Ivabradine restores tonic cardiovascular autonomic control and reduces tachycardia, hypertension and left ventricular inflammation in post-weaning protein malnourished rats.

Malnutrition results in autonomic imbalance and heart hypertrophy. Overexpression of hyperpolarization-activated cyclic nucleotide-gated channels (HCN) in the left ventricles (LV) is linked to hypertrophied hearts and abnormal myocardium automaticity. Given that ivabradine (IVA) has emerging pleiotropic effects, in addition to the widely known bradycardic response, this study evaluated if IVA treatment could repair the autonomic control and cardiac damages in malnourished rats. AIM: Assess the impact of IVA on tonic cardiovascular autonomic control and its relationship with hemodynamics regulation, LV inflammation, and HCN gene expression in post-weaning protein malnutrition condition. MAIN METHODS: After weaning, male rats were divided into control (CG; 22 % protein) and malnourished (MG; 6 % protein) groups. At 35 days, groups were subdivided into CG-PBS, CG-IVA, MG-PBS and MG-IVA (PBS 1 ml/kg or IVA 1 mg/kg) received during 8 days. We performed jugular vein cannulation and electrode implant for drug delivery and ECG registration to assess tonic cardiovascular autonomic control; femoral cannulation for blood pressure (BP) and heart rate (HR) assessment; and LV collection to evaluate ventricular remodeling and HCN gene expression investigation. KEY FINDINGS: Malnutrition induced BP and HR increases, sympathetic system dominance, and LV remodeling without affecting HCN gene expression. IVA reversed the cardiovascular autonomic imbalance; prevented hypertension and tachycardia; and inhibited the LV inflammatory process and fiber thickening caused by malnutrition. SIGNIFICANCE: Our findings suggest that ivabradine protects against malnutrition-mediated cardiovascular damage. Moreover, our results propose these effects were not attributed to HCN expression changes, but rather to IVA pleiotropic effects on autonomic control and inflammation.

Independent Determinants of Appetite Impairment among Patients with Stage 3 or Higher Chronic Kidney Disease: A Prospective Study.

Protein-energy wasting (PEW) is an important complication resulting from chronic kidney disease (CKD). Appetite impairment contributes significantly to PEW in these patients, but risk factors associated with having appetite impairment in patients with CKD remain elusive. Patients with an estimated glomerular filtration rate <60 mL/min/1.73 m2 for ≥2 times at least three months apart were prospectively enrolled during 2017, with their demographic features, comorbidities, anthropometric parameters, physical and performance indices, functional status, frailty, sensory organ integrity, and laboratory data collected. Their appetite status was measured using the Council on Nutrition Appetite Questionnaire (CNAQ). We examined independent determinants of appetite impairment in these CKD patients using multiple regression analyses. Among 78 patients with CKD, 42.3% had CNAQ-identified impaired appetite. Those with an impaired appetite also had poorer physical performance, a higher degree of functional impairment, higher frail severities, lower serum sodium levels, less intact oral cavity, and a trend toward having less intact nasal structures than those without. Multiple regression analyses revealed that a higher frail severity, in the forms of increasing Study of Osteoporotic Fractures (SOF) scores (odds ratio (OR), 2.74; 95% confidence interval (CI), 1.15-6.57) and a less intact nasal structure (OR, 0.96; 95% CI, 0.92-0.995) were associated with a higher probability of having an impaired appetite, while higher serum sodium (OR, 0.76; 95% CI, 0.6-0.97) correlated with a lower probability. Based on our findings, in patients with CKD, the severity of frailty, serum sodium, and nasal structural integrity might modify appetite status. Therapies targeting these factors might be beneficial for appetite restoration in patients with CKD.

Maintenance of Skeletal Muscle to Counteract Sarcopenia in Patients with Advanced Chronic Kidney Disease and Especially Those Undergoing Hemodialysis.

Life extension in modern society has introduced new concepts regarding such disorders as frailty and sarcopenia, which has been recognized in various studies. At the same time, cutting-edge technology methods, e.g., renal replacement therapy for conditions such as hemodialysis (HD), have made it possible to protect patients from advanced lethal chronic kidney disease (CKD). Loss of muscle and fat mass, termed protein energy wasting (PEW), has been recognized as prognostic factor and, along with the increasing rate of HD introduction in elderly individuals in Japan, appropriate countermeasures are necessary. Although their origins differ, frailty, sarcopenia, and PEW share common components, among which skeletal muscle plays a central role in their etiologies. The nearest concept may be sarcopenia, for which diagnosis techniques have recently been reported. The focus of this review is on maintenance of skeletal muscle against aging and CKD/HD, based on muscle physiology and pathology. Clinically relevant and topical factors related to muscle wasting including sarcopenia, such as vitamin D, myostatin, insulin (related to diabetes), insulin-like growth factor I, mitochondria, and physical inactivity, are discussed. Findings presented thus far indicate that in addition to modulation of the aforementioned factors, exercise combined with nutritional supplementation may be a useful approach to overcome muscle wasting and sarcopenia in elderly patients undergoing HD treatments.

