Three compartment bioimpedance spectroscopy in the nutritional assessment and the outcome of patients with advanced or end stage kidney disease: What have we learned so far?

Bioimpedance spectroscopy (BIS) is an easily applicable tool to assess body composition. The three compartment model BIS (3C BIS) conventionally expresses body composition as lean tissue index (LTI) (lean tissue mass [LTM]/height in meters squared) and fat tissue index (FTI) (adipose tissue mass/height in meters squared), and a virtual compartment reflecting fluid overload (FO). It has been studied extensively in relation to diagnosis and treatment guidance of fluid status disorders in patients with advanced‐stage or end‐stage renal disease. It is the aim of this article to provide a narrative review on the relevance of 3C BIS in the nutritional assessment in this population. At a population level, LTI decreases after the start of hemodialysis, whereas FTI increases. LTI below the 10th percentile is a consistent predictor of outcome whereas a low FTI is predominantly associated with outcome when combined with a low LTI. Recent research also showed the connection between low LTI, inflammation, and FO, which are cumulatively associated with an increased mortality risk. However, studies toward nutritional interventions based on BIS data are still lacking in this population. In conclusion, 3C BIS, by disentangling the components of body mass index, has contributed to our understanding of the relevance of abnormalities in different body compartments in chronic kidney disease patients, and appears to be a valuable prognostic tool, at least at a population level. Studies assessing the effect of BIS guided nutritional intervention could further support its use in the daily clinical care for renal patients.

Related papers:

title: Management of protein-energy wasting in non-dialysis-dependent chronic kidney disease: reconciling low protein intake with nutritional therapy.
abstract: Protein-energy wasting (PEW), characterized by a decline in body protein mass and energy reserves, including muscle and fat wasting and visceral protein pool contraction, is an underappreciated condition in early to moderate stages of chronic kidney disease (CKD) and a strong predictor of adverse outcomes. The prevalence of PEW in early to moderate CKD is ≥20-25% and increases as CKD progresses, in part because of activation of proinflammatory cytokines combined with superimposed hypercatabolic states and declines in appetite. This anorexia leads to inadequate protein and energy intake, which may be reinforced by prescribed dietary restrictions and inadequate monitoring of the patient's nutritional status. Worsening uremia also renders CKD patients vulnerable to potentially deleterious effects of uncontrolled diets, including higher phosphorus and potassium burden. Uremic metabolites, some of which are anorexigenic and many of which are products of protein metabolism, can exert harmful effects, ranging from oxidative stress to endothelial dysfunction, nitric oxide disarrays, renal interstitial fibrosis, sarcopenia, and worsening proteinuria and kidney function. Given such complex pathways, nutritional interventions in CKD, when applied in concert with nonnutritional therapeutic approaches, encompass an array of strategies (such as dietary restrictions and supplementations) aimed at optimizing both patients' biochemical variables and their clinical outcomes. The applicability of many nutritional interventions and their effects on outcomes in patients with CKD with PEW has not been well studied. This article reviews the definitions and pathophysiology of PEW in patients with non-dialysis-dependent CKD, examines the current indications for various dietary modification strategies in patients with CKD (eg, manufactured protein-based supplements, amino acids and their keto acid or hydroxyacid analogues), discusses the rationale behind their potential use in patients with PEW, and highlights areas in need of further research.

title: Latest consensus and update on protein-energy wasting in chronic kidney disease
abstract: energy wasting (PEW) is a state of metabolic and nutritional derangements in chronic disease states including chronic kidney disease (CKD). Cumulative evidence suggests that PEW, muscle wasting and cachexia are common and strongly associated with mortality in CKD, which is reviewed here. Recent findingsThe malnutrition-inflammation score (KALANTAR Score) is among the comprehensive and outcome-predicting nutritional scoring tools. The association of obesity with poor outcomes is attenuated across more advanced CKD stages and eventually reverses in the form of obesity paradox. Frailty is closely associated with PEW, muscle wasting and cachexia. Muscle loss shows stronger associations with unfavorable outcomes than fat loss. Adequate energy supplementation combined with low-protein diet for the management of CKD may prevent the development of PEW and can improve adherence to low-protein diet, but dietary protein requirement may increase with aging and is higher under dialysis therapy. Phosphorus burden may lead to poor outcomes. The target serum bicarbonate concentration is normal range and at least 23 mEq/l for nondialysis-dependent and dialysis-dependent CKD patients, respectively. A benefit of exercise is suggested but not yet conclusively proven. SummaryPrevention and treatment of PEW should involve individualized and integrated approaches to modulate identified risk factors and contributing comorbidities.

title: A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease.
abstract: The recent research findings concerning syndromes of muscle wasting, malnutrition, and inflammation in individuals with chronic kidney disease (CKD) or acute kidney injury (AKI) have led to a need for new terminology. To address this need, the International Society of Renal Nutrition and Metabolism (ISRNM) convened an expert panel to review and develop standard terminologies and definitions related to wasting, cachexia, malnutrition, and inflammation in CKD and AKI. The ISRNM expert panel recommends the term 'protein-energy wasting' for loss of body protein mass and fuel reserves. 'Kidney disease wasting' refers to the occurrence of protein-energy wasting in CKD or AKI regardless of the cause. Cachexia is a severe form of protein-energy wasting that occurs infrequently in kidney disease. Protein-energy wasting is diagnosed if three characteristics are present (low serum levels of albumin, transthyretin, or cholesterol), reduced body mass (low or reduced body or fat mass or weight loss with reduced intake of protein and energy), and reduced muscle mass (muscle wasting or sarcopenia, reduced mid-arm muscle circumference). The kidney disease wasting is divided into two main categories of CKD- and AKI-associated protein-energy wasting. Measures of chronic inflammation or other developing tests can be useful clues for the existence of protein-energy wasting but do not define protein-energy wasting. Clinical staging and potential treatment strategies for protein-energy wasting are to be developed in the future.

title: EBPG guideline on nutrition.
abstract: Guideline 1. Prevalence of malnutrition and outcomeGuideline 2. Diagnosis and monitoring of malnutrition2.1. Diagnosis of malnutrition2.2. Monitoring and follow-up of nutritionalstatusGuideline 3. Recommendations for protein and energyintake3.1. Recommended protein intake3.2. Recommended energy intakeRecommendation 4. Recommendations for vitamins,minerals and trace elementsadministration in maintenancehaemodialysis patients.4.1. Vitamins4.2.  Trace elementsGuideline 5. Treatment of malnutrition5.1. Dietary intervention5.2. Oral supplements and enteral feeding5.3. Intradialytic parenteral nutrition5.4. Anabolic  daily dialysisGuideline 6. Metabolic

title: Techniques for assessing fluids status in patients with kidney disease
abstract: Purpose of reviewThe aim of this article is to present current information on techniques for fluid status assessment in patients with kidney disease. The methods can be broadly categorized into biomarkers, ultrasound, blood volume monitoring, and bioimpedance. Recent findingsBiomarkers including atrial natriuretic peptide and B-type natriuretic peptide have been shown to provide information about relative changes in fluid status. Ultrasound is applied to measure inferior vena cava indices, pulmonary indicators, and vascular indicators of fluid overload. Relative blood volume monitoring is used to measure change in intravascular fluid during hemodialysis. While in principle appealing, measurement of absolute blood volume has seen limited use to date. Bioimpedance techniques such as vector analysis, whole body, and regional bioimpedance spectroscopy, have shown their ability to estimate fluid status. SummaryThe interpretation of biomarkers is complicated by the presence of cardiac disease. All ultrasound methods have some correlation with fluid status; however, operator dependency limits their routine use. Bioimpedance methods and relative blood volume monitoring are increasingly used to assess fluid status in patients with acute or chronic kidney disease. Measurement of absolute blood volume holds promise for the future.

title: Chronic Fluid Overload and Mortality in ESRD.
abstract: Sustained fluid overload (FO) is considered a major cause of hypertension, heart failure, and mortality in patients with ESRD on maintenance hemodialysis. However, there has not been a cohort study investigating the relationship between chronic exposure to FO and mortality in this population. We studied the relationship of baseline and cumulative FO exposure over 1 year with mortality in 39,566 patients with incident ESRD in a large dialysis network in 26 countries using whole-body bioimpedance spectroscopy to assess fluid status. Analyses were applied across three discrete systolic BP (syst-BP) categories (<130, 130-160, and >160 mmHg), with nonoverhydrated patients with syst-BP=130-160 mmHg as the reference category; >200,000 FO measurements were performed over follow-up. Baseline FO value predicted excess risk of mortality across syst-BP categories (<130 mmHg: hazard ratio [HR], 1.51; 95% confidence interval [95% CI], 1.38 to 1.65; 130-160 mmHg: HR, 1.25; 95% CI, 1.16 to 1.36; >160 mmHg: HR, 1.30; 95% CI, 1.19 to 1.42; all P<0.001). However, cumulative 1-year FO exposure predicted a higher death risk (P<0.001) across all syst-BP categories (<130 mmHg: HR, 1.94; 95% CI, 1.68 to 2.23; 130-160 mmHg: HR, 1.51; 95% CI, 1.35 to 1.69; >160 mmHg: HR, 1.62; 95% CI, 1.39 to 1.90). In conclusion, chronic exposure to FO in ESRD is a strong risk factor for death across discrete BP categories. Whether treatment policies that account for fluid status monitoring are preferable to policies that account solely for predialysis BP measurements remains to be tested in a clinical trial.

