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Dysregulated Handling of Dietary Protein and Muscle Protein Synthesis After Mixed-Meal Ingestion in Maintenance Hemodialysis Patients.

ABSTRACT: Introduction:Skeletal muscle loss is common in patients with renal failure who receive maintenance hemodialysis (MHD) therapy. Regular ingestion of protein-rich meals are recommended to help offset muscle protein loss in MHD patients, but little is known about the anabolic potential of this strategy. Methods:Eight MHD patients (age: 56 ± 5 years; body mass index [BMI]: 32 ± 2 kg/m2) and 8 nonuremic control subjects (age: 50 ± 2 years: BMI: 31 ± 1 kg/m2) received primed continuous L-[ring-2H5]phenylalanine and L-[1-13C]leucine infusions with blood and muscle biopsy sampling on a nondialysis day. Participants consumed a mixed meal (546 kcal; 20-g protein, 59-g carbohydrates, 26-g fat) with protein provided as L-[5,5,5-2H3]leucine-labeled eggs. Results:Circulating dietary amino acid availability was reduced in MHD patients (41 ± 5%) versus control subjects (61 ± 4%; P = 0.03). Basal muscle caspase-3 protein content was elevated (P = 0.03) and large neutral amino acid transporter 1 (LAT1) protein content was reduced (P = 0.02) in MHD patients versus control subjects. Basal muscle protein synthesis (MPS) was ?2-fold higher in MHD patients (0.030 ± 0.005%/h) versus control subjects (0.014 ± 0.003%/h) (P = 0.01). Meal ingestion failed to increase MPS in MHD patients (absolute change from basal: 0.0003 ± 0.007%/h), but stimulated MPS in control subjects (0.009 ± 0.002%/h; P = 0.004). Conclusions:MHD patients demonstrated muscle anabolic resistance to meal ingestion. This blunted postprandial MPS response in MHD patients might be related to high basal MPS, which results in a stimulatory ceiling effect and/or reduced plasma dietary amino acid availability after mixed-meal ingestion.

SUBMITTER: van Vliet S

PROVIDER: S-EPMC6224635 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Dysregulated Handling of Dietary Protein and Muscle Protein Synthesis After Mixed-Meal Ingestion in Maintenance Hemodialysis Patients.

van Vliet Stephan S Skinner Sarah K SK Beals Joseph W JW Pagni Brandon A BA Fang Hsin-Yu HY Ulanov Alexander V AV Li Zhong Z Paluska Scott A SA Mazzulla Michael M West Daniel W D DWD Moore Daniel R DR Wilund Kenneth R KR Burd Nicholas A NA

Kidney international reports 20180817 6

<h4>Introduction</h4>Skeletal muscle loss is common in patients with renal failure who receive maintenance hemodialysis (MHD) therapy. Regular ingestion of protein-rich meals are recommended to help offset muscle protein loss in MHD patients, but little is known about the anabolic potential of this strategy.<h4>Methods</h4>Eight MHD patients (age: 56 ± 5 years; body mass index [BMI]: 32 ± 2 kg/m<sup>2</sup>) and 8 nonuremic control subjects (age: 50 ± 2 years: BMI: 31 ± 1 kg/m<sup>2</sup>) recei ...[more]

PMID: 30450467

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Project description:Rationale & objectiveMore than 50% of hemodialysis patients experience sleep disturbance and most have coexisting sleep apnea. However, how sleep apnea affects sleep and the overall experience of patients with chronic kidney disease treated by hemodialysis has not been evaluated.Study designA mixed-methods design, incorporating cross-sectional observational and descriptive qualitative methodologies.Setting & participantsPatients receiving maintenance hemodialysis in Newcastle, New South Wales, Australia, with newly diagnosed sleep apnea (apnea-hypopnea index ≥ 5 per hour).AssessmentsIn-laboratory polysomnography to assess sleep apnea and objective sleep parameters. Epworth Sleepiness Scale to assess daytime symptoms. A semi-structured qualitative interview to explore patient experience.Analytical approachDescriptive and iterative thematic analysis.ResultsWe analyzed 36 patients with newly diagnosed sleep apnea and interviewed 26 (mean age, 62 years, median apnea-hypopnea index, 32 per hour). Severity of sleep apnea did not affect patients' sleep duration, sleep efficiency, or self-reported Epworth Sleepiness Scale score. From the qualitative interviews, 4 themes emerged: "broken sleep" related to short sleep duration, with waking and dozing off a common sleep cycle, caused by uncontrolled pain and dialysis. Many participants reported regularly "feeling unrefreshed" on waking. "Impact of sleep disturbance" included reduced physical, mental, and self-management capacity. Finally, interviewees described the need to use strategies to "soldier on" with symptoms.LimitationsParticipants' views are only transferrable to hemodialysis patients with sleep apnea.ConclusionsOur findings suggest that severity of sleep apnea does not affect sleep time or patient-reported daytime sleepiness; however, hemodialysis patients with sleep apnea report disturbed and unrefreshed sleep and the debilitating effects of sleep disturbance is profound. Broken and unrefreshed sleep were the dominant symptoms of sleep apnea and should be assessed routinely to identify patients with sleep apnea and improve quality of life in patients with chronic kidney disease treated with hemodialysis.