Post-weaning protein malnutrition induces myocardial dysfunction associated with oxidative stress and altered calcium handling proteins in adult rats.

Hypercaloric low-protein diet may lead to a state of malnutrition found in the low-income population of Northeastern Brazil. Although malnutrition during critical periods in the early life is associated with cardiovascular diseases in adulthood, the mechanisms of cardiac dysfunction are still unclear. Here we studied the effects of post-weaning malnutrition due to low protein intake induced by a regional basic diet on the cardiac contractility of young adult rats. In vivo arterial hemodynamic and in vitro myocardial contractility were evaluated in 3-month-old rats. Additionally, protein content of the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), total phospholamban (PLB) and phosphorylated at serine 16 (p-Ser(16)-PLB), α2-subunit of the Na(+)/K(+)-ATPase (α2-NKA), and Na(+)/Ca(2+) exchanger (NXC) and in situ production of superoxide anion (O2(-)) were measured in the heart. Blood pressure and heart rate increased in the post-weaning malnourished (PWM) rats. Moreover, malnutrition decreased twitch force and inotropic responses of the isolated cardiac muscle. Protein expression of SERCA, PLB/SERCA, and p-Ser(16)-PLB/PLB ratios and α2-NKA were decreased without changing NCX. The contraction dependent on transsarcolemmal calcium influx was unchanged but responsiveness to Ca(2+) and tetanic peak contractions were impaired in the PWM group. Myocardial O2(-) production was significantly increased by PWM. Our data demonstrated that this hypercaloric low-protein diet in rats is associated with myocardial dysfunction, altered expression of major calcium handling proteins, and increased local oxidative stress. These findings reinforce the attention needed for pediatric care, since chronic malnutrition in early life is related to increased cardiovascular risk in adulthood. Graphical Abstract.

Urinary 3-hydroxyisovaleryl carnitine excretion, protein energy malnutrition and risk of all-cause mortality in kidney transplant recipients: Results from the TransplantLines cohort studies.

BACKGROUND: Leucine is an essential amino acid and a potent stimulator of muscle protein synthesis. Since muscle wasting is a major risk factor for mortality in kidney transplant recipients (KTR), dietary leucine intake might be linked to long-term mortality. Urinary 3-hydroxyisovaleryl carnitine (3-HIC) excretion, a functional marker of marginal biotin deficiency, may also serve as a marker for dietary leucine intake. OBJECTIVE: In this study we aimed to investigate the cross-sectional determinants of urinary 3-HIC excretion and to prospectively investigate the association of urinary 3-HIC excretion with all-cause mortality in KTR. DESIGN: Urinary 3-HIC excretion and plasma biotin were measured in a longitudinal cohort of 694 stable KTR. Cross-sectional and prospective analyses were performed using ordinary least squares linear regression analyses and Cox regression analyses, respectively. RESULTS: In KTR (57% male, 53 ± 13 years, estimated glomerular filtration rate 45 ± 19 mL/min/1.73 m2), urinary 3-HIC excretion (0.80 [0.57-1.16] µmol/24 h) was significantly associated with plasma biotin (std. ß = -0.17; P < 0.001). Subsequent adjustment for potential covariates revealed urinary creatinine excretion (std. ß = 0.24; P < 0.001) and urinary urea excretion (std. ß = 0.53; P < 0.001) as the primary determinant of urinary 3-HIC excretion. Whereas plasma biotin explained only 1% of the variance in urinary 3-HIC excretion, urinary urea excretion explained >45%. During median follow-up for 5.4 [4.8-6.1] years, 150 (22%) patients died. Log2-transformed urinary 3-HIC excretion was inversely associated with all-cause mortality (HR: 0.52 [0.43-0.63]; P < 0.001). This association was independent of potential confounders. CONCLUSIONS: Urinary 3-HIC excretion more strongly serves as a marker of leucine intake than of biotin status. A higher urinary 3-HIC excretion is associated with a lower risk of all-cause mortality. Future studies are warranted to explore the underlying mechanism. TRIAL REGISTRATION ID: NCT02811835. TRIAL REGISTRATION URL: https://clinicaltrials.gov/ct2/show/NCT02811835.

Association of Ultrasound-Derived Metrics of the Quadriceps Muscle with Protein Energy Wasting in Hemodialysis Patients: A Multicenter Cross-Sectional Study.

