Pilot Study of Probiotic Supplementation on Uremic Toxicity and Inflammatory Cytokines in Chronic Kidney Patients

2020 ◽  
Vol 16 (4) ◽  
pp. 470-480
Author(s):  
Cristina T. Roth-Stefanski ◽  
Carla Dolenga ◽  
Lia S. Nakao ◽  
Roberto Pecoits-Filho ◽  
Thyago P. de Moraes ◽  
...  
Keyword(s):  
Pilot Study ◽  
Inflammatory Cytokines ◽  
Lactobacillus Acidophilus ◽  
Serum Levels ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Bacterial Metabolism ◽  
Probiotic Supplementation ◽  
Primary Endpoints ◽  
Inflammatory Profile

Background: Bacterial metabolism contributes to the generation of uremic toxins in patients with chronic kidney disease (CKD). It has been investigated the use of probiotics in the reduction of uremic toxins intestinal production. Objective: The aim of this pilot study was to evaluate the effect of probiotic supplementation on reducing the production of uremic toxins and the inflammatory profile of CKD patients. Methods: We performed a randomized, blind, placebo-controlled, crossover study on patients with CKD stages 3 and 4. The intervention was a probiotic formulation composed of Lactobacillus acidophilus strains given orally three times a day for 3 months. Changes in uremic toxins (p-Cresylsulfate and Indoxyl Sulfate) and serum inflammatory cytokines were the primary endpoints. Results: Of the 44 patients randomized, 25 completed the study (mean age 51 ± 9.34, 64% female, mean eGFR 36 ± 14.26 mL/min/1.73m², mean BMI 28.5 ± 5.75 kg/m²). At 3 months, there were no significant changes in any of the studied biomarkers including p-cresylsulfate (p = 0.57), Indoxyl sulfate (p = 0.08) and interleukin-6 (p = 0.55). Conclusion: Lactobacillus acidophilus strains given as probiotic were not able to reduce serum levels of uremic toxins and biomarkers of inflammation in CKD patients in stage 3 and 4.

scholarly journals Efficacy of Divinylbenzenic Resin in Removing Indoxyl Sulfate and P-cresol Sulfate in Hemodialysis Patients: Results from an In Vitro Study and an In Vivo Pilot Trial (xuanro4-Nature 3.2)

Toxins ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 170
Author(s):  
Maria Teresa Rocchetti ◽  
Carmela Cosola ◽  
Ighli di Bari ◽  
Stefania Magnani ◽  
Vanessa Galleggiante ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Pilot Trial ◽  
In Vitro Study ◽  
Serum Levels ◽  
Cardiovascular Complications ◽  
High Serum ◽  
Uremic Toxins ◽  
Indoxyl Sulfate

High serum levels of microbiota-derived uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), are associated with chronic kidney disease (CKD) progression and cardiovascular complications. IS and PCS cannot be efficiently removed by conventional hemodialysis (HD), due to their high binding affinity for albumin. This study evaluates the efficacy of a divinylbenzene-polyvinylpyrrolidone (DVB-PVP) cartridge and a synbiotic to reduce uremic toxins in HD patients. First, the in vitro efficacy of DVB-PVP in adsorbing IS and PCS was evaluated. Second, a randomized, placebo-controlled pilot study in HD patients was carried out to establish whether the administration of a synbiotic, either individually and in association with DVB-PVP-HD, could reduce the production of uremic toxins. In vitro data showed that DVB-PVP resin removed a mean of 56% PCS and around 54% IS, after 6 h of perfusion. While, in the in vivo study, the DVB-PVP cartridge showed its adsorbing efficacy only for IS plasma levels. The combination of synbiotic treatment with DVB-PVP HD decreased IS and PCS both at pre- and post-dialysis levels. In conclusion, this study provides the first line of evidence on the synergistic action of gut microbiota modulation and an innovative absorption-based approach in HD patients, aimed at reducing plasma levels of IS and PCS.

scholarly journals Removal of Protein-Bound Uremic Toxins during Hemodialysis Using a Binding Competitor

