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Circulating 20S proteasome for assessing protein energy wasting syndrome in hemodialysis patients.

ABSTRACT: Protein energy wasting (PEW) including muscle atrophy is a common complication in chronic hemodialysis patients. The ubiquitin proteasome system (UPS) is the main proteolytic system causing muscle atrophy in chronic kidney disease and proteasome 20S is the catalytic component of the UPS. Circulating proteasome 20S (c20S proteasome) is present in the blood and its level is related to disease severity and prognosis in several disorders. We hypothesized that c20S proteasome could be related with muscle mass, other PEW criteria and their evolution in hemodialysis patients. Stable hemodialysis patients treated at our center for more than 3 months were followed over 2 years. C20S proteasome assay was performed at baseline. Biological and clinical data were collected, muscle mass was assessed by multi-frequency bio-impedancemetry, and nutritional scores were calculated at baseline, 1 year and 2 years. Hospitalizations and mortality data were collected over the 2 years. Forty-nine patients were included. At baseline, the c20S proteasome level was 0.40[0.26-0.55] ?g/ml. Low muscle mass as defined by a lean tissue index (LTI) < 10th in accordance with the International Society of Renal Nutrition and Metabolism guidelines was observed in 36% and PEW in 62%. Increased c20S proteasome levels were related with LTI at baseline (R = 0.43, p = 0.004) and with its 2 year-variation (R = -0.56, p = 0.003). Two-year survival rate was not different between higher and lower c20S proteasome values (78.9 vs 78.4%, p = 0.98 log-rank test). C20S proteasome is not a good marker for assessing nutritional status in hemodialysis patients and predicting patient outcomes.

SUBMITTER: Aniort J

PROVIDER: S-EPMC7394422 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Circulating 20S proteasome for assessing protein energy wasting syndrome in hemodialysis patients.

Aniort Julien J Freist Marine M Piraud Aurélien A Philipponnet Carole C Hadj Abdelkader Mohamed M Garrouste Cyril C Gentes Elodie E Pereira Bruno B Heng Anne-Elisabeth AE

PloS one 20200731 7

Protein energy wasting (PEW) including muscle atrophy is a common complication in chronic hemodialysis patients. The ubiquitin proteasome system (UPS) is the main proteolytic system causing muscle atrophy in chronic kidney disease and proteasome 20S is the catalytic component of the UPS. Circulating proteasome 20S (c20S proteasome) is present in the blood and its level is related to disease severity and prognosis in several disorders. We hypothesized that c20S proteasome could be related with mu ...[more]

PMID: 32735636

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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:Background and aimProtein-energy wasting (PEW) is critically associated with the reduced quality of life and poor prognosis of hemodialysis patients. However, the diagnosis criteria of PEW are complex, characterized by difficulty in estimating dietary intake and assessing muscle mass loss objectively. We performed a cross-sectional study in hemodialysis patients to propose a novel PEW prediction model.Materials and methodsA total of 380 patients who underwent maintenance hemodialysis were enrolled in this cross-sectional study. The data were analyzed with univariate and multivariable logistic regression to identify influencing factors of PEW. The PEW prediction model was presented as a nomogram by using the results of logistic regression. Furthermore, receiver operating characteristic (ROC) and decision curve analysis (DCA) were used to test the prediction and discrimination ability of the novel model.ResultsBinary logistic regression was used to identify four independent influencing factors, namely, sex (P = 0.03), triglycerides (P = 0.009), vitamin D (P = 0.029), and NT-proBNP (P = 0.029). The nomogram was applied to display the value of each influencing factor contributed to PEW. Then, we built a novel prediction model of PEW (model 3) by combining these four independent variables with part of the International Society of Renal Nutrition and Metabolism (ISRNM) diagnostic criteria including albumin, total cholesterol, and BMI, while the ISRNM diagnostic criteria served as model 1 and model 2. ROC analysis of model 3 showed that the area under the curve was 0.851 (95%CI: 0.799-0.904), and there was no significant difference between model 3 and model 1 or model 2 (all P > 0.05). DCA revealed that the novel prediction model resulted in clinical net benefit as well as the other two models.ConclusionIn this research, we proposed a novel PEW prediction model, which could effectively identify PEW in hemodialysis patients and was more convenient and objective than traditional diagnostic criteria.

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.

Dataset Information

Circulating 20S proteasome for assessing protein energy wasting syndrome in hemodialysis patients.

Publications

Circulating 20S proteasome for assessing protein energy wasting syndrome in hemodialysis patients.

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