title: Impact of fluid status and inflammation and their interaction on survival: a study in an international hemodialysis patient cohort.
abstract: In hemodialysis patients extracellular fluid overload is a predictor of all-cause and cardiovascular mortality, and a relation with inflammation has been reported in previous studies. The magnitude and nature of this interaction and the effects of moderate fluid overload and extracellular fluid depletion on survival are still unclear. We present the results of an international cohort study in 8883 hemodialysis patients from the European MONDO initiative database where, during a three-month baseline period, fluid status was assessed using bioimpedance and inflammation by C-reactive protein. All-cause mortality was recorded during 12 months of follow up. In a second analysis a three-month baseline period was added to the first baseline period, and changes in fluid and inflammation status were related to all-cause mortality during six-month follow up. Both pre-dialysis estimated fluid overload and fluid depletion were associated with an increased mortality, already apparent at moderate levels of estimated pre-dialysis fluid overload (1.1-2.5L); hazard ratio 1.64 (95% confidence interval 1.35-1.98). In contrast, post-dialysis estimated fluid depletion was associated with a survival benefit (0.74 [0.62-0.90]). The concurrent presence of fluid overload and inflammation was associated with the highest risk of death. Thus, while pre-dialysis fluid overload was associated with inflammation, even in the absence of inflammation, fluid overload remained a significant risk factor for short-term mortality, even following improvement of fluid status.

title: A whole-body model to distinguish excess fluid from the hydration of major body tissues.
abstract: Excess fluid (ExF) accumulates in the body in many conditions. Currently, there is no consensus regarding methods that adequately distinguish ExF from fat-free mass.



The aim was to develop a model to determine fixed hydration constants of primary body tissues enabling ExF to be calculated from whole-body measurements of weight, intracellular water (ICWWB), and extracellular water (ECWWB).



Total body water (TBW) and ECWWB were determined in 104 healthy subjects by using deuterium and NaBr dilution techniques, respectively. Body fat was estimated by using a reference 4-component model, dual-energy X-ray absorptiometry, and air-displacement plethysmography. The model considered 3 compartments: normally hydrated lean tissue (NH_LT), normally hydrated adipose tissue (NH_AT), and ExF. Hydration fractions (HF) of NH_LT and NH_AT were obtained assuming zero ExF within the diverse healthy population studied.



The HF of NH_LT mass was 0.703 +/- 0.009 with an ECW component of 0.266 +/- 0.007. The HF of NH_AT mass was 0.197 +/- 0.042 with an ECW component of 0.127 +/- 0.015. The ratio of ECW to ICW in NH_LT was 0.63 compared with 1.88 in NH_AT. ExF can be estimated with a precision of 0.5 kg.



To calculate ExF over a wide range of body compositions, it is important that the model takes into account the different ratios of ECW to ICW in NH_LT and NH_AT. This eliminates the need for adult age and sex inputs into the model presented. Quantification of ExF will be beneficial in the guidance of treatment strategies to control ExF in the clinical setting.

title: The mortality risk of overhydration in haemodialysis patients
abstract: While cardiovascular events remain the primary form of mortality in haemodialysis (HD) patients, few centres are aware of the impact of the hydration status (HS). The aim of this study was to investigate how the magnitude of the prevailing overhydration influences long-term survival.  We measured the hydration status in 269 prevalent HD patients (28% diabetics, dialysis vintage = 41.2 ± 70 months) in three European centres with a body composition monitor (BCM) that enables quantitative assessment of hydration status and body composition. The survival of these patients was ascertained after a follow-up period of 3.5 years. The cut off threshold for the definition of hyperhydration was set to 15% relative to the extracellular water (ECW), which represents an excess of ECW of ∼2.5 l. Cox-proportional hazard models were used to compare survival according to the baseline hydration status for a set of demographic data, comorbid conditions and other predictors.  The median hydration state (HS) before the HD treatment (ΔHSpre) for all patients was 8.6 ± 8.9%. The unadjusted gross annual mortality of all patients was 8.5%. The hyperhydrated subgroup (n = 58) presented ΔHSpre = 19.9 ± 5.3% and a gross mortality of 14.7%. The Cox adjusted hazard ratios (HRs) revealed that age (HRage = 1.05, 1/year; P < 0.001), systolic blood pressure (BPsys) (HRBPsys = 0.986 1/mmHg; P = 0.014), diabetes (HRDia = 2.766; P < 0.001), peripheral vascular disease (PVD) (HRPVD = 1.68; P = 0.045) and relative hydration status (ΔHSpre) (HRΔHSpre = 2.102 P = 0.003) were the only significant predictors of mortality in our patient population.  The results of our study indicate that the hydration state is an important and independent predictor of mortality in chronic HD patients secondary only to the presence of diabetes. We believe that it is essential to measure the hydration status objectively and quantitatively in order to obtain a more clearly defined assessment of the prognosis of haemodialysis patients.

title: Update on body composition tools in clinical settings: computed tomography, ultrasound, and bioimpedance applications for assessment and monitoring
abstract: Patients with acute/critical illness are particularly vulnerable to muscle loss and fluid shifts, which adversely impact clinical outcomes. Assessment of these parameters in hospital settings is often subjective and imprecise, which creates discrepancies in identification and difficulty in assessing longitudinal changes. Body composition (BC) technologies provide objective information about muscle and fluid status that can enhance clinical assessment, and BC variables could be biomarkers for prognosis and targets to monitor intervention. There is growing interest in computed tomography (CT), ultrasound (US), and bioimpedance techniques as bedside assessment tools in clinical populations, and specific muscle measures, whole-body BC estimates, and select BC variables show promise as biomarkers of muscle health, nutrition risk, and fluid status. This brief review highlights work within the past 5 years on the use of BC variables generated from CT, US, and bioimpedance in clinical populations with an emphasis on those with acute/critical illness and a brief discussion of implementation challenges in these populations. Consensus on measurement protocols will facilitate identification of BC targets that best reflect prognosis and outcomes and will ultimately allow clinicians to identify individuals who would benefit most from targeted nutrition and physical therapy interventions and reliably monitor their response to treatment.

title: The role of bioimpedance and biomarkers in helping to aid clinical decision-making of volume assessments in dialysis patients.
abstract: Bioimpedance analysis (BIA) derives two main pieces of information--total tissue fluid content, which when referring to the whole patient is equivalent to the total body water (TBW), and cell mass, which in the limbs mainly reflects muscle. The relationship between these measures, expressed in different ways, is abnormal in dialysis patients due to muscle wasting combined with tissue overhydration. In both dialysis modalities this is associated with aging, comorbidity, and inflammation, and there is a conflict between achieving euvolemia to improve blood pressure control and prevent left ventricular hypertrophy on one hand, but risking episodes of hypovolemia and loss of residual renal function on the other. In peritoneal dialysis, the situation is exacerbated by hypoalbuminemia, whereas in hemodialysis BIA is unable to distinguish between the plasma volume and tissue edema components of interdialytic weight gain. In longitudinal studies BIA can identify changes in hydration following a defined intervention, and spontaneous loss in TBW consequent on muscle wasting not appreciated clinically, resulting in a failure to sufficiently reduce the dry weight. Cardiac biomarkers provide additional information but it is not clear whether this reflects fluid status or underlying structural organ damage. Intervention studies are now needed that show how this information is best used to improve patient outcomes, including meaningful end points such as hospitalization and survival.

title: Body fluid volume determination via body composition spectroscopy in health and disease.
abstract: The assessment of extra-, intracellular and total body water (ECW, ICW, TBW) is important in many clinical situations. Bioimpedance spectroscopy (BIS) has advantages over dilution methods in terms of usability and reproducibility, but a careful analysis reveals systematic deviations in extremes of body composition and morbid states. Recent publications stress the need to set up and validate BIS equations in a wide variety of healthy subjects and patients with fluid imbalance. This paper presents two new equations for determination of ECW and ICW (referred to as body composition spectroscopy, BCS) based on Hanai mixture theory but corrected for body mass index (BMI). The equations were set up by means of cross validation using data of 152 subjects (120 healthy subjects, 32 dialysis patients) from three different centers. Validation was performed against bromide/deuterium dilution (NaBr, D2O) for ECW/TBW and total body potassium (TBK) for ICW. Agreement between BCS and the references (all subjects) was -0.4 +/- 1.4 L (mean +/- SD) for ECW, 0.2 +/- 2.0 L for ICW and -0.2 +/- 2.3 L for TBW. The ECW agreement between three independent reference methods (NaBr versus D2O-TBK) was -0.1 +/- 1.8 L for 74 subjects from two centers. Comparing the new BCS equations with the standard Hanai approach revealed an improvement in SEE for ICW and TBW by 0.6 L (24%) for all subjects, and by 1.2 L (48%) for 24 subjects with extreme BMIs (<20 and >30). BCS may be an appropriate method for body fluid volume determination over a wide range of body compositions in different states of health and disease.