This study aimed to assess muscle wasting and risk of protein energy wasting (PEW) in hemodialysis (HD) patients using an ultrasound (US) imaging method. PEW was identified using the ISRNM criteria in 351 HD patients. Quadriceps muscle thickness of rectus femoris (RF) and vastus intermedius (VI) muscles and cross-sectional area (CSA) of the RF muscle (RFCSA) were measured using US and compared with other physical measures. Associations of US indices with PEW were determined by logistic regression. Irrespective of gender, PEW vs. non-PEW patients had smaller RF, VI muscles, and RFCSA (all p < 0.001). US muscle sites (all p < 0.001) discriminated PEW from non-PEW patients, but the RFCSA compared to bio-impedance spectroscopy had a greater area under the curve (AUC, 0.686 vs. 0.581), sensitivity (72.8% vs. 65.8%), and specificity (55.6% vs. 53.9%). AUC of the RFCSA was greatest for PEW risk in men (0.74, 95% CI: 0.66-0.82) and women (0.80, 95% CI: 0.70-0.90) (both p < 0.001). Gender-specific RFCSA values (men < 6.00 cm2; women < 4.47 cm2) indicated HD patients with smaller RFCSA were 8 times more likely to have PEW (AOR = 8.63, 95% CI: 4.80-15.50, p < 0.001). The US approach enabled discrimination of muscle wasting in HD patients with PEW. The RFCSA was identified as the best US site with gender-specific RFCSA values to associate with PEW risk, suggesting potential diagnostic criteria for muscle wasting.

Bioelectrical impedance analysis-derived phase angle as a determinant of protein-energy wasting and frailty in maintenance hemodialysis patients: retrospective cohort study.

BACKGROUND: Phase angle (PA), measured by bioelectrical impedance analysis (BIA) has been studied as indicator of nutritional status or muscle function in hemodialysis (HD) patients. It remains unclear if the phase angle is associated protein-energy wasting (PEW) or frailty, which are common complication in hemodialysis patients. The aim of this study is to determine whether BIA-derived PA is a marker of PEW or frailty in HD patients. METHODS: This retrospective observational study included 116 adult HD patients (35% female, 64 ± 12 years of age) in a single dialysis center. Patients were classified according to the PA quartiles into four groups; 1) first quartile: PA < 3.7°, 2) second quartile: PA 3.7-4.1°, 3) third quartile: PA 4.2-4.9°and 4) forth quartile: PA ≥ 5.0°. International Society of Renal Nutrition and Metabolism (ISRNM) criteria and Japanese version of Cardiovascular Health Study (J-CHS) criteria were used to identify PEW and frailty. RESULTS: The lower PA group was associated with a greater risk of PEW (35% vs. 24% vs. 21% vs. 3%; p = 0.032), frailty (59% vs. 40% vs. 21% vs. 3%; p < 0.001). In multivariate logistic regression analysis, the first quartile group was at a significantly greater risk of both PEW and frailty compared with the fourth quartile group after adjusting for other confounding factors. CONCLUSIONS: Lower PA was associated with a greater risk of PEW and frailty in HD patients.

[Characteristics of the metabolic status of children of the first year of life with protein-energy deficiency depending on the gestational age at birth.] / Характеристика метаболического статуса детей первого года жизни с белково-энергетической недостаточностью в зависимости от гестационного возраста при рождении.

Comparative analysis of energy-plastic exchange indicators in mature and premature children of the first year of life in the development of protein-energy malnutrition (PEM) was carried out. Unidirectional changes are revealed, including an increase in creatinine, lactate and creatine phosphokinase activity levels, suggesting a n increasing muscle mass deficit against the background of glucose anaerobic oxidation activation. In preterm infants, glucose and triacylglicerine levels decrease, which reflects uncompensated insufficiency of energy substrates and, accordingly, ATP level. Multidirectional deviations in metabolism are pyruvate and ATP content: increase in full-term infants and decrease in preterm infants, that should be taken into account when monitoring condition of children with PEM. A significant decrease of pyruvic acid in preterm infants against the background of the levels of total protein, albumin, hemoglobin, and transferrin, not exceeding reference values, can obviously testify to the active use of this integral metabolite to maintain the fund of substituted amino acids. Development of this pathology in both mature and premature infants creates a pre-morbid background for iron deficiency anemia-diagnostic panel, which should be supplemented by calculation of transferrin saturation coefficient. Regardless of gestational age in childbirth during the formation of PEM, the lipid spectrum is rearranged according to atherogenic type: at normal values of total cholesterol, there is a significant increase in low and very low density lipoproteins with an increase in the atherogenicity coefficient. This singles out children with the pathology in question as a risk group for the development of the atherosclerotic process later, which justifies the recommendation to control the lipid profile in children of the first year of life.

