Browsing by Subject "Chronic kidney disease (CKD)"

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    Assessing Global Kidney Nutrition Care
    (Wolters Kluwer, 2022) Wang, Angela Yee-Moon; Okpechi, Ikechi G.; Ye, Feng; Kovesdy, Csaba P.; Brunori, Giuliano; Burrowes, Jerrilynn D.; Campbell, Katrina; Damster, Sandrine; Fouque, Denis; Friedman, Allon N.; Garibotto, Giacomo; Guebre-Egziabher, Fitsum; Harris, David; Iseki, Kunitoshi; Jha, Vivekanand; Jindal, Kailash; Kalantar-Zadeh, Kamyar; Kistler, Brandon; Kopple, Joel D.; Kuhlmann, Martin; Lunney, Meaghan; Mafra, Denise; Malik, Charu; Moore, Linda W.; Price, S. Russ; Steiber, Alison; Wanner, Christoph; Wee, Pieter Ter; Levin, Adeera; Johnson, David W.; Bello, Aminu K.; Medicine, School of Medicine
    Background and objectives: Nutrition intervention is an essential component of kidney disease management. This study aimed to understand current global availability and capacity of kidney nutrition care services, interdisciplinary communication, and availability of oral nutrition supplements. Design, setting, participants, & measurements: The International Society of Renal Nutrition and Metabolism (ISRNM), working in partnership with the International Society of Nephrology (ISN) Global Kidney Health Atlas Committee, developed this Global Kidney Nutrition Care Atlas. An electronic survey was administered among key kidney care stakeholders through 182 ISN-affiliated countries between July and September 2018. Results: Overall, 160 of 182 countries (88%) responded, of which 155 countries (97%) answered the survey items related to kidney nutrition care. Only 48% of the 155 countries have dietitians/renal dietitians to provide this specialized service. Dietary counseling, provided by a person trained in nutrition, was generally not available in 65% of low-/lower middle-income countries and "never" available in 23% of low-income countries. Forty-one percent of the countries did not provide formal assessment of nutrition status for kidney nutrition care. The availability of oral nutrition supplements varied globally and, mostly, were not freely available in low-/lower middle-income countries for both inpatient and outpatient settings. Dietitians and nephrologists only communicated "sometimes" on kidney nutrition care in ≥60% of countries globally. Conclusions: This survey reveals significant gaps in global kidney nutrition care service capacity, availability, cost coverage, and deficiencies in interdisciplinary communication on kidney nutrition care delivery, especially in lower-income countries.
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    Calcimimetics Alter Periosteal and Perilacunar Bone Matrix Composition and Material Properties in Early Chronic Kidney Disease
    (Wiley, 2022) Damrath, John G.; Moe, Sharon M.; Wallace, Joseph M.; Medicine, School of Medicine
    Chronic kidney disease (CKD) affects 15% of Americans and greatly increases fracture risk due to elevated parathyroid hormone, cortical porosity, and reduced bone material quality. Calcimimetic drugs are used to lower parathyroid hormone (PTH) in CKD patients, but their impact on bone matrix properties remains unknown. We hypothesized that tissue-level bone quality is altered in early CKD and that calcimimetic treatment will prevent these alterations. To test this hypothesis, we treated Cy/+ rats, a model of spontaneous and progressive CKD-mineral and bone disorder (CKD-MBD), with KP-2326, a preclinical analogue of etelcalcetide, early in the CKD disease course. To measure tissue-level bone matrix composition and material properties, we performed colocalized Raman spectroscopy and nanoindentation on new periosteal bone and perilacunar bone using hydrated femur sections. We found that CKD and KP treatment lowered mineral type B carbonate substitution whereas KP treatment increased mineral crystallinity in new periosteal bone. Reduced elastic modulus was lower in CKD but was not different in KP-treated rats versus CTRL. In perilacunar bone, KP treatment lowered type B carbonate substitution, increased crystallinity, and increased mineral-to-matrix ratio in a spatially dependent manner. KP treatment also increased reduced elastic modulus and hardness in a spatially dependent manner. Taken together, these data suggest that KP treatment improves material properties on the tissue level through a combination of lowering carbonate substitution, increasing mineral crystallinity, and increasing relative mineralization of the bone early in CKD. As a result, the mechanical properties were improved, and in some regions, were the same as control animals. Therefore, calcimimetics may help prevent CKD-induced bone deterioration by improving bone quality in new periosteal bone and in bone tissue near osteocyte lacunae.
