeutic challenges

BackgroundInitial presentation of peritoneal dialysis associated infectious peritonitis can be clinically indistinguishable from Clostridioides difficile infection (CDI) and both may demonstrate a cloudy dialysate. Empiric treatment of the former entails use of 3rd-generation cephalosporins, which could worsen CDI. We present a logical management approach of this clinical scenario providing examples of two cases with CDI associated peritonitis of varying severity where the initial picture was concerning for peritonitis and treatment for CDI resulted in successful cure.Case presentationA 73-year-old male with ESRD managed with PD presented with fever, abdominal pain, leukocytosis and significant diarrhea. Cell count of the peritoneal dialysis effluent revealed 1050 WBCs/mm3 with 71% neutrophils. C. difficile PCR on the stool was positive. Patient was started on intra-peritoneal (IP) cefepime and vancomycin for treatment of the peritonitis and intravenous (IV) metronidazole and oral vancomycin for treatment of the C. difficile colitis but worsened. PD fluid culture showed no growth. He responded well to IV tigecycline, oral vancomycin and vancomycin enemas. Similarly, a 55-year-old male with ESRD with PD developed acute diarrhea and on the third day noted a cloudy effluent from his dialysis catheter. PD fluid analysis showed 1450 WBCs/mm3 with 49% neutrophils. IP cefepime and vancomycin were initiated. CT of the abdomen showed rectosigmoid colitis. C. difficile PCR on the stool was positive. IP cefepime and vancomycin were promptly discontinued. Treatment with oral vancomycin 125 mg every six hours and IV Tigecycline was initiated. PD fluid culture produced no growth. PD catheter was retained.ConclusionsIn patients presenting with diarrhea with risk factors for CDI, traditional empiric treatment of PD peritonitis may need to be reexamined as they could have detrimental effects on CDI course and patient outcomes.

Effluent lipopolysaccharide is a prompt marker of peritoneal dialysis-related gram-negative peritonitis.

To investigate the value of effluent lipopolysaccharide (LPS) for early detection of gram-negative peritonitis (GNP) in peritoneal dialysis (PD) patients. PD-related peritonitis episodes occurring between January 2016 and December 2018 were included in the study. Effluent LPS and the other infectious parameters were measured at peritonitis presentation, and peritonitis was categorized as GNP, non-GNP, and culture-negative peritonitis. Receiver operating characteristic (ROC) analysis was employed to evaluate the efficacy of effluent LPS to distinguish GNP. A total of 161 peritonitis episodes were analyzed, including 49 GNP episodes and 82 non-GNP episodes. In contrast with non-GNP, GNP presented with higher effluent leukocyte count (3236 (1497-6144) vs. 1904 (679-4071) cell mm-3, p = 0.008), increased effluent LPS (1.552 (0.502-2.500) vs. 0.016 (0.010-0.030) EU mL-1, p < 0.001), lower blood leukocyte count (9.95 ± 3.18 vs. 11.56 ± 4.37 × 109 L-1, p = 0.017), greater neutrophil predominance (87.1 ± 4.6% vs. 83.4 ± 7.7%, p = 0.001), and greater "procalcitonin" (PCT, 4.90 (2.20-12.60) vs. 1.00 (0.51-4.07) µg L-1, p < 0.001). It took 5.2 ± 3.1 h to report the results of effluent LPS. Effluent LPS cutoff value of >0.035 EU mL-1 showed an area under the ROC curve of 0.972 (95% CI 0.951-0.994, p < 0.001) in differentiating GNP from non-GNP with a sensitivity of 100% and a specificity of 80.5%, and its joint utilization with PCT further increased the specificity (91.4%) to discriminate GNP. PD effluent LPS could be an applicable early marker of gram-negative organism-related peritonitis in PD patients.

