Toxins In Patients Research Articles

Elevated Urinary Levels of Fungal and Environmental Toxins in Patients with Pancreatic Ductal Adenocarcinoma

BackgroundRisk factors for pancreatic ductal adenocarcinoma (PDAC) include tobacco/alcohol abuse, genetic predisposition, insulin resistance, and pancreatic cysts. Despite these well-established risk factors and the screening of high-risk individuals, some people still develop PDAC. This study aims to explore a potential risk factor for PDAC by investigating the association between fungal toxins (FT) and environmental toxins (ET) and the disease. We predicted that individuals with PDAC would have higher levels of these toxins compared to healthy controls. The rationale behind this hypothesis is that exposure to FT and ET might contribute to the development of PDAC by elevating cancer risk.MethodsA pilot retrospective cohort study was conducted at Moffitt Cancer Center from 2022 to 2023. This study compared FT and ET levels, demographic data, and PDAC features between subjects with PDAC and healthy controls.ResultsForty subjects were enrolled in the study, comprising 20 with pancreatic ductal adenocarcinoma (PDAC) and 20 healthy controls. Baseline demographics were similar between the two groups. Among the PDAC subjects, the most common tumor location was the head of the pancreas (55%); 30% had locally advanced disease, 45% were borderline resectable, and 10% had metastatic disease.Compared to the controls, subjects with PDAC had significantly higher levels of fungal toxins (FTs) including ochratoxin, gliotoxin, and citrinin (p < 0.05). Additionally, PDAC patients had significantly elevated levels of environmental toxins (ETs) such as methyl tert-butyl ether (MTBE), xylene, styrene, acrylonitrile, perchlorate, diphenyl phosphate, bromopropane, organophosphates, acrolein, tiglylglycine, and diethylphosphate (p < 0.05).ConclusionOur study demonstrates that subjects with PDAC, without other risk factors, have higher FT and ET levels than controls. Further studies are needed to evaluate whether ET and FT exposure can be clinically utilized as a risk factor for PDAC development.

Identification of Gut Microbiota Involved in the Production of Uremic Toxins in Patients with CKD

Identification of Gut Microbiota Involved in the Production of Uremic Toxins in Patients with CKD

Impact of the mediterranean diet on dietary fiber intake and serum uremic toxins in patients treated with peritoneal dialysis

Impact of the mediterranean diet on dietary fiber intake and serum uremic toxins in patients treated with peritoneal dialysis

Effects of Propolis Supplementation on Gut Microbiota and Uremic Toxin Profiles of Patients Undergoing Hemodialysis.

Propolis possesses many bioactive compounds that could modulate the gut microbiota and reduce the production of uremic toxins in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). This clinical trial aimed to evaluate the effects of propolis on the gut microbiota profile and uremic toxin plasma levels in HD patients. These are secondary analyses from a previous double-blind, randomized clinical study, with 42 patients divided into two groups: the placebo and propolis group received 400 mg of green propolis extract/day for eight weeks. Indole-3 acetic acid (IAA), indoxyl sulfate (IS), and p-cresyl sulfate (p-CS) plasma levels were evaluated by reversed-phase liquid chromatography, and cytokines were investigated using the multiplex assay (Bio-Plex Magpix®). The fecal microbiota composition was analyzed in a subgroup of patients (n = 6) using a commercial kit for fecal DNA extraction. The V4 region of the 16S rRNA gene was then amplified by the polymerase chain reaction (PCR) using short-read sequencing on the Illumina NovaSeq PE250 platform in a subgroup. Forty-one patients completed the study, 20 in the placebo group and 21 in the propolis group. There was a positive correlation between IAA and TNF-α (r = 0.53, p = 0.01), IL-2 (r = 0.66, p = 0.002), and between pCS and IL-7 (r = 0.46, p = 0.04) at the baseline. No significant changes were observed in the values of uremic toxins after the intervention. Despite not being significant, microbial evenness and observed richness increased following the propolis intervention. Counts of the Fusobacteria species showed a positive correlation with IS, while counts of Firmicutes, Lentisphaerae, and Proteobacteria phyla were negatively correlated with IS. Two months of propolis supplementation did not reduce the plasma levels of uremic toxins (IAA, IS, and p-CS) or change the fecal microbiota.

