Browsing by Subject "Uremic toxins"

Now showing 1 - 4 of 4
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    Dietary Phosphorus Levels Influence Protein-Derived Uremic Toxin Production in Nephrectomized Male Rats
    (MDPI, 2024-06-08) Cladis, Dennis P.; Burstad, Kendal M.; Biruete, Annabel; Jannasch, Amber H.; Cooper, Bruce R.; Hill Gallant, Kathleen M.; Nutrition and Dietetics, School of Health and Human Sciences
    Gut microbiota-derived uremic toxins (UT) accumulate in patients with chronic kidney disease (CKD). Dietary phosphorus and protein restriction are common in CKD treatment, but the relationship between dietary phosphorus, a key nutrient for the gut microbiota, and protein-derived UT is poorly studied. Thus, we explored the relationship between dietary phosphorus and serum UT in CKD rats. For this exploratory study, we used serum samples from a larger study on the effects of dietary phosphorus on intestinal phosphorus absorption in nephrectomized (Nx, n = 22) or sham-operated (sham, n = 18) male Sprague Dawley rats. Rats were randomized to diet treatment groups of low or high phosphorus (0.1% or 1.2% w/w, respectively) for 1 week, with serum trimethylamine oxide (TMAO), indoxyl sulfate (IS), and p-cresol sulfate (pCS) analyzed by LC-MS. Nx rats had significantly higher levels of serum TMAO, IS, and pCS compared to sham rats (all p < 0.0001). IS showed a significant interaction between diet and CKD status, where serum IS was higher with the high-phosphorus diet in both Nx and sham rats, but to a greater extent in the Nx rats. Serum TMAO (p = 0.24) and pCS (p = 0.34) were not affected by dietary phosphorus levels. High dietary phosphorus intake for 1 week results in higher serum IS in both Nx and sham rats. The results of this exploratory study indicate that reducing dietary phosphorus intake in CKD may have beneficial effects on UT accumulation.
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    Effect of Dietary Inulin Supplementation on the Gut Microbiota Composition and Derived Metabolites of Individuals Undergoing Hemodialysis: A Pilot Study
    (Elsevier, 2021) Biruete, Annabel; Cross, Tzu-Wen L.; Allen, Jacob M.; Kistler, Brandon M.; de Loor, Henriette; Evenepoel, Pieter; Fahey, George C., Jr.; Bauer, Laura; Swanson, Kelly S.; Wilund, Kenneth R.; Medicine, School of Medicine
    Objective: The prebiotic fiber inulin has been studied in individuals undergoing hemodialysis (HD) due to its ability to reduce gut microbiota-derived uremic toxins. However, studies examining the effects of inulin on the gut microbiota and derived metabolites are limited in these patients. We aimed to assess the impact of a 4-week supplementation of inulin on the gut microbiota composition and microbial metabolites of patients on HD. Design and methods: In a randomized, double-blind, placebo-controlled, crossover study, twelve HD patients (55 ± 10 y, 50% male, 58% Black American, BMI 31.6 ± 8.9 kg/m2, 33% diabetes mellitus) were randomized to consume inulin [10 g/d for females; 15 g/d for males] or maltodextrin [6 g/d for females; 9 g/d for males] for 4 weeks, with a 4-week washout period. We assessed the fecal microbiota composition, fecal metabolites (short-chain fatty acids (SCFA), phenols, and indoles), and plasma indoxyl sulfate and p-cresyl sulfate. Results: At baseline, factors that explained the gut microbiota variability included BMI category and type of phosphate binder prescribed. Inulin increased the relative abundance of the phylum Verrucomicrobia and its genus Akkermansia (P interaction = 0.045). Inulin and maltodextrin resulted in an increased relative abundance of the phylum Bacteroidetes and its genus Bacteroides (P time = 0.04 and 0.03, respectively). Both treatments increased the fecal acetate and propionate (P time = 0.032 and 0.027, respectively), and there was a trend toward increased fecal butyrate (P time = 0.06). Inulin did not reduce fecal p-cresol or indoles, or plasma concentrations of p-cresyl sulfate or indoxyl sulfate. Conclusions: A 4-week supplementation of inulin did not lead to major shifts in the fecal microbiota and gut microbiota-derived metabolites. This may be due to high variability among participants and an unexpected increase in fecal excretion of SCFA with maltodextrin. Larger studies are needed to determine the effects of prebiotic fibers on the gut microbiota and clinical outcomes to justify their use in patients on HD.
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    Mapping cardiac remodeling in chronic kidney disease
    (American Association for the Advancement of Science, 2023) Kaesler, Nadine; Cheng, Mingbo; Nagai, James; O’Sullivan, James; Peisker, Fabian; Bindels, Eric M. J.; Babler, Anne; Moellmann, Julia; Droste, Patrick; Franciosa, Giulia; Dugourd, Aurelien; Saez-Rodriguez, Julio; Neuss, Sabine; Lehrke, Michael; Boor, Peter; Goettsch, Claudia; Olsen, Jesper V.; Speer, Thimoteus; Lu, Tzong-Shi; Lim, Kenneth; Floege, Jürgen; Denby, Laura; Costa, Ivan; Kramann, Rafael; Medicine, School of Medicine
    Patients with advanced chronic kidney disease (CKD) mostly die from sudden cardiac death and recurrent heart failure. The mechanisms of cardiac remodeling are largely unclear. To dissect molecular and cellular mechanisms of cardiac remodeling in CKD in an unbiased fashion, we performed left ventricular single-nuclear RNA sequencing in two mouse models of CKD. Our data showed a hypertrophic response trajectory of cardiomyocytes with stress signaling and metabolic changes driven by soluble uremia-related factors. We mapped fibroblast to myofibroblast differentiation in this process and identified notable changes in the cardiac vasculature, suggesting inflammation and dysfunction. An integrated analysis of cardiac cellular responses to uremic toxins pointed toward endothelin-1 and methylglyoxal being involved in capillary dysfunction and TNFα driving cardiomyocyte hypertrophy in CKD, which was validated in vitro and in vivo. TNFα inhibition in vivo ameliorated the cardiac phenotype in CKD. Thus, interventional approaches directed against uremic toxins, such as TNFα, hold promise to ameliorate cardiac remodeling in CKD.
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    Skeletal Muscle Complications in Chronic Kidney Disease
    (Springer, 2022-12) Troutman, Ashley D.; Arroyo, Eliott; Lim, Kenneth; Moorthi, Ranjani N.; Avin, Keith G.; Physical Therapy, School of Health and Human Sciences
    Purpose of Review To provide an overview of the recent literature investigating the pathophysiology of skeletal muscle changes, interventions for skeletal muscle, and effects of exercise in chronic kidney disease (CKD). Recent Findings There are multiple CKD-related changes that negatively impact muscle size and function. However, the variability in the assessment of muscle size, in particular, hinders the ability to truly understand the impact it may have in CKD. Exercise interventions to improve muscle size and function demonstrate inconsistent responses that warrant further investigation to optimize exercise prescription. Summary Despite progress in the field, there are many gaps in the knowledge of the pathophysiology of sarcopenia of CKD. Identifying these gaps will help in the design of interventions that can be tested to target muscle loss and its consequences such as impaired mobility, falls, and poor quality of life in patients with CKD.