Neuroprotection Induced by Energy and Protein-Energy Undernutrition Is Phase-Dependent After Focal Cerebral Ischemia in Mice.

Malnutrition predisposes to poor stroke outcome. In animal models, undernutrition protected against ischemic injury in some, but not in other studies. In view of diverse stroke models and food restriction paradigms, the consequences of undernutrition are poorly understood. Herein, we exposed mice to energy-reduced and protein-energy-reduced diets for 7-30 days and subsequently induced intraluminal middle cerebral artery occlusion. Undernutrition phase dependently influenced ischemic injury. Short-lasting 7 days of protein-energy undernutrition, but not energy undernutrition, decreased post-ischemic brain leukocyte infiltration and microglial activation and reduced brain Il-1ß mRNA, but did not protect against ischemic injury. Fourteen days of energy and protein-energy undernutrition, on the other hand, reduced ischemic injury despite absence of anti-inflammatory effects. Anti-oxidant genes (Sod-1, Sod-2, and Cat mRNAs) were regulated in the liver and, to a lesser extent, the ischemic brain, indicating an adapted, compensated stage. Conversely, 30 days of energy and protein-energy undernutrition caused progressive animal exhaustion associated with post-ischemic hypoperfusion, rise of metabolic markers (Sirt-1 and Glut-1 mRNAs, Sirt-1 protein) in the ischemic brain, and reregulation of pro- and anti-oxidant markers (now also Nox-4 and Gpx-3 mRNAs) in the liver. In the latter condition, no neuroprotection was noted. Our study suggests an adaptation of metabolic systems that provides neuroprotection in a circumscribed time window.

Predictors of nutritional and inflammation risk in hemodialysis patients.

BACKGROUND: Malnutrition and chronic inflammation are prevalent complications in hemodialysis (HD) patients. Different nutritional assessment tools are used to identify patients at risk. A composite and comprehensive malnutrition inflammation score (MIS) has been correlated with morbidity and mortality, and appears to be a robust and quantitative tool. OBJECTIVES: Determine malnutrition risk profile in a sample of portuguese HD patients; determine the association of clinical and laboratory factors with MIS, and the impact of each parameter on MIS. METHODS AND RESULTS: We performed, between September 15th of 2015 and January 31st of 2016, a cross sectional analysis of 2975 patients, representing 25% of portuguese HD patients. 59% were men (66.7 ± 14.8 years); 31% diabetic; 79% and 21% performed, respectively, high-flux HD and HDF. A MIS >5 was considered to indicate higher risk and was present in 1489 patients (50%). Amongst all parameters, comorbilities/dialysis vintage, transferrin, functional capacity, changes in body weight and decreased fat stores showed the higher impact, while albumin had one of the lowest impact on the nutritional risk. MULTIVARIABLE ANALYSIS: Higher age (>75 years, OR 1.71, p < 0.001), diabetes (OR 1.25, p = 0.026), lower P levels (OR 1.57,p = 0.001), higher Ca levels (OR 1.51, p < 0.001), higher ERI (OR 1.05, p < 0.001), higher Kt/V (OR 2.14, p < 0.001) and higher CRP (OR 1.01, p < 0.001) were independently associated with a higher risk of MIS>5; higher nPNA (OR 0.29, p < 0.001) and higher Pcreat (OR 0.88, p < 0.001) were associated with a risk reduction of MIS>5 (95% CI). CONCLUSIONS: Routine clinical and analytic parameters were found to be associated with MIS range that might indicate higher risk, and may represent a simple alert sign for the need of further assessments.

Cachexia/Protein energy wasting syndrome in CKD: Causation and treatment.

Cachexia is a multifactorial syndrome defined by significant body weight loss, fat and muscle mass reduction, and increased protein catabolism. Protein energy wasting (PEW) is characterized as a syndrome of adverse changes in nutrition and body composition being highly prevalent in patients with CKD, especially in those undergoing dialysis, and it is associated with high morbidity and mortality in this population. Multiple mechanisms are involved in the genesis of these adverse nutritional changes in CKD patients. There is no obvious distinction between PEW and cachexia from a pathophysiologic standpoint and should be considered as part of the spectrum of the same nutritional disorder in CKD with similar management approaches for prevention and treatment based on current understanding. A plethora of factors can affect the nutritional status of CKD patients requiring a combination of therapeutic approaches to prevent or reverse protein and energy depletion. At present, there is no effective pharmacologic intervention that prevents or attenuates muscle atrophy in catabolic conditions like CKD. Prevention and treatment of uremic muscle wasting involve optimal nutritional support, correction of acidosis, and physical exercise. There has been emerging consistent evidence that active treatment, perhaps by combining nutritional interventions and resistance exercise, may be able to improve but not totally reverse or prevent the supervening muscle wasting and weakness. Active research into more direct pharmacological treatment based on basic mechanistic research is much needed for this unmet medical need in patients with CKD.