Changes in the composition of the gut microbiota and content of microbial-derived uremic toxins in patients undergoing hemodialysis

Recent data highlight a significant role of the gut microbiota in the pathogenesis of chronic kidney disease, particularly in its terminal stage. However, little is known about the features of intestinal dysbiosis in people undergoing programed hemodialysis. Changes in the intestinal microbiota and blood levels of uremic toxins of microbial origin in patients with terminal renal insufficiency receiving hemodialysis were analyzed. This cross-sectional study included 80 patients receiving hemodialysis and 20 individuals with normal kidney function. The state of the microbiocenosis of the colon was studied using a polymerase chain reaction with a commercial set Colonoflor 16 (premium) manufactured by Alfalab (Russia). Serum levels of trimethylamine and its metabolite trimethylamine-N-oxide were determined by liquid chromatography/mass spectrometry. The concentrations of indoxyl sulfate and p-cresyl sulfate were evaluated by enzyme immunoassay according to the instructions of a commercial kit. In patients undergoing programed hemodialysis, increased colonization of enterococci was combined with the reduction of lacto and bifidophlora, E. coli, ruminococci, bacteria producing short-chain fatty acids (Faecalibacterium prausnitzii, Eubacterium rectale, Roseburia inulinivorans, and Blautia spp.) and microorganisms involved in maintaining the integrity of the intestinal barrier (Bacteroides thetaomicron and Akkermansia muciniphila). In addition, high titer levels of representatives of opportunistic and even pathogenic flora were often found in this group. Intestinal dysbiosis in patients undergoing programed hemodialysis was accompanied by a significant increase in the concentration of uremic toxins in the blood. Compared with individuals with normal renal function, the trimethylamine level in patients undergoing programed hemodialysis was increased 22 times; trimethylamine-N-oxide, 23 times; indoxyl sulfate, 21 times; and p-cresyl sulfate, 5 times. Thus, patients receiving hemodialysis exhibited pronounced pathological changes in intestinal microbiocenosis, accompanied by a significant increase in serum levels of uremic toxins of microbial origin.

Design and rationale for an open-label, randomized, controlled pilot trial to evaluate the changes in blood uremic toxins in patients with chronic kidney disease by dietary therapy with sake lees

BackgroundPatients with chronic kidney disease (CKD) reportedly show dysbiosis, which is the imbalance of gut microbiome. Dysbiosis increases the uremic toxin level in the intestine, and uremic toxins transfer into the blood, causing CKD progression. Sake lees, a traditional Japanese fermented food, may help reduce uremic toxins by altering the gut microbiome. Additionally, D-alanine, which is present in sake lees, may have a renoprotective effect. The present pilot study aims to evaluate the effect of adding sake lees to the standard CKD dietary therapy in reducing blood uremic toxins.MethodsThis pilot study is a single-center, open-label, randomized controlled trial. Twenty-four patients with CKD will be enrolled and allocated 1:1 to the intervention and control groups. The intervention group will receive standard CKD dietary therapy with an additional intake of 50 g of sake lees per day for 8 weeks, whereas the control group will only receive standard CKD dietary therapy. The primary endpoint is the change in serum indoxyl sulfate after 8 weeks. The secondary endpoint is the plasma D-alanine and fecal microbiome changes.ConclusionThis pilot study provides insight into the development of a new diet focused on gut microbiome and D-amino acids in patients with CKD.Clinical trial registrationThis protocol was approved by the Clinical Trial Review Board of Kanazawa University Hospital on October 27, 2022 (2022-001 [6139]) and available to the public on the website of the Japan Registry of Clinical Trials on November 22, 2022 (jRCT1040220095).

