MO660INTERRELATIONSHIP BETWEEN PROTEIN BOUND UREMIC TOXIN INDOXYL SULFATE CONCENTRATION IN BLOOD AND SPENT DIALYSATE DURING HEMODIALYSIS TREATMENT

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Joosep Paats ◽  
Annika Adoberg ◽  
Jürgen Arund ◽  
Ivo Fridolin ◽  
Kai Lauri ◽  
...  
Keyword(s):  
Strong Correlation ◽  
Uremic Toxins ◽  
Interquartile Range ◽  
Indoxyl Sulfate ◽  
Total Serum ◽  
Uremic Toxin ◽  
Optical Monitoring ◽  
On Line ◽  
Spent Dialysate ◽  
Treatment Settings

Abstract Background and Aims Indoxyl sulfate (IS) is a representative of the protein-bound uremic retention solutes [1]. Among CKD patients, high serum levels of IS are associated with high cardiovascular and all-cause mortality – IS is linked to cardiovascular outcomes, induces acceleration of atherosclerosis and abnormal bone metabolism [2,3]. Optical monitoring of the uremic marker molecules in the spent dialysate has been proposed [4] to estimate on-line concentration and removal of uremic toxins, allowing to assess total removed solute and removal rate of uremic toxins. Although several studies have been published covering the on-line optical monitoring of the spent dialysate, there is scarce knowledge about relation between spent dialysate and blood concentrations for protein-bound uremic solutes. The aim of this study was to evaluate the relationship between protein bound uremic toxin IS concentration in blood and spent dialysate during hemodialysis (HD) and hemodiafiltration (HDF) with different treatment settings, with the potential of evaluating uremic toxins’ levels in blood by assessing uremic toxins’ concentration in spent dialysate. Method 22 ESKD patients (16 male and 8 female, 55±17 years) on chronic HDF were enrolled into the study (fistula N=15, graft N=7). For each patient 4 midweek dialysis sessions (length 240min, HD: N=1, Qb=200ml/min, Qd=300ml/min, 1,5m2; HDF: N=3, median (interquartile range) Qb = 298 (296-356) ml/min, Qd= 795 (500-800) ml/min, Vsubst = 21.8 (15-24.5) L, 1,8m2 and 2,2m2) were included. During each dialysis session, blood samples were taken at 0 min (start) and 240 min from the arterial blood line, and dialysate samples were taken at 7 min and 240 min from the outlet of the dialysis machine. After sample processing, serum total, serum free and spent dialysate IS concentrations were determined by HPLC. Regression analysis was carried out. Results Median (interquartile range) IS concentrations in blood were 10.02 (6.68 - 14.68) µmol/L for free IS, 101.33 (56.99- 125.66) µmol/L for total IS, and 3.74 (2.35- 5.93) µmol/L in dialysate at the beginning of dialysis, and 6.07 (3.58- 9.00) µmol/L, 56.70 (28.91-80.67) µmol/L, 1.94 (1.15-2.98) µmol/L at the end of dialysis, respectively. There was a strong correlation between IS concentration in blood and dialysate at the beginning and at the end of dialysis even without data normalization by treatment settings (Fig. 1), with the strongest correlation between free IS concentration and IS in dialysate at 240 min (R2 = 0,976) and at the beginning of dialysis (R2 = 0,962). The reason for the higher correlation between free IS in blood and IS in dialysate is that only protein non-bound fraction of IS is available for removal by dialysis from blood into dialysate. Conclusion There is a strong correlation between IS concentrations in blood and dialysate with different treatment settings during whole dialysis. Assessment of protein bound uremic toxins’ concentration in the spent dialysate by optical sensor could thus also provide information about the concentration of uremic toxins in blood. [1] Vanholder et al 2018; [2] Yamamoto et al 2020; [3] Barreto et al 2009; [4] Lauri et al 2019;

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.

The uremic toxin indoxyl sulfate reflects cardio-renal risk and intestinal-renal relationship

2011 ◽  
Vol 152 (43) ◽  
pp. 1724-1730 ◽  
Author(s):  
István Kiss
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Morbidity And Mortality ◽  
Renal Diseases ◽  
Uremic Toxin ◽  
Cardiovascular Risks ◽  
Endogenous Protein ◽  
Uremic Syndrome

Uremic syndrome and condition is primarily a result of kidney failure in which uremic toxins are accumulated. More and more attention is paid to possibilities for removal of uremic toxins, which not only means dialysis, but also takes into account special dietary considerations and treatments, which aim to absorb the toxins or reduce their production. These uremic toxins, which also increase the cardiovascular risks, play a major part in morbidity and mortality of patients suffering from chronic renal failure and those receiving renal replacement therapy. One of them is a member of the indol group, the indoxyl sulfate. This toxin is difficult to remove with dialysis and is an endogenous protein-bound uremic toxin. Today we know that indoxyl sulfate is a vascular-nephrotoxic agent, which is able to enhance progression of cardiovascular and renal diseases. It is of particular importance that because of its redox potency, this toxin causes oxidative stress and antioxidant effects at the same time and, on top of that, it is formed in the intestinal system. Its serum concentration depends on the nutrition and the tubular function and, therefore, it can also signal the progression of chronic renal failure independently of glomerular filtration rate. Successful removal of indoxyl sulfate reduces the morbidity and mortality and improves survival. Therefore, it could be a possible target or area to facilitate the reduction of uremia in chronic renal failure. The use of probiotics and prebiotics with oral adsorbents may prove to be a promising opportunity to reduce indoxyl sulfate accumulation. Orv. Hetil., 2011, 152, 1724–1730.

