Peritoneal Dialysis Fluid Research Articles

Change in Vancomycin Absorption after Intraperitoneal Injection and Correlation between Intraperitoneal Vancomycin Absorption and Peritoneal Equilibration Test Score in Mice with Peritoneal Injuries

Peritonitis is a serious complication in peritoneal dialysis patients and requires antibiotic administration. Intraperitoneal vancomycin is an empiric therapy for peritonitis caused by Gram-positive cocci; however, there is no way to predict vancomycin absorption after intraperitoneal administration. Therefore, we aimed to evaluate the changes in vancomycin absorption after intraperitoneal injection into mice with chlorhexidine gluconate (CG) induced peritoneal injuries. Additionally, we examined the correlation between intraperitoneal vancomycin absorption and peritoneal equilibration test (PET) score. PET score was determined using glucose concentration in the peritoneal dialysis fluid at each dwell time (Dt) and D2 (2 h of dwell time)/D0 (0 h of dwell time) glucose ratio. Vancomycin was injected into the peritoneal cavity of mice, blood was collected after 1-8 h, and peritoneal fluid was recovered. The residual ratio of intraperitoneal vancomycin was significantly decreased in the CG group at all time points compared to that in the vehicle group. CG group significantly exhibited higher serum vancomycin concentrations than the vehicle group, and the maximum serum concentration increased depending on CG concentration, with 0.05 and 0.1% CG groups showing 3.9- and 6.1-times higher vancomycin concentrations, respectively, than the vehicle group. A significant correlation was observed between the Dt/D0 glucose ratios and residual vancomycin ratios in the peritoneal fluid 2 or 6 h after intraperitoneal injection. A good correlation was observed between the D2/D0 glucose and residual vancomycin ratios 6 h after intraperitoneal vancomycin injection. Thus, PET score can predict residual intraperitoneal vancomycin, aiding in dosing decisions.

Peritoneal dialysis-associated peritonitis caused by Coxiella Burnetii: A case report.

Peritoneal dialysis (PD)-associated peritonitis (PDAP) is the leading cause of PD failure and discontinuation of PD. Several zoonotic pathogens could lead to the development of PDAP. Coxiella burnetii (C. burnetii) was a zoonotic pathogen and the cause of Q fever. However, reports of PDAP caused by C. burnetii are rare. We herein report the first case of PDAP caused by C. burnetii in mainland China. A 45-year-old woman was admitted to our hospital with chief complaint of yellow and cloudy PD effluent for 2 days. She had undergone PD for 5 years due to end-stage renal disease. She was engaged in cattle and sheep breeding. The culture of PD effluent was negative, even for specific species, such as Mycobacteria and fungi. The culture from the PD effluent tested positive for C. burnetii by adopting metagenomic next-generation sequencing on day 37. We diagnosed her as PDAP caused by C. burnetii. Empirical treatment with multiple broad-spectrum antibiotics (including vancomycin, etimicin, piperacillin) was initially adopted. After identifying C. burnetii as the culprint as the PDAP, the regimen was changed to doxycycline (100 mg twice daily) and moxifloxacin (400 mg once daily) orally, leading to clinical improvement. The white blood cell count of the PD effluent decreased to within the normal range and the culture of PD effluent was negative for C. burnetii at the visit of 4 months after discharge. Also, there was no sign for recurrence. Vigilance should be heightened for PDAP cases with negative culture of PD fluid and poor response to standard broad-spectrum antibiotic treatment, along with a history of cattle and sheep breeding. In such conditions, PD effluent should be tested to detect possible peritonitis caused by C. burnetii, even in patients without symptoms of fever. Prompt pathogen identification and appropriate treatment are crucial for clinical improvement of such cases.

Improvement of lactic acidosis in pyruvate dehydrogenase complex deficiency using custom-made amino acid-based dialysate for peritoneal dialysis.