title: The Theory and Fundamentals of Bioimpedance Analysis in Clinical Status Monitoring and Diagnosis of Diseases
abstract: Bioimpedance analysis is a noninvasive, low cost and a commonly used approach for body composition measurements and assessment of clinical condition. There are a variety of methods applied for interpretation of measured bioimpedance data and a wide range of utilizations of bioimpedance in body composition estimation and evaluation of clinical status. This paper reviews the main concepts of bioimpedance measurement techniques including the frequency based, the allocation based, bioimpedance vector analysis and the real time bioimpedance analysis systems. Commonly used prediction equations for body composition assessment and influence of anthropometric measurements, gender, ethnic groups, postures, measurements protocols and electrode artifacts in estimated values are also discussed. In addition, this paper also contributes to the deliberations of bioimpedance analysis assessment of abnormal loss in lean body mass and unbalanced shift in body fluids and to the summary of diagnostic usage in different kinds of conditions such as cardiac, pulmonary, renal, and neural and infection diseases.

title: Comparison of Bioimpedance and Dual-Energy X-Ray Absorptiometry for Measurement of Fat Mass in Hemodialysis Patients
abstract: Fat mass (FM) is measured with dual-energy X-ray absorptiometry (DXA), but is expensive and not portable. Multifrequency bioimpedance spectroscopy (BIS) measures total body water (TBW), intracellular water (ICW) and extracellular water (ECW). FM is calculated by subtracting fat-free mass (FFM) from weight assuming a fractional hydration of FFM of 0.73. Hemodialysis (HD) patients, however, have nonphysiologic expansion of ECW. Our aim was to apply a model to estimate FM in HD patients and controls.  We estimated the hydration of FFM in healthy subjects and HD patients with BIS (Impedimed multifrequency) assuming a hydration of 0.73 or using a model allowing ECW and ICW to vary, deriving a value for FM accounting for variances in ECW and ICW. FM was measured by DXA (Hologic Discovery W) in 25 controls and in 11 HD patients. We measured TBW, ECW and ICW with BIS and calculated FM using either weight - TBW/0.73 or with a model accounting for variations in ECW/ICW to estimate FM.  ECW/ICW was greater in HD patients than in controls (0.83 ± 0.08 vs. 0.76 ± 0.04; p = 0.001). FM (kg) measured by DXA or estimated from TBW using constant hydration or accounting for variations in ECW/ICW was not significantly different in controls or in HD patients. Values obtained by all methods correlated (p < 0.001) and none of the Bland-Altman plots regressed (r2 = 0.00). FM measured by DXA and by BIS in both controls and HD patients combined correlated (r2 = 0.871).  Expansion of ECW in HD patients is statistically significant; however, the effect on hydration of FFM was insufficient to cause significant deviation from values derived using a hydration value of 0.73 within the range of expansion of ECW in the HD patient population studied here.

title: Body composition in dialysis patients: a functional assessment of bioimpedance using different prediction models.
abstract: The assessment of body composition (BC) in dialysis patients is of clinical importance given its role in the diagnosis of malnutrition and sarcopenia. Bioimpedance techniques routinely express BC as a 2-compartment (2-C) model distinguishing fat mass (FM) and fat-free mass (FFM), which may be influenced by the hydration of adipose tissue and fluid overload (OH). Recently, the BC monitor was introduced which applies a 3-compartment (3-C) model, distinguishing OH, adipose tissue mass, and lean tissue mass. The aim of this study was to compare BC between the 2-C and 3-C models and assess their relation with markers of functional performance (handgrip strength [HGS] and 4-m walking test), as well as with biochemical markers of nutrition.



Forty-seven dialysis patients (30 males and 17 females) (35 hemodialysis, 12 peritoneal dialysis) with a mean age of 64.8 ± 16.5 years were studied. 3-C BC was assessed by BC monitor, whereas the obtained resistivity values were used to calculate FM and FFM according to the Xitron Hydra 4200 formulas, which are based on a 2-C model.



FFM (3-C) was 0.99 kg (95% confidence interval [CI], 0.27 to 1.71, P = .008) higher than FFM (2-C). FM (3-C) was 2.43 kg (95% CI, 1.70-3.15, P < .001) lower than FM (2-C). OH was 1.4 ± 1.8 L. OH correlated significantly with ΔFFM (FFM 3-C - FFM 2-C) (r = 0.361; P < .05) and ΔFM (FM 3-C - FM 2-C) (r = 0.387; P = .009). HGS correlated significantly with FFM (2-C) (r = 0.713; P < .001), FFM (3-C) (r = 0.711; P < .001), body cell mass (2-C) (r = 0.733; P < .001), and body cell mass (3-C) (r = 0.767; P < .001). Both physical activity (r = 0.456; P = .004) and HGS (r = 0.488; P = .002), but not BC, were significantly related to walking speed.



Significant differences between 2-C and 3-C models were observed, which are partly explained by the presence of OH. OH, which was related to ΔFFM and ΔFM of the 2-C and 3-C models, is therefore an important parameter for the differences in estimation of BC parameters of the 2-C and 3-C models. Both FFM (3-C) and FFM (2-C) were significantly related to HGS. Bioimpedance, HGS, and the 4-m walking test may all be valuable tools in the multidimensional nutritional assessment of both hemodialysis and peritoneal dialysis patients.

title: Influence of Fluid Status on Techniques Used to Assess Body Composition in Peritoneal Dialysis Patients
abstract: A reliable assessment of nutritional state in peritoneal dialysis (PD) patients is of great importance. Nevertheless, techniques used to assess body composition in patients on PD may be affected by abnormalities in fluid status. The primary aim of the present study was to compare different techniques used to evaluate body composition and to assess the influence of fluid status on the assessment of body composition. The secondary aim was to assess the relevance of handgrip muscle strength in the nutritional evaluation of the patient.  In 40 PD patients, dual-energy x-ray absorptiometry (DEXA), multifrequency bioimpedance analysis (MF-BIA), and anthropometry were compared with respect to the evaluation of body composition [fat mass and lean body mass (LBM; by DEXA), and fat-free mass (FFM; by MF-BIA, anthropometry]. The influence of fluid status on the measurement of LBM/FFM by the various techniques was assessed by their relation to left ventricular end-diastolic diameter (LVEDD), assessed by echocardiography, and by estimating the ratio between extracellular water (ECW) and total body water (TBW), assessed by bromide and deuterium dilution, with LBM (DEXA). The relevance of handgrip muscle strength as a nutritional parameter was assessed by its relation to LBM and other nutritional parameters.  Despite highly significant correlations, wide limits of agreement between the various techniques were present with respect to assessment of body composition (expressed as % body weight) and were most pronounced for anthropometry: LBM (DEXA) – FFM (MF-BIA) = 3.4% ± 12.2%; LBM (DEXA) – FFM (anthropometry) = –5.7% ± 7.8%; fat mass (DEXA – MF-BIA) = –4.2%± 7.9%; fat mass (DEXA – anthropometry) = 2.9% ± 7.2%. The ratio between ECW and LBM (DEXA) was 0.36 ± 0.08 L/kg (range 0.25 – 0.67 L/kg), and the ratio between TBW and LBM was 0.75 ± 0.06 L/kg (range 0.63 – 0.86 L/kg), which shows the variability in hydration state of LBM/FFM between individual patients. LBM/FFM measured by all three techniques was significantly related to LVEDD, suggesting an important influence of hydration state on this parameter. Handgrip muscle strength was significantly related to LBM/FFM, as measured by all three techniques, but not to other nutritional parameters.  Wide limits of agreement were found between various techniques used to assess body composition in PD patients. The assessment of body composition was strongly influenced by hydration state. The handgrip test is related to body composition, but not to other nutritional parameters.

title: Changes in Body Composition in the Two Years after Initiation of Haemodialysis: A Retrospective Cohort Study
abstract: Malnutrition is common in haemodialysis (HD) and is linked to poor outcomes. This study aimed to describe changes in body composition after the initiation of HD and investigate whether any routinely collected parameters were associated with these changes. The study cohort came from the HD population of a single centre between 2009 and 2014. Body composition measurements were obtained from a database of bioimpedance results using the Body Composition Monitor (BCM), while demographics and laboratory values came from the renal unit database. Primary outcomes were changes in normohydration weight, lean tissue mass and adipose tissue mass over the two years after HD initiation. A total of 299 patients were included in the primary analyses, showing an increase in adipose tissue, loss of lean tissue and no significant change in normohydration weight. None of the routinely collected parameters were associated with the lean tissue changes. Loss of lean tissue over the first year of dialysis was associated with increased mortality. The results showing loss of lean tissue that is not limited to those traditionally assumed to be at high risk supports interventions to maintain or improve lean tissue as soon as possible after the initiation of HD. It highlights the importance of monitoring nutrition and the potential for routine use of bioimpedance.

title: Importance of Whole-Body Bioimpedance Spectroscopy for the Management of Fluid Balance
abstract: Achieving normohydration remains a non-trivial issue in haemodialysis therapy. Preventing the deleterious effects of fluid overload and dehydration is difficult to achieve. Objective and clinically applicable methods for the determination of a target representing normohydration are needed.  Whole-body bioimpedance spectroscopy (50 frequencies, 5–1,000 kHz) in combination with a physiologic tissue model can provide an objective target for normohydration based on the concept of excess extracellular volume. We review the efficacy of this approach in a number of recent clinical applications. The accuracy to determine fluid volumes (e.g. extracellular water), body composition (e.g. fat mass) and fluid overload was evaluated in more than 1,000 healthy individuals and patients against available gold standard reference methods (e.g. bromide, deuterium, dual-energy X-ray absorptiometry, air displacement plethysmography, clinical assessment).  The comparison with gold standard methods showed excellent accordance [e.g. R2 (total body water) = 0.88; median ± SD (total body water) = –0.17 ± 2.7 litres]. Agreement with high-quality clinical assessment of fluid status was demonstrated in several hundred patients (median ± SD = –0.23 ± 1.5 litres). The association between ultrafiltration volume and change in fluid overload was reflected well by the method (median ± SD = 0.015 ± 0.8 litres). The predictive value of fluid overload on mortality underlines forcefully the clinical relevance of the normohydration target, being secondary only to the presence of diabetes. The objective normohydration target could be achieved in prevalent haemodialysis patients leading to an improvement in hypertension and reduction of adverse events.  Whole-body bioimpedance spectroscopy in combination with a physiologic tissue model provides for the first time an objective and relevant target for clinical dry weight assessment.