Sarcopenia is Associated with Malnutrition but Not with Systemic Inflammation in Older Persons with Advanced CKD.

BACKGROUND: In patients with chronic kidney disease (CKD), sarcopenia can be determined by a wide spectrum of risk factors. We evaluated the association of sarcopenia with nutritional, behavioral and inflammatory patterns in older patients with advanced CKD. METHODS: we cross-sectionally evaluated 113 patients with CKD stages 3b-5. Sarcopenia was defined according to the EWGSOP2 criteria. We assessed: anthropometry, bioelectrical impedance analysis, physical, and psychological performance. Nutritional status was assessed using the Malnutrition Inflammation Score (MIS) and by verifying the eventual presence Protein Energy Wasting syndrome (PEW). Systemic inflammation was assessed by dosing: CRP, IL6, TNFα, MCP1, IL10, IL17, fetuin, IL12. RESULTS: 24% of patients were sarcopenic. Sarcopenic individuals had lower creatinine clearance (18 ± 11 vs. 23 ± 19 mL/min; p = 0.0087) as well as lower BMI (24.8 ± 3.0 vs. 28.4 ± 5.5 Kg/m2; p < 0.0001) and a lower FTI (11.6 ± 3.9 vs. 14.4 ± 5.1 kg/m2, p = 0.023). Sarcopenic persons had higher prevalence of PEW (52 vs. 20%, p < 0.0001) and a tendency to have higher MIS (6.6 ± 6.5 vs. 4.5 ± 4.0, p = 0.09); however, they did not show any difference in systemic inflammation compared to non-sarcopenic individuals. CONCLUSIONS: CKD sarcopenic patients were more malnourished than non-sarcopenic ones, but the two groups did not show any difference in systemic inflammation.

Appetite and Protein Intake Strata of Older Adults in the European Union: Socio-Demographic and Health Characteristics, Diet-Related and Physical Activity Behaviours.

Considerable efforts have been directed towards stimulating healthy ageing regarding protein intake and malnutrition, yet large-scale consumer studies are scarce and fragmented. This study aims to profile older adults in the European Union (EU) according to appetite (poor/good) and protein intake (lower/higher) strata, and to identify dietary and physical activity behaviours. A survey with older (aged 65 years or above) adults (n = 1825) in five EU countries (Netherlands, United Kingdom, Finland, Spain and Poland) was conducted in June 2017. Four appetite and protein intake strata were identified based on simplified nutritional appetite questionnaire (SNAQ) scores (≤14 versus >14) and the probability of a protein intake below 1.0 g/kg adjusted BW/day (≥0.3 versus <0.3) based on the 14-item Pro55+ screener: "appi"-Poor appetite and lower level of protein intake (12.2%); "APpi"-Good appetite but lower level of protein intake (25.5%); "apPI"-Poor appetite but higher level of protein intake (14.8%); and "APPI"-Good appetite and higher level of protein intake (47.5%). The stratum of older adults with a poor appetite and lower level of protein intake (12.2%) is characterized by a larger share of people aged 70 years or above, living in the UK or Finland, having an education below tertiary level, who reported some or severe financial difficulties, having less knowledge about dietary protein and being fussier about food. This stratum also tends to have a higher risk of malnutrition in general, oral-health related problems, experience more difficulties in mobility and meal preparation, lower confidence in their ability to engage in physical activities in difficult situations, and a lower readiness to follow dietary advice. Two multivariate linear regression models were used to identify the behavioural determinants that might explain the probability of lower protein intake, stratified by appetite status. This study provides an overview and highlights the similarities and differences in the strata profiles. Recommendations for optimal dietary and physical activity strategies to prevent protein malnutrition were derived, discussed and tailored according to older adults' profiles.