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    CHRONIC KIDNEY DISEASE, MUSCLE WEAKNESS, AND MOBILITY LIMITATION
    (Oxford University Press, 2019-11) Latham-Mintus, Kenzie; Doshi, Simit; Moorthi, Ranjani; Medicine, School of Medicine
    Objectives: Chronic kidney disease (CKD) is associated with increased mobility limitation. Prior research has documented that peripheral nerve abnormalities occur early in CKD and progressively worsen. Loss of balance, impaired muscle strength, and slow gait predispose older adults to falls and frailty. However, the current literature is limited by a lack of nationally representative data that includes objective measures of kidney disease and physical functioning. Thus, this research examines whether CKD is associated with muscle strength, balance, gait, and self-reported mobility limitations. Methods: Data come from the 2016 Health and Retirement Study (HRS). Estimated GFR, a measure of kidney functioning derived from creatinine levels in the blood, was used to classify CKD (i.e, eGFR<45 or Stage 3b CKD). Logistic and linear regression models were generated to examine the association of CKD with physical functioning, net of demographic characteristics (i.e., age, sex, race, and education) and comorbidities (i.e., obesity, pain, and number of diagnosed medical conditions). Results: In unadjusted models, CKD was significantly associated (p<0.05) with more mobility limitations, slower walking speeds, stronger grip strengths, and non-participation in balance tests. After adjusting for covariates, CKD (β=-1.43, p=0.01) was negatively associated with grip strength. In sex-stratified models, CKD was associated with slower walking speeds among men, whereas CKD was associated with more mobility limitations among women. Discussion: In a nationally representative sample of older adults, CKD was associated with poorer physical functioning on multiple measures. After adjusting for demographic characteristics and comorbidities, CKD was associated with increased muscle weakness.
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    Cortical porosity is elevated after a single dose of zoledronate in two rodent models of chronic kidney disease
    (Elsevier, 2022-02-07) Swallow, Elizabeth A.; Metzger, Corrine E.; Chen, Neal X.; Wallace, Joseph M.; Tippen, Samantha P.; Kohler, Rachel; Moe, Sharon M.; Allen, Matthew R.; Anatomy, Cell Biology and Physiology, School of Medicine
    Purpose: Patients with chronic kidney disease (CKD) have high risk of fracture in part due to cortical bone deterioration. The goal of this study was to assess the impact of two different bisphosphonates and dosing regimens on cortical microstructure (porosity, thickness, area) and bone mechanical properties in animal models of CKD. Methods: In experiment 1, Male Cy/+ (CKD) rats were treated with either a single dose or ten fractionated doses of zoledronate at 18 weeks of age. Fractionated animals received 1/10th of single dose given weekly for 10 weeks, with study endpoint at 28 weeks of age. In experiment 2, male C57Bl/6 J mice were given dietary adenine (0.2%) to induce CKD. Bisphosphonate treated groups were given either a single dose of zoledronate or weekly risedronate injections for 4 weeks. Cortical microstructure was assessed via μCT and mechanical parameters evaluated by monotonic bending tests. Results: Exp 1: CKD rats had higher blood urea nitrogen (BUN) and parathyroid hormone (PTH) compared to NL littermate controls. Single dose zoledronate had significantly higher cortical porosity in CKD S.Zol (2.29%) compared to NL control (0.04%) and untreated CKD (0.14%) (p = 0.004). Exp 2: All adenine groups had significantly higher BUN and PTH compared to control mice. Mice treated with single dose zoledronate (Ad + Zol) had the highest porosity (~6%), which was significantly higher compared to either Ad or Ad + Ris (~3%; p < 0.0001) and control mice had the lowest cortical porosity (0.35%). In both experiments, mechanics were minimally affected by any bisphosphonate dosing regimen. Conclusion: A single dose of zoledronate leads to higher cortical porosity compared to more frequent dosing of bisphosphonates (fractionated zoledronate or risedronate). Bisphosphonate treatment demonstrated limited effectiveness in preventing cortical bone microstructure deterioration with mechanical parameters remaining compromised due to CKD and/or secondary hyperparathyroidism irrespective of bisphosphonate treatment.
