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Browsing by Author "Biruete, Annabel"
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Item 445 The effects of dietary fiber based on fermentability and viscosity on phosphorus absorption and the gut microbiome in chronic kidney disease-mineral and bone disorder(Cambridge University Press, 2023-04-24) Biruete, Annabel; Chen, Neal X.; Srinivasan, Shruthi; O'Neill, Kalisha; Nelson, David; Hill Gallant, Kathleen M.; Moe, Sharon M.; Medicine, School of MedicineOBJECTIVES/GOALS: To compare the effects of dietary fiber supplementation based on fermentability and viscosity on phosphorus fractional absorption and the gut microbiome in a rat model of chronic kidney disease-mineral and bone disorder (CKD-MBD). METHODS/STUDY POPULATION: 25-week-old Cy/+ male rats (CKD hereafter) will be randomly assigned to receive one of four fiber treatments (10% w/w each) based on fermentability and viscosity: 1) Cellulose (-fermentability, -viscosity), 2) inulin (+fermentability, -viscosity), 3) psyllium husk (-fermentability, +viscosity), or 4) pectin (+ fermentability, +viscosity). Diets will be formulated with a semipurified diet containing 0.7% phosphorus. Treatments will last for 10 weeks, and rats will be euthanized at 35 weeks of age, where animals have reached kidney failure. Intravenous and oral 33P will be used for intestinal phosphorus fractional absorption and cecal/fecal samples will be obtained at euthanasia for microbiome assessment using shotgun metagenomics. RESULTS/ANTICIPATED RESULTS: Our preliminary data show that fermentable dietary fiber (inulin) impacted phosphorus homeostasis by increasing the circulating levels of fibroblast growth factor-23 (a bone-derived hormone that increases phosphorus excretion in urine) and lowering circulating levels of phosphorus in the Cy/+ male rat model of progressive chronic kidney disease. We hypothesize that dietary fiber impacts phosphorus absorption in gut microbiome-dependent and independent mechanisms. For example, fermentable fiber enhances the production of short-chain fatty acids, lowering the intraluminal pH, and enhancing mineral solubility and absorption. Meanwhile, viscous fibers may encapsulate minerals limiting their absorption if these fibers are non-fermentable. DISCUSSION/SIGNIFICANCE: Hyperphosphatemia, or high circulating phosphorus, is a major factor in the pathogenesis of CKD-MBD. Treatment of hyperphosphatemia is focused on reducing intestinal absorption. However, available therapies vary in their efficacy and focus on phosphorus absorption in the small intestine, ignoring the possible impact of the large intestine.Item 547 The viscous and fermentability properties of dietary fiber impact on chronic kidney disease-mineral and bone disorder(Cambridge University Press, 2024-04-03) Biruete, Annabel; Chen, Neal X.; Srinivasan, Shruthi; O’Neill, Kalisha; Siles, Samantha; Hill Gallant, Kathleen; Moe, Sharon M.; Medicine, School of MedicineOBJECTIVES/GOALS: Dietary fiber has been used in other clinical populations to improve mineral disorders, but there is limited data in chronic kidney disease, despite the high prevalence of mineral and bone disorder (known as CKD-MBD). Our objective was to evaluate the effect of dietary fiber based on viscosity and fermentability on CKD-MBD outcomes. METHODS/STUDY POPULATION: 22-week-old male CKD rats (mild-to-moderate CKD) were randomly assigned to receive one of four fiber treatments (10% w/w each) based on fermentability and viscosity: 1) Cellulose (-fermentability, -viscosity), 2) Inulin (+fermentability, -viscosity), 3) Psyllium husk (-fermentability, +viscosity), or 4) Pectin (+ fermentability, +viscosity). Treatments lasted 10 weeks, and rats were euthanized at 32 weeks of age (kidney failure). Rats were placed in metabolic cages for 3 consecutive days the last week before euthanasia for mineral balance. At euthanasia, blood, tibia, heart, and aorta were collected for CKD-MBD assessment. Additional tissues collected included kidneys and all intestinal segments. RESULTS/ANTICIPATED RESULTS: Our preliminary data indicates that weight trajectories and survival were similar between treatment groups. At 33 weeks of age, kidney weight index (an indirect measurement of kidney function as this animal model develops polycystic kidneys) was lower in the psyllium-treated rats compared to all of the other treatments. Plasma phosphorus was lower with Psyllium and Pectin compared to Cellulose-treated rats. Left ventricular mass index was lower in the Inulin, Psyllium, and Pectin-treated rats compared to the Cellulose-treated rats. Ongoing tissue analyses include biochemical markers of mineral and bone metabolism (parathyroid hormone, fibroblast growth factor-23, and phosphorus balance), bone parameters (dynamic histomorphometry and microCT), and cardiovascular calcification. DISCUSSION/SIGNIFICANCE: Our preliminary data indicate that dietary fiber based on fermentability and viscosity impacts CKD-MBD outcomes and may be an innovative, low-cost intervention that can be trialed in people with CKD for the prevention and treatment of CKD-MBD.Item Acute High Dietary Phosphorus Following Low-Phosphorus Diet Acclimation Does Not Enhance Intestinal Fractional Phosphorus Absorption in Nephrectomized Male Rats(Wiley, 2022-11-16) Burstad, Kendal M.; Cladis, Dennis P.; Vorland, Colby J.; Wastney, Meryl E.; Biruete, Annabel; Dominguez, James M., II; O’Neill, Kalisha D.; Chen, Neal X.; Moe, Sharon M.; Hill Gallant, Kathleen M.; Medicine, School of MedicineDietary phosphorus restriction and phosphorus binders are commonly prescribed for patients with chronic kidney disease (CKD). However, occurrences of non-adherence to these interventions are common. As low-phosphorus (LP) diets have been consistently experimentally shown in vitro to increase intestinal phosphorus absorption efficiency, a bout of non-adherence to diet or binders may cause an unintended consequence of enhanced intestinal phosphorus absorption. Thus, we aimed to determine the effect of a single bout of high-phosphorus (HP) intake after acclimation to a LP diet. Male Sprague Dawley rats with 5/6 nephrectomy (n = 36) or sham operation (n = 36) were block-randomized to 1 of 3 diets: LP (0.1% P w/w), HP (1.2%), or LP followed by acute HP (LPHP 0.1% then 1.2%). Phosphorus absorption tests were conducted using 33P radioisotope administrated by oral gavage or intravenously (iv). Although the overall two-way ANCOVA model for intestinal fractional phosphorus absorption was non-significant, exploratory comparisons showed intestinal fractional phosphorus absorption efficiency tended to be higher in rats in the LP compared with HP or LPHP groups. Rats in the HP or LPHP groups had higher plasma phosphorus compared with rats in the LP group, but the LPHP group was not different from the HP group. Gene expression of the major intestinal phosphate transporter, NaPi-2b, was lower in the jejunum of rats in the LPHP group compared with rats in the HP group but not different in the duodenum. These results demonstrate that an acute HP load after acclimation to a LP diet does not lead to enhanced intestinal fractional phosphorus absorption efficiency in 5/6 nephrectomized male rats. These data provide evidence against the notion that dietary phosphorus restriction or binder use adversely increases absorption efficiency after a single instance of dietary or binder non-adherence. However, other adverse consequences of fluctuating dietary phosphorus intake cannot be ruled out.Item Adverse effects of autoclaved diets on the progression of chronic kidney disease (CKD) and CKD-Mineral Bone Disorder in rats(Karger, 2020) Biruete, Annabel; Srinivasan, Shruthi; O’Neill, Kalisha D.; Vorland, Colby J.; Hill Gallant, Kathleen M.; Cai, Weijing; Uribarri, Jaime; Johnston, Nancy; Allen, Matthew R.; Chen, Neal X.; Moe, Sharon M.; Medicine, School of MedicineBackground: Autoclaving rodent diets is common in laboratory animals, but autoclaving increases the formation of dietary advanced glycation end-products (AGE). We studied the effect of autoclaved (AC) diet alone or in combination with a diet high in bioavailable phosphorus on biochemistries of chronic kidney disease-mineral and bone disorder (CKD-MBD), intestinal gene expression, and oxidative stress. Methods: Male CKD rats (Cy/+) and normal littermates were fed 1 of 3 diets: AC 0.7% phosphorus grain-based diet for 28 weeks (AC); AC diet for 17 weeks followed