title: Bioelectrical impedance analysis for body composition assessment: reflections on accuracy, clinical utility, and standardisation
abstract: Bioelectrical impedance analysis is an extremely popular method for assessment of body composition. Despite its wide-spread use over the past thirty years, its accuracy and clinical value is still questioned. Most frequently, criticisms focus on its purported poor absolute accuracy and that different impedance analysers or prediction equations fail to measure body composition identically. This perspective review highlights that the magnitude of errors associated with impedance methods are not dissimilar to those observed for so-called gold standard methods. It is argued that the focus on statistically significant but small differences between methods can obscure operational equivalence and that such differences may be of minor clinical significance. Finally, the need for better standardization of protocols and the need for consensus on what is a minimal clinically important difference between methods is highlighted.

title: Use of the Body Composition Monitor for Fluid Status Measurements in Subjects with High Body Mass Index
abstract: Fluid management is a central aspect of haemodialysis (HD). Body composition monitor (BCM)-measured overhydration (OH) can improve fluid management strategies, but there remains uncertainty about its use in subjects with high body mass index (BMI). This study explored whether the observed tendency for HD patients with high BMI to complete dialysis fluid depleted according to BCM is associated with an artefact in the BCM models, or with systematic differences in the prescription and delivery of treatment.  To isolate the effect of BMI from effects relating to treatment, BCM measurements were made on 20 healthy subjects with high BMI. Mean OH was compared with a previously reported cohort of healthy subjects with normal BMI. To further explore BCM-measured OH in HD patients, measurements were made pre- and post-dialysis on 10 patients with high BMI alongside relative blood volume monitoring. Body shape was classified to assess associations between shape and OH.  The mean OH for healthy subjects with high BMI was -0.1 litres, which was not different from that of healthy subjects with normal BMI. Median BCM-measured OH for HD patients was 1.8 and -1.8 litres pre- and post-dialysis respectively, while blood volume and blood pressure were maintained. Body shape correlated with OH in control subjects but not HD patients.  We found no evidence of systematic bias in BCM-measured OH with high BMI in healthy subjects. BCM-measured post-dialysis fluid depletion in asymptomatic patients with high BMI appears to result from greater tolerance of ultrafiltration and ability to maintain blood volume.

title: Comparison of fluid volume estimates in chronic hemodialysis patients by bioimpedance, direct isotopic, and dilution methods.
abstract: Bioimpedance analysis (BIA) is accepted for the assessment of total-body water (TBW), intracellular fluid (ICF) and extracellular fluid (ECF). We aimed to compare precision and accuracy of single and multi-frequency-BIA to direct estimation methods (DEMs) of TBW, ECF, and ICF in hemodialysis patients. Linear regression analysis of volume estimates in 49 patients by single- and multi-frequency-BIA correlated significantly with DEMs. Bland-Altman analysis (BAA) found systemic bias for ECF single-frequency-BIA vs. ECF-DEMs. No other systematic biases were found. Proportional errors were found by BAA of ICF and ECF assessments with single- and multi-frequency bioimpedance spectroscopy compared to the DEMs. Comparisons of indirect methods (IEMs) to DEMs showed no significant differences and proportional errors. Root mean-squared-error analysis suggested slightly better accuracy and precision of ICF single-frequency-BIA vs. DEMs over ICF multi-frequency-BIA and IEMs to DEMs, and slightly better performance for ECF multi-frequency-BIA over both respective other methods. Compared to DEMs, there is slightly better accuracy for ECF multi- over single-frequency-BIA and ICF single- over multi-frequency-BIA. However the margin of differences between direct and indirect methods suggests that none of the analyzed methods served as a true "gold standard", because indirect methods are almost equally precise compared to DEMs.

title: Validating Body Fat Assessment by Bioelectric Impedance Spectroscopy in Taiwanese Hemodialysis Patients.
abstract: Obesity is becoming increasingly common in hemodialysis (HD) patients and is associated with inflammation and increased mortality. The primary aim of the present study was to evaluate the accuracy and variability of the bioimpedance device in measuring body fat in Taiwanese dialysis patients.



Cross-sectional study.



One hundred twenty-two adult patients receiving HD in a single hospital in Taiwan.



We compared the results of fat mass (FM) measured by dual-energy x-ray absorptiometry (DEXA) and bioelectrical impedance spectroscopy device (Body composition monitor, BCM).



FM measured by BCM was calculated by subtracting fat-free mass (FFM) from body mass assuming fractional hydration of FFM of 0.73 or the proprietary prediction equations from the BCM model.



Assessment of whole-body composition showed that percentage FM measured using the 2 techniques was highly correlated when using the BCM model or estimating from total body water using constant (0.73) hydration (r = 0.87, P < .001). There was no evident difference in measurement between patients gender. The Bland-Altman plot also showed good agreement of percentage of FM (t = 3.82; P < .001). In female patients, it was found that BCM significantly underestimated mean FM as compared to DEXA. However, the mean differences of the estimates between the methods were small (0.35 ± 3.00 kg) and with Bland-Altman plot the limits of agreements were -5.5 to 6.2 kg (P = .40) for FM in female patients.



Using DEXA as the reference test, BCM is a valid tool for the assessment of total body fat in HD patients. Hence, it may provide a more accessible tool for early detection of changes in body composition in these high-risk patients.

title: Comparison of Dual Energy X-ray Absorptiometry and Bioimpedance in Assessing Body Composition and Nutrition in Peritoneal Dialysis Patients.
abstract: Peritoneal dialysis (PD) patients are characterized by protein malnutrition and muscle wasting. Reliable, easy, and cheap methods for evaluating nutrition are desirable. Three methods are commonly available: dual-energy X-ray absorptiometry (DXA), bioimpedance (BI), and subjective global assessment (SGA).The objective of the study was to compare the previously mentioned methods for assessment of body composition and nutritional status in PD patients.



The study is cross-sectional and consisted of 72 PD patients from a single center PD ambulatorium.



Participants were measured twice by DXA, twice by BI, and once by SGA. Measurements included lean tissue mass (LTM), fat tissue mass (FT) and, for BI, overhydration (OH), intracellular water (ICW), and extracellular water (ECW). LTM and FT were indexed to body area (Lean Tissue Index [LTI] and Fat Tissue Index [FTI], respectively), and ICW for height (ICW/ht). We assessed conventional biochemical and clinical variables, using values for normal individuals as a reference.



There was good overall agreement between BI and DXA but considerable intra-individual variation (1 standard deviation: FT 5.7 kg; LTM 5.6 kg). Factors affecting the differences were FT, ICW, LTM, and ICW. Obesity (DXA 43%; BI 54%) and muscle wasting (BI 28%; SGA 53%) were common. Agreement between BI and SGA was poor. Thirty-eight percent of patients judged malnourished by SGA also had a low LTI; 23% with normal SGA had low LTI. SGA was closer related to LTI (BI) than LTI (DXA). Plasma albumin was correlated to LTI, FTI, and ICW/ht, and comorbidity to OH, clinical malnutrition, reduced FTI, but not LTI.



Agreement between DXA and BI was high on a population basis but not at an individual level. Obesity and muscle wasting were common in this population. OH might reduce DXA accuracy in PD patients. LTI and ICW may be useful measures to supplement SGA in assessing nutrition.

title: Comparison of DEXA and Bioimpedance for Body Composition Measurements in Nondialysis Patients With CKD.
abstract: The aims of this study are (1) to compare dual-energy X-ray absorptiometry (DEXA) and bioimpedance for body composition measurements in nondialysis patients with chronic kidney disease, and (2) to investigate factors associated with any measurement differences.



This is a substudy using some baseline data from a randomized controlled clinical trial. One hundred twenty patients (aged 65 ± 14 years) with a measured glomerular filtration rate 8 to 55 mL/min/1.73m2, not on renal replacement therapy, irrespective of age and number of comorbidities, were included from 2011 to 2016. For DEXA measurements, Lunar Prodigy or Lunar iDXA were used. For bioimpedance measurements, body composition monitor (BCM) was used. Glomerular filtration rate was measured with iohexol clearance. Data were analyzed using R software. Bland-Altman analysis was performed to compare the 2 measurements. The measurement difference was DEXA minus BCM. Multiple linear regression analysis was performed to analyze relationships between variables.



The estimation of fat-free mass was higher using BCM than DEXA, with a mean difference of -2.8 kg and limits of agreement (mean ± 2 SD) ranging from -12 kg to 6.5 kg. The estimation of fat mass was lower using BCM than DEXA, with a mean difference of 3.1 kg and limits of agreement (mean ± 2 SD) ranging from -6.8 kg to 13 kg. The measurement differences were significantly related to lean tissue index, fat tissue index, extracellular water, intracellular water, extracellular water/intracellular water, total body water, and overhydration.