This case report presents a newborn with pyruvate dehydrogenase complex deficiency who developed significant lactic acidosis and acute kidney injury after birth. Peritoneal dialysis with glucose-based peritoneal dialysis fluid was initially started, but the patient had worsening hyperglycemia and lactic acidosis, likely related to excess glucose reabsorption with shunting to lactate due to the underlying metabolic disorder. As amino acid-based dialysis solution was not available in our formulary, a dialysis fluid was manually created with Vaminolact, which was commonly used in neonatal parenteral nutrition. Switching to the new dialysis fluid led to significant biochemical improvement.

Peritoneal dialysis fluid promotes the permeability in peritoneal vascular endothelial cells not through caveolae/caveolin‐1‐mediated endocytosis

AbstractIntroductionTo clarify the expression of caveolin‐1 in human peritoneal vascular endothelial cells (HUM‐CELL‐0116) and investigate whether peritoneal dialysis fluid (PDF) can promote the permeability through caveolae/caveolin‐1‐mediated endocytosis.MethodsHUM‐CELL‐0116 were passaged and divided into the following groups: control group, PDF group, Filipin group, DMSO group, and caveolin‐1 antibody group. The cells were cultured for 0, 4, 12, 24, and 48 h. Then, we detected the permeability of monolayer cells and the expression of caveolin‐1.Results(1) Expression of caveolin‐1: In the PDF group, Filipin group, and caveolin‐1 antibody group, the expression decreases after intervention. (2) Monolayer cell permeability: After culture, the permeability of monolayer cells in the PDF group, Filipin group, and caveolin‐1 antibody group was significantly higher than that in the control group.ConclusionCaveolae/caveolin‐1‐mediated endocytosis may exist in these cells. PDF can increase the permeability of HUM‐CELL‐0116 and albumin loss, but not through caveolae/caveolin‐1‐mediated endocytosis.

Danshen Injection inhibits peritoneal dialysis fluid-induced endothelial-mesenchymal transition in HMrSV5 cells by regulating the TGF-β/Smad signaling pathway

To investigate the inhibitory effect of Danshen Injection on endothelial-mesenchymal transition (EndMT) induced by peritoneal dialysis fluid in HMrSV5 cells and the role of the TGF‑β/Smad signaling pathway in mediating this effect. HMrSV5 cells cultured in 40% peritoneal dialysis solution for 72 h to induce EndMT were treated with 0.05%, 0.1% and 0.5% Danshen Injection. CCK-8 assay was used to assess the changes in viability of the treated cells, and the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and vascular endothelial growth factor (VEGF) in the cell supernatant were detected using ELISA; Western blotting was performed to detect the protein expressions of E-cadherin, α-smooth muscle actin (α-SMA), p-Smad 2/3, and Smad 7 in the cells. Culture in 40% peritoneal dialysis fluid for 72 induced significant EndMT in HMrSV5 cells, which exhibited obviously lowered cell viability. Danshen Injection within the concentration range of 0.025%-1.5% did not significantly affect the viability of the cells. Exposure of HMrSV5 cells to peritoneal dialysis fluid for 72 h significantly increased the production of IL-6, TNF‑α, TGF‑β and VEGF, upregulated the protein expressions of α‑SMA and p-Smad 2/3, and lowered the expressions of E-cadherin and Smad7 proteins. Treatment of the exposed cells with Danshen injection significantly increased cell viability and cellular expressions of E-cadherin and Smad 7 proteins and reduced the production of IL-6, TNF-α, TGF-β and VEGF and the protein expressions of α‑SMA and p-Smad 2/3. Danshen Injection can suppress peritoneal dialysis fluid-induced EndMT in HMrSV5 cells possibly by regulating the TGF-β/Smad signaling pathway.

Improving peritoneal dialysis fluid culture-positivity yield from 2022 to 2023.