Pruritus and protein-bound uremic toxins in patients undergoing hemodialysis: a cross-sectional study.

Patients undergoing hemodialysis frequently experience pruritus; its severity is associated with poor quality of life and mortality. Recent progress in hemodialysis treatment has improved the removal of small- and middle-molecular-weight molecules; however, the removal of protein-bound uremic toxins (PBUTs) remains difficult. It is possible that pruritus is associated with serum PBUTs in patients undergoing hemodialysis. We conducted a multicenter cross-sectional study in patients undergoing hemodialysis (n=135). The severity of pruritus was assessed using the 5D-itch scale and medication use. Serum PBUTs, including indoxyl sulfate, p-cresyl sulfate, indole acetic acid, phenyl sulfate, and hippuric acid, were measured using mass spectrometry; the PBUT score was calculated from these toxins using principal component analysis. Univariate and multiple regression analyses were performed to examine independent predictors of pruritus. Pruritus was reported by 62.2%, 21.5%, and 13.3%, 1.5% and 0.7% as 5 (not at all), 6-10, 11-15, 16-20, and 21-25 points, respectively. The PBUT score was higher in patients undergoing dialysis having pruritus than those without pruritus (0.201 [-0.021 to 0.424] vs -0.120 [-0.326 to 0.087]; P=0.046). The PBUT score was shown to have an association with the presence of pruritus (coefficient 0.498[Formula: see text]0.225, odds ratio: 1.65 [1.06-2.56]; P=0.027). Uremic pruritus was frequently found and associated with the PBUT score in patients undergoing hemodialysis. Further studies are required to clarify the impact of PBUTs on uremic pruritus and to explore therapeutic strategies in patients undergoing hemodialysis.

Metagenome-wide analysis uncovers gut microbial signatures and implicates taxon-specific functions in end-stage renal disease

BackgroundThe gut microbiota plays a crucial role in regulating host metabolism and producing uremic toxins in patients with end-stage renal disease (ESRD). Our objective is to advance toward a holistic understanding of the gut ecosystem and its functional capacity in such patients, which is still lacking.ResultsHerein, we explore the gut microbiome of 378 hemodialytic ESRD patients and 290 healthy volunteers from two independent cohorts via deep metagenomic sequencing and metagenome-assembled-genome-based characterization of their feces. Our findings reveal fundamental alterations in the ESRD microbiome, characterized by a panel of 348 differentially abundant species, including ESRD-elevated representatives of Blautia spp., Dorea spp., and Eggerthellaceae, and ESRD-depleted Prevotella and Roseburia species. Through functional annotation of the ESRD-associated species, we uncover various taxon-specific functions linked to the disease, such as antimicrobial resistance, aromatic compound degradation, and biosynthesis of small bioactive molecules. Additionally, we show that the gut microbial composition can be utilized to predict serum uremic toxin concentrations, and based on this, we identify the key toxin-contributing species. Furthermore, our investigation extended to 47 additional non-dialyzed chronic kidney disease (CKD) patients, revealing a significant correlation between the abundance of ESRD-associated microbial signatures and CKD progression.ConclusionThis study delineates the taxonomic and functional landscapes and biomarkers of the ESRD microbiome. Understanding the role of gut microbiota in ESRD could open new avenues for therapeutic interventions and personalized treatment approaches in patients with this condition.

