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Exploring Metabolic Signature of Protein Energy Wasting in Hemodialysis Patients.

ABSTRACT: End-stage renal disease patients undergoing maintenance hemodialysis (HD) are vulnerable to the protein energy wasting (PEW) syndrome. Identification and diagnosis of PEW relies on clinical processes of judgment dependent on fulfilling multiple criteria drawn from serum biochemistry, weight status, predictive muscle mass, dietary energy and protein intakes. Therefore, we sought to explore the biomarkers' signature with plasma metabolites of PEW by using 1H-nuclear magnetic resonance for an untargeted metabolomics approach in the HD population, to understand metabolic alteration of PEW. In this case-controlled study, a total of 53 patients undergoing chronic HD were identified having PEW based on established diagnostic criteria and were age- and sex-matched with non-PEW (n = 53) HD patients. Fasting predialysis plasma samples were analyzed. Partial least square discriminant analysis demonstrated a significant separation between groups for specific metabolic pattern alterations. Further quantitative analysis showed that the level of 3-hydroxybutyrate, acetate, arabinose, maltose, ribose, sucrose and tartrate were significantly increased whilst creatinine was significantly decreased (all p < 0.05) in PEW subjects. Pathway analysis indicated that PEW-related metabolites reflected perturbations in fatty acid mechanism and induction of glyoxylate and dicarboxylate pathway attributed to gluconeogenesis. These results provide preliminary data in understanding metabolic alteration of PEW and corresponding abnormal metabolites that could potentially serve as biomarkers of PEW.

SUBMITTER: Pauzi FA

PROVIDER: S-EPMC7408592 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Exploring Metabolic Signature of Protein Energy Wasting in Hemodialysis Patients.

Pauzi Fatin Athirah FA Sahathevan Sharmela S Khor Ban-Hock BH Narayanan Sreelakshmi Sankara SS Zakaria Nor Fadhlina NF Abas Faridah F Karupaiah Tilakavati T Daud Zulfitri Azuan Mat ZAM

Metabolites 20200716 7

End-stage renal disease patients undergoing maintenance hemodialysis (HD) are vulnerable to the protein energy wasting (PEW) syndrome. Identification and diagnosis of PEW relies on clinical processes of judgment dependent on fulfilling multiple criteria drawn from serum biochemistry, weight status, predictive muscle mass, dietary energy and protein intakes. Therefore, we sought to explore the biomarkers' signature with plasma metabolites of PEW by using <sup>1</sup>H-nuclear magnetic resonance f ...[more]

PMID: 32708829

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Project description:Background: Muscle wasting, observed in patients with end-stage kidney disease and protein energy wasting (PEW), is associated with increased mortality for those on hemodialysis (HD). Oral nutritional supplementation (ONS) and nutrition counseling (NC) are treatment options for PEW but research targeting muscle status, as an outcome metric, is limited. Aim: We compared the effects of combined treatment (ONS + NC) vs. NC alone on muscle status and nutritional parameters in HD patients with PEW. Methods: This multi-center randomized, open label-controlled trial, registered under ClinicalTrials.gov (Identifier no. NCT04789031), recruited 56 HD patients identified with PEW using the International Society of Renal Nutrition and Metabolism criteria. Patients were randomly allocated to intervention (ONS + NC, n = 29) and control (NC, n = 27) groups. The ONS + NC received commercial renal-specific ONS providing 475 kcal and 21.7 g of protein daily for 6 months. Both groups also received standard NC during the study period. Differences in quadriceps muscle status assessed using ultrasound (US) imaging, arm muscle area and circumference, bio-impedance spectroscopy (BIS), and handgrip strength (HGS) methods were analyzed using the generalized linear model for repeated measures. Results: Muscle indices as per US metrics indicated significance (p < 0.001) for group × time interaction only in the ONS + NC group, with increases by 8.3 and 7.7% for quadriceps muscle thickness and 4.5% for cross-sectional area (all p < 0.05). This effect was not observed for arm muscle area and circumference, BIS metrics and HGS in both the groups. ONS + NC compared to NC demonstrated increased dry weight (p = 0.039), mid-thigh girth (p = 0.004), serum prealbumin (p = 0.005), normalized protein catabolic rate (p = 0.025), and dietary intakes (p < 0.001), along with lower malnutrition-inflammation score (MIS) (p = 0.041). At the end of the study, lesser patients in the ONS + NC group were diagnosed with PEW (24.1%, p = 0.008) as they had achieved dietary adequacy with ONS provision. Conclusion: Combination of ONS with NC was effective in treating PEW and contributed to a gain in the muscle status as assessed by the US, suggesting that the treatment for PEW requires nutritional optimization via ONS.

Project description:BACKGROUND:Muscle weakness is associated with increased mortality risk in chronic haemodialysis (CHD) patients. Protein energy wasting (PEW) and low physical activity could impair muscle quality and contribute to muscle weakness beyond muscle wasting in these patients. Aim of this study was to assess clinical and biological parameters involved in the reduction of muscle strength of CHD patients. METHODS:One hundred and twenty-three CHD patients (80 males, 43 females; 68,8 [57.9-78.8] y.o.) were included in this study. Maximal voluntary force (MVF) of quadriceps was assessed using a belt-stabilized hand-held dynamometer. Muscle quality was evaluated by muscle specific torque, defined as the strength per unit of muscle mass. Muscle mass was estimated using lean tissue index (LTI), skeletal muscle mass (SMM) assessed by bioelectrical impedance analysis and creatinine index (CI). Voorrips questionnaire was used to estimate physical activity. Criteria for the diagnosis of PEW were serum albumin, body mass index < 23 kg/m2, creatinine index < 18.82 mg/kg/d and low dietary protein intake estimated by nPCR < 0.80g/kg/d. RESULTS:MVF was 76.1 [58.2-111.7] N.m. and was associated with CI (? = 5.3 [2.2-8.4], p = 0.001), LTI (? = 2.8 [0.6-5.1], p = 0.013), Voorrips score (? = 17.4 [2.9-31.9], p = 0.02) and serum albumin (? = 1.9 [0.5-3.2], p = 0.006). Only serum albumin (? = 0.09 [0.03-0.15], p = 0.003), Voorrips score (? = 0.8 [0.2-1.5], p = 0.005) and CI (? = 0.2 [0.1-0.3], p<0.001) remained associated with muscle specific torque. Thirty patients have dynapenia defined as impaired MVF with maintained SMM and were younger with high hs-CRP (p = 0.001), PEW criteria (p<0.001) and low Voorrips score (p = 0.001), and reduced dialysis vintage (p<0.046). CONCLUSIONS:Beyond atrophy, physical inactivity and PEW conspire to impair muscle strength and specific torque in CHD patients and could be related to muscle quality. TRIAL REGISTRATION:ClinicalTrials.gov NCT02806089.

Dataset Information

Exploring Metabolic Signature of Protein Energy Wasting in Hemodialysis Patients.

Publications

Exploring Metabolic Signature of Protein Energy Wasting in Hemodialysis Patients.

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