Microbiological testing of peritoneal dialysis bags for peritonitis often yields culture-negative results. Culture-negative samples should not exceed > 15% according to the International Society for Peritoneal Dialysis. To reduce this issue, the addition of a blood culture bottle incubation step to the culture process was introduced at the Infection Control Services Laboratory (ICSL) of the National Health Laboratory Services (NHLS). The aim of the study was to ascertain if the change in methodology increased the culture-positivity yield and reduced the culture-negative percentage. Data from the NHLS Central Data Warehouse (CDW) were analysed to compare the culture-positive results over two periods: June-December 2022 when the non-blood culture (B/C) bottle method was used and January-July 2023 when the B/C bottle method was implemented. The non-B/C culture method yielded a 23% culture-positivity yield, whereas the B/C bottle-based method yielded a 51% culture-positivity yield. However, the culture-negative yield for the B/C bottle-based method was high at 49%. The change in dialysis bag processing in 2023 led to a more than doubling in culture-positivity yield. However, the culture-negative percentage remained high. As a result, further modifications to the methodology are needed. The study findings illustrate that the addition of the B/C bottle incubation step significantly improved peritoneal dialysis bag culture yields which directly impacts patient management.

Delaying treatment for peritonitis could be related to longer hospitalization in patients on peritoneal dialysis

Abstract Background When peritoneal dialysis (PD)-related peritonitis occurs in PD patients, diagnostic and therapeutic approaches should be started as soon as possible. However, medical attention may be delayed in patients experiencing minimal symptoms with cloudy PD fluid (PDF). This study investigated differences between the first and later episodes of peritonitis and relationships between interval from peritonitis onset to attending hospital and both duration of hospitalization and medical expenses. Methods We retrospectively investigated 36 patients with multiple episodes of PD-related peritonitis among 125 patients receiving PD therapy from January 2016 during a 6-year period at a single center. Results In 50 episodes of PD-related peritonitis among outpatients, median interval from recognition of cloudy PDF to hospital visit was 4.0 h (interquartile range [IQR] 2.0–12.0 h). With the first episode of peritonitis, the median interval was 8.5 h (IQR 3.6–18.0 h), improving to 2.0 h (IQR2.0–3.3 h) with second and subsequent episodes of peritonitis after patients were provided with education in PD-related issues. Median duration of hospitalization associated with PD-related peritonitis was 16.0 days (IQR 14–22 days) when the interval to hospital visit was < 6 h, significantly shorter than the 20 days (IQR 16–39 days) when the interval from the patient recognizing peritonitis to hospital visit was ≥ 6 h. Conclusions Our results suggest that delaying the hospital visit might lead to longer duration of hospitalization, suggesting that effective educational approaches might be warranted to change behaviors during initial peritonitis.

The future of peritoneal dialysis.

Peritoneal dialysis (PD), long established as the leading form of home dialysis, has comparatively good 5-year outcomes and cost-utility analyses have consistently demonstrated benefits to both patients and payers. Future improvements should still be sought, such as the further development of promising technologies designed to limit PD-associated harm, but given the physical and anatomical constraints of PD, these are unlikely to be transformational through the dialysis process itself. Rather, future focus should be on interventions that are effective across the whole dialysis population, such as mitigating the rate of loss in residual kidney function, pharmacological interventions for symptoms of kidney failure and suppressing inflammation. The greatest future challenge for the modality is inequity of access. In Europe, variation in PD uptake is >10-fold across the continent, with several contributing factors: differing economic drivers, variation in the empowerment of patients, physician attitudes and bias, small centre size, lack of experience, a nursing staff crisis, poor organizational culture and a lack of motivation and educational opportunities. It is time for a collective effort to address this and recently EuroPD convened a policy forum to initiate a multistakeholder approach to the problem, which extends to home haemodialysis. Use of PD worldwide is also highly variable, for some of the same reasons listed above, but with the additional challenges of the high cost of PD fluid and the lack of universal healthcare coverage. In the future, PD could and should play an important part in providing equitable access to dialysis worldwide, but to achieve this-and for the sake of the planet-point-of-care dialysis fluid generation would be transformative.