by non-autoclaved (Non-AC) 0.7% phosphorus casein diet until 28 weeks (AC + Casein); or Non-AC diet for 16 weeks followed by a Non-AC purified diet until 30 weeks (Non-AC + Casein). Results: AC diets contained ~3× higher AGEs and levels varied depending on the location within the autoclave. Rats fed the AC and AC + Casein diets had higher total AGEs and oxidative stress, irrespective of kidney function. Kidney function was more severely compromised in CKD rats fed AC or AC + Casein compared to Non-AC + Casein. There was a disease-by-diet interaction for plasma phosphorus, parathyroid hormone, and c-terminal fibroblast growth factor-23, driven by high values in the CKD rats fed the AC + Casein diet. Compared to Non-AC + Casein, AC and AC + Casein-fed groups had increased expression of receptor of AGEs and intestinal NADPH oxidase dual oxidase-2, independent of kidney function. Conclusions: Autoclaving rodent diets impacts the progression of CKD and CKD-MBD, highlighting the critical importance of standardizing diets in experiments.Item A Comparison of Dietary Intake Between Individuals Undergoing Maintenance Hemodialysis in the United Kingdom and China(Elsevier, 2022-03) Song, Yan; March, Daniel S.; Biruete, Annabel; Kistler, Brandon M.; Nixon, Daniel D. G.; Highton, Patrick J.; Vogt, Barbara P.; Ruddock, Nicola; Wilund, Kenneth R.; Smith, Alice C.; Burton, James O.; Medicine, School of MedicineOBJECTIVE: Protein-energy wasting is highly prevalent in people with end-stage kidney disease receiving regular hemodialysis. Currently, it is unclear what the optimal nutritional recommendations are, which is further complicated by differences in dietary patterns between countries. The aim of the study was to understand and compare dietary intake between individuals receiving hemodialysis in Leicester, UK and Nantong, China. METHODS: The study assessed 40 UK and 44 Chinese participants' dietary intake over a period of 14 days using 24-hour diet recall interviews. Nutritional blood parameters were obtained from medical records. Food consumed by participants in the UK and China was analyzed using the Nutritics and Nutrition calculator to quantify nutritional intake. RESULTS: Energy and protein intake were comparable between UK and Chinese participants, but with both below the recommended daily intake. Potassium intake was higher in UK participants compared to Chinese participants (2,115 [888] versus 1,159 [861] mg/d; P < .001), as was calcium (618 [257] versus 360 [312] mg/d; P < .001) and phosphate intake (927 [485] versus 697 [434] mg/d; P = .007). Vitamin C intake was lower in UK participants compared to their Chinese counterparts (39 [51] versus 64 [42] mg/d; P = .024). Data are reported here as median (interquartile range). CONCLUSION: Both UK and Chinese hemodialysis participants have insufficient protein and energy in their diet. New strategies are required to increase protein and energy intakes. All participants had inadequate daily intake of vitamins C and D; there may well be a role in the oral supplementation of these vitamins, and further studies are urgently needed.Item Deconstructing Disease-Related Malnutrition: A New Assessment Framework for Clinical Practice(Elsevier, 2023-04-27) St-Jules, David E.; Lloyd, Lyn; Meade, Anthony; Biruete, Annabel; Kistler, Brandon; Carrero, Juan-Jesus; Medicine, School of MedicineProtein-energy wasting (PEW) is a key cause of functional impairment and poor health outcomes in people with chronic kidney disease. While PEW can be mitigated with nutrition therapy, it is a complex myriad of disorders with numerous interacting etiologies and corresponding presentations, which make it difficult to diagnose and manage in practice. A variety of scoring rubrics have been developed to facilitate malnutrition assessment. Although these tools have greatly benefited the recognition and treatment of PEW, the typical format of grading specified PEW indicators has the potential to overlook or overstate highly relevant individual-specific factors. This review presents a simple framework for malnutrition assessment that can be used to complement and evaluate conventional assessment tools. Unlike standard tools, which are designed to identify and rate malnutrition