2019 ◽  
Vol 14 (3) ◽  
pp. 394-402 ◽  
Author(s):  
Magdalena Madero ◽  
Karla B. Cano ◽  
Israel Campos ◽  
Xia Tao ◽  
Vaibhav Maheshwari ◽  
...  
Keyword(s):  
Serum Levels ◽  
Uremic Toxins ◽  
Interquartile Range ◽  
Indoxyl Sulfate ◽  
Maintenance Hemodialysis ◽  
Albumin Binding ◽  
Uremic Toxin ◽  
Median Serum ◽  
High Degree ◽  
Marked Drop

Background and objectivesCurrent hemodialysis techniques fail to efficiently remove the protein-bound uremic toxins p-cresyl sulfate and indoxyl sulfate due to their high degree of albumin binding. Ibuprofen, which shares the same primary albumin binding site with p-cresyl sulfate and indoxyl sulfate, can be infused during hemodialysis to displace these toxins, thereby augmenting their removal.Design, setting, participants, & measurementsWe infused 800 mg ibuprofen into the arterial bloodline between minutes 21 and 40 of a conventional 4-hour high-flux hemodialysis treatment. We measured arterial, venous, and dialysate outlet concentrations of indoxyl sulfate, p-cresyl sulfate, tryptophan, ibuprofen, urea, and creatinine before, during, and after the ibuprofen infusion. We report clearances of p-cresyl sulfate and indoxyl sulfate before and during ibuprofen infusion and dialysate concentrations of protein-bound uremic toxins normalized to each patient’s average preinfusion concentrations.ResultsWe studied 18 patients on maintenance hemodialysis: age 36±11 years old, ten women, and mean vintage of 37±37 months. Compared with during the preinfusion period, the median (interquartile range) clearances of indoxyl sulfate and p-cresyl sulfate increased during ibuprofen infusion from 6.0 (6.5) to 20.2 (27.1) ml/min and from 4.4 (6.7) to 14.9 (27.1) ml/min (each P<0.001), respectively. Relative median (interquartile range) protein-bound uremic toxin dialysate outlet levels increased from preinfusion 1.0 (reference) to 2.4 (1.2) for indoxyl sulfate and to 2.4 (1.0) for p-cresyl sulfate (each P<0.001). Although median serum post- and predialyzer levels in the preinfusion period were similar, infusion led to a marked drop in serum postdialyzer levels for both indoxyl sulfate and p-cresyl sulfate (−1.0 and −0.3 mg/dl, respectively; each P<0.001). The removal of the nonprotein-bound solutes creatinine and urea was not increased by the ibuprofen infusion.ConclusionsInfusion of ibuprofen into the arterial bloodline during hemodialysis significantly increases the dialytic removal of indoxyl sulfate and p-cresyl sulfate and thereby, leads to greater reduction in their serum levels.

A pilot study on the effect of ulipristal acetate on myoma angiogenesis, measured by 2D ultrasound and VEGF serum levels

2020 ◽  
pp. 19-29
Author(s):  
Patricia Diaz Ortega ◽  
Manuel García Manero
Keyword(s):  
Pilot Study ◽  
Power Doppler ◽  
Uterine Fibroids ◽  
Premenopausal Women ◽  
Serum Levels ◽  
Ulipristal Acetate ◽  
Before And After ◽  
Angiogenesis Process ◽  
2D Ultrasound ◽  
Average Size