Significant effects of late evening snack on liver functions in patients with liver cirrhosis: A meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Reducing post-absorptive (fasting) phase by eating late evening snacks (LESs) is a potential intervention to improve substrate utilization and reverse sarcopenia. This study analyzed the results of published randomized controlled trials and controlled clinical trials to evaluate the effects of LES on liver function of patients with cirrhosis. METHODS: A meta-analysis was conducted. The search strategy included electronic database searches, and 300 articles were searched. Eight of these articles provided qualified data for pooling and analysis. Outcomes assessments included serum albumin, total bilirubin, alanine aminotransferase, prothrombin time, and aspartate aminotransferase, complications of cirrhosis, severity of liver disease, and blood glucose levels. RESULTS: Our analysis included eight studies comprising 341 patients (167 in LES groups and 174 in control groups). The results showed that LES intervention helped to maintain liver reserves. These eight studies demonstrated that LES intervention had significant effects for liver biochemical parameters on albumin, ammonia, and prothrombin time, with respective effect sizes of 0.233, -0.425, and -0.589; liver enzymes include aspartate aminotransferase and alanine aminotransferase, with respective effect sizes of -0.320 and -0.284. Studies on clinical signs of liver dysfunction showed lower occurrence rates of ascites and hepatic encephalopathy than in the control group. LES had no significant effect on Child-Pugh score. CONCLUSIONS: The overall results of the meta-analysis indicated that having LES can improve liver function reserve for patients with liver cirrhosis, with or without hepatocellular carcinoma. LES is a promising intervention for reversing anabolic resistance and the sarcopenia of cirrhosis, resulting in an improved quality of life for patients with cirrhosis.

El selenio y la desnutrición e inflamación. Estudio preliminar en enfermedad renal crónica avanzada / Selenium, malnutrition and inflammation. A preliminary study in end-stage chronic kidney disease

Introducción: El desgaste proteico-energético y la inflamación crónica en el enfermo renal se relacionan con un aumento de la mortalidad, así como con la aparición de anemia refractaria y alteraciones en el metabolismo óseo-mineral. Entre las causas está el aumento del estrés oxidativo, en el que el selenio desempeña un papel a través de la actividad de varias selenoproteínas. Se investiga la relación entre el selenio plasmático y sérico y la desnutrición e inflamación en pacientes adultos en tratamiento sustitutivo renal. Material y métodos: Estudio observacional transversal que incluyó 85 plasmas o sueros de pacientes en diálisis y 118 de sujetos control. Se midieron selenio y marcadores bioquímicos de nutrición, inflamación y otras comorbilidades. Las comparaciones se realizaron mediante U de Mann-Whitney, ANOVA y chi-cuadrado. Las correlaciones se estimaron mediante Rho de Spearman. Resultados: La mediana de selenio fue 58,2μg/L en el grupo de pacientes y 89,3μg/L en el grupo control (p<0,001). El selenio se correlacionó con la albúmina (Rho=0,440), el colesterol (Rho=0,278) y la creatinina (Rho=0,367) en los pacientes. La clasificación en función de la hiposelenemia llevó a 2 grupos con diferencia significativa en el tiempo en diálisis (p=0,018), la albúmina (p=0,003), la creatinina (p=0,004), el colesterol (p=0,038) y el fosfato (p=0,025). Conclusiones: El selenio se correlaciona con los marcadores nutricionales en el grupo de pacientes. La clasificación de los pacientes según hiposelenemia lleva a 2 poblaciones diferenciadas en el estado nutricional y en el tiempo en diálisis. El selenio podría ser un marcador útil en el diagnóstico de desgaste proteico-energético

Introduction: Protein-energy wasting and chronic inflammation in renal patients are related to an increase in mortality, as well as the occurrence of unresponsive anaemia and mineral and bone disease. The increase in oxidative stress, in which selenium plays a role, is among the causes of malnutrition and inflammation. The relationship between plasma or serum selenium and malnutrition and inflammation in adult patients undergoing renal replacement therapy is investigated. Material and methods: Cross-sectional observational study that included 85 plasma specimens from patients on dialysis, and 118 from control subjects. Selenium and biochemical markers of nutrition, inflammation, and co-morbidities were measured. The comparisons were using Mann-Whitney, ANOVA and chi-squared tests. Correlations were estimated using Spearman's Rho. Results: The median selenium was 58.2μg/L in the patient group, and 89.3μg/L in the control group (p<.001). Selenium correlated with albumin (Rho=0.440), cholesterol (Rho=0.278) and creatinine (Rho=0.367) in the patient group. Patients classification based on selenium level led to significant differences between the 2 groups in time on dialysis (p<.018), albumin (p<.003), creatinine (p<.004), cholesterol (p<.038) and phosphate (p<.025). Conclusions: Selenium positively correlates with nutritional markers in the group of patient group. According to selenium level, there are 2 populations differentiated by nutritional status and time on dialysis. Plasma selenium is a potentially useful marker for protein-energy wasting diagnosis

What are the criteria for response to cachexia treatment?