Biobased chitosan-derived self-nitrogen-doped porous carbon nanofibers containing nitrogen-doped zeolites for efficient removal of uremic toxins during hemodialysis

Highly efficient adsorbents are needed to remove uremic toxins and reduce the economic and societal burden of the current dialysis treatments in resource-limited environments. In this study, nanostructured porous carbon nanofibers with nitrogen-doped zeolites (NZ-PCNF) were prepared, by electrospinning zeolites with chitosan-poly(ethylene oxide) blends, followed by a one-step carbonization process, without further activation steps or aggressive chemical additives for N-doping. The results showed that N-zeolites were successfully integrated into an ultrafine carbon nanofiber network, with a uniform nanofiber diameter of approximately 25 nm, hierarchical porous structure (micro- and mesopores), and high specific surface area (639.29 m2/g), facilitating uremic toxin diffusion and adsorption. The self-N-doped structure in the NZ-PCNF removed more creatinine (∼1.8 times) than the porous carbon nanofibers when using the same weight of precursor materials. Cytotoxicity and hemolysis tests were performed to verify the safety of NZ-PCNF. This study provides a novel strategy for transforming chitosan-based materials into state-of-the-art porous carbon nanofiber/zeolite self-N-doped composites, affording an efficient bioderived adsorbent for the removal of uremic toxins in patients with chronic kidney disease.

Immunosenescence and Immune Exhaustion Are Associated with Levels of Protein-Bound Uremic Toxins in Patients on Hemodialysis.

The accumulation of protein-bound uremic toxins (PBUTs) in chronic kidney disease may affect patients' immune status. The aim of the study was to evaluate their potential impacts on lymphocyte alterations in patients on hemodialysis (HD). The plasma levels of PBUTs were assessed in 54 patients on HD and 31 healthy individuals, using ultra-performance liquid chromatography. The results correlated with the senescent and exhausted status of lymphocytes, based on certain surface molecules, analyzed by flow cytometry. The plasma levels of PBUTs were significantly increased in the patients on HD compared with the healthy controls. The patients with residual kidney function had reduced hippuric acid (HA) levels, total (p = 0.03) and free (p = 0.04), and free IxS levels (p = 0.02). The total and free HA levels correlated negatively with less differentiated subpopulations, CD4+CD45RA+CD31+ (p = 0.037 and p = 0.027), CD8+CD28+CD57- (p = 0.01, p = 0.01), and naïve B cells (CD19+IgD+CD27-) (p = 0.04, p = 0.03). Both the total and the free pCS levels correlated positively with exhausted CD4 cells, p = 0.02 and p = 0.01, respectively. A multivariate analysis showed that IxS and age were the main independent parameters implicated in the reduction intotal CD4 and B lymphocytes and their naïve and early differentiated subsets. Increased PBUTs levels are associated with immune disturbances of patients on HD, HA, and IxS in the immunosenescent and pCS in the immunoexhaustion alterations.

Comparison of the medium cutoff dialyzer and postdilution hemodiafiltration on the removal of small and middle molecule uremic toxins.

The medium cutoff (MCO) dialyzer increases the removal of several middle molecules more effectively than high-flux hemodialysis (HD). However, comparative data addressing the efficacy and safety of MCO dialyzers vs. postdilution hemodiafiltration (HDF) in Korean patients are lacking. Nine patients with chronic HD were included in this pre-post study. Patients underwent HD with an MCO dialyzer for 4 weeks, followed by a 2-week washout period using a high-flux dialyzer to minimize carryover effects, and then turned over to postdilution HDF for 4 weeks. Reduction ratios and differences in the uremic toxins before and after dialysis were calculated from the MCO dialysis, postdilution HDF, and high-flux HD. In the in vitro study, EA.hy926 cells were incubated with dialyzed serum. Compared to postdilution HDF, the MCO dialyzer achieved significantly higher reduction ratios for larger middle molecules (myoglobin, kappa free light chain [κFLC], and lambda FLC [λFLC]). Similarly, the differences in myoglobin, κFLC, and λFLC concentrations before and after the last dialysis session were significantly greater in MCO dialysis than in postdilution HDF. The expression of Bax and nuclear factor κB was decreased in the serum after dialysis with the MCO dialyzer than with HDF. Compared with high-volume postdilution HDF, MCO dialysis did not provide greater removal of molecules below 12,000 Da, whereas it was superior in the removal of larger uremic middle molecule toxins in patients with kidney failure. Moreover, these results may be expected to have an anti-apoptotic effect on the human endothelium.

