Browsing by Author "Hill Gallant, Kathleen M."

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    4438 Twenty-four-hour Urinary Sodium Excretion Estimated from a Spot Urine Sample May Be Used as an Indicator of Intake in CKD Patients
    (Cambridge University Press, 2020-07-29) Lobene, Andrea; Stremke, Elizabeth; Moorthi, Ranjani; Moe, Sharon; Hill Gallant, Kathleen M.; Medicine, School of Medicine
    OBJECTIVES/GOALS: Sodium (Na) intake can elevate blood pressure and is a factor in developing chronic kidney disease (CKD). Twenty-four-hour urinary Na (24hUNa) is the gold standard for assessing Na intake but is burdensome. Validated equations estimate 24hUNa (e24hUNa) from a spot urine sample, but these estimations are not validated against a known Na intake in CKD. METHODS/STUDY POPULATION: The current study is a secondary analysis of a 9-day controlled feeding study in moderate CKD patients matched to healthy adults. Only CKD patients were used for the current analyses (n = 8). Participants consumed a controlled diet for 9 days, providing ~2400 mg Na/d as determined by inductively coupled plasma optical emission spectroscopy (ICP). On days 7 and 8, participants collected all urine in an inpatient setting, beginning with a fasting sample on day 7. Urine sample mineral analyses were performed by ICP and urinary creatinine by the Jaffe reaction. The day 7 fasting urine sample was used to calculate e24hUNa using 6 published equations. Log-transformed Na intake, measured 24hUNa, and e24hUNa were compared by repeated-measures ANOVA with planned contrasts using SAS. RESULTS/ANTICIPATED RESULTS: Fifty percent of the CKD patients (n = 4) were female; 63% (n = 5) were white, and 37% (n = 3) were black. On average, participants were aged 56.6 ± 13.8 y with a BMI of 31.7 ± 9.4 kg/m2 and eGFR of 40.7 ± 7.9 mL/min. Based on actual food intake, average Na intake on day 7 was 2024 ± 388 mg. Average measured 24hUNa was 2529 ± 1334 mg. The main ANOVA was significant (p = 0.02). Results from the planned contrasts found that e24hUNa from the SALTED cohort, an equation developed specifically for CKD patients, was significantly higher than both Na intake (p<0.001) and measured 24hUNa (p = 0.007). For the remaining 5 equations, e24hUNa was not significantly different from measured 24hUNa nor dietary Na intake. DISCUSSION/SIGNIFICANCE OF IMPACT : Our results suggest that e24hUNa calculated using most published equations may provide a reliable and low-burden method of assessing dietary Na intake in moderate CKD patients. These findings should be confirmed in larger samples. Additional studies are needed to validate or dispute the use of the SALTED equation for estimating Na intake.
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    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 Medicine
    OBJECTIVES/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.
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    A Systematic Review and Qualitative Analysis of Existing Dietary Mobile Applications for People With Chronic Kidney Disease
    (Elsevier, 2022) Russell, Carl R., III; Zigan, Clarisse; Wozniak, Kirsten; Soni, Kshaunish; Hill Gallant, Kathleen M.; Friedman, Allon N.; Medicine, School of Medicine
    Objective: The goal of this study was to systematically evaluate the quality of electronic applications (apps) available for chronic kidney disease (CKD) dietary management. Methods: The review consisted of (1) a systematic search for all mobile CKD diet apps available on the App Store and Google Play Store, (2) an evaluation to determine how well existing apps met criteria for an ideal app, and (3) a systematic literature review of publications found through Google Scholar, Mendeley, and PubMed that reviewed specific CKD diet apps and the broader field. Results: After applying systematic search criteria, 10 unique apps were identified. Ten of 14 criteria considered necessary in an ideal CKD diet app were applied to the 13 apps. Important criteria such as tailoring recommendations to CKD stage or individual dietary needs, tracking nutrient intake, allowing data to be accessible to clinicians, availability on different app platforms, and including CKD-friendly recipes were not consistently available in the apps. None of the apps used the most contemporary nutrition guidelines on which to base their recommendations. While the literature suggests there is demand for CKD diet apps, common shortcomings of available apps including barriers to usability, inclusion of erroneous information, the requirement of a high e-literacy level, user costs, lack of privacy, security, and interactive features, and the inability of caregivers or family members to use apps to assist in patient care. Conclusions: The few CKD dietary apps currently on the market for people with CKD have notable limitations in terms of content and software design. Opportunities therefore exist for improving on available CKD diet apps and thereby fulfilling an important unmet need for patients with CKD.
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    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 Medicine
    Dietary 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.
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    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 Medicine
    Background: 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.