Our study showed a limited agreement between DEXA and bioimpedance, indicating that these 2 measurements are not interchangeable in nondialysis patients with chronic kidney disease. Lean tissue index, fat tissue index, and body water might contribute to the measurement differences, while measured glomerular filtration rate is not a factor associated with the measurement differences for body composition. Thus, we suggest that the same measure of body composition be used over time.

title: Bioimpedance Spectroscopy as a Practical Tool for the Early Detection and Prevention of Protein-Energy Wasting in Hemodialysis Patients.
abstract: To evaluate whether body composition monitor (BCM) could be a practical instrument for nephrologists to assess nutritional status in patients on hemodialysis (HD) and whether it is more effective in identifying patients at highest risk of developing protein-energy wasting (PEW) alone or in combination with other tools currently used for that purpose.



Observational cross-sectional study in 91 HD patients (60 ± 14 years, 70.3% male, 24 ± 4.1 kg/m2 body mass index) from 2 different locations.



Nutritional status was evaluated by anthropometric methods (biceps and triceps skinfold thickness, waist circumference, and arm muscular circumference), biochemical nutritional markers, malnutrition-inflammation score (MIS), and BCM. The patients were grouped into those with and without PEW by using classical criteria and then classified as being adequately or inadequately nourished according to a BCM flow chart to detect those requiring preferential nutritional intervention. A multivariate approach was used to calculate the risk of developing PEW.



Anthropometric measurements revealed significantly lower body mass index (<23 kg/m2; odds ratios [OR] = 13.3 and P = 0.001) and arm muscular circumference < p10 (OR = 34, P < 0.001) in the PEW group. MIS was above 5 in all the patients classified as having PEW. BCM showed that fat tissue index < p10 was significantly lower in this group (OR = 1.52), and a decision tree using the lean tissue index < p10, fat tissue index < p10, and extracellular water > 15% revealed that 42.9% of the patients would need nutritional monitoring. On multivariate analysis, insufficient nutritional status detected by BCM decision tree was an independent prognostic factor for developing PEW. About 9.89% of the patients were classified as PEW, with MIS > 5, and insufficient nutritional status detected by BCM required preferential nutritional intervention.



BCM is a practical instrument for nephrologists to assess nutritional status in patients on HD and is useful for the early prevention and detection of PEW, as is able to identify differences in body composition, predict clinically important outcomes, and classify patients requiring preferential nutritional intervention.

title: Body composition and survival in dialysis patients: results from an international cohort study.
abstract: High body mass index appears protective in hemodialysis patients, but uncertainty prevails regarding which components of body composition, fat or lean body mass, are primarily associated with survival.



Data between April 2006 and December 2012 were extracted from the Fresenius Medical Care Europe subset of the international MONitoring Dialysis Outcomes initiative. Fresenius Medical Care Europe archives a unique repository of predialysis body composition measurements determined by multifrequency bioimpedance (BCM Body Composition Monitor). The BCM Body Composition Monitor reports lean tissue indices (LTIs) and fat tissue indices (FTIs), which are the respective tissue masses normalized to height squared, relative to an age- and sex-matched healthy population. The relationship between LTI and FTI and all-cause mortality was studied by Kaplan-Meier analysis, multivariate Cox regression, and smoothing spline ANOVA logistic regression.



In 37,345 hemodialysis patients, median (25th-75th percentile) LTI and FTI were 12.2 (10.3-14.5) and 9.8 (6.6-12.4) kg/m(2), respectively. Median (25th-75th percentile) follow-up time was 266 (132-379) days; 3458 (9.2%) patients died during follow-up. Mortality was lowest with both LTI and FTI in the 10th-90th percentile (reference group) and significantly higher at the lower LTI and FTI extreme (hazard ratio [HR], 3.37; 95% confidence interval [95% CI], 2.94 to 3.87; P<0.001). Survival was best with LTI between 15 and 20 kg/m(2) and FTI between 4 and 15 kg/m(2) (probability of death during follow-up: <5%). When taking the relation between both compartments into account, the interaction was significant (P=0.01). Higher FTI appeared protective in patients with low LTI (HR, 3.37; 95% CI, 2.94 to 3.87; P<0.001 at low LTI-low FTI, decreasing to HR, 1.79; 95% CI, 1.47 to 2.17; P<0.001 at low LTI-high FTI).



This large international study indicates best survival in patients with both LTI and FTI in the 10th-90th percentiles of a healthy population. In analyses of body composition, both lean tissue and fat tissue compartments and also their relationship should be considered.

title: Nutritional Markers and Body Composition in Hemodialysis Patients
abstract: The aims of this study were to analyse body composition, to detect the presence of undernutrition, and to establish a relationship between undernutrition and the biological markers routinely used as indicators of nutritional status in hemodialysis (HD) patients (pts). We used a body composition monitor (BCM) that expresses body weight in terms of lean tissue mass (LTM) and fat tissue mass (FTM) independent of hydration status. From nine HD units, 934 pts were included. Undernutrition was defined as having a lean tissue index (LTI = LTM/height2) below the 10th percentile of a reference population. Biochemical markers and parameters delivered by BCM were used to compare low LTI and normal LTI groups. Undernutrition prevalence was 58.8% of the population studied. Low LTI pts were older, were significantly more frequently overhydrated, and had been on HD for a longer period of time than the normal LTI group. FTI (FTI = FTM/ height2) was significantly higher in low LTI pts and increased according to BMI. LTI was not influenced by different BMI levels. Albumin and C-reactive protein correlated inversely (r = −0.28). However neither of them was statistically different when considering undernourished and normal LTI pts. Our BCM study was able to show a high prevalence of undernutrition, as expressed by low LTI. In our study, BMI and other common markers, such as albumin, failed to predict malnutrition as determined by BCM.

title: Fat-to-Lean Mass Ratio Can Predict Cardiac Events and All-Cause Mortality in Patients Undergoing Hemodialysis
abstract: Although higher body mass index (BMI) is associated with better survival in patients undergoing dialysis, BMI is not an adequate obesity indicator. We hypothesized that the fat-to-lean (F/L) mass ratio could be a suitable marker of nutritional status and evaluated its prognostic impact on long-term outcomes in patients undergoing hemodialysis (HD).  In total, 131 patients undergoing HD were recruited and monitored prospectively for up to 5 years. Body composition was analyzed, and other nutritional and inflammatory parameters were measured.  The mean age of the cohort was 60.7 ± 13.6 years, and 65 patients were diabetic. Age, sex, diabetes, comorbidity, and inflammation were associated significantly with the F/L mass ratio. During the follow-up period, 21 patients experienced cardiac events and 22 patients died. Patients with higher F/L mass ratios had significantly higher risks of all-cause death (hazard ratio [HR] 3.61, 95% CI 1.07–12.13; p = 0.038) and cardiac events (HR 3.54, 95% CI 1.05-11.94; p = 0.041) than those with lower F/L mass ratios.  The F/L mass ratio was a useful surrogate marker of nutritional and inflammatory status, and an independent predictor of cardiac events and all-cause mortality, in patients undergoing HD.

title: Longitudinal Changes in Body Composition in Patients After Initiation of Hemodialysis Therapy: Results From an International Cohort.
abstract: In patients with advanced kidney disease, metabolic and nutritional derangements induced by uremia interact and reinforce each other in a deleterious vicious circle. Literature addressing the effect of dialysis initiation on changes in body composition (BC) is limited and contradictory. The aim of this study was to evaluate changes in BC in a large international cohort of incident hemodialysis patients.



A total of 8,227 incident adult end-stage renal disease patients with BC evaluation within the initial first 6 months of baseline, defined as 6 months after renal replacement therapy initiation, were considered. BC, including fat tissue index (FTI) and lean tissue index (LTI), were evaluated by Body Composition Monitor (BCM, Fresenius Medical Care, Bad Homburg, Germany). Exclusion criteria at baseline were lack of a BCM measurement before or after baseline, body mass index (BMI) < 18.5 kg/m(2), presence of metastatic solid tumors, treatment with a catheter, and prescription of less or more than 3 treatments per week. Maximum follow-up was 2 years. Descriptive analysis was performed comparing current values with the baseline in each interval (delta analysis). Linear mixed models considering the correlation structure of the repeated measurements were used to evaluate factors associated with different trends in FTI and LTI.



BMI increased about 0.6 kg/m(2) over 24 months from baseline. This was associated with increase in FTI of about 0.95 kg/m(2) and a decrease in LTI of about 0.4 kg/m(2). Female gender, diabetic status, and low baseline FTI were associated with a significant greater increase of FTI. Age > 67 years, diabetes, male gender, high baseline LTI, and low baseline FTI were associated with a significant greater decrease of LTI.



With the transition to hemodialysis, end-stage renal disease patients presented with distinctive changes in BC. These were mainly associated with gender, older age, presence of diabetes, low baseline FTI, and high baseline LTI. BMI increases did not fully represent the changes in BC.

title: Accelerated lean body mass loss in incident chronic dialysis patients with diabetes mellitus.
abstract: End-stage renal disease (ESRD) patients display a higher incidence of poor nutritional status and are at high risk of hospitalization and death. Patients on renal replacement therapy (RRT) with a primary diagnosis of diabetes mellitus have the lowest survival rates along with highest hospitalization incidence.