Perforative peritonitis confused with peritoneal dialysis-related peritonitis: Report of three cases

IntroductionPerforative peritonitis in patients on peritoneal dialysis (PD) is a serious adverse event associated with significant mortality. The signs and symptoms of perforative peritonitis in patients on PD are often confused with those of PD-related peritonitis; therefore, early diagnosis is often difficult. Presentation of casesIn all three cases, antibiotic therapy was started for peritonitis. Although contrast-enhanced computed tomography (CT) was not performed, perforative peritonitis was suspected due to severe cloudiness of PD effluents, and emergency surgeries were performed 8, 5, and 6 days after therapy onset in cases 1, 2, and 3, respectively. In case 1, the ileum was perforated owing to ischemia, and partial ileal resection and divided ileostomy were performed. The patient died 18 days postoperatively. In case 2, partial ileal resection and divided ileostomy were performed for an incarcerated obturator hernia and perforated ileum. The patient was transferred for hemodialysis (HD) and discharged 117 days postoperatively. In case 3, lavage drainage was performed for peritonitis because of mesenteric penetration of a sigmoid colon diverticulum. The patient was then transferred for HD, and colostomy was subsequently performed. He was discharged 159 days postoperatively. DiscussionEarly diagnosis between PD-related peritonitis and perforative peritonitis is often difficult since the washing effect of the peritoneal dialysate might relieve peritoneal irritation. ConclusionIn PD patients with refractory peritonitis, it is necessary to keep in mind the possibility of perforative peritonitis, and the differential diagnosis should be performed using contrast-enhanced CT within at least 5 days after antibiotic therapy.

IL-6 trans-signaling drives a STAT3-dependent pathway that leads to structural alterations of the peritoneal membrane.

IL-6 is a vital inflammatory factor in the peritoneal cavity of patients undergoing peritoneal dialysis (PD). The present study examined the effect of IL-6 trans-signaling on structural alterations of the peritoneal membrane. We investigated whether the epithelial-to-mesenchymal transition (EMT) process of human peritoneal mesothelial cells (HPMCs) and the production of proangiogenic factors were controlled by IL-6 trans-signaling. Its role in the peritoneal alterations was detected in a mouse model. The morphology of HPMCs and levels of cytokines in PD effluent were also explored. Stimulation of HPMCs with the IL-6 and soluble IL-6 receptor complex (IL-6/S) promoted the EMT process of HPMCs depending on the STAT3 pathway. In a coculture system of HPMCs and human umbilical vein endothelial cells, IL-6/S mediated the production of VEGF and angiopoietins so as to downregulate the expression of endothelial junction molecules and finally affect vascular permeability. Daily intraperitoneal injection of high glucose-based dialysis fluid induced peritoneal fibrosis, angiogenesis, and macrophage infiltration in a mouse model, accompanied by phosphorylation of STAT3. Blockade of IL-6 trans-signaling prevented these peritoneum alterations. The fibroblast-like appearance of HPMCs ex vivo was upregulated in patients undergoing prevalent PD accompanied by increasing levels of IL-6, VEGF, and angiopoietin-2 in the PD effluent. Taken together, these findings identified a critical link between IL-6 trans-signaling and structural alterations of the peritoneal membrane, and it might be a potential target for the treatment of patients undergoing PD who have developed peritoneal alterations.

Rhodococcus induced false-positive galactomannan (GM), a biomarker of fungal presentation, in patients with peritoneal dialysis: case reports

BackgroundGalactomannan index (GMI) at a level higher than 0.5 provides high sensitivity and specificity for the diagnosis of fungal peritonitis. Here, we report the false-positive of GMI in peritoneal dialysis (PD) effluent (PDE) due to Rhodococcus peritonitis in PD patients.Case presentationGMI in PDE of case #1 and case #2 were 1.53 and 0.76, respectively, while serum GMI of both cases was less than 0.5. In addition, GMI from the specimens obtained directly from the stationary phase of Rhodococcus colonies were 1.27 and 1.56, which were isolated from case #1 and #2, accordingly.ConclusionHigh GMI in PDE of PD patients is not specific just for fungal infections but may also be secondary to other infections, such as Rhodococcus spp., especially in endemic areas.

The Role of Cathepsin B in Peritoneal Fibrosis due to Peritoneal Dialysis.