Impact of Peritoneal Neutrophil Extracellular Traps on Peritoneal Characteristics and Technical Failure in Patients Undergoing Peritoneal Dialysis

Introduction: Peritoneal dialysis (PD) is an effective home therapy for end-stage kidney disease. However, continuous exposure to PD fluids with high glucose concentration and recurrent peritonitis may lead to the activation of cellular and molecular processes of peritoneal damage, including inflammation and fibrosis. In particular, recent studies have highlighted the role of neutrophils in chronic inflammation. This study explores how neutrophil extracellular traps (NETs) affect peritoneal membrane function and contribute to technical failures in PD patients. Methods: We conducted a prospective observational study involving 250 noninfectious and 30 acute peritonitis patients. NETs were measured using nucleosome and myeloperoxidase DNA levels in PD fluids. Monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-8 (MMP-8) were also measured to assess peritoneal inflammation and damage. Results: A significant increase in peritoneal NETs, as determined by nucleosome and myeloperoxidase DNA levels, was observed in patients with acute peritonitis compared to patients without peritonitis. Even in noninfectious samples, NET levels were widely distributed and closely correlated with levels of MCP-1 and MMP-8. Higher levels of peritoneal NETs were closely associated with increased 4-h dialyzate/peritoneal (D/P) creatinine ratio and 1-h D/P sodium levels, indicating a higher prevalence of fast transport and limited free water transport. These factors were associated with a higher risk of technical failure. During a mean follow-up of 34 months, 39.2% (98 patients) switched from PD to hemodialysis, with higher NET levels significantly increasing the risk by 1.9 times (95% confidence interval: 1.27–2.83, p = 0.020). Conclusion: This study suggests the importance of peritoneal NETs not only as markers of acute inflammation but also as significant immunological predictors of chronic peritoneal membrane inflammation and dysfunction and as potential risk factors for technical failure.

Genomic characteristics of antimicrobial resistance and virulence factors of carbapenem-resistant Stutzerimonas nitrititolerans isolated from the clinical specimen

BackgroundStutzerimonas nitrititolerans (S. nitrititolerans) is a rare human pathogenic bacterium and has been inadequately explored at the genomic level. Here, we report the first case of carbapenem-resistant S. nitrititolerans isolated from the peritoneal dialysis fluid of a patient with chronic renal failure. This study analyzed the genomic features, antimicrobial resistance, and virulence factors of the isolated strain through whole genome sequencing (WGS).MethodsThe bacterial isolate from the peritoneal dialysis fluid was named PDI170223, and preliminary identification was conducted through Matrix-assisted laser desorption ionization/time of flight mass spectrometry (MALDI-TOF MS). WGS of the strain PDI170223 was performed using the Illumina platform, and a phylogenetic tree was constructed based on the 16S rRNA gene sequences. Antimicrobial susceptibility test (AST) was conducted using the TDR-200B2 automatic bacteria identification/drug sensitivity tester.ResultsS. nitrititolerans may emerge as a human pathogen due to its numerous virulence genes, including those encoding toxins, and those involved in flagellum and biofilm formation. The AST results revealed that the strain is multidrug- and carbapenem-resistant. The antimicrobial resistance genes of S. nitrititolerans are complex and diverse, including efflux pump genes and β⁃lactam resistance genes.ConclusionThe analysis of virulence factors and antimicrobial resistance of S. nitrititolerans provides clinical insight into the pathogenicity and potential risks of this bacterium. It is crucial to explore the mechanisms through which S. nitrititolerans causes diseases and maintains its antimicrobial resistance, thereby contributing to development of effective treatment and prevention strategies.