Introduction: Symptomatic uterine fibroids can cause symptoms that can be disabling. There are many treatments, including ulipristal acetate, whose role in reducing symptoms and decreasing the size of the fibroid is well known. With this preliminary study, we also try to evaluate the correlation between myoma vascularization measured by ultrasound (Power Doppler 2D) and serum VEGF levels, before and after treatment with ulipristal acetate; in patients diagnosed with symptomatic uterine fibroids. Materials and Methods: A preliminary, prospective observational pilot study was designed. Twenty-four premenopausal women, diagnosed with symptomatic uterine fibroids, were included and all of them completed the study. Four cycles of ulipristal acetate were administered according to the dose and indications specified in the data sheet. In order to assess the influence of this treatment on the angiogenesis process of the fibroids, measurements of VEGF serum levels were made and their vascularization was assessed by means of 2D power doppler ultrasound; at the beginning and the end of treatment. In addition, several determinations of the same parameters were made throughout the successive visits. Endpoints were defined as the decrease in VEGF levels from previous levels, the decrease in myoma vascularization on ultrasound, and the reduction in myoma size. Result: 24 patients who met the inclusion criteria were enrolled (n=24). The average size of myomas was reduced from 45,08 ? 24,02mm to 29?16,96mm after treatment. The average VEGF serum level significantly decreased after the first treatment cycle (from 147,17 ? 153,51 pg/ml to 102,04 ? 186,08pg/ml). Vascularization of myomas after treatment with ulipristal acetate was analyzed, and a significantly decrease was achieved in 83,3% of cases. Conclusion: There is a correlation between myoma vascularization and treatment with Ulipristal acetate. SPRMs may provide effective treatment for women with symptomatic fibroids by two ways: supports selective progesterone receptor modulators and reduced angiogenesis. Keywords: Angiogenesis; Ulipristal Acetate; Uterine fibroids; VEGF

scholarly journals IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1686
Author(s):  
Adelaida M. Celaya ◽  
Lourdes Rodríguez-de la Rosa ◽  
Jose M. Bermúdez-Muñoz ◽  
José M. Zubeldia ◽  
Carlos Romá-Mateo ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inflammatory Cytokines ◽  
Noise Exposure ◽  
Sensorineural Deafness ◽  
Serum Levels ◽  
Genetic Syndromes ◽  
Expression Ratio ◽  
Postnatal Maturation ◽  
Age Related ◽  
Underlying Mechanisms

Insulin-like growth factor 1 (IGF-1) deficiency is an ultrarare syndromic human sensorineural deafness. Accordingly, IGF-1 is essential for the postnatal maturation of the cochlea and the correct wiring of hearing in mice. Less severe decreases in human IGF-1 levels have been associated with other hearing loss rare genetic syndromes, as well as with age-related hearing loss (ARHL). However, the underlying mechanisms linking IGF-1 haploinsufficiency with auditory pathology and ARHL have not been studied. Igf1-heterozygous mice express less Igf1 transcription and have 40% lower IGF-1 serum levels than wild-type mice. Along with ageing, IGF-1 levels decreased concomitantly with the increased expression of inflammatory cytokines, Tgfb1 and Il1b, but there was no associated hearing loss. However, noise exposure of these mice caused increased injury to sensory hair cells and irreversible hearing loss. Concomitantly, there was a significant alteration in the expression ratio of pro- and anti-inflammatory cytokines in Igf1+/− mice. Unbalanced inflammation led to the activation of the stress kinase JNK and the failure to activate AKT. Our data show that IGF-1 haploinsufficiency causes a chronic subclinical proinflammatory age-associated state and, consequently, greater susceptibility to stressors. This work provides the molecular bases to further understand hearing disorders linked to IGF-1 deficiency.

scholarly journals Effect of probiotic supplementation along with calorie restriction on metabolic endotoxemia, and inflammation markers in coronary artery disease patients: a double blind placebo controlled randomized clinical trial

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jalal Moludi ◽  
Hossein Samadi Kafil ◽  
Shaimaa A. Qaisar ◽  
Pourya Gholizadeh ◽  
Mohammad Alizadeh ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Lactobacillus Rhamnosus ◽  
Serum Levels ◽  
Interleukin 10 ◽  
Probiotic Supplementation ◽  
Related Factors ◽  
Double Blind ◽  
Artery Disease ◽  
Metabolic Endotoxemia