In this study, we examined the importance of diabetes mellitus along with certain demographic and clinical variables in predicting the change in lean body mass (LBM) by dual-energy x-ray absorptiometry (DEXA), as a surrogate marker of somatic protein stores, in 142 incident ESRD patients (91 males, 52.8 +/- 1.0 years, 74.2 +/- 1.2 kg body weight) among which 34 had diabetes mellitus (19 insulin-dependent and 15 noninsulin dependent).



Our results show that patients with diabetes mellitus had significantly accelerated loss of LBM compared to nondiabetic patients during the first year of RRT (3.4 +/- 0.6 kg vs. 1.1 +/- 0.2 kg) (P < 0.05). Multivariate linear regression analyses revealed that the presence of diabetes mellitus was the strongest predictor of LBM loss independently of several clinically-relevant variables such as age, gender, serum albumin, presence of malnutrition, presence of inflammation, and RRT modality.



We conclude that the presence of diabetes mellitus is the most significant independent predictor of LBM loss in renal replacement therapy patients, providing a potential explanation as to why ESRD patients with diabetes mellitus are more prone to muscle wasting.

title: A multicentric, international matched pair analysis of body composition in peritoneal dialysis versus haemodialysis patients.
abstract: Volume status, lean and fat tissue are gaining interest as prognostic predictors in patients on dialysis. Comparative data in peritoneal dialysis (PD) versus haemodialysis (HD) patients are lacking.



In a cohort of PD (EuroBCM) and HD (Euclid database) patients, matched for country, gender, age and dialysis vintage, body composition was assessed by bioimpedance spectroscopy (BCM, Fresenius Medical Care). Time-averaged volume overload (TAVO) was defined as the mean of pre- and post-dialysis volume overload (VO), and relative (%) (TA)VO as (TA)VO/ECV.



Four hundred and ninety-one matched pairs (55.2% males, median age 60.0 years) were included. The body mass index (BMI, PD = 26.5 ± 4.7 versus HD = 25.9 ± 4.6 kg/m(2), P = 0.18 in males and 27.4 ± 5.8 versus 27.5 ± 6.6 kg/m(2), P = 0.75 in females) and fat tissue index (males: 11.5 ± 5.3 versus 11.4 ± 5.4 kg/m(2), P = 0.90, females: 14.8 ± 6.7 versus 15.4 ± 7.2 kg/m(2), P = 0.30) were not different in PD versus HD patients, whereas the lean tissue index (LTI) was higher in PD versus HD patients (males: 14.5 ± 3.4 versus 13.7 ± 3.1 kg/m(2), P = 0.001, females: 12.6 ± 3.3 versus 11.5 ± 2.6 kg/m(2), P < 0.0001). VO/extracellular water (ECW) was not different between PD versus just before the HD treatment (males: 10.8 ± 12.1 versus 9.2 ± 10.2%, P = 0.09; females: 6.5 ± 10.8 versus 7.7 ± 9.4%, P = 0.19). The relative TAVO was higher in PD versus HD (10.8 ± 12.1% versus 3.2 ± 11.2%, and 6.5 ± 10.8% versus 1.2 ± 10.9%, both P < 0.0001).



The LTI was impaired, and this was more in males versus females, but was better preserved on PD versus HD, whereas fat tissue index (FTI) was increased, but not different between PD and HD. Volume overload was more present in PD versus HD when TAVO, but not when predialysis volume status, was used as a reference.

title: Season affects body composition and estimation of fluid overload in haemodialysis patients: variations in body composition; a survey from the European MONDO database.
abstract: Seasonal variations in blood pressure (BP) and inter-dialytic weight gain (IDWG) are well established in dialysis patients. However, no study has assessed changes in body composition (BC) in this population.



In this survey, seasonal variations in fat mass (FM), lean tissue mass (LTM), extracellular water (ECW) and fluid overload (FO) were assessed in 42 099 dialysis patients (mean age 61.2 years, 58% males) from the Fresenius Medical Care Europe database, as part of the MONitoring Dialysis Outcomes (MONDO) consortium, in relation to other nutritional parameters, IDWG and BP. BC was assessed by a body composition monitor (BCM®, Fresenius Medical Care, Bad Homburg, Germany).



FM was highest in winter and lowest in summer (▵FM -1.17 kg; P < 0.001), whereas LTM was lowest during winter and highest in summer (▵LTM 0.86 kg; P < 0.0001). ECW and FO were lowest in winter, and highest in spring (▵ECW: 0.13 L; P < 0.0001, ▵FO: 0.31 L; P < 0.0001) and summer (▵ECW: 0.15 L; P < 0.0001 and ▵FO: 0.2 L; P < 0.0001), despite a higher systolic blood pressure (SBP; 136.7 ± 17.4 mmHg) and IDWG (3.0 ± 1.1 kg) during winter. C-reactive protein (CRP), serum sodium and haemoglobin levels were highest in winter, whereas serum albumin was lowest in fall. Normalized protein catabolic rate (nPCR) was lowest in winter and matched variations in BC only to a minor degree.



BC and hydration state, assessed by bio-impedance spectroscopy, follows a seasonal pattern which may be of relevance for the estimation of target weight, and for the interpretation of longitudinal studies including estimates of BC. Whether these changes should lead to therapeutic interventions could be the focus of future studies.

title: Body Mass Index and All-cause Mortality in Chronic Kidney Disease: A Dose-response Meta-analysis of Observational Studies.
abstract: This article provides a dose-response meta-analysis to evaluate the relationship between body mass index (BMI) and all-cause and disease-specific mortality in chronic kidney disease (CKD) by pooling together early stage, hemodialysis, and peritoneal dialysis patients. We evaluated eligible studies that published between 1966 and December 2014 by searching in PubMed, Object View and Interaction Design (OVID), and the Scopus databases. We used random-effects generalized least squares spline models for trend estimation to derive pooled dose-response estimates. Nonlinear associations of BMI with all-cause mortality were observed (P-nonlinearity < .0001), with an increased rate of mortality with BMIs > 30 kg/m2 in all stages of CKD together. However, reanalysis of data separately by stage of CKD (hemodialysis and peritoneal dialysis) showed that the risk of all-cause mortality decreased with a steep slope in individuals with BMIs > 30 kg/m2. This meta-analysis indicates that higher BMI has protective effects with respect to all-cause mortality in patients with both type of dialysis.

title: Body composition monitor assessing malnutrition in the hemodialysis population independently predicts mortality.
abstract: Malnutrition is a known predictor of mortality in the general and hemodialysis populations. However, diagnosing malnutrition in dialysis patients remains problematic. Body composition monitoring (BCM) is currently used mainly for assessing overhydratation in hemodialysis patients, but it also offers the possibility of evaluating nutrition status. This study explored whether malnutrition diagnosed by BCM predicts mortality at up to 54 months follow-up in prevalent hemodialysis patients.



This was a retrospective epidemiology cohort study. Dialysis patients with baseline BCM measurement between 2008 and 2013 were enrolled. The observation period was up to 54 months follow-up.



A total sample consisted of 960 chronic hemodialysis participants.



All data were retrieved from medical records. Nutrition status was estimated by BCM; malnutrition was diagnosed as lean tissue index less than 10% of the normal value.



Cox regression was performed to identify whether low LTI predicted mortality in hemodialysis patients.



BCM-diagnosed malnutrition (hazard ratio [HR] 1.66; 95% confidence interval [CI] 1.1; 2.44), higher age (HR 1.05; 95% CI 1.03; 1.07), longer dialysis vintage (HR 1.00; 95% CI 1.00; 1.00), central venous catheter use (HR 1.96; 95% CI 1.28; 2.99), and low serum albumin (HR 0.91; 95% CI 0.87; 0.95) contributed significantly to the Cox regression model on mortality.



BCM-diagnosed malnutrition in chronic hemodialysis patients is an independent predictor of mortality at up to 54 months follow-up and is associated with a 1.66-fold higher risk of dying compared with normal nutrition status. Whether intervention (e.g., nutritional supplementation) might improve nutrition and reduce the higher risk of mortality in malnutrition patients on hemodialysis remains a challenge for future research.

title: Body Composition and Mortality Predictors in Hemodialysis Patients.
abstract: To evaluate how different compartments of body composition can affect survival in hemodialysis (HD) patients.



Multicenter longitudinal observational study of a cohort of patients in HD with 12 months of follow-up.



Patients from 34 Nephrocare dialysis units in Portugal were included.



A total of 697 patients on maintenance HD during 4 hours 3 days per week were enrolled.



Dry weight, presence of diabetes, body mass index (BMI), lean tissue index (LTI), fat tissue index (FTI), body cell mass index (BCMI), albumin and hydration status were recorded at baseline. In all patients, the assessment of body composition was carried out using the Body Composition Monitor (BCM; Fresenius Medical Care a Deutschland GmbH, Germany).



Survival during a 12-month period of follow-up.



Patient's mean (±standard deviation) age was 65.4 ± 14.3 years, and median (interquartile range) HD vintage was 41 (19-81) months. Patients who died during the study period, had higher age (P < .001), lower dry weight (P = .001), BMI (P < .001), albumin (P < .001), LTI (P = .015), and also lower BCMI (P = .046). Patients with diabetes (P = .045), BMI < 18.5 kg/m(2) (P < .001), albumin < 4.0 g/dL (P < .001), relative overhydration ≥ 15% (P = .001), low FTI (P = .019), and also those in the lowest tertile of BCMI (P = .022) displayed a significantly worse survival. In the Cox regression analysis, the overall mortality of patient was related to low FTI, relative overhydration, BMI < 18.5 kg/m(2), BCMI ≤ 5.2 kg/m(2), and albumin < 4.0 g/dL.