Project description:BACKGROUND:Systemic inflammation and muscle wasting are highly prevalent and coexist in patients on maintenance hemodialysis (MHD). We aimed to determine the effects of systemic inflammation on skeletal muscle protein metabolism in MHD patients. METHODS:Whole body and skeletal muscle protein turnover were assessed by stable isotope kinetic studies. We incorporated expressions of E1, E214K, E3?I, E3?II, MuRF-1, and atrogin-1 in skeletal muscle tissue from integrin ?1 gene KO CKD mice models. RESULTS:Among 129 patients with mean (± SD) age 47 ± 12 years, 74% were African American, 73% were male, and 22% had diabetes mellitus. Median high-sensitivity C-reactive protein (hs-CRP) concentration was 13 (interquartile range 0.8, 33) mg/l. There were statistically significant associations between hs-CRP and forearm skeletal muscle protein synthesis, degradation, and net forearm skeletal muscle protein balance (P < 0.001 for all). The associations remained statistically significant after adjustment for clinical and demographic confounders, as well as in sensitivity analysis, excluding patients with diabetes mellitus. In attempting to identify potential mechanisms involved in this correlation, we show increased expressions of E1, E214K, E3?I, E3?II, MuRF-1, and atrogin-1 in skeletal muscle tissue obtained from an animal model of chronic kidney disease. CONCLUSION:These data suggest that systemic inflammation is a strong and independent determinant of skeletal muscle protein homeostasis in MHD patients, providing rationale for further studies using anticytokine therapies in patients with underlying systemic inflammation. FUNDING:This study was in part supported by NIH grants R01 DK45604 and 1K24 DK62849, the Clinical Translational Science Award UL1-TR000445 from the National Center for Advancing Translational Sciences, the Veterans Administration Merit Award I01 CX000414, the SatelliteHealth Normon Coplon Extramural Grant Program, and the FDA grant 000943.

Project description:Background and objectivesProtein energy wasting and systemic inflammation are prevalent in maintenance hemodialysis (MHD) patients. Omega-3 (ω-3) fatty acids have anti-inflammatory properties and have been shown to improve protein homeostasis. We hypothesized that administration of high-dose (2.9 g/d) ω-3 would be associated with decreased muscle protein breakdown in MHD patients with systemic inflammation.Design, setting, participants & measurementsThis is a substudy from a randomized, placebo-controlled study (NCT00655525). Patients were recruited between September 2008 and June 2011. Primary inclusion criteria included signs of chronic inflammation (average C-reactive protein of ≥5 mg/L over three consecutive measurements), lack of active infectious or inflammatory disease, no hospitalization within 1 month prior to the study, and not receiving steroids (>5 mg/d) and/or immunosuppressive agents. The primary outcomes were forearm muscle and whole body protein breakdown and synthesis before and after the intervention. The patients received ω-3 (n=11) versus placebo (n=9) for 12 weeks. Analysis of covariance was used to compare outcome variables at 12 weeks. Models were adjusted for a propensity score that was derived from age, sex, race, baseline high sensitivity C-reactive protein, diabetes mellitus, and fat mass because the groups were not balanced for several characteristics.ResultsCompared with placebo, ω-3 supplementation was significantly associated with decreased muscle protein breakdown at 12 weeks (-31, [interquartile range, -98--13] versus 26 [interquartile range, 13-87] µg/100 ml per min; P=0.01), which remained significant after multivariate adjustment (-46, [95% confidence interval, -102 to -1] µg/100 ml per min). ω-3 Supplementation resulted in decreased forearm muscle protein synthesis while the rate in the placebo group increased; however, there is no longer a statistically significant difference in skeletal muscle protein synthesis or in net protein balance after multivariate adjustment. There was no statistically significant effect of ω-3 supplementation on whole body protein synthesis or breakdown.ConclusionsHigh-dose ω-3 supplementation over 12 weeks in MHD patients with systemic inflammation was associated with attenuation of forearm muscle protein breakdown but did not influence skeletal muscle protein synthesis, skeletal muscle net protein balance or any component of the whole-body protein balance. These results should be interpreted cautiously given the imbalance in the two groups and the short duration of the intervention.