Linking clinical manifestations and causative organisms may provide clues for the treatment of peritoneal dialysis-associated peritonitis

IntroductionDifferent initial manifestations of peritoneal dialysis-associated peritonitis (PDAP) may depend on the type of pathogenic organism. We investigated the association between the clinical characteristics of PDAP and susceptibility to vancomycin and investigated the possibility of using vancomycin monotherapy alone as an initial treatment regimen for some PDAP patients to avoid unnecessary antibiotic exposure and secondary infection.MethodsPatients with culture-positive PDAP were retrospectively analyzed and divided into two groups: peritonitis with only cloudy effluent (PDAP-cloudy) or with cloudy effluent, abdominal pain and/or fever (PDAP-multi). The bacterial culture of PD effluent and antibiotic sensitivity test results were compared between groups. Logistic regression was used to investigate factors predicting susceptibility to vancomycin.ResultsOf 162 episodes of peritonitis which had a positive bacterial culture of PD fluid, 30 peritonitis were in the PDAP-cloudy group, and 132 peritonitis were in the PDAP-multi group. Thirty (100%) peritonitis in the PDAP-cloudy group had gram-positive bacterial infections, which was significantly greater than that in the PDAP-multi group (51.5%) (P < 0.001). Twenty-nine (96.7%) peritonitis in the PDAP-cloudy group were susceptible to vancomycin, compared to 67 (50.8%) in the PDAP-multi group (P < 0.001). The specificity of PDAP-cloudy for vancomycin-sensitive peritonitis was 98.48%. Only one patient (3.3%) in the PDAP-cloudy group experienced vancomycin-resistant peritonitis caused by Enterococcus gallinarum, which could neither be covered by vancomycin nor by the initial antibiotic regimen recommended by the current ISPD guidelines. The presence of only cloudy effluent was an independent predictor of susceptibility to vancomycin according to multivariate analysis (OR = 27.678, 95% CI 3.191-240.103, p = 0.003), in addition to PD effluent WBC counts (OR = 0.988, 95% CI 0.980–0.996, p = 0.004), diabetes mellitus (OR = 3.646, 95% CI 1.580–8.416, p = 0.002), first episode peritonitis (OR = 0.447, 95% CI 0.207–0.962, p = 0.039) and residual renal creatinine clearance (OR = 0.956, 95% CI 0.918–0.995, p = 0.027). Addition of these characteristics increased the AUC to 0.813 (95% CI 0.0.749–0.878, P < 0.001). The specificity of presenting with only cloudy effluent for vancomycin-sensitive peritonitis was 98.48%.ConclusionsCloudy dialysate, as the only symptom at PDAP onset, was an independent predictor of vancomycin-sensitive PDAP, which is an important new insight that may guide the choice of initial antibiotic treatment.

Pantoea peritonitis in peritoneal dialysis: a report of two cases and literature review

BackgroundPantoea spp., a non-encapsulated, non-spore-forming Gram-negative rod bacterium that belongs to the Erwiniaceae family, can be found as a colonizer in humans, plants, and the environment, such as water and soil. Although it has the pathogenic potential to cause disease in humans, patients infected with this pathogen generally experience favorable outcomes. In this article, we present two cases of peritoneal dialysis (PD)-associated peritonitis caused by Pantoea spp. along with literature review.Case presentationThe first case is a 66-year-old male patient with end-stage kidney disease (ESKD) on PD, admitted for P. dispersa peritonitis. He presented with abdominal pain and cloudy dialysis effluent, responding well to intraperitoneal vancomycin and cefepime. Antibiotics were deescalated to ceftazidime monotherapy on the basis of antibiotic susceptibility testing. Despite initial recovery with a 3-week course of antibiotics, he developed recurrent peritonitis with P. dispersa, necessitating PD catheter removal and transition to hemodialysis. The second case is a 42-year-old male patient with ESKD on PD who was admitted after 6 days of bloody PD fluid without trauma or associated symptoms. With elevated PD fluid cell counts and positive PD fluid culture showing Streptococcus mitis and P. agglomerans, he was empirically treated for PD-associated peritonitis with intraperitoneal vancomycin and cefepime. Due to a suboptimal response in repeat PD fluid cell counts at day 5, the PD catheter was removed, and he was switched to hemodialysis, followed by a 3-week course of intravenous ceftriaxone.ConclusionsWe described two unique cases of Pantoea peritonitis in PD, recurrent P. dispersa peritonitis and refractory P. agglomerans peritonitis, both of which resulted in PD catheter removal. Our cases indicate the formation of bacterial biofilm as a potential reason for recurrence of infection and underscores the importance of vigilant monitoring and need for PD catheter removal in Pantoea peritonitis.