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    Cortical porosity occurs at varying degrees throughout the skeleton in rats with chronic kidney disease
    (Elsevier, 2022-08-17) Metzger, Corinne E.; Newman, Christopher L.; Tippen, Samantha P.; Golemme, Natalie T.; Chen, Neal X.; Moe, Sharon M.; Allen, Matthew R.; Anatomy, Cell Biology and Physiology, School of Medicine
    Cortical porosity develops in chronic kidney disease (CKD) and increases with progressing disease. Cortical porosity is likely a prominent contributor to skeletal fragility/fracture. The degree to which cortical porosity occurs throughout the skeleton is not fully known. In this study, we assessed cortical bone porosity via micro-computed tomography at multiple skeletal sites in rats with progressive chronic kidney disease. We hypothesized that cortical porosity would occur in long bones throughout the body, but to a lesser degree in flat bones and irregular bones. Porosity was measured, using micro-CT, at 17 different skeletal sites in 6 male rats with CKD. Varying degrees of porosity were seen throughout the skeleton with higher porosity in flat and irregular bone (i.e. parietal bone, mandible) vs. long bones (p = 0.01) and in non-weightbearing bones vs. weightbearing bones (p = 0.01). Porosity was also higher in proximal sites vs. distal sites in long bones (p < 0.01 in all comparisons). There was large heterogeneity in porosity within skeletal sites across rats and within the same rat across skeletal sites. Correlations showed cortical porosity of the proximal tibia was positively associated with porosity at the other sites with the strongest correlation to the parietal bone and the weakest to the ulna. Overall, our data demonstrates varying and significant cortical bone porosity across the skeleton of animals with chronic kidney disease. These data point to careful selection of skeletal sites to assess porosity in pre-clinical studies and the potential for fractures at multiple skeletal sites in patients with CKD.
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    DEPOT: graph learning delineates the roles of cancers in the progression trajectories of chronic kidney disease using electronic medical records
    (medRxiv, 2023-08-16) Song, Qianqian; Liu, Xiang; Li, Zuotian; Zhang, Pengyue; Eadon, Michael; Su, Jing; Biostatistics and Health Data Science, School of Medicine
    Chronic kidney disease (CKD) is a common, complex, and heterogeneous disease impacting aging populations. Determining the landscape of disease progression trajectories from midlife to senior age in a real-world context allows us to better understand the progression of CKD, the heterogeneity of progression patterns among the risk population, and the interactions with other clinical conditions like cancers. In this study, we use electronic health records (EHRs) to outline the CKD progression trajectory roadmap for the Wake Forest Baptist Medical Center (WFBMC) patient population. We establish an EHR cohort (n = 79,434) with patients' health status identified by 18 Essential Clinical Indices across 508,732 clinical encounters. We develop the DisEase PrOgression Trajectory (DEPOT) approach to model CKD progression trajectories and individualize clinical decision support. The DEPOT is an evidence-driven, graph-based clinical informatics approach that addresses the unique challenges in longitudinal EHR data by systematically using the graph artificial intelligence (graph-AI) model for representation learning and reverse graph embedding for trajectory reconstruction. Moreover, DEPOT includes a prediction model to assign new patients along the progression trajectory. We successfully establish the EHR-based CKD progression trajectories with DEPOT in the WFUBMC cohort. We annotate the trajectories with clinical features, including kidney function, age, and other indices, including cancer. This CKD progression trajectory roadmap reveals diverse kidney failure pathways associated with different clinical conditions. Specifically, we have identified one high-risk trajectory and two low-risk trajectories. Switching pathways from low-risk trajectories to the high-risk one is associated with accelerated decline in kidney function. On this roadmap, high-risk patients are enriched in the skin and GU cancers, which differs from low-risk patients, suggesting fundamentally different disease progression mechanisms. Overall, the CKD progression trajectory roadmap reveals novel diverse renal failure pathways in type 2 diabetes mellitus and highlights disease progression patterns associated with cancer phenotypes.