Glucose-containing peritoneal dialysis (PD) solution causes peritoneal fibrosis (PF) characterized by accumulation of extracellular matrix (ECM) in the submesothelial layer. Cathepsin B is a lysosomal cysteine protease that degrades ECM, but its role in the PF remains unclear. Thus, we investigated the role of cathepsin B in PF. Procathepsin B was measured in the 73 PD effluents of 68 patients. Procathepsin B and cathepsin B after exposure of glucose and the effects of cathepsin B on the expression of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), and urokinase-type plasminogen activator (uPA) were measured in the supernatant of cultured human peritoneal mesothelial cells (HPMCs). The effect of cathepsin B and its inhibitor, cystatin C, on PF was investigated in the murine model. Procathepsin B was measured at 3.6 μg/L in serum and 5.4 μg/L in PD effluent and positively correlated to the cancer antigen (CA) 125. The treatment with 4.25% glucose increased procathepsin B by 3.1-fold and cathepsin B by 5.9-fold in the HPMCs. Cathepsin B induced the secretion of MMP-1, -2, and -3 and TIMP-1 in the HPMCs, but uPA was not excreted. In the PF murine models, cathepsin B reduced the thickness of the submesothelial layer and cystatin C attenuated the effect of cathepsin B. HPMCs secrete cathepsin B with exposure of PD solution, and cathepsin B might help protect against PF.

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.

Proteomic profiling of peritoneal dialysis effluent-derived extracellular vesicles: a longitudinal study.

Peritoneal dialysis (PD) is an optimal renal replacement therapy for patients while waiting for kidney transplantation, but functional failure of the peritoneal membrane (PM), mainly induced by exposure to PD solutions, force many patients to early abandon PD therapy. PM function is evaluated by the peritoneal equilibration test (PET), a tedious technique only detecting alterations in extensively damaged PM. In a previous study, we showed that peritoneal dialysis effluent contained extracellular vesicles (PDE-EV), and that their proteome was significantly different between newly enrolled and long-term PD patients. Here, we report the results of a longitudinal study and compare PDE-EV proteome changes with PET results. PDE was collected from 11 patients every 6months (coincident with PET controls) from 0months up to 24months on PD. PDE-EV were isolated by size-exclusion chromatography and the proteome was analyzed by mass spectrometry (LC-MS/MS). Bioinformatic analyses were conducted to evaluate differences between groups. At follow-up endpoint, patients were classified as Stable (n = 7) or Unstable (n = 4) according to PET evolution. Strikingly, PDE-EV from the Stable group showed a significantly higher protein expression compared to Unstable patients already at 6months on PD, when PET alterations had not been detected yet. PDE-EV proteome show alterations much earlier than PET monitoring, thus unveiling the potential of PDE-EV proteins as feasible biomarkers of PM alteration in PD patients.

Protection of the Peritoneal Membrane by Peritoneal Dialysis Effluent-Derived Mesenchymal Stromal Cells in a Rat Model of Chronic Peritoneal Dialysis.

Peritoneal dialysis (PD) is a renal replacement option for patients with end-stage renal disease. However, a long-term exposure to hypertonic PD solutions leads to peritoneal membrane (PM) injury, resulting in ultrafiltration (UF) failure. This study was designed to primarily evaluate efficacy of PD effluent-derived mesenchymal stromal cells (pMSCs) in the prevention of PM injury in rats. The pMSCs were isolated from PD effluent. Male Wistar rats received daily intraperitoneal (IP) injection of 10 mL of Dianeal (4.25% dextrose) and were treated with pMSCs (1.2‐1.5 × 106/rat/wk, IP). UF was determined by IP injection of 30 mL of Dianeal (4.25% dextrose) with dwell time of 1.5 h, and PM injury was examined by histology. Apoptosis was quantitated by using flow cytometric analysis, and gene expression by using the PCR array and Western blot. Here, we showed that as compared to naive control, daily IP injection of the Dianeal PD solution for 6 weeks without pMSC treatment significantly reduced UF, which was associated with an increase in both PM thickness and blood vessel, while pMSC treatment prevented the UF loss and reduced PM injury and blood vessels. In vitro incubation with pMSC-conditioned medium prevented cell death in cultured human peritoneal mesothelial cells (HPMCs) and downregulated proinflammatory (i.e., CXCL6, NOS2, IL1RN, CCL5, and NR3C1) while upregulated anti-inflammatory (i.e., CCR1, CCR4, IL9, and IL-10) gene expression in activated THP1 cells. In conclusion, pMSCs prevent bioincompatible PD solution-induced PM injury and UF decline, suggesting that infusing back ex vivo-expanded pMSCs intraperitoneally may have therapeutic potential for reduction of UF failure in PD patients.