scholarly journals Association between Cardiac Outcomes and Indoxyl Sulfate Levels in Hemodialysis Patients: A Cross-sectional Study

2021 ◽  
Author(s):  
Zhuo Li ◽  
Guibao Ke ◽  
Li Song ◽  
Junlin Huang ◽  
Yamei Zhang ◽  
...  
Keyword(s):  
Mitral Regurgitation ◽  
Linear Regression Analysis ◽  
Multiple Linear Regression Analysis ◽  
Cross Sectional Study ◽  
Indoxyl Sulfate ◽  
Total Serum ◽  
Uremic Toxin ◽  
Cross Sectional ◽  
Factors Affecting ◽  
Septal Thickness

Objective Indoxyl sulfate (IS) is a protein-bound uremic toxin that is associated with cardiovascular events and mortality in hemodialysis (HD) patients. However, the factors affecting the levels of IS are currently unclear. This study aimed to investigate the factors influencing serum IS concentrations in HD patients. Methods We included 100 HD patients from Guangdong Provincial People’s Hospital. Baseline characteristics, including sex, age, clinical features, duration of HD, echocardiography findings, electrocardiogram results, and biochemical indicators, were collected and analyzed in relation to serum total-form IS levels. Results Among all 100 patients, serum IS levels were significantly higher in patients aged ≥ 60 years, males, and patients with mitral regurgitation and inadequate dialysis. Among patients aged < 60 years, IS levels were significantly higher among patients with mitral regurgitation compared with those without. Furthermore, multiple linear regression analysis identified sex, age, ventricular septal thickness, and mitral regurgitation as factors independently associated with serum IS (STDβ = −0.475, 0.162, −0.153, 0.142, and 0.136, respectively; all P < 0.05) adjusted for body mass index, smoking, and fasting plasma glucose. Conclusions Male sex, age ≥ 60 years, ventricular septal thickness, and mitral regurgitation are factors associated with high total serum IS concentrations in Chinese HD patients. Elevated IS levels may play a role in the process of mitral regurgitation in HD patients < 60 years old.

scholarly journals Protein-Bound Uremic Toxins Lowering Effect of Sevelamer in Pre-Dialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized Controlled Trial

Toxins ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 688
Author(s):  
Kullaya Takkavatakarn ◽  
Pongpratch Puapatanakul ◽  
Jeerath Phannajit ◽  
Warumphon Sukkumme ◽  
Pajaree Chariyavilaskul ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Randomized Controlled Trial ◽  
Calcium Carbonate ◽  
Kidney Disease ◽  
Controlled Trial ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Total Serum ◽  
Randomized Controlled ◽  
Significant Difference

P-cresyl sulfate and indoxyl sulfate are strongly associated with cardiovascular events and all-cause mortality in chronic kidney disease (CKD). This randomized controlled trial was conducted to compare the effects between sevelamer and calcium carbonate on protein-bound uremic toxins in pre-dialysis CKD patients with hyperphosphatemia. Forty pre-dialysis CKD patients with persistent hyperphosphatemia were randomly assigned to receive either 2400 mg of sevelamer daily or 1500 mg of calcium carbonate daily for 24 weeks. A significant decrease of total serum p-cresyl sulfate was observed in sevelamer therapy compared to calcium carbonate therapy (mean difference between two groups −5.61 mg/L; 95% CI −11.01 to −0.27 mg/L; p = 0.04). There was no significant difference in serum indoxyl sulfate levels (p = 0.36). Sevelamer had effects in terms of lowering fibroblast growth factor 23 (p = 0.01) and low-density lipoprotein cholesterol levels (p = 0.04). Sevelamer showed benefits in terms of retarding CKD progression. Changes in vascular stiffness were not found in this study.

scholarly journals Indoxyl sulfate has a dominant role regarding the risks during different stages of chronic kidney disease

2020 ◽  
Author(s):  
Cheng-Hsu Chen ◽  
Shih-Chien Huang ◽  
Pei-Chih Lin ◽  
Shang-Feng Tsai ◽  
Yi-Chia Huang
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Dominant Role ◽  
Plasma Homocysteine ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Antioxidant Enzyme Activities ◽  
Uremic Toxin ◽  
Ckd Stage