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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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    Effects of Plant-Based Protein Consumption on Kidney Function and Mineral Bone Disorder Outcomes in Adults With Stage 3-5 Chronic Kidney Disease: A Systematic Review
    (Elsevier, 2023) Burstad, Kendal M.; Cladis, Dennis P.; Wiese, Gretchen N.; Butler, Mary; Hill Gallant, Kathleen M.; Medicine, School of Medicine
    Introduction Plant-based protein is of growing interest for dietary management of chronic kidney disease (CKD) and is hypothesized to preserve kidney function and reduce CKD-mineral bone disorder (MBD) complications, among other benefits. This systematic review aimed to summarize the available clinical trial evidence for the effect of plant-based protein on kidney function and CKD-MBD outcomes in adults with stage 3-5 CKD not on dialysis. Methods Searches of Medline, Embase, Agricola, CAB abstracts, Web of Science, Scopus, and hand searching were performed. Clinical trials with ≥8 participants ≥18 years of age with an estimated glomerular filtration rate <60 mL/min/1.73 m2 but not on dialysis were included. Additionally, only clinical trials with ≥1-week interventions with ≥50% dietary protein from plant-based sources and reported at least one outcome for both kidney function and CKD-MBD outcomes were included. Of the 10,962 identified abstracts, 32 met inclusion criteria and were assessed for risk of bias. Results Results for kidney function and CKD-MBD outcomes were heterogenous, with most studies having suboptimal methodological quality. In most of the studies (27/32), protein source was altered only secondarily to low-protein diet interventions. Thus, data synthesis and interpretation were focused on a subset of five studies that investigated a change in protein source only (i.e., animal vs. plant). Of this subset, four studies reported no change in kidney function, while one study reported a decrease. Three studies reported no change in serum phosphorus, and one study reported lower serum phosphorus following a vegetarian diet. Further, limited data and inconclusive results were observed for phosphaturic hormones, parathyroid hormone, and fibroblast growth factor-23. Conclusion Current clinical trial evidence on plant-based protein interventions for preserving kidney function and preventing CKD-MBD is limited to inform clinical guidelines at this time. This systematic review emphasizes the ongoing need to research the effects of plant-based protein on kidney function and CKD-MBD outcomes.
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    Feeling gutted in chronic kidney disease (CKD): Gastrointestinal disorders and therapies to improve gastrointestinal health in individuals CKD, including those undergoing dialysis
    (Wiley, 2021-10-27) Biruete, Annabel; Shin, Andrea; Kistler, Brandon M.; Moe, Sharon M.; Nutrition and Dietetics, School of Health and Human Sciences
    Chronic kidney disease (CKD) affects 9.1% of the population worldwide. CKD may lead to structural and functional gastrointestinal alterations, including impairment in the intestinal barrier, digestion and absorption of nutrients, motility, and changes to the gut microbiome. These changes can lead to increased gastrointestinal symptoms in people with CKD, even in early grades of kidney dysfunction. Gastrointestinal symptoms have been associated with lower quality of life and reduced nutritional status. Therefore, there has been considerable interest in improving gastrointestinal health in this clinical population. Gastrointestinal health can be influenced by lifestyle and medications, particularly in advanced grades of kidney dysfunction. Therapies focused on gastrointestinal health have been studied, including the use of probiotics, prebiotics, and synbiotics, yielding limited and conflicting results. This review summarizes the alterations in the gastrointestinal tract structure and function and provides an overview of potential nutritional interventions that kidney disease professionals can provide to improve gastrointestinal health in individuals with CKD.
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    Heart failure with reduced ejection fraction and the intersection of cardio-renal-metabolic medicine #CaReMe
    (Oxford University Press, 2022-12-19) Marx, Nikolaus; Cheng, Alice Y. Y.; Agarwal, Rajiv; Greene, Stephen J.; Abuhantash, Hadi; Medicine, School of Medicine
    Diabetes and chronic kidney disease (CKD) are important comorbidities in patients with heart failure (HF) that can complicate the clinical management and have major implications for morbidity and mortality. In addition, the presence of these comorbidities, particularly advanced CKD, is a limitation for the implementation of guideline-directed therapies in patients with HF with reduced ejection fraction (HFrEF). Though clinical trials in patients with HFrEF trials included varying percentages of patients with diabetes and/or CKD, patients with advanced CKD have been excluded in most HF studies. Thus, management recommendations for these patients often have to be extrapolated from subgroup analyses. This article summarizes pathophysiological aspects of the interaction of HFrEF, CKD, and diabetes and addresses clinical aspects for the screening of these comorbidities. Moreover, current treatment options for patients with HFrEF and CKD and/or diabetes are discussed and novel strategies such as the use of the selective mineralocorticoid receptor antagonist Finerenone are addressed.