Glucose-Free Solutions Mediated Inhibition of Oxidative Stress and Oxidative Stress-Related Damages in Peritoneal Dialysis: A Promising Solution.

Oxidative stress (OxSt) and inflammation are common in end-stage renal disease and dialysis patients; they are known risk factors for cardiovascular disease and mortality. In peritoneal dialysis (PD), OxSt and inflammation are even further increased compared to the already increased oxidative stress of their pre-dialysis phase. This is due to the high glucose-based solutions currently used, whose continuous contact with the peritoneal membrane can induce significant long-term morphological and functional changes (mesothelial to mesenchymal transition, thickening, neo-angiogenesis and fibrosis) of the peritoneal membrane. Oxidative stress plays a very important role in these processes, which may compromise the peritoneal dialysis procedure. There is, therefore, the need for more biocompatible dialysis fluids with polymers other than glucose to prevent and treat OxSt and inflammation. The most known and used of such glucose-free and more biocompatible peritoneal dialysis solutions is icodextrin, which has shown a protective effect from oxidative stress. This has supported the consideration of the use of glucose-free-based peritoneal dialysis fluids in order to reduce oxidative stress and improve peritoneal membrane survival. Studies investigating peritoneal dialysis with the use of osmo-metabolic agents (L-carnitine, xylitol and their combination) in peritoneal fluids replacing glucose-based fluids are, in fact, ongoing. They represent a promising strategy to reduce OxSt, preserve the peritoneal membrane's integrity and improve patients' outcome.

Peritoneal-dialysis-associated peritonitis due to Staphylococcus sciuri: a case report and literature review

BackgroundPeritoneal-dialysis-associated peritonitis is a serious complication of peritoneal dialysis; prevention and treatment are crucial to reduce patient morbidity and mortality. Staphylococcus sciuri is an organism that, although present in several animal species, rarely causes disease in humans, particularly in patients undergoing peritoneal dialysis.Case presentationA 54-year-old man with end-stage kidney disease on continuous ambulatory peritoneal dialysis was admitted to the emergency department with nausea, vomiting, slight abdominal distention, and cloudy peritoneal dialysis effluent. Relevant medical history included occupational exposure to different animal species. The white blood cell count in the peritoneal dialysis fluid sample was 11,200 cells/mm3 with 90% polymorphonuclear cells. Peritoneal-dialysis-associated peritonitis was diagnosed. Empirical antibiotic treatment was started according to the International Society for Peritoneal Dialysis guidelines. Staphylococcus sciuri was identified in the peritoneal dialysis effluent culture by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The treatment was modified on the basis of the sensitivity results. Medical cure was established on the basis of the negative result of the dialysate culture and absence of alterations in the cell count with differential after the end of treatment. The patient was instructed to be careful when administering peritoneal dialysis, especially in the care involved in being in contact with animals.ConclusionsThis article highlights the importance of Staphylococcus sciuri as a significant pathogen due to its virulence and antibiotic resistance, especially in patients undergoing peritoneal dialysis. Prevention strategies as well as timely diagnosis and treatment compliance according to the International Society for Peritoneal Dialysis are essential for successful outcomes.