Abstract Background: Increased levels of uremic toxins and decreased antioxidant capacities have a significant impact on the progression of chronic kidney disease (CKD). However, it is unclear whether they interact with each other in order to mediate the damage of renal function. The purpose of this study was to determine whether uremic toxins [i.e., homocysteine and indoxyl sulfate (IS)] and glutathione-dependent antioxidant enzyme activities are dependently or independently associated with each other in affecting renal function during different stages of CKD patients.Methods: One hundred thirty-two patients diagnosed with CKD stage 1 to 5 participated in this cross-sectional study.Results: Patients who had reached an advanced CKD stage experienced a gradual increase in plasma uremic toxin levels, along with decreased glutathione peroxidase (GSH-Px) activities. Plasma homocysteine, cysteine and IS concentrations were positively associated with each other, but negatively correlated to GSH-Px activity levels after adjusting potential confounders in all CKD patients. Although plasma homocysteine, cysteine, IS and GSH-Px levels were significantly associated with renal function, only plasma IS levels still had a significant association with renal function after these parameters were simultaneously adjusted.Conclusions: IS plays a more dominant role than other factors in affecting renal function, where a higher IS concentration needs to be controlled in order to defer the progressive loss of renal function.

scholarly journals Optical Method and Biochemical Source for the Assessment of the Middle-Molecule Uremic Toxin β2-Microglobulin in Spent Dialysate

Toxins ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 255
Author(s):  
Joosep Paats ◽  
Annika Adoberg ◽  
Jürgen Arund ◽  
Ivo Fridolin ◽  
Kai Lauri ◽  
...  
Keyword(s):  
Optical Method ◽  
Optical Signal ◽  
Uremic Toxins ◽  
Water Soluble ◽  
Uremic Toxin ◽  
Small Peptides ◽  
Entire Cohort ◽  
Β2 Microglobulin ◽  
Spent Dialysate ◽  
End Stage

Optical monitoring of spent dialysate has been used to estimate the removal of water-soluble low molecular weight as well as protein-bound uremic toxins from the blood of end stage kidney disease (ESKD) patients. The aim of this work was to develop an optical method to estimate the removal of β2-microglobulin (β2M), a marker of middle molecule (MM) uremic toxins, during hemodialysis (HD) treatment. Ultraviolet (UV) and fluorescence spectra of dialysate samples were recorded from 88 dialysis sessions of 22 ESKD patients, receiving four different settings of dialysis treatments. Stepwise regression was used to obtain the best model for the assessment of β2M concentration in the spent dialysate. The correlation coefficient 0.958 and an accuracy of 0.000 ± 0.304 mg/L was achieved between laboratory and optically estimated β2M concentrations in spent dialysate for the entire cohort. Optically and laboratory estimated reduction ratio (RR) and total removed solute (TRS) of β2M were not statistically different (p > 0.35). Dialytic elimination of MM uremic toxin β2M can be followed optically during dialysis treatment of ESKD patients. The main contributors to the optical signal of the MM fraction in the spent dialysate were provisionally identified as tryptophan (Trp) in small peptides and proteins, and advanced glycation end-products.

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 Uremic toxin indoxyl sulfate promotes proinflammatory macrophage activation by regulation of β-catenin and YAP pathways

2021 ◽  
Author(s):  
Ying Li ◽  
Jing Yan ◽  
Minjia Wang ◽  
Jing Lv ◽  
Fei Yan ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Inflammatory Response ◽  
Macrophage Polarization ◽  
Indoxyl Sulfate ◽  
Uremic Toxin ◽  
Lps Challenge ◽  
Hla Dr ◽  
M1 Macrophage

AbstractEvidence has been shown that indoxyl sulfate (IS) could impair kidney and cardiac functions. Moreover, macrophage polarization played important roles in chronic kidney disease and cardiovascular disease. IS acts as a nephron-vascular toxin, whereas its effect on macrophage polarization during inflammation is still not fully elucidated. In this study, we aimed to investigate the effect of IS on macrophage polarization during lipopolysaccharide (LPS) challenge. THP-1 monocytes were incubated with phorbol 12-myristate-13-acetate (PMA) to differentiate into macrophages, and then incubated with LPS and IS for 24 h. ELISA was used to detect the levels of TNFα, IL-6, IL-1β in THP-1-derived macrophages. Western blot assay was used to detect the levels of arginase1 and iNOS in THP-1-derived macrophages. Percentages of HLA-DR-positive cells (M1 macrophages) and CD206-positive cells (M2 macrophages) were detected by flow cytometry. IS markedly increased the production of the pro-inflammatory factors TNFα, IL-6, IL-1β in LPS-stimulated THP-1-derived macrophages. In addition, IS induced M1 macrophage polarization in response to LPS, as evidenced by the increased expression of iNOS and the increased proportion of HLA-DR+ macrophages. Moreover, IS downregulated the level of β-catenin, and upregulated the level of YAP in LPS-stimulated macrophages. Activating β-catenin signaling or inhibiting YAP signaling suppressed the IS-induced inflammatory response in LPS-stimulated macrophages by inhibiting M1 polarization. IS induced M1 macrophage polarization in LPS-stimulated macrophages via inhibiting β-catenin and activating YAP signaling. In addition, this study provided evidences that activation of β-catenin or inhibition of YAP could alleviate IS-induced inflammatory response in LPS-stimulated macrophages. This finding may contribute to the understanding of immune dysfunction observed in chronic kidney disease and cardiovascular disease.

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