Comparison of sodium removal in peritoneal dialysis patients treated by continuous ambulatory and automated peritoneal dialysis

BackgroundOptimal fluid balance for peritoneal dialysis (PD) patients requires both water and sodium removal. Previous studies have variously reported that continuous ambulatory peritoneal dialysis (CAPD) removes more or equivalent amounts of sodium than automated PD (APD) cyclers. We therefore wished to determine peritoneal dialysate losses with different PD treatments.MethodsPeritoneal and urinary sodium losses were measured in 24-h collections of urine and PD effluent in patients attending for their first assessment of peritoneal membrane function. We adjusted fluid and sodium losses for CAPD patients for the flush before fill technique.ResultsWe reviewed the results from 659 patients, mean age 57 ± 16 years, 56.3% male, 38.9% diabetic, 24.0% treated by CAPD, 22.5% by APD and 53.5% APD with a day-time exchange, with icodextrin prescribed to 72.8% and 22.7 g/L glucose to 31.7%. Ultrafiltration was greatest for CAPD 650 (300–1100) vs 337 (103–598) APD p < 0.001, vs 474 (171–830) mL/day for APD with a day exchange. CAPD removed most sodium 79 (33–132) vs 23 (− 2 to 51) APD p < 0.001, and 51 (9–91) for APD with a day exchange, and after adjustment for the CAPD flush before fill 57 (20–113), p < 0.001 vs APD. APD patients with a day exchanged used more hypertonic glucose dialysates [0 (0–5) vs CAPD 0 (0–1) L], p < 0.001.ConclusionCAPD provides greater ultrafiltration and sodium removal than APD cyclers, even after adjusting for the flush-before fill, despite greater hypertonic usage by APD cyclers. Ultrafiltration volume and sodium removal were similar between CAPD and APD with a day fill.

Randomized Controlled Trial on Adjunctive Lavage for Severe Peritonitis.

Background:In severe peritoneal dialysis (PD)-related peritonitis, patients' response to antibiotic can be poor. We postulated that adjunctive lavage may improve the outcome in severe cases by enhancing the removal of bacteria and inflammatory cells from the peritoneum.Methods:Severe PD peritonitis was defined as poor clinical response to empirical cefazolin/ceftazidime and a PD effluent (PDE) leukocyte count > 1,090/mm3 on day 3. Enrolled patients were randomized into either the lavage group (n = 20) or control group (n = 20). In the lavage group, continuous lavage by an automated PD machine from day 3 to 5 or 6 was performed, whereas the usual PD schedule was maintained in the control group. The primary outcome was treatment success. Post hoc analysis was also performed to compare the outcome between subgroups with different severity.Results:Baseline parameters were similar in the lavage and control groups, including PDE leukocyte count on day 3 (4,871/mm3 vs 4,143/mm3, p = 0.46). Treatment success rates were high in both groups (75% vs 70%, p = 0.72). C-reactive protein (CRP) on day 3 was found to be the only predictor of treatment failure and was used to stratify all patients into tertiles of severity. Whilst a significant decline in treatment success was evident across the tertiles of increasing CRP in the control group (100% vs 85.7% vs 28.6%, p = 0.005), treatment success was relatively maintained in the lavage group (85.7% vs 71.4% vs 66.7%, p = 0.43).Conclusions:Adjunctive lavage did not improve the overall outcome, although it may be beneficial for the more severe peritonitis patients who have high CRP.

Connective tissue growth factor is correlated with peritoneal lymphangiogenesis

Lymphatic absorption in the peritoneal cavity may contribute to ultrafiltration failure in peritoneal dialysis (PD). Lymphatic vessels develop during PD-related peritoneal fibrosis. Connective tissue growth factor (CTGF, also called CCN2) is an important determinant of fibrotic tissue remodeling, but little is known about its possible involvement in lymphangiogenesis. In this study, we investigated the relationship between CTGF and peritoneal lymphangiogenesis. A positive correlation was observed between vascular endothelial growth factor-C (VEGF-C), a major lymphangiogenic growth factor, and the CTGF concentration in human PD effluents. CTGF expression was positively correlated with expression of lymphatic markers and VEGF-C in human peritoneal biopsies. We found a positive correlation between the increase in CTGF and the increase in VEGF-C in cultured human peritoneal mesothelial cells (HPMCs) treated with transforming growth factor-β1 (TGF-β1). The diaphragm is a central player in peritoneal lymphatic absorption. CTGF expression was also correlated with expression of VEGF-C and lymphatics in a rat diaphragmatic fibrosis model induced by chlorhexidine gluconate (CG). Furthermore, CTGF gene deletion reduced VEGF-C expression and peritoneal lymphangiogenesis in the mouse CG model. Inhibition of CTGF also reduced VEGF-C upregulation in HPMCs treated with TGF-β1. Our results suggest a close relationship between CTGF and PD-associated lymphangiogenesis.