Several body composition parameters demonstrated to have an important role in predicting 1-year mortality in HD patients. Albumin, FTI, and BMI were useful predictors of mortality in these patients.

title: Low lean tissue mass can be a predictor of one-year survival in hemodialysis patients
abstract: Nutritional status has a significant impact on the outcomes in the dialysis population. The aim of this study was to evaluate the association between body composition and a one-year survival of hemodialysis patients.  Forty-eight patients with chronic kidney disease stage V treated with hemodialysis for more than three months were included. Body composition was assessed by bioimpedance spectroscopy (Body Composition Monitor, Fresenius Medical Care). Blood samples for serum creatinine, serum albumin, serum prealbumin, high sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), insulin-like growth factor 1(IGF-1) concentrations were taken before the midweek dialysis session.  Over the course of a one-year observation, seven patients died. We observed a significantly lower lean tissue index (LTI) (p = .013) and higher IL-6 (p = .032) and hsCRP levels (p = .011) among the patients who died. The remaining biochemical markers did not differ between these two groups. Kapplan–Meier analysis revealed a worse survival rate in patients with sarcopenia (lower than the 10th percentile for their age and gender) in comparison with those with normal LTI. However, it was not of statistical significance (p = .055). LTI inversely correlated with age and IL-6 and positively with IGF-1.  Sarcopenia defined as decreased LTI, is a relatively common condition among patients undergoing maintenance hemodialysis, it can also be associated with a lower one-year survival rate. Decreased lean tissue mass can be associated with old age, lower IGF-1 levels and higher IL-6 levels. Body composition assessment may provide prognostic data for hemodialysis patients.

title: Clinical value of body composition monitor to evaluate lean and fat tissue mass in peritoneal dialysis
abstract: ObjectivesBioimpedance analysis is often routinely performed in any dialysis unit to guide fluid management but can provide a reproduceable assessment of fat and muscle mass. We wished to determine the clinical significance of low muscle or high fat mass and the determinants that influence their change.Subjects/MethodsWe performed retrospective analysis of 824 patients on peritoneal dialysis who underwent routine repeated bioimpedance analysis measurements using the body composition monitor (BCM).ResultsLean tissue index (LTI) was an independent predictor of mortality when sex, age, PD vintage and diabetes status were included in the models (HR 0.93; 95% CI 0.86–1.00, p < 0.05) and when baseline serum albumin was included in a separate model (HR 0.86; 95% CI: 0.79–0.93, p < 0.001). High fat tissue index (FTI) was an independent predictor of mortality when demographic factors were included (HR 0.87; 95% CI: 0.78–0.97, p < 0.02), but not with the addition biochemical parameters. Changes in body composition of 206 patients over a 2-year follow-up period could not be predicted by baseline demographics, functional or biochemical assessments. However, there was a strong inverse relationship between changes in LTI and FTI. There were no associations between changes in body composition with prescribed dialysate glucose.ConclusionsWe showed body composition changes are common and complex. LTI was an independent predictor of survival. Changes in LTI and FTI could not be predicted by baseline parameters. BCM may be a sensitive and accurate tool to monitor changes in body composition during dialysis treatment.

title: Body composition is associated with clinical outcomes in patients with non-dialysis-dependent chronic kidney disease.
abstract: An inverse relationship between body mass index (BMI) and mortality (the obesity paradox) has been found in patients with non-dialysis-dependent chronic kidney disease (CKD). However, it is unclear whether increased muscle mass or body fat confers the survival advantage. To resolve this we investigated the impact of body makeup on a composite outcome of death or cardiovascular events in a prospective cohort of 326 patients with stage 3-5 CKD not yet on dialysis. Lean mass and body fat were determined using the Body Composition Monitor, a multifrequency bioimpedance spectroscopy device, and were expressed as the lean tissue or fat tissue index, respectively. Patients were stratified as High (above median) or Low (below median) BMI, High or Low lean tissue index, or as High or Low fat tissue index. During a median follow-up of 4.6 years, there were 40 deaths and 68 cardiovascular events. In Cox proportional hazards models, a High lean tissue index, but not High BMI or High fat tissue index, predicted a lower risk of both the composite or its component outcomes (reference: below median). When patients were further stratified into four distinct body composition groups based on both the lean and fat tissue index, only the High lean/fat tissue index group had a significantly lower risk of the composite outcome (hazard ratio 0.36, 95% confidence interval 0.14-0.87; reference: Low lean/fat tissue index group). Thus, the lean tissue index can provide better risk prediction than the BMI alone in non-dialysis-dependent patients with CKD. The High lean/fat tissue index appears to be associated with best outcomes. An optimal body composition for improving the prognosis of CKD needs to be determined.

title: Sarcopenic obesity: A Critical appraisal of the current evidence.
abstract: Sarcopenic obesity (SO) is assuming a prominent role as a risk factor because of the double metabolic burden derived from low muscle mass (sarcopenia) and excess adiposity (obesity). The increase in obesity prevalence rates in older subjects is of concern given the associated disease risks and more limited therapeutic options available in this age group. This review has two main objectives. The primary objective is to collate results from studies investigating the effects of SO on physical and cardio-metabolic functions. The secondary objective is to evaluate published studies for consistency in methodology, diagnostic criteria, exposure and outcome selection. Large between-study heterogeneity was observed in the application of diagnostic criteria and choice of body composition components for the assessment of SO, which contributes to the inconsistent associations of SO with cardio-metabolic outcomes. We propose a metabolic load:capacity model of SO given by the ratio between fat mass and fat free mass, and discuss how this could be operationalised. The concept of regional fat distribution could be incorporated into the model and tested in future studies to advance our understanding of SO as a predictor of risk for cardio-metabolic diseases and physical disability.

title: The Obesity Paradox in Kidney Disease: How to Reconcile It With Obesity Management
abstract: Obesity, a risk factor for de novo chronic kidney disease (CKD), confers survival advantages in advanced CKD. This so-called obesity paradox is the archetype of the reverse epidemiology of cardiovascular risks, in addition to the lipid, blood pressure, adiponectin, homocysteine, and uric acid paradoxes. These paradoxical phenomena are in sharp contradistinction to the known epidemiology of cardiovascular risks in the general population. In addition to advanced CKD, the obesity paradox has also been observed in heart failure, chronic obstructive lung disease, liver cirrhosis, and metastatic cancer, as well as in elderly individuals. These are populations in whom protein−energy wasting and inflammation are strong predictors of early death. Both larger muscle mass and higher body fat provide longevity in these patients, whereas thinner body habitus and weight loss are associated with higher mortality. Muscle mass appears to be superior to body fat in conferring an even greater survival. The obesity paradox may be the result of a time discrepancy between competing risk factors, that is, overnutrition as the long-term killer versus undernutrition as the short-term killer. Hemodynamic stability of obesity, lipoprotein defense against circulating endotoxins, protective cytokine profiles, toxin sequestration of fat mass, and antioxidation of muscle may play important roles. Despite claims that the obesity paradox is a statistical fallacy and a result of residual confounding, the consistency of data and other causality clues suggest a high biologic plausibility. Examining the causes and consequences of the obesity paradox may help uncover important pathophysiologic mechanisms leading to improved outcomes in patients with CKD.

title: Visceral Fat Level Is an Independent Risk Factor for Cardiovascular Mortality in Hemodialysis Patients
abstract: Obesity is an independent risk factor for morbidity and mortality in cardiovascular diseases not only in the general population, but also in hemodialysis (HD) patients. We previously reported that an increased visceral fat area (VFA) determined using computed tomography (CT) scans was associated with atherosclerosis in HD patients. However, whether a high VFA is associated with increased cardiovascular mortality in HD patients remains unknown. Therefore, we investigated the relationship between VFA and prognosis in HD patients.  VFA was estimated in 126 patients on maintenance HD using CT scans. These patients were followed for 60 months.  Kaplan-Meier analysis revealed that the cardiovascular survival rate was significantly lower in the high-VFA group, with a VFA of 71.5 cm2 or greater, than in the low-VFA group, with a VFA of less than 71.5cm2. In univariate Cox proportional hazards analyses, age, albumin, low-density lipoprotein cholesterol, cardio-thoracic ratio and VFA above 71.5 cm2 were significantly correlated with cardiovascular deaths. In multivariate analyses testing these factors as dependent variables, VFA above 71.5 cm2 was estimated to be an independent predictor of cardiovascular deaths.  These results suggest that an increased VFA is a stronger risk factor for cardiovascular deaths in HD patients. Measuring VFA may be recommended for predicting the risk of cardiovascular diseases in HD patients.