Effect of Low Protein Diet Supplemented with Ketoanalogs on Endothelial Function and Protein-Bound Uremic Toxins in Patients with Chronic Kidney Disease.

Studies have demonstrated that a low-protein diet supplemented with ketoanalogs (KAs) could significantly retard progression of renal function in patients with chronic kidney disease (CKD) stages 3-5. However, its effects on endothelial function and serum levels of protein-bound uremic toxins remain elusive. Therefore, this study explored whether a low-protein diet (LPD) supplemented with KAs affects kidney function, endothelial function, and serum uremic toxin levels in a CKD-based cohort. In this retrospective cohort, we enrolled 22 stable CKD stage 3b-4 patients on LPD (0.6-0.8 g/day). Patients were categorized into control (LPD only) and study groups (LPD + KAs 6 tab/day). Serum biochemistry, total/free indoxyl sulfate (TIS/FIS), total/free p-cresyl sulfate (TPCS/FPCS), and flow-mediated dilation (FMD) were measured before and after 6 months of KA supplementation. Before the trial, there were no significant differences in kidney function, FMD, or uremic toxin levels between the control and study groups. When compared with the control group, the paired t-test showed a significant decrease in TIS and FIS (all p < 0.05) and a significant increase in FMD, eGFR, and bicarbonate (all p < 0.05). In multivariate regression analysis, an increase in FMD (p < 0.001) and a decrease in FPCS (p = 0.012) and TIS (p < 0.001) remained persistent findings when adjusted for age, systolic blood pressure (SBP), sodium, albumin, and diastolic blood pressure (DBP). LPD supplemented with KAs significantly preserves kidney function and provides additional benefits on endothelial function and protein-bound uremic toxins in patients with CKD.

Proton-Pump Inhibitors and Serum Concentrations of Uremic Toxins in Patients with Chronic Kidney Disease.

Use of proton-pump inhibitors (PPIs) is common in patients with chronic kidney disease (CKD). PPIs and many uremic toxins (UTs) are eliminated by the kidney's tubular organic anion transporter system. In a cross-sectional study, we sought to evaluate the association between PPI prescription and serum concentrations of various UTs. We studied a randomly selected sub-group of participants in the CKD-REIN cohort (adult patients with a confirmed diagnosis of CKD and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) with available frozen samples collected at baseline. PPI prescription was recorded at baseline. Serum concentrations of 10 UTs were measured using a validated liquid chromatography tandem mass spectrometry technique. Multiple linear regression was performed, with the log UT concentration as the dependent variable. Of the 680 included patients (median age: 68 years; median eGFR: 32 mL/min/1.73 m2), 31% had PPI prescriptions at baseline. Patients using PPIs had higher levels of certain UTs in comparison to other patients, including total and free indoxyl sulfate (IS), total and free p-cresylsulfate, total and free p-cresylglucuronide (PCG), phenylacetylglutamine (PAG), free kynurenine, and free hippuric acid. After adjustment for baseline co-morbidities, number of co-prescribed drugs, and laboratory data, including eGFR, associations between PPI prescription and elevated serum concentrations of free and total IS, free and total PCG, and PAG remained significant. Our results indicate that PPI prescription is independently associated with serum UT retention. These findings are interesting to better understand the factors that may modulate serum UT concentration in CKD patients, however, they will need to be confirmed by longitudinal studies.