Abstract Purpose Alterations in the gut microbiome (dysbiosis) has been associated with increased microbial translocation, leading to chronic inflammation in coronary artery disease (CAD). It has been proposed that modulation of gut microbiota by probiotic might modify metabolic endotoxemia. Therefore, the purpose of this study was to examine the effects of Lactobacillus rhamnosus GG (LGG) on endotoxin level, and biomarkers of inflammation in CAD participants. Methods This study was a 12-weeks randomized, double-blind, and intervention on 44 patients with CAD. Patients were randomly allocated to receive either one LGG capsule 1.6 × 109 colony-forming unit (CFU) or the placebo capsules for 12 weeks. In addition, all the participants were also prescribed a calorie-restricted diet. Serum levels of interleukin-1β (IL-1β), Toll-like receptor 4 (TLR4), interleukin-10 (IL-10), and lipopolysaccharide (LPS), were assessed before and after the intervention. Results A significant decrease in IL1-Beta concentration (− 1.88 ± 2.25, vs. 0.50 ± 1.58 mmol/L, P = 0.027), and LPS levels (− 5.88 ± 2.70 vs. 2.96+ 5.27 mg/L, P = 0.016), was observed after the probiotic supplementation compared with the placebo. Participants who had ≥2.5 kg weight loss showed significantly improved cardiovascular-related factors, compared to patients with < 2.5 kg weight reduction, regardless of the supplement they took. Conclusion These data provide preliminary evidence that probiotic supplementation has beneficial effects on metabolic endotoxemia, and mega inflammation in participants with CAD.

scholarly journals The relationship of indoxyl sulfate and p-cresyl sulfate with target cardiovascular proteins in hemodialysis patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ping-Hsun Wu ◽  
Yi-Ting Lin ◽  
Yi-Wen Chiu ◽  
Gabriel Baldanzi ◽  
Jiun-Chi Huang ◽  
...  
Keyword(s):  
Hemodialysis Patients ◽  
Complement Component ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Free Form ◽  
Negatively Associated ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Related Proteins ◽  
The Relationship

AbstractProtein-bound uremic toxins (Indoxyl sulfate [IS] and p-cresyl sulfate [PCS]) are both associated with cardiovascular (CV) and all-cause mortality in subjects with chronic kidney disease (CKD). Possible mechanisms have not been elucidated. In hemodialysis patients, we investigated the relationship between the free form of IS and PCS and 181 CV-related proteins. First, IS or PCS concentrations were checked, and high levels were associated with an increased risk of acute coronary syndrome (ACS) in 333 stable HD patients. CV proteins were further quantified by a proximity extension assay. We examined associations between the free form protein-bound uremic toxins and the quantified proteins with correction for multiple testing in the discovery process. In the second step, the independent association was evaluated by multivariable-adjusted models. We rank the CV proteins related to protein-bound uremic toxins by bootstrapped confidence intervals and ascending p-value. Six proteins (signaling lymphocytic activation molecule family member 5, complement component C1q receptor, C–C motif chemokine 15 [CCL15], bleomycin hydrolase, perlecan, and cluster of differentiation 166 antigen) were negatively associated with IS. Fibroblast growth factor 23 [FGF23] was the only CV protein positively associated with IS. Three proteins (complement component C1q receptor, CCL15, and interleukin-1 receptor-like 2) were negatively associated with PCS. Similar findings were obtained after adjusting for classical CV risk factors. However, only higher levels of FGF23 was related to increased risk of ACS. In conclusion, IS and PCS were associated with several CV-related proteins involved in endothelial barrier function, complement system, cell adhesion, phosphate homeostasis, and inflammation. Multiplex proteomics seems to be a promising way to discover novel pathophysiology of the uremic toxin.