LCZ696, an angiotensin receptor-neprilysin inhibitor, ameliorates epithelial-mesenchymal transition of peritoneal mesothelial cells and M2 macrophage polarization

Aims To investigate the effects and mechanisms of LCZ696, an angiotensin receptor-neprilysin inhibitor (ARNI), on epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells and on macrophage M2 polarization. Methods We examined the effects of LCZ696 in a 4.25% high glucose peritoneal dialysis fluid (PDF)-induced peritoneal fibrosis (PF) mouse model, and explored the mechanisms of LCZ696 on human peritoneal mesothelial cells (HPMCs) stimulated by TGF-β1 (5 ng/mL) and on Raw264.7 cells stimulated by IL-4 (10 ng/mL). To further elucidate the mechanism, we treated HPMCs with the conditioned medium of Raw264.7 cells. Results LCZ696 effectively improved PF and inhibited the process of EMT in PDF mice. In vitro, LCZ696 also significantly alleviated the EMT of TGF-β1 induced HPMCs, although there was no statistically significant difference when compared to the Valsartan treatment group. Moreover, LCZ696 ameliorates the increased expression of Snail and Slug, two nuclear transcription factors that drive the EMT. Mechanistically, TGF-β1 increased the expression of TGFβRI, p-Smad3, p-PDGFRβ and p-EGFR, while treatment with LCZ696 abrogated the activation of TGF-β/Smad3, PDGFRβ and EGFR signaling pathways. Additionally, exposure of Raw264.7 to IL-4 results in increasing expression of Arginase-1, CD163 and p-STAT6. Treatment with LCZ696 inhibited IL-4-elicited M2 macrophage polarization by inactivating the STAT6 signaling pathway. Furthermore, we observed that LCZ696 inhibits EMT by blocking TGF-β1 secretion from M2 macrophages. Conclusion Our study demonstrated that LCZ696 improves PF and ameliorates TGF-β1-induced EMT of HPMCs by blocking TGF-β/Smad3, PDGFRβ and EGFR pathways. Meanwhile, LCZ696 also inhibits M2 macrophage polarization by regulating STAT6 pathway.

Pathophysiological Mechanisms of Peritoneal Fibrosis and Peritoneal Membrane Dysfunction in Peritoneal Dialysis.

The characteristic feature of chronic peritoneal damage in peritoneal dialysis (PD) is a decline in ultrafiltration capacity associated with pathological fibrosis and angiogenesis. The pathogenesis of peritoneal fibrosis is attributed to bioincompatible factors of PD fluid and peritonitis. Uremia is associated with peritoneal membrane inflammation that affects fibrosis, neoangiogenesis, and baseline peritoneal membrane function. Net ultrafiltration volume is affected by capillary surface area, vasculopathy, peritoneal fibrosis, and lymphangiogenesis. Many inflammatory cytokines induce fibrogenic growth factors, with crosstalk between macrophages and fibroblasts. Transforming growth factor (TGF)-β and vascular endothelial growth factor (VEGF)-A are the key mediators of fibrosis and angiogenesis, respectively. Bioincompatible factors of PD fluid upregulate TGF-β expression by mesothelial cells that contributes to the development of fibrosis. Angiogenesis and lymphangiogenesis can progress during fibrosis via TGF-β-VEGF-A/C pathways. Complement activation occurs in fungal peritonitis and progresses insidiously during PD. Analyses of the human peritoneal membrane have clarified the mechanisms by which encapsulating peritoneal sclerosis develops. Different effects of dialysates on the peritoneal membrane were also recognized, particularly in terms of vascular damage. Understanding the pathophysiologies of the peritoneal membrane will lead to preservation of peritoneal membrane function and improvements in technical survival, mortality, and quality of life for PD patients.

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.

Enterogenic bacterial peritonitis and delayed chylous ascites associated with overheated peritoneal dialysis fluid infusion.