Adsorption resin/polyethersulfone membrane used for plasma separation and middle molecular toxins adsorption

Accumulation of endogenous and exogenous toxins in patients with chronic kidney disease increases the kidney burden. The newly developed plasma separation adsorption membranes provide a new model for the removal of middle molecular toxins. In this study, the adsorption resin LX-1000H is physically pulverized and blended into polyethersulfone matrixes to prepare adsorption resin/polyethersulfone (AR/PES) membranes by nonsolvent-induced phase separation for plasma separation and middle molecular toxins absorption. The results show that the static adsorption capacity of AR/PES membrane for lysozyme (a typical mimic of middle molecular toxins) is up to 108.90 mg/g, which is 4 times that of AR. The maximum dynamic adsorption capacity reaches 102.80 mg/g, which is 93.4% of static adsorption. The adsorption process is more consistent with the Langmuir model and the quasi-first-order kinetic model. The permeability of bovine serum albumin in simulated blood surpasses 90% and the cattle blood separated by AR/PES membrane is colorless and transparent. The AR/PES membrane surface presents electronegative at pH 7.4 and the water wettability is enhanced with the doping amount. No hemolysis and negligible leakage indicated favorable hemocompatibility. This paper is devoted to providing a strategy for plasma separation and adsorption membranes.

Modulasi Mikrobiota untuk Memperbaiki Laju Filtrasi Glomerulus, Toksin Uremik, dan Penanda Inflamasi pada Gagal Ginjal Kronik: Telaah Sistematik dan Meta-Analisis

Introduction. Dysbiosis microbiota is considered as one of the consequences and impacts of high uremic toxins in patients with Chronic Kidney Disease (CKD), which can lead to an increased risk of progression and mortality. The aim of this systematic review and meta-analysis was to perform quantitative effect of microbiota modulation for estimated Glomerular Filtration Rate (eGFR), uremic toxin (total-p cresyl/total pCS), and inflammatory marker (hs-CRP) outcome among CKD patients. Methods. Article searches were conducted from PubMed, ScienceDirect, and Cochrane Library data sources from 2010-2022. Assessment of article quality follows the rules of PRISMA (Preferred Reporting Items in Systematic Review and Meta-Analysis). Only randomized controlled trial (RCT) articles investigating the effect of symbiotic, prebiotic, of probiotic for CKD were included in the analysis. Effect size quantify from Standardized Mean Difference (SMD), using a continuous random effect model and described in the forest plot model. Results. A total of 17 RCT studies with a total 867 CKD stage 1-5 subjects (440 subjects in the intervention group and 427 subjects in the control group). The intervention duration ranging from 1-12 months. The studies included had varied on methodologies, with significant heterogenicity (I296,96%, p Conclusions. The administration of probiotic/prebiotic/symbiotic supplements to CKD patients resulted in significant improvements in e-GFR and reductions in total pCS. These results suggest the potential of symbiotic, prebiotic, and probiotic supplementation to improve CKD outcome.

Expanding the potential therapeutic options of hemoperfusion in the era of improved sorbent biocompatibility.

Hemoperfusion has been considered a promising adjuvant treatment for chronic diseases and some acute states when specific removal of pathogenic factors from the bloodstream is desired. Over the years, advances in adsorption materials (e.g., new synthetic polymers, biomimetic coating, and matrixes with novel structures) have renewed scientific interest and expanded the potential therapeutic indications of hemoperfusion. There is growing evidence to suggest a prominent place for hemoperfusion as an adjuvant treatment in the setting of sepsis or severe coronavirus disease 2019 and as a therapeutic option for chronic complications associated with accumulated uremic toxins in patients with end-stage renal disease. This literature review will describe the principles, therapeutic perspectives, and the emerging role of hemoperfusion as a complementary therapy for patients with kidney disease.

Double Filtration Plasmapheresis with Polyvinyl Alcohol-Based Membrane Lowers Serum Inflammation and Toxins in Patients with Hyperlipidemia.