Acute Ischemic Stroke is Associated with Increased Serum Levels of Pro-inflammatory Cytokines

2020 ◽  
Author(s):  
Bhagirath Ramawat ◽  
Alvee Saluja ◽  
Jayashree Bhatacharjee ◽  
Anshuman Srivastava ◽  
Rajinder K. Dhamija
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Inflammatory Cytokines ◽  
Serum Levels ◽  
Pro Inflammatory Cytokines

scholarly journals Association of Sarcopenia and Gut Microbiota Composition in Older Patients with Advanced Chronic Kidney Disease, Investigation of the Interactions with Uremic Toxins, Inflammation and Oxidative Stress

Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 472
Author(s):  
Elisabetta Margiotta ◽  
Lara Caldiroli ◽  
Maria Luisa Callegari ◽  
Francesco Miragoli ◽  
Francesca Zanoni ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Inflammatory Cytokines ◽  
Interleukin 10 ◽  
Uremic Toxins ◽  
Interleukin 12 ◽  
European Working ◽  
And Oxidative Stress

Background: Sarcopenia is a prevalent condition in chronic kidney disease (CKD). We determined gut microbiota (gMB) composition in CKD patients with or without sarcopenia. Furthermore, we investigated whether in these patients, there was any association between gMB, uremic toxins, inflammation and oxidative stress. Methods: We analyzed gMB composition, uremic toxins (indoxyl sulphate and p-cresyl sulphate), inflammatory cytokines (interleukin 10, tumor necrosis factor α, interleukin 6, interleukin 17, interleukin 12 p70, monocyte chemoattractant protein-1 and fetuin-A) and oxidative stress (malondialdehyde) of 64 elderly CKD patients (10 < eGFR < 45 mL/min/1.73 m2, not on dialysis) categorized as sarcopenic and not-sarcopenic. Sarcopenia was defined according to European Working Group on Sarcopenia in Older People 2 criteria. Results: Sarcopenic patients had a greater abundance of the Micrococcaceae and Verrucomicrobiaceae families and of Megasphaera, Rothia, Veillonella, Akkermansia and Coprobacillus genera. They had a lower abundance of the Gemellaceae and Veillonellaceae families and of Acidaminococcus and Gemella genera. GMB was associated with uremic toxins, inflammatory cytokines and MDA. However, uremic toxins, inflammatory cytokines and MDA were not different in sarcopenic compared with not-sarcopenic individuals, except for interleukin 10, which was higher in not-sarcopenic patients. Conclusions: In older CKD patients, gMB was different in sarcopenic than in not-sarcopenic ones. Several bacterial families and genera were associated with uremic toxins and inflammatory cytokines, although none of these latter substantially different in sarcopenic versus not-sarcopenic patients.

Inhibition of monocyte-derived inflammatory cytokines by IL-25 occurs via p38 Map kinase–dependent induction of Socs-3

Blood ◽  
2009 ◽  
Vol 113 (15) ◽  
pp. 3512-3519 ◽  
Author(s):  
Roberta Caruso ◽  
Carmine Stolfi ◽  
Massimiliano Sarra ◽  
Angelamaria Rizzo ◽  
Massimo C. Fantini ◽  
...  
Keyword(s):  
Map Kinase ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Human Peripheral Blood ◽  
Serum Levels ◽  
Cell Types ◽  
P38 Map Kinase ◽  
Negative Regulator ◽  
Therapeutic Implications

Abstract IL-25, a member of the IL-17 cytokine family, is known to enhance Th2-like responses associated with increased serum levels of IgE, IgG1, IgA, blood eosinophilia, and eosinophilic infiltrates in various tissues. However, IL-25 also abrogates inflammatory responses driven by Th17 cells. However, the cell types that respond to IL-25 and the mechanisms by which IL-25 differentially regulates immune reactions are not well explored. To identify potential targets of IL-25, we initially examined IL-25 receptor (IL-25R) in human peripheral blood cells. IL-25R was predominantly expressed by CD14+ cells. We next assessed the functional role of IL-25 in modulating the response of CD14+ cells to various inflammatory signals. CD14+ cells responded to IL-25 by down-regulating the synthesis of inflammatory cytokines induced by toll-like receptor (TLR) ligands and inflammatory cytokines. Inhibition of cytokine response by IL-25 occurred via a p38 Map kinase–driven Socs-3–dependent mechanism. In vivo, IL-25 inhibited monocyte-derived cytokines and protected against LPS-induced lethal endotoxemia in mice. These data indicate that IL-25 is a negative regulator of monocyte proinflammatory cytokine responses, which may have therapeutic implications.

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