Neutrophil-derived miR-223 as local biomarker of bacterial peritonitis

Infection remains a major cause of morbidity, mortality and technique failure in patients with end stage kidney failure who receive peritoneal dialysis (PD). Recent research suggests that the early inflammatory response at the site of infection carries diagnostically relevant information, suggesting that organ and pathogen-specific “immune fingerprints” may guide targeted treatment decisions and allow patient stratification and risk prediction at the point of care. Here, we recorded microRNA profiles in the PD effluent of patients presenting with symptoms of acute peritonitis and show that elevated peritoneal miR-223 and reduced miR-31 levels were useful predictors of bacterial infection. Cell culture experiments indicated that miR-223 was predominantly produced by infiltrating immune cells (neutrophils, monocytes), while miR-31 was mainly derived from the local tissue (mesothelial cells, fibroblasts). miR-223 was found to be functionally stabilised in PD effluent from peritonitis patients, with a proportion likely to be incorporated into neutrophil-derived exosomes. Our study demonstrates that microRNAs are useful biomarkers of bacterial infection in PD-related peritonitis and have the potential to contribute to disease-specific immune fingerprints. Exosome-encapsulated microRNAs may have a functional role in intercellular communication between immune cells responding to the infection and the local tissue, to help clear the infection, resolve the inflammation and restore homeostasis.

MON-075 DISCORDANT CULTURE-NEGATIVE PERITONITIS RATES IN DIFFERENT MICROBIOLOGY LAB: A RESULT FROM THAILAND PDOPPS STUDY

Most of Thailand peritoneal dialysis (PD) centers have culture-negative peritonitis (CNP) rate above the International Society of PD guideline’s threshold level (< 20%). The causes of high CNP rate in Thailand may result from different culture protocol which is yet to be elucidated. The PD bags were retrieved from PD patients with peritonitis from Thailand PDOPPS sites. The bag was submitted to local and central laboratories. The bags with delayed shipment (>24 hours), minute tear or damage were discarded. At local laboratories, the causative organism was identified using an individual lab protocol. At central laboratory, 50 ml of PD effluent was centrifuged and directly inoculated into broth and different agar plates. From 991 consented patients, 234 cases had 275 peritonitis episodes during June 2016 to December 2017. Ninety five and 93 episodes had random (with empirical/specific antibiotic) and first cloudy specimens (without antibiotic), respectively, submitted centrally. CNP rate was 10% lower in central lab compared to local lab (42.1% vs. 31.6%). The better yield results from a two-fold increase in the yield of fungal, mycobacterial and polymicrobial identifications (6.3% vs. 3.2%, 1.1% vs. 0%, and 10.5% vs. 4.2%, respectively). Positive locally cultured but negative centrally cultured rate was 5 in 95 episodes (5.3%). CNP rate was reduced by only 0.4% in specimen with concurrent antibiotic (31.6 vs. 31.2 %). Large volume of submitted PD effluent seems to play an important role in reducing CNP rate at least in Thailand. However, the differences in lab quality control cannot be excluded. Concurrent antibiotic does not play an important role in nowadays broth culture technique.

The Peritoneal Surface Proteome in a Model of Chronic Peritoneal Dialysis Reveals Mechanisms of Membrane Damage and Preservation.