Hyperlipidemia is increasing in prevalence and is highly correlated with cardiovascular disease (CVD). Lipid-lowering medications prevent CVD but may not be suitable when the side effects are intolerable or hypercholesterolemia is too severe. Double-filtration plasmapheresis (DF) has shown its therapeutic effect on hyperlipidemia, but its side effects are not yet known. We enrolled 45 adults with hyperlipidemia in our study. The sera before and two weeks after DF were evaluated, and we also analyzed perfluorochemicals to see if DF could remove these lipophilic toxins. After DF, all lipid profile components (total cholesterol, triglycerides, high-density lipoprotein [HDL], and low-density lipoprotein [LDL]) had significantly decreased. Leukocyte counts increased while platelet levels decreased, which may have been caused by the puncture wound from DF and consumption of platelets during the process. As for uremic toxins and inflammation, levels of C-reactive protein, uric acid, and alanine transaminase (ALT) all decreased, which may be related to the removal of serum perfluorooctane sulfonate (PFOS) and improvement of renal function. The total cholesterol/HDL ratio and triglycerides were significantly higher in the diabetes mellitus (DM) group at baseline but did not significantly differ after DF. In conclusion, DF showed potential for improving inflammation and removing serum lipids and PFOS in adults with hyperlipidemia.

Assessment of the Influence of Asymmetric Triacetate Cellulose Membrane on the Rate of Removal of Middle Molecular Weight Uremic Toxins in Patients Treated with Postdilution Online Hemodiafiltration

BACKGROUND: Postdilution online hemodiafiltration (OL-HDF) effectively removes uremic toxins of middle molecular weight from the blood of patients with end-stage chronic kidney disease. The rate of removal of uremic toxins depends on the type of dialysis membrane, blood flow rate (Qb), net ultrafiltration flow rate (Qnuf), and total convective volume (Vconv). AIM: The aim of this study was to examine the efficacy of asymmetric triacetate cellulose dialysis membrane in patients on post-dilution OL-HDF. METHODS: Thirty-five patients treated with post-dilution OL-HDF hemodiafiltration for at least 3 months were examined. The main parameters for assessing the efficiency of removal of uremic toxins of middle molecular weight are the concentration of β2-microglobulin (β2-M) and interleukin-6 (IL-6) in serum before and after a single session of post-dilution OL-HDF. The followings were used for statistical analysis: Kolmogorov–Smirnov test, Student’s T test for bound samples and Wilcoxon test. RESULTS: The average Vconv was 20.90 ± 3.30 liters/session. The β2-M reduction index during a single session of postdilution OL-HDF was 71.10 ± 6.39%, the IL-6 reduction index was 43.75 ± 15.60%, and the albumin reduction index was 4.55 ± 2.31%. CONCLUSION: The asymmetric triacetate cellulose dialysis membrane effectively removes β2-M and IL-6 during a single session of postdilution OL-HDF. The β2-M reduction index is ∼70%, the IL-6 reduction index is ∼40%, and albumin loss is &lt;4.0 g/4 h. The examined dialysis membrane and dialysis modality prevent the development of amyloidosis associated with dialysis, microinflammation and reduce the risk of developing atherosclerotic cardiovascular diseases in the population of patients treated with regular hemodiafiltration.

Uremic Encephalopathy.