risk and severity, the malnutrition framework is conceptual model that organizes PEW assessment into three distinct, but interacting facets of PEW risk: nutrient balance, nutrition status, and malnutrition risk. The new framework encourages critical thinking about PEW risk that may help clinicians plan and interpret assessments to efficiently and effectively manage this condition.Item Dieta de la Milpa: A Culturally-Concordant Plant-Based Dietary Pattern for Hispanic/Latine People with Chronic Kidney Disease(MDPI, 2024-02-20) Biruete, Annabel; Leal-Escobar, Gabriela; Espinosa-Cuevas, Ángeles; Mojica, Luis; Kistler, Brandon M.; Medicine, School of MedicineChronic kidney disease (CKD) disproportionately affects minorities in the United States, including the Hispanic/Latine population, and is a public health concern in Latin American countries. An emphasis on healthy dietary patterns, including the Mediterranean and the Dietary Approaches to Stop Hypertension (DASH) diets, has been suggested as they are associated with a lower incidence of CKD, slower CKD progression, and lower mortality in kidney failure. However, their applicability may be limited in people from Latin America. The Dieta de la Milpa (Diet of the Cornfield) was recently described as the dietary pattern of choice for people from Mesoamerica (Central Mexico and Central America). This dietary pattern highlights the intake of four plant-based staple foods from this geographical region, corn/maize, common beans, pumpkins/squashes, and chilies, complemented with seasonal and local intake of plant-based foods and a lower intake of animal-based foods, collectively classified into ten food groups. Limited preclinical and clinical studies suggest several health benefits, including cardiometabolic health, but there is currently no data concerning CKD. In this narrative review, we describe and highlight the potential benefits of the Dieta de la Milpa in CKD, including acid-base balance, protein source, potassium and phosphorus management, impact on the gut microbiota, inflammation, and cultural appropriateness. Despite these potential benefits, this dietary pattern has not been tested in people with CKD. Therefore, we suggest key research questions targeting measurement of adherence, feasibility, and effectiveness of the Dieta de la Milpa in people with CKD.Item 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 SciencesGut 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.Item Dietary protein intake and bone across stages of chronic kidney disease(SpringerLink, 2020-06) Stremke, Elizabeth R.; Biruete, Annabel; Hill Gallant, Kathleen M.; Medicine, School of MedicinePurpose of review: This review aims to summarize the current evidence on the effect of very-low-, low-, and high-protein diets on outcomes related to chronic kidney disease-mineral and bone disorder (CKD-MBD) and bone health in patients with CKD. Recent findings: Dietary protein restriction in the form of low- and very-low-protein diets have been used to slow down the progression of CKD. These diets can be supplemented with alpha-keto acid (KA) analogues of amino acids. Observational and randomized controlled trials have shown improvements in biochemical markers of CKD-MBD, including reductions in phosphorus, parathyroid hormone, and fibroblast growth factor-23. However, few studies have assessed changes in bone quantity and quality. Furthermore, studies assessing the effects of high-protein diets on CKD-MBD are scarce. Importantly, very-low- and low-protein diets supplemented with KA provide supplemental calcium in amounts that surpass current dietary recommendations, but to date there are no studies on calcium balance with KA. Current evidence suggests that dietary protein restriction in CKD may slow disease progression, which may subsequently benefit CKD-MBD and bone health outcomes. However, prospective randomized controlled trials assessing the effects of modulating dietary protein and supplementing with KA on all aspects of CKD-MBD and particularly bone health are needed.Item 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 MedicineObjective: 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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