Enterogenic bacterial peritonitis and delayed chylous ascites associated with overheated peritoneal dialysis fluid infusion.

Detections of Chemicals and Migratory Plastics in Peritoneal Dialysis Fluids.

Peritoneal dialysis (PD) is an important modality of renal replacement therapy (RRT). Peritonitis and ultrafiltration failure are complications that have a long-term impact on PD patients. Besides touch contamination, procedural errors and clinical reasons of peritonitis, contaminants, and constituents of peritoneal dialysis fluids (PDFs) have been implicated in causing peritonitis and ultrafiltration failure. This study was aimed to test the PDFs in India for the presence of migratory plastics. PDFs from the two manufacturers in India were tested using liquid chromatography mass spectrometry (LCMS) and gas chromatography mass spectrometry (GCMS) with headspace analysis (volatile compounds) and pyrolysis of plastics (polymer compounds). The storage conditions and handling were uniform. The results revealed impurities of acetate compounds and aldehyde derivatives of glucose degradation products (GDPs) with contaminants and leachable plastics. There were high levels of GDP derivative in the form of 5-hydroxymethylfurfural compounds (5-HMF). The analysis revealed the presence of plastic softeners in very high concentrations. The study unmasks the presence of chemicals and GDPs that can be implicated in pathogenesis of sterile peritonitis and ultrafiltration failure. The study demonstrated the presence of leachable plastics. In conclusion, LCMS and GCMS studies can be used to test PDFs for unwanted chemicals prior to human use.

Astragalus polysaccharides augment BMSC homing via SDF-1/CXCR4 modulation: a novel approach to counteract peritoneal mesenchymal transformation and fibrosis

PurposeThis study aimed to evaluate the potential of astragalus polysaccharide (APS) pretreatment in enhancing the homing and anti-peritoneal fibrosis capabilities of bone marrow mesenchymal stromal cells (BMSCs) and to elucidate the underlying mechanisms.MethodsForty male Sprague-Dawley rats were allocated into four groups: control, peritoneal dialysis fluid (PDF), PDF + BMSCs, and PDF + APSBMSCs (APS-pre-treated BMSCs). A peritoneal fibrosis model was induced using PDF. Dil-labeled BMSCs were administered intravenously. Post-transplantation, BMSC homing to the peritoneum and pathological alterations were assessed. Stromal cell-derived factor-1 (SDF-1) levels were quantified via enzyme-linked immunosorbent assay (ELISA), while CXCR4 expression in BMSCs was determined using PCR and immunofluorescence. Additionally, a co-culture system involving BMSCs and peritoneal mesothelial cells (PMCs) was established using a Transwell setup to examine the in vitro effects of APS on BMSC migration and therapeutic efficacy, with the CXCR4 inhibitor AMD3100 deployed to dissect the role of the SDF-1/CXCR4 axis and its downstream impacts.ResultsIn vivo and in vitro experiments confirmed that APS pre-treatment notably facilitated the targeted homing of BMSCs to the peritoneal tissue of PDF-treated rats, thereby amplifying their therapeutic impact. PDF exposure markedly increased SDF-1 levels in peritoneal and serum samples, which encouraged the migration of CXCR4-positive BMSCs. Inhibition of the SDF-1/CXCR4 axis through AMD3100 application diminished BMSC migration, consequently attenuating their therapeutic response to peritoneal mesenchyme-to-mesothelial transition (MMT). Furthermore, APS upregulated CXCR4 expression in BMSCs, intensified the activation of the SDF-1/CXCR4 axis’s downstream pathways, and partially reversed the AMD3100-induced effects.ConclusionAPS augments the SDF-1/CXCR4 axis’s downstream pathway activation by increasing CXCR4 expression in BMSCs. This action bolsters the targeted homing of BMSCs to the peritoneal tissue and amplifies their suppressive influence on MMT, thereby improving peritoneal fibrosis.