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Amino Acid Homeostasis and Fatigue in Chronic Hemodialysis Patients.

ABSTRACT: Patients dependent on chronic hemodialysis treatment are prone to malnutrition, at least in part due to insufficient nutrient intake, metabolic derangements, and chronic inflammation. Losses of amino acids during hemodialysis may be an important additional contributor. In this study, we assessed changes in plasma amino acid concentrations during hemodialysis, quantified intradialytic amino acid losses, and investigated whether plasma amino acid concentrations and amino acid losses by hemodialysis and urinary excretion are associated with fatigue. The study included a total of 59 hemodialysis patients (65 ± 15 years, 63% male) and 33 healthy kidney donors as controls (54 ± 10 years, 45% male). Total plasma essential amino acid concentration before hemodialysis was lower in hemodialysis patients compared with controls (p = 0.006), while total non-essential amino acid concentration did not differ. Daily amino acid losses were 4.0 ± 1.3 g/24 h for hemodialysis patients and 0.6 ± 0.3 g/24 h for controls. Expressed as proportion of protein intake, daily amino acid losses of hemodialysis patients were 6.7 ± 2.4% of the total protein intake, compared to 0.7 ± 0.3% for controls (p < 0.001). Multivariable regression analyses demonstrated that hemodialysis efficacy (Kt/V) was the primary determinant of amino acid losses (Std. β = 0.51; p < 0.001). In logistic regression analyses, higher plasma proline concentrations were associated with higher odds of severe fatigue (OR (95% CI) per SD increment: 3.0 (1.3; 9.3); p = 0.03), while higher taurine concentrations were associated with lower odds of severe fatigue (OR (95% CI) per log2 increment: 0.3 (0.1; 0.7); p = 0.01). Similarly, higher daily taurine losses were also associated with lower odds of severe fatigue (OR (95% CI) per log2 increment: 0.64 (0.42; 0.93); p = 0.03). Lastly, a higher protein intake was associated with lower odds of severe fatigue (OR (95% CI) per SD increment: 0.2 (0.04; 0.5); p = 0.007). Future studies are warranted to investigate the mechanisms underlying these associations and investigate the potential of taurine supplementation.

SUBMITTER: Post A

PROVIDER: S-EPMC9318329 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionA large body of evidence has established a pattern of altered functioning in the immune system, autonomic nervous system and hypothalamic pituitary adrenal axis in chronic fatigue syndrome. However, the relationship between components within and between these systems is unclear. In this paper we investigated the underlying network structure of the autonomic system in patients and controls, and a larger network comprising all three systems in patients alone.MethodsIn a sample of patients and controls we took several measures of autonomic nervous system output during 10 minutes of supine rest covering tests of blood pressure variability, heart rate variability and cardiac output. Awakening salivary cortisol was measured on each of two days with participants receiving 0.5mg dexamethasone during the afternoon of the first day. Basal plasma cytokine levels and the in vitro cytokine response to dexamethasone were also measured. Symptom outcome measures used were the fatigue impact scale and cognitive failures questionnaire. Mutual information criteria were used to construct networks describing the dependency amongst variables. Data from 42 patients and 9 controls were used in constructing autonomic networks, and 15 patients in constructing the combined network.ResultsThe autonomic network in patients showed a more uneven distribution of information, with two distinct modules emerging dominated by systolic blood pressure during active stand and end diastolic volume and stroke volume respectively. The combined network revealed strong links between elements of each of the three regulatory systems, characterised by three higher modules the centres of which were systolic blood pressure during active stand, stroke volume and ejection fraction respectively.ConclusionsCFS is a complex condition affecting physiological systems. It is important that novel analytical techniques are used to understand the abnormalities that lead to CFS. The underlying network structure of the autonomic system is significantly different to that of controls, with a small number of individual nodes being highly influential. The combined network suggests links across regulatory systems which shows how alterations in single nodes might spread throughout the network to produce alterations in other, even distant, nodes. Replication in a larger cohort is warranted.