Project description:The association between dietary patterns and health outcomes, such as quality of life (QOL), in maintenance hemodialysis (MHD) patients with certain racial backgrounds has not been studied in detail. QOL is a powerful outcome measure in which dietary patterns could be a modifying factor. This study is a secondary analysis examining the association between dietary patterns and health outcomes in 101 African American (AA) maintenance hemodialysis (MHD) patients participating in the Palm Tocotrienols in Chronic Hemodialysis (PATCH) study. Quality of life (QOL) was assessed using the Kidney Disease Quality of Life 36-item survey (KDQOL-36™). Blood samples were analyzed for lipids, lipoprotein subfractions, and inflammatory markers. Food intake was measured using six non-consecutive 24-h dietary recalls over 15 months. Implausible energy intake reports were screened out by comparing reported energy intake (rEI) with predicted total energy expenditure (pTEE). Cluster analysis, using the k-means algorithm, identified two distinct dietary patterns in the study population: a high "sugar sweetened beverage" pattern (hiSSB) and a low "sugar sweetened beverage pattern" (loSSB). In the hiSSB group, consumption of SSB accounted for ~28% of energy intake, while SSB represented only 9% of energy intake in the loSSB group. The hiSSB group was characterized by a higher intake of total calories, sugar and percentage of kilocalories from carbohydrates, whereas the percentage of kilocalories from protein and fat was lower. While additional micronutrient intakes differed between groups (vitamin C, zinc, chromium), these were significantly lower than recommended values in the entire cohort. Patients in the hiSSB group presented with lower high-density lipoprotein cholesterol (HDL-C), lower large HDL particles and smaller low density lipoprotein (LDL) particle diameters. Antidepressant usage was significantly higher in the hiSSB group. Patients in the hiSSB group scored lower across all five KDQOL domains and scored significantly lower in the mental composite domain. MHD patients following a hiSSB dietary pattern had smaller dense LDL particles, lower HDL-C, and a lower QOL. Suboptimal intakes of fruits, vegetables, and grains as well as key micronutrients were evident in both patterns.

Project description:BackgroundChronic alcohol abuse contributes not only to an increased risk of health-related complications, but also to a premature mortality in adults. Myocardial dysfunction, including the development of a syndrome referred to as alcoholic cardiomyopathy, appears to be a major contributing factor. One mechanism to account for the pathogenesis of alcoholic cardiomyopathy involves alterations in protein expression secondary to an inhibition of protein synthesis. However, the full extent to which myocardial proteins are affected by chronic alcohol consumption remains unresolved.MethodsThe purpose of this study was to examine the effect of chronic alcohol consumption on the expression of cardiac proteins. Male rats were maintained for 16 weeks on a 40% ethanol-containing diet in which alcohol was provided both in drinking water and agar blocks. Control animals were pair-fed to consume the same caloric intake. Heart homogenates from control- and ethanol-fed rats were labeled with the cleavable isotope coded affinity tags (ICAT). Following the reaction with the ICAT reagent, we applied one-dimensional gel electrophoresis with in-gel trypsin digestion of proteins and subsequent MALDI-TOF-TOF mass spectrometric techniques for identification of peptides. Differences in the expression of cardiac proteins from control- and ethanol-fed rats were determined by mass spectrometry approaches.ResultsInitial proteomic analysis identified and quantified hundreds of cardiac proteins. Major decreases in the expression of specific myocardial proteins were observed. Proteins were grouped depending on their contribution to multiple activities of cardiac function and metabolism, including mitochondrial-, glycolytic-, myofibrillar-, membrane-associated, and plasma proteins. Another group contained identified proteins that could not be properly categorized under the aforementioned classification system.ConclusionsBased on the changes in proteins, we speculate modulation of cardiac muscle protein expression represents a fundamental alteration induced by chronic alcohol consumption, consistent with changes in myocardial wall thickness measured under the same conditions.

Dataset Information

Dysregulated Handling of Dietary Protein and Muscle Protein Synthesis After Mixed-Meal Ingestion in Maintenance Hemodialysis Patients.

Publications

Dysregulated Handling of Dietary Protein and Muscle Protein Synthesis After Mixed-Meal Ingestion in Maintenance Hemodialysis Patients.

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