The treatment of cancer cachexia remains an unmet medical need. One of the barriers to the development and approval of effective interventions has been the lack of agreement on the proper endpoints for study. The international consensus definition of cancer cachexia focuses on 3 major components of the syndrome. This includes altered body composition characterized specifically by loss of skeletal muscle mass. The muscle loss in turn is a result of negative protein and energy balance secondary to reduced food intake and abnormal metabolism. The result of muscle loss is progressive functional impairment. The assessment of interventions for cancer cachexia should include measures of all 3 components of cancer cachexia. For patients with cancer cachexia, body composition measurements of lean body mass (LBM) and fat mass may be best determined by CT imaging. Nutritional endpoints and measures of metabolism can be quite complex. However, change in appetite and body weight remain extremely useful measures of clinical benefit. The most controversial area relates to assessment of physical function. While stair climb power, 6-minute walk, hand grip strength and other measures have been used in clinical trials, none of them have shown consistent benefit that correlates with change in LBM. While we have much to learn about the inter-relationship between muscle mass and muscle function, improvement in physical function may be best measured by patient reported outcomes. Ongoing and future clinical trials in cancer cachexia should assess all 3 domains, which will improve our understanding of this syndrome and ultimately lead to better treatment options for our patients.

Noninvasive evaluation of muscle mass by ultrasonography of quadriceps femoris muscle in End-Stage Renal Disease patients on hemodialysis.

BACKGROUND & AIMS: Protein-Energy Wasting (PEW) is a pathological condition of renal patients with advanced Chronic Kidney Disease characterized by a progressive reduction of energy and protein assets. Nutritional status assessment, especially for what concerns muscle mass, is essential for both the identification of patients at risk for the development of PEW, as well as monitoring the effects of nutritional interventions. Ultrasound methods are easily applicable at the bedside for quantitative assessment of skeletal muscle. The present study was aimed at evaluating quadriceps rectus femoris thickness (QRFT) and quadriceps vastus intermedius thickness (QVIT) in patients on chronic hemodialysis. METHODS: This was a prospective observational study. Three groups of adult patients were studied: young healthy subjects, well-nourished hospitalized patients with normal renal function, and End-Stage Renal Disease patients on hemodialysis (ESRD-HD). QRFT and QVIT were measured at two sites bilaterally (8 measures/patient) and were compared between groups, and also between subgroups of ESRD-HD patients stratified on the basis of conventional nutritional status parameters. RESULTS: We enrolled 35 healthy subjects, 30 hospitalized patients, and 121 ESRD-HD patients on hemodialysis. QRFT and QVIT of ESRD patients on hemodialysis were lower than those of both control groups (P < 0.001). After stratifying ESRD patients into subgroups based on nutritional variable cut-offs commonly used to define PEW in this clinical setting (BMI [≥ 23 vs <23 kg/m2], albumin [≥3.8 vs <3.8 g/dL]) and malnutrition inflammation score (MIS) status (<6 vs ≥6), QRFT and QVIT of patients with worse nutritional status were significantly lower than those of well-nourished ESRD-HD patients (P value range: <0.001 to <0.05). CONCLUSION: Skeletal muscle ultrasound is a simple and easily applicable bedside technique in the dialysis units, and could represent an adequate tool for the identification of patients with reduced muscle mass.

Association between change in serum bicarbonate and change in thyroid hormone levels in patients receiving conventional or more frequent maintenance haemodialysis.

AIM: Correction of metabolic acidosis in patients with chronic kidney disease has been associated with improvement in thyroid function. We examined whether changes in bicarbonate were associated with changes in thyroid function in patients with end-stage renal disease receiving conventional or more frequent haemodialysis. METHODS: In the Frequent Hemodialysis Network Trials, the relationship between changes in serum bicarbonate, free triiodothyronine (FT3) and free thyroxine (FT4) was examined among 147 and 48 patients with endogenous thyroid function who received conventional (3×/week) or more frequent (6×/week) haemodialysis (Daily Trial) or who received conventional or more frequent nocturnal haemodialysis (Nocturnal Trial). Equilibrated normalized protein catabolic rate (enPCR) was examined to account for nutritional factors affecting both acid load and thyroid function. RESULTS: Increasing dialysis frequency was associated with increased bicarbonate level. Baseline bicarbonate level was not associated with baseline FT3 and FT4. Change in bicarbonate level was not associated with changes in FT3 and FT4 in the Daily Trial nor for FT4 in the Nocturnal Trial (r ≤ 0.14, P > 0.21). While, a significant correlation between change in serum bicarbonate and change in FT3 (r = 0.44, P = 0.02) was observed in the Nocturnal Trial; findings were no longer significant after adjusting for change in enPCR (r = 0.37, P = 0.08). For participants with baseline bicarbonate <23 mmol/L, no association between change in bicarbonate and change in thyroid indices were seen in the Daily Trial; for the Nocturnal Trial, findings were also not significant for change in FT3 and the association between change in bicarbonate and change in FT4 (r = 0.54, P = 0.03) was no longer significant after adjusting for enPCR (r = 0.45, P = 0.11). CONCLUSION: Changes in bicarbonate were not associated with changes in thyroid hormone levels after adjusting for enPCR, as a marker of nutritional status. Future studies should examine whether improvement in acid base status improves thyroid function in haemodialysis patients with evidence of thyroid hypofunction.