Peritoneal dialysis (PD) fluids are cytotoxic to the peritoneum. Recent studies have shown that alanyl-glutamine (AlaGln) modulates the cellular stress response, improves mesothelial cell survival, reduces submesothelial thickening in experimental models of PD, and in clinical studies improves PD effluent cell stress and immune responses. However, the mechanisms of AlaGln-mediated membrane protection are not yet fully understood. Here, we explore those mechanisms through application of a novel proteomics approach in a clinically relevant in vivo model in rats. Experimental PD was performed for 5 weeks using conventional single-chamber bag (SCB) or neutral dual-chamber bag (DCB), PD fluid (PDF), with or without AlaGln supplementation, via a surgically implanted catheter. Rats subjected to a single dwell without catheter implantation served as controls. The peritoneal surface proteome was directly harvested by detergent extraction and subjected to proteomic analysis by two-dimensional difference gel electrophoresis (2D-DiGE) with protein identification by mass spectrometry. An integrated bioinformatic approach was applied to identify proteins significantly affected by the treatments despite biological variation and interfering high abundance proteins. From 505 of 744 common spots on 59 gels, 222 unique proteins were identified. Using UniProt database information, proteins were assigned either as high abundance plasma proteins, or as cellular proteins. Statistical analysis employed an adapted workflow from RNA-sequencing, the trimmed mean of M-values (TMM) for normalization, and a mixed model for computational identification of significantly differentially abundant proteins. The most prominently enriched pathways after 5 weeks chronic treatment with SCB or DCB, PDFs belonged to clusters reflecting tissue damage and cell differentiation by cytoskeletal reorganization, immune responses, altered metabolism, and oxidative stress and redox homeostasis. Although the AlaGln effect was not as prominent, associated enriched pathways showed mostly regression to control or patterns opposite that of the PDF effect. Our study describes the novel peritoneal surface proteome through combined proteomic and bioinformatic analyses, and assesses changes elicited by chronic experimental PD. The biological processes so identified promise to link molecular mechanisms of membrane damage and protection in the in vivo rat model to pathomechanisms and cytoprotective effects observed in vitro and in clinical PD.

Peritoneal Dialysis-Associated Peritonitis.

Peritonitis is a common and severe complication in peritoneal dialysis (PD). Detailed recommendations on the prevention and treatment of PD-associated peritonitis have been published by the International Society for Peritoneal Dialysis (ISPD), but there is a substantial variation in clinical practice among dialysis units. Prophylactic antibiotics administered before PD catheter insertion, colonoscopy, or invasive gynecologic procedures, daily topical application of antibiotic cream or ointment to the catheter exit site, and prompt treatment of exit site or catheter infection are key measures to prevent PD-associated peritonitis. When a patient on PD presents with clinical features compatible with PD-associated peritonitis, empirical antibiotic therapy, with coverage of both Gram-positive and Gram-negative organisms (including Pseudomonas species), should be started once the appropriate microbiologic specimens have been obtained. Intraperitoneal is the preferred route of administration. Antifungal prophylaxis, preferably oral nystatin, should be added to prevent secondary fungal peritonitis. Once the PD effluent Gram stain or culture and sensitivity results are available, antibiotic therapy can be adjusted accordingly. A detailed description on the dosage of individual antibiotic can be found in the latest recommendations by the ISPD. The duration of antibiotics is usually 2-3 weeks, depending on the specific organisms identified. Catheter removal and temporary hemodialysis support is recommended for refractory, relapsing, or fungal peritonitis. In some patients, a new PD catheter could be inserted after complete resolution of the peritonitis. PD catheter removal should also be considered for refractory exit site or tunnel infections. After the improvement in clinical practice, there is a worldwide trend of reduction in PD-associated peritonitis rate, supporting the use of PD as a first-line dialysis modality.

AQP1-Containing Exosomes in Peritoneal Dialysis Effluent As Biomarker of Dialysis Efficiency.

The water channel Aquaporin 1 (AQP1) plays a fundamental role in water ultrafiltration during peritoneal dialysis (PD) and its reduced expression or function may be responsible for ultrafiltration failure (UFF). In humans, AQP1 is expressed in the endothelium of the peritoneal capillaries but its expression in mesothelial cells (MC) and its functional role in PD is still being debated. Here, we studied a cohort of 30 patients using PD in order to determine the presence of AQP1 in peritoneal biopsies, AQP1 release in the PD effluent through exosomes and the correlation of AQP1 abundance with the efficiency of peritoneal ultrafiltration. The experiments using immunofluorescence showed a strong expression of AQP1 in MCs. Immunoblotting analysis on vesicles isolated from PD effluents showed a consistent presence of AQP1, mesothelin and Alix and the absence of the CD31. Thus, this suggests that they have an exclusive mesothelial origin. The immunoTEM analysis showed a homogeneous population of nanovesicles and confirmed the immunoblotting results. Interestingly, the quantitative analysis by ELISA showed a positive correlation between AQP1 in the PD effluent and ultrafiltration (UF), free water transport (FWT) and Na-sieving. This evidence opens the discussion on the functional role of mesothelial AQP1 during PD and suggests that it may represent a potential non-invasive biomarker of peritoneal barrier integrity, with predictive potential of UFF in PD patients.