Project description:Muscle wasting, low protein intake, hypoalbuminemia, low body mass, and chronic fatigue are prevalent in hemodialysis patients. Impaired creatine status may be an often overlooked, potential contributor to these symptoms. However, little is known about creatine homeostasis in hemodialysis patients. We aimed to elucidate creatine homeostasis in hemodialysis patients by assessing intradialytic plasma changes as well as intra- and interdialytic losses of arginine, guanidinoacetate, creatine and creatinine. Additionally, we investigated associations of plasma creatine concentrations with low muscle mass, low protein intake, hypoalbuminemia, low body mass index, and chronic fatigue. Arginine, guanidinoacetate, creatine and creatinine were measured in plasma, dialysate, and urinary samples of 59 hemodialysis patients. Mean age was 65 ± 15 years and 63% were male. During hemodialysis, plasma concentrations of arginine (77 ± 22 to 60 ± 19 μmol/L), guanidinoacetate (1.8 ± 0.6 to 1.0 ± 0.3 μmol/L), creatine (26 [16-41] to 21 [15-30] μmol/L) and creatinine (689 ± 207 to 257 ± 92 μmol/L) decreased (all P < 0.001). During a hemodialysis session, patients lost 1939 ± 871 μmol arginine, 37 ± 20 μmol guanidinoacetate, 719 [399-1070] μmol creatine and 15.5 ± 8.4 mmol creatinine. In sex-adjusted models, lower plasma creatine was associated with a higher odds of low muscle mass (OR per halving: 2.00 [1.05-4.14]; P = 0.04), low protein intake (OR: 2.13 [1.17-4.27]; P = 0.02), hypoalbuminemia (OR: 3.13 [1.46-8.02]; P = 0.008) and severe fatigue (OR: 3.20 [1.52-8.05]; P = 0.006). After adjustment for potential confounders, these associations remained materially unchanged. Creatine is iatrogenically removed during hemodialysis and lower plasma creatine concentrations were associated with higher odds of low muscle mass, low protein intake, hypoalbuminemia, and severe fatigue, indicating a potential role for creatine supplementation.

Project description:BackgroundHemodialysis is one of the common therapies in patients with end-stage renal disease. Even patients who receive regular treatment suffer from fatigue, which is one of the main factors leading to poor quality of life. This study aimed to determine the effectiveness of exercising on mini-bikes on fatigue in hemodialysis patients.MethodsThis study is a randomized controlled clinical trial. Thirty-seven hemodialysis patients participated in the study. The patients were randomly allocated to either the intervention group (n = 20) or the control group (n = 17). The participants in the intervention group exercised on mini-bikes for 20 min twice a week for 3 months. The patients' fatigue was measured four times during and after the intervention. Multidimensional Fatigue Inventory was used to measure the fatigue level. The total score in the MFI is 4 to 20 for each domain, with the resulting total fatigue score ranging from 20 to 100; thus, the higher the score, the higher the level of fatigue. Data were analyzed by SPSS 18. The repeated measures ANOVA was used to compare the fatigue scores within each group and between the groups at different times.ResultsThe mean score of fatigue in the intervention group at the beginning was 58.80 ± 15.29, which steadily decreased to 58.78 ± 13.54, 58.75 ± 14.73, 54.20 ± 15.16, and 54.23 ± 13.60 for the 3 months of intervention and 1 month post-intervention, respectively. In contrast, in the control group, this score was 62.53 ± 16.32 in the beginning, increasing to 64.03 ± 13.91, 64.22 ± 13.07, 69.53 ± 9.22, for the 3 months of intervention and 70.34 ± 7.69 one-month post-intervention. There were significant differences between the intervention group and the control group in the third month (P = 0.001) and 1 month after the intervention (P < 0.001).ConclusionsThe results showed that rehabilitation through exercising using mini-bikes had a significant impact on preventing further fatigue build-up in hemodialysis patients, making the mini-bike an effective non-pharmaceutical intervention preventing the increase in fatigue experienced by patients undergoing hemodialysis.Trial registrationIranian Registry of Clinical Trials: IRCT20180314039100N1. Registered 10 June 2018.