Nutritional recovery with a soybean diet impaired the glucagon response but did not alter liver gluconeogenesis in the adult offspring of rats deprived of protein during pregnancy and lactation.

Nutritional recovery of early malnutrition with a soybean diet reduces liver glycogen stores in the fed state and produces liver insulin resistance. We investigated whether nutritional recovery on a soybean flour diet alters hepatic gluconeogenesis in the adult offspring of rats deprived of protein during pregnancy and lactation. Male rats from mothers that were fed either 17% (C) or 6% (L) protein during pregnancy and lactation were maintained on a 17% casein (CC, n = 16 and LC, n = 17), 17% soybean flour (CS, n = 10 and LS, n = 10), or 6% casein (LL, n = 10) diet after weaning. The soybean diet reduced basal serum glucose (soybean diet, 5.6 ± 0.6 mmol/L vs. casein diet, 6.2 ± 0.6 mmol/L; p < 0.05) but increased alanine aminotransferase mRNA/GAPDH (soybean diet, 0.062 ± 0.038 vs. casein diet, 0.024 ± 0.011; p < 0.01), phosphoenolpyruvate carboxykinase mRNA/GAPDH (soybean diet, 1.53 ± 0.52 vs. casein diet, 0.95 ± 0.43; p < 0.05), and glycerokinase protein content (soybean diet, 0.86 ± 0.08 vs. casein diet, 0.75 ± 0.11; p < 0.05). The serum glucose concentration (recovered groups, 5.6 ± 0.5 mmol/L vs. control groups, 6.2 ± 0.7 mmol/L; p < 0.05) and phosphoenolpyruvate carboxykinase activity (recovered groups, 2.8 ± 0.6 µU/mg vs. control groups, 3.6 ± 0.6 µU/mg; p < 0.05) were decreased in rats subjected to protein restriction in early life. The glucose area under the curve during the pyruvate tolerance test did not differ among groups, whereas glucose area under the curve after glucagon infusion was reduced by early malnutrition (recovered groups, 4210 ± 572 mg/dL·40 min vs. control groups, 4493 ± 688 mg/dL·40 min; p < 0.001) and by the soybean diet (soybean diet, 3995 ± 500 mg/dL·40 min vs. casein diet, 4686 ± 576 mg/dL·40 min; p < 0.05). Thus, the soybean diet impaired the response to glucagon but did not alter gluconeogenesis.

Evaluating haemodialysis patient's nutritional status: Body mass index or body cell mass index?

OBJECTIVE: Evaluate which of two combinations of parameters based on International Society of Renal Nutrition and Metabolism recommendations could better identify patients with protein-energy wasting (PEW) and to compare the relationship of these two combinations with other clinical and body composition parameters. METHODS: This was a multicentre longitudinal study with 24 months of follow-up. The PEW patients were characterized by: Group A (GA ) - normalized protein catabolic rate (nPCR) < 1.0 g/kg per day, albumin <3.8 g/dL and body cell mass index (BCMI) < 6.4 kg/m2 (n = 203); Group B (GB ) - nPCR <1.0 g/kg per day, albumin <3.8 g/dL and body mass index (BMI) <23 kg/m2 (n = 109). All the patients who did not meet these requirements were considered "well-nourished" (GA : n = 1818; GB : n = 3292). RESULTS: When compared to the well-nourished patients, PEW patients in the GA presented higher age, Kt/V, C-reactive protein, relative overhydration, fat tissue index (FTI); lower creatinine, albumin, nPCR, PTH, haemoglobin, phosphorus, calcium X phosphorus product, potassium, dry weight, BMI, BCMI, lean tissue index, %IDWG . In the GB , well-nourished patients FTI was significantly higher. In Cox analysis, the combination with BCMI was a strong independent predictor of mortality in these patients (hazard ratio: 1.48; confidence interval: 1.00-2.19; P = 0.048), even after adjustment. Although GB combination seemed to be also a predictor of death (hazard ratio: 2.67; confidence interval: 1.92-3.71; P < 0.001), when adjusted, the association remained no longer significant. CONCLUSION: A new combination of parameters including protein intake, albumin and BCMI demonstrated significant associations with other nutrition and inflammation parameters as well as with mortality.