The relationship between overhydration, increased oxidative stress and peritoneal dialysis adequacy

The present study was undertaken to investigate the association of hydration status measured by bioimpedance analysis with oxidative stress biomarkers and peritoneal dialysis (PD) adequacy.&#x0D; Methods. It was a case-control study involved 85 PD patients from 2 dialysis centers in Ukraine. Among the examined patients, there were 56/85 (65.9%) men and 29/85 (34.1%) women. All patients had been undergoing PD for more than 3 months (median was 25.4 [14.0-49.5] months). Average age was 48.8 ± 12.5 years.&#x0D; Fluid compartments [extracellular water (ECW) and overhydration index (OH)] were measured using Multifrequency bio-impedance (BCM®, Fresenius Medical Care, Germany). Overhydration was defined as OH/ECW&gt; 15%.&#x0D; Malondialdehyde concentration in serum (MDAs) and erythrocytes (MDAe) was defined as an indicator of lipid peroxidation. Such parameters as the concentration of ceruloplasmin (CP), transferrin (TR) and sulfhydryl groups (SH-groups) in the blood and total peroxidase activity in erythrocyte (TPAe) were studied as the indicators of antioxidant system. Moreover, to determine the intraperitoneal oxidative stress induction, we studied MDA and TPO in PD effluent.&#x0D; Results. Among 85 PD participants, there were 38(44.7%) patients in normohydration range and 47 (55.3%) overhydrated pаtients according to the OH/ECW ratio. There were a significant increase in serum and PD effluent MDA (p = 0.01 and p = 0.001, respectively) in overhydrated PD patients whereas the concentrations of serum CP and TPA in PD effluent were significantly lower compared with normohydrated patients (p = 0.008 and p = 0.04, respectively). In addition, ECW had an inverse correlation with SH-groups (r = -0.37; p = 0.003) and MDAs (r = -0.48; p = 0.004). An odds ratio of PD inadequacy was 3.6 times higher among overhydrated patients than in normovolemic one: OR = 3.6 (95% CI 1.3-10.3; p = 0.01).&#x0D; Conclusions. Extracellular fluid overload promotes intraperitoneal and systemic oxidative stress which could be one of the pathway explanations of technique survival failure and cardiovascular mortality in overhydrated PD patients.

MicroRNA-302c modulates peritoneal dialysis-associated fibrosis by targeting connective tissue growth factor.

Long‐term peritoneal dialysis (PD) can lead to the induction of mesothelial/epithelial‐mesenchymal transition (MMT/EMT) and fibrosis; these effects eventually result in ultrafiltration failure and the discontinuation of PD. MicroRNA‐302c (miR‐302c) is believed to be involved in regulating tumour cell growth and metastasis by suppressing MMT, but the effect of miR‐302c on MMT in the context of PD is unknown. MiR‐302c levels were measured in mesothelial cells isolated from the PD effluents of continuous ambulatory peritoneal dialysis patients. After miR‐302c overexpression using lentivirus, human peritoneal mesothelial cell line (HMrSV5) and PD mouse peritoneum were treated with TGF‐β1 or high glucose peritoneal dialysate respectively. MiR‐302c expression level and MMT‐related factors alteration were observed. In addition, fibrosis of PD mouse peritoneum was alleviated by miR‐302c overexpression. Furthermore, the expression of connective tissue growth factor (CTGF) was negatively related by miR‐302c, and LV‐miR‐302c reversed the up‐regulation of CTGF induced by TGF‐β1. These data suggest that there is a novel TGF‐β1/miR‐302c/CTGF pathway that plays a significant role in the process of MMT and fibrosis during PD. MiR‐302c might be a potential biomarker for peritoneal fibrosis and a novel therapeutic target for protection against peritoneal fibrosis in PD patients.