HomeRadiologyVol. 307, No. 1 PreviousNext Reviews and CommentaryFree AccessImages in RadiologyUremic EncephalopathyDavid A. Lizarazo , Jairo LizarazoDavid A. Lizarazo , Jairo LizarazoAuthor AffiliationsFrom the Department of Diagnostic Imaging, Fundación Santa Fe de Bogotá, Universidad El Bosque, Ave 116 No. 9-02, Bogotá 110246, Colombia (D.A.L.); and Department of Internal Medicine, Hospital Universitario Erasmo Meoz, Universidad de Pamplona, Cúcuta, Colombia (J.L.).Address correspondence to D.A.L. (email: [email protected]).David A. Lizarazo Jairo LizarazoPublished Online:Dec 20 2022https://doi.org/10.1148/radiol.221602MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In A 54-year-old man was admitted for a 3-day history of dysarthria, hand tremors, hypokinesia, and generalized muscle rigidity. His past medical history included diabetes mellitus and end-stage renal disease on hemodialysis. On admission, there were elevated blood urea nitrogen and creatinine levels with a metabolic acidosis. Axial CT scan of the brain showed symmetrical hypoattenuation of both basal ganglia (Figure). Noncontrast brain T2-weighted MRI demonstrated symmetrical high signal intensity in the basal ganglia surrounded by a more hyperintense rim delineating the lentiform nucleus (Figure). This is the lentiform fork sign, wherein the internal and external capsules and the medullary laminae become hyperintense with axial T2-weighted images (Figure). After correction of the metabolic acidosis with prompt dialysis and glycemic control, the neurologic examination returned to normal, and his symptoms completely resolved. A follow-up MRI examination was not performed.Images in a 54-year-old man who presented with a 3-day evolution of dysarthria, hand tremors, hypokinesia, and generalized muscle rigidity. He had diabetes mellitus and end-stage renal disease and was undergoing hemodialysis. Laboratory tests showed azotemia and metabolic acidosis. (A) Axial CT scan of brain shows symmetrical hypoattenuation in the bilateral basal ganglia. (B) Axial T2-weighted fluid-attenuated inversion recovery noncontrast brain MRI scan demonstrates bilateral symmetrical swollen lentiform nuclei with a hyperintense rim delineating the lentiform nucleus with a typical fork-like appearance representing the “lentiform fork sign.” (C) Schematic drawing shows the “lentiform fork sign.” At follow-up after correction of metabolic acidosis with prompt dialysis and glycaemic control, the neurologic examination was normal, and symptoms completely resolved. Follow-up scan was not performed. EC = external capsule, IC = internal capsule, LME = external medullary lamina, LMI = internal medullary lamina, TS = the stem.Download as PowerPointOpen in Image Viewer Uremic encephalopathy is a neurologic complication resulting from endogenous uremic toxins in patients with severe renal failure. The pathogenesis is complex and unclear (1). The lentiform fork sign (Figure) is attributed to metabolic acidosis in patients with diabetes and renal failure with a history of incomplete dialysis leading to reversible basal ganglia and adjacent white matter injury (2). The edematous external capsule represents the lateral arm of the fork, with both the external and internal capsule joining to build the stem of the fork. Edema of the medial lentiform margin forms the medial arm, which splits into two along the medullary laminae to envelop the globus pallidus (3). The lentiform fork sign is nonspecific for uremic encephalopathy. Differential diagnosis of pathologic conditions manifesting with this sign includes severe metabolic acidosis, ketoacidosis, dialysis disequilibrium syndrome, and intoxication (ie, methanol, ethylene glycol); this can also be drug induced (ie, metformin) (4).Disclosures of conflicts of interest: D.A.L. No relevant relationships. J.L. No relevant relationships.

Comparative Evaluation of Luminex xTAG® Gastrointestinal Pathogen Panel and Direct-From-Stool Real-Time PCR for Detection of C. difficile Toxin tcdB in Stool Samples from a Pediatric Population.

Detection of Clostridioides difficile toxins in patients with gastroenteritis has increasingly been accomplished through the use of enteric multiplex syndromic panels. Comparisons of the performance of these panels to both direct-from-stool (DFS) and culture-enriched stools followed by polymerase chain reaction (PCR) methods in pediatric populations are limited. Here, we compare the performance of the Luminex xTAG® Gastrointestinal Pathogen Panel (GPP) to our DFS in-house real-time PCR (DFS RT-PCR) assay for the detection of C. difficile toxin gene, tcdB, using 2641 stool specimens collected from children enrolled in the Alberta Provincial Pediatric EnTeric Infection Team (APPETITE) study in Alberta, Canada. We used culture enrichment followed by in-house RT-PCR to resolve discordant results between the two assays. We found excellent agreement (k = 0.89) between the GPP and our DFS RT-PCR assay: the positive percent agreement between the two assays was 97%, and the negative percent agreement was 99%. GPP, a multi-analyte platform can easily be implemented into a routine diagnostic laboratory for detecting enteric pathogens including C. difficile.