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    Associations among osteocalcin, leptin and metabolic health in children ages 9-13 years in the United States
    (BioMed Central, 2017-03-07) Virecoulon Giudici, Kelly; Kindler, Joseph M.; Martin, Berdine R.; Laing, Emma M.; McCabe, George P.; McCabe, Linda D.; Hausman, Dorothy B.; Martini, Lígia Araújo; Lewis, Richard D.; Weaver, Connie M.; Peacock, Munro; Hill Gallant, Kathleen M.; Department of Medicine, IU School of Medicine
    BACKGROUND: This study aimed to investigate the relationships among osteocalcin, leptin and metabolic health outcomes in children ages 9-13 years. METHODS: This was a cross-sectional analysis of baseline data from 161 boys and 157 girls (ages 9-13 years) who previously participated in a double-blinded randomized placebo controlled trial of vitamin D supplementation. Relationships among fasting serum total osteocalcin (tOC), undercarboxylated osteocalcin (ucOC), leptin, and metabolic health outcomes were analyzed. RESULTS: Approximately 52% of study participants were obese based on percent body fat cutoffs (>25% for boys and >32% for girls) and about 5% had fasting serum glucose within the prediabetic range (i.e. 100 to 125 mg/dL). Serum tOC was not correlated with leptin, glucose, insulin, HOMA-IR, or HOMA-β after adjusting for percent body fat. However, serum ucOC negatively correlated with leptin (partial r = -0.16; p = 0.04) and glucose (partial r = -0.16; p = 0.04) after adjustment for percent body fat. Leptin was a positive predictor of insulin, glucose, HOMA-IR, and HOMA-β after adjusting for age, sex and percent body fat (all p < 0.001). CONCLUSIONS: These data depict an inverse relationship between leptin and various metabolic health outcomes in children. However, the notion that tOC or ucOC link fat with energy metabolism in healthy children was not supported.
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    Blueberry Polyphenols do not Improve Bone Mineral Density or Mechanical Properties in Ovariectomized Rats
    (Springer, 2022) Cladis, Dennis P.; Swallow, Elizabeth A.; Allen, Matthew R.; Hill Gallant, Kathleen M.; Weaver, Connie M.; Anatomy, Cell Biology and Physiology, School of Medicine
    Osteoporosis-related bone fragility fractures are a major public health concern. Given the potential for adverse side effects of pharmacological treatment, many have sought alternative treatments, including dietary changes. Based on recent evidence that polyphenol-rich foods, like blueberries, increase calcium absorption and bone mineral density (BMD), we hypothesized that blueberry polyphenols would improve bone biomechanical properties. To test this, 5-month-old ovariectomized Sprague-Dawley rats (n = 10/gp) were orally gavaged for 90 days with either a purified extract of blueberry polyphenols (0-1000 mg total polyphenols/kg bw/day) or lyophilized blueberries (50 mg total polyphenols/kg bw/day). Upon completion of the dosing regimen, right femur, right tibia, and L1-L4 vertebrae were harvested and assessed for bone mineral density (BMD), with femurs being further analyzed for biomechanical properties via three-point bending. There were no differences in BMD at any of the sites analyzed. For bone mechanical properties, the only statistically significant difference was the high dose group having greater ultimate stress than the medium dose, although in the absence of differences in other measures of bone mechanical properties, we concluded that this result, while statistically significant, had little biological significance. Our results indicate that blueberry polyphenols had little impact on BMD or bone mechanical properties in an animal model of estrogen deficiency-induced bone loss.
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    Diet and Diabetic Kidney Disease: Plant Versus Animal Protein
    (Springer, 2017-03) Moorthi, Ranjani N.; Vorland, Colby J.; Hill Gallant, Kathleen M.; Medicine, School of Medicine
    PURPOSE OF REVIEW: The goal of this review is to present an overview of the evidence on the effectiveness of plant-based diets in delaying progression of diabetic kidney disease (DKD). RECENT FINDINGS: The ideal quantity of dietary protein has been a controversial topic for patients with DKD. Smaller studies have focused on protein source, plant versus animal, for preventing progression. Limited evidence suggests that dietary patterns that focus on plant-based foods, those that are lower in processed foods, or those that are lower in advanced glycation end products (AGE) may be useful in prevention of DKD progression. Increasing plant-based foods, incorporating diet patterns that limit processed foods, or potentially lowering AGE contents in diets may be beneficial for dietary management of DKD. However, dietary studies specifically targeted at DKD treatment are sparse. Further, large trials powered to assess outcomes including changes in kidney function, end-stage kidney disease, and mortality are needed to provide more substantial evidence for these diets.
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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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    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 Medicine
    Purpose 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.