Project description:Background and objectivesFatigue is a very common and debilitating symptom and identified by patients as a critically important core outcome to be included in all trials involving patients receiving hemodialysis. A valid, standardized measure for fatigue is needed to yield meaningful and relevant evidence about this outcome. This study validated a core patient-reported outcome measure for fatigue in hemodialysis.Design, setting, participants, & measurementsA longitudinal cohort study was conducted to assess the validity and reliability of a new fatigue measure (Standardized Outcomes in Nephrology-Hemodialysis Fatigue [SONG-HD Fatigue]). Eligible and consenting patients completed the measure at three time points: baseline, a week later, and 12 days following the second time point. Cronbach α and intraclass correlation coefficient were calculated to assess internal consistency, and Spearman rho was used to assess convergent validity. Confirmatory factor analysis was also conducted. Hemodialysis units in the United Kingdom, Australia, and Romania participated in this study. Adult patients aged 18 years and over who were English speaking and receiving maintenance hemodialysis were eligible to participate. Standardized Outcomes in Nephrology-Hemodialysis, the Visual Analog Scale for fatigue, the 12-Item Short Form Survey, and Functional Assessment of Chronic Illness Therapy-Fatigue were used.ResultsIn total, 485 participants completed the study across the United Kingdom, Australia, and Romania. Psychometric assessment demonstrated that Standardized Outcomes in Nephrology-Hemodialysis is internally consistent (Cronbach α =0.81-0.86) and stable over a 1-week period (intraclass correlation coefficient =0.68-0.74). The measure demonstrated convergence with Functional Assessment of Chronic Illness Therapy-Fatigue and had moderate correlations with other measures that assessed related but not the same concept (the 12-Item Short Form Survey and the Visual Analog Scale). Confirmatory factor analysis supported the one-factor model.ConclusionsSONG-HD Fatigue seems to be a reliable and valid measure to be used in trials involving patients receiving hemodialysis.

Project description:BackgroundSarcopenia, which is strongly associated with mortality and quality of life, occurs in up to 40% of hemodialysis patients. Here, we investigated the preventive effects of leucine-enriched amino acid supplementation and resistance exercise in non-sarcopenic hemodialysis patients, and characterized the biochemical and immunophenotypic profiles of those who benefited from the intervention.MethodsTwenty-two patients on maintenance hemodialysis at our hospital were enrolled in this single center, prospective, single-arm pilot trial. For the first 12 weeks, the subjects were administered a total of 6 g of leucine per day. Three grams were supplied via capsules, and the remaining three grams were provided via beverages containing macro- and micro- nutrients, such as 10 μg of vitamin D and 290 mg of calcium. The supplements were not provided for the next 12 weeks. Muscle mass, grip strength, and physical performance were measured using the bioimpedance analyzer (BIA), handgrip strength (HGS), and short physical performance battery (SPPB) protocols, respectively, at baseline, 12 weeks, and 24 weeks. In addition, serum biochemistry, immunophenotype of peripheral blood mononuclear cells, and nutritional status was assessed at the three time points. Those who showed 5% or more improvement in parameters were defined as responders, otherwise, as non-responders (ClinicalTrials.gov identification number: NCT04927208).ResultsTwenty-one out of twenty-two patients (95.4%) showed improvement in at least one or more parameters among muscle mass, grip strength, and physical performance. After 12 weeks of intervention, skeletal muscle index was increased in 14 patients (63.6%), and grip strength was improved in 7 patients (31.8%). Baseline grip strength lower than 35.0 kg was the strongest predictor of improvement in grip strength (AUC 0.933 from ROC curve). Grip strength showed a significant increase in females than males (7.6 ± 8.2 vs. -1.6 ± 7.2%, p = 0.03), in age over 60 than under 60 (5.3 ± 6.2 vs. -1.4 ± 9.1%, p = 0.04), and in higher (≥95%) than lower (<95%) exercise compliance (6.8 ± 7.7 vs. -3.2 ± 6.4%, p = 0.004). In SPPB study, gait speed and sit-to-stand time was improved in 13 patients (59.1%) and 14 patients (63.6%), respectively. Baseline hemoglobin lower than 10.5 g/dl and hematocrit lower than 30.8% were predictor of improvement in the sit-to-stand time (AUC 0.862 and 0.848, respectively). Serum biochemistry results showed that, compared to non-responders, responders in muscle mass had lower baseline monocyte fraction (8.4 ± 1.9 vs. 6.9 ± 1.1%, p = 0.03), and responders in grip strength had lower baseline total protein (6.7 ± 0.4 vs. 6.4 ± 0.3 g/dL, p = 0.04). Immunophenotypic analysis found that the intervention tended to increase the naïve/memory CD8+ T cell ratio (from 1.2 ± 0.8 to 1.4 ± 1.1, p = 0.07).ConclusionLeucine-enriched amino acid supplementation and resistance exercise induced significant improvement in muscle mass, strength, and physical function in subpopulation of the non-sarcopenic hemodialysis patients. Those who benefited from the intervention were old-age females with lower baseline grip strength or lower hemoglobin or hematocrit, and who have good exercise compliance. Therefore, we propose that the intervention will help to prevent sarcopenia in selected patients on maintenance hemodialysis.

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Amino Acid Homeostasis and Fatigue in Chronic Hemodialysis Patients.

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