title: The malnutrition, inflammation, and atherosclerosis (MIA) syndrome -- the heart of the matter.
abstract: The majority of patients starting dialysis already have signs of advanced atherosclerosis, and the risk factors for cardiovascular morbidity and mortality seen in patients with end-stage renal disease (ESRD) develop with the disease progression. Therefore, the predialysis period is the ideal time to start therapeutic interventions. Traditional risk factors alone may not adequately predict cardiovascular disease (CVD) outcome in patients with ESRD. Inflammation has been identified as playing a key role in atherosclerotic CVD. Pro-inflammatory cytokines are pivotal to the inflammation that is associated with malnutrition and atherosclerosis in ESRD. Malnutrition may worsen patient outcome by aggravating existing inflammation and heart failure, accelerating atherosclerosis and increasing susceptibility to infection. Atherosclerosis is itself a major risk factor for CVD mortality. Moreover, inflammation is associated with congestive heart failure. Strong associations between malnutrition, inflammation and atherosclerosis in this patient population suggest the presence of a syndrome we have called malnutrition, inflammation, and atherosclerosis (MIA), which is associated with an exceptionally high mortality rate.

title: Volume overload correlates with cardiovascular risk factors in patients with chronic kidney disease.
abstract: Volume overload is a predictor of mortality in dialysis patients. However, the fluid status of patients with chronic kidney disease (CKD) but not yet on dialysis has not been accurately characterized. We used the Body Composition Monitor, a multifrequency bioimpedance device, to measure the level of overhydration in CKD patients, focusing on the association between overhydration and cardiovascular disease risk factors. Overhydration was the difference between the amount of extracellular water measured by the Body Composition Monitor and the amount of water predicted under healthy euvolemic conditions. Volume overload was defined as an overhydration value at and above the 90th percentile for the normal population. Of the 338 patients with stages 3-5 CKD, only 48% were euvolemic. Patients with volume overload were found to use significantly more antihypertensive medications and diuretics but had higher systolic blood pressures and an increased arterial stiffness than patients without volume overload. In a multivariate analysis, male sex, diabetes, pre-existing cardiovascular disease, systolic blood pressure, serum albumin, TNF-α, and proteinuria were independently all associated with overhydration. Thus, volume overload is strongly associated with both traditional and novel risk factors for cardiovascular disease. Bioimpedance devices may aid in clinical assessment by helping to identify a high-risk group with volume overload among stages 3-5 CKD patients.

title: Factors Associated with Decreased Lean Tissue Index in Patients with Chronic Kidney Disease
abstract: Muscle wasting is common and is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD). However, factors associated with decreased muscle mass in CKD patients are seldom reported. We performed a cross-sectional study of 326 patients (age 65.8 ± 13.3 years) with stage 3–5 CKD who were not yet on dialysis. Muscle mass was determined using the Body Composition Monitor (BCM), a multifrequency bioimpedance spectroscopy device, and was expressed as the lean tissue index (LTI, lean tissue mass/height2). An LTI of less than 10% of the normal value (low LTI) indicates muscle wasting. Patients with low LTI (n = 40) tended to be diabetic, had significantly higher fat tissue index, urine protein creatinine ratio, and interleukin-6 and tumor necrosis factor-α levels, but had significantly lower serum albumin and hemoglobin levels compared with those with normal LTI. In multivariate linear regression analysis, age, sex, cardiovascular disease, and interleukin-6 were independently associated with LTI. Additionally, diabetes mellitus remained an independent predictor of muscle wasting according to low LTI by multivariate logistic regression analysis. We conclude that LTI has important clinical correlations. Determination of LTI may aid in clinical assessment by helping to identify muscle wasting among patients with stage 3–5 CKD.

title: Association of fluid overload with cardiovascular morbidity and all-cause mortality in stages 4 and 5 CKD.
abstract: Fluid overload is a common characteristic associated with renal progression in CKD. Additionally, fluid overload is an independent predictor of all-cause or cardiovascular mortality in patients on dialysis, but its influence on patients not on dialysis is uncertain. The aim of the study was to assess the relationship between the severity of fluid status and clinical outcomes in an advanced CKD cohort.



In total, 478 predialysis patients with stages 4 and 5 CKD in the integrated CKD care program were enrolled from January of 2011 to December of 2011 and followed-up until August of 2013. The clinical outcomes included cardiovascular morbidity and all-cause mortality. The relative hydration status (overhydration/extracellular water) was used as the presentation of the severity of fluid status and measured using a body composition monitor. Overhydration/extracellular water >7% was defined as fluid overload.



Over a median follow-up period of 23.2 (12.6-26.4) months, 66 (13.8%) patients reached all-cause mortality or cardiovascular morbidity. The adjusted hazard ratio of the combined outcome of all-cause mortality or cardiovascular morbidity for every 1% higher overhydration/extracellular water was 1.08 (95% confidence interval, 1.04 to 1.12; P<0.001). The adjusted overhydration/extracellular water for the combined outcome of all-cause mortality or cardiovascular morbidity in participants with overhydration/extracellular water ≥7% compared with those with overhydration/extracellular water <7% was 1.93 (95% confidence interval, 1.01 to 3.69; P=0.04). In subgroup analysis, higher overhydration/extracellular water was consistently associated with increased risk for the combined outcome independent of diabetes, cardiovascular disease, and serum albumin. There was no significant interaction between all subgroups.



These findings suggest that fluid overload is an independent risk factor of the combined outcome of all-cause mortality or cardiovascular morbidity in patients with advanced CKD.

title: Interactions Between Malnutrition, Inflammation, and Fluid Overload and Their Associations With Survival in Prevalent Hemodialysis Patients.
abstract: Predialysis fluid overload (FO) in hemodialysis (HD) patients is associated with an increased risk of death, further increased by the presence of inflammation. Malnutrition is also associated with outcome. Study objectives were, firstly, to investigate if the presence of FO is associated with malnutrition and whether this association is influenced by the presence of inflammation. Second, we assessed the associations of FO, malnutrition, and inflammation with outcome individually and in combination.



International cohort study.



European patients of the Monitoring Dialysis Outcome Initiative cohort where bioimpedance and C-reactive protein measurements are performed as standard of care.



8883 prevalent HD patients.



Body composition, nutritional and inflammation status were assessed during a 3-month baseline period, and all-cause mortality was noted during 1 year follow-up. Malnutrition was defined as a lean tissue index <10th percentile (of age and gender matched healthy controls), FO as a predialysis overhydration >+1.1 L and inflammation as a C-reactive protein > 6.0 mg/L. We used Cox models to investigate the association with outcome.



The presence of malnutrition was associated with higher levels of FO, this amount further increased when inflammation was present. Only 11.6% of the patients did not have any of the 3 risk factors and only 6.5% of the patients were only malnourished, which was not associated with an increased risk of death (Hazard Ratio [HR] 1.22 [95% Confidence Interval [CI]: 0.75-1.97]), whereas the combination of severe malnutrition, FO, and inflammation comprised the highest risk of death (HR 5.89 [95% CI: 2.28-8.01]).



In HD patients, predialysis FO associates with both malnutrition and the presence of inflammation, with the highest levels of FO observed when both are present. Malnutrition as singular risk factor was not associated with increased mortality risk. The highest mortality risk was observed in patients where all 3 risk factors were present.

title: Fluid Overload and Inflammation Axis
abstract: Extracellular fluid overload (FO), which is assessed using bioimpedance technologies, is an important predictor of outcome in dialysis patients and in patients with early stages of chronic kidney disease. While traditional cardiovascular abnormalities are assumed to mediate this risk, recently also, the importance of noncardiovascular factors, such as systemic inflammation and malnutrition has been shown. While both FO and inflammation are independent risk factors for mortality, recent studies have shown that their combined presence can lead to a cumulative risk profile. From a pathophysiologic viewpoint, FO and inflammation can also be mutually reinforcing. Inflammation could contribute to FO by hypoalbuminemia, capillary leakage, and a (unnoticed) decline in lean and/or fat tissue mass resulting in incorrect estimation of dry weight. Reciprocally, FO could lead to inflammation by the translocation of endotoxins through a congested bowel wall or by a proinflammatory effect of tissue sodium. The relative importance of these putative factors is, however, not clear yet and epidemiological studies have shown no clear temporal direction regarding the relationship between FO and inflammation. FO and inflammation appear to be part of (dynamic) clusters of risk factors, including malnutrition and hyponatremia. Technology-guided fluid management of the often vulnerable dialysis patient with FO and inflammation cannot yet be based on evidence from randomized controlled trials, in which these specific patients were in general not included. In the absence of those trials, treatment should be based on identifying actionable causes of inflammation and on the judicious removal of excess volume based on frequent clinical reassessment.

title: Volume and composition of the body fluid compartments in severe infantile malnutrition.
abstract: The following observations were made in infants and children suffering from malnutrition of different causes: 1. A percentage increase in extracellular fluid volume in relation to the actual body weight was the only consistent change in the extracellular fluid compartment. 2. The occurrence of edema (i.e., absolute volume expansion of extracellular fluid) was associated only with malnutrition due to low protein intake. In patients with edema, hypoproteinemia and reduced enzymatic activity of the duodenal juice were invariably observed. 3. The important factors leading to formation of edema in malnourished infants and children were a decrease in plasma colloid osmotic pressure and a loss of skin elasticity. Ineffective cardiac and perhaps renal compensatory capacities in these malnourished children were thought to contribute to formation of edema when there was too rapid expansion of the intravascular volume by infusions of plasma, intercurrent infections, or overfeeding. 4. The occurrence of diarrheal disease in patients with malnutrition may cause hyponatremia or cerebral anoxia from circulatory shock. These alterations were, however, less common than in normal infants suffering from diarrhea. Because of lower body metabolism in malnutrition, such infants were better able to withstand the circulatory stasis and anoxia. These patients had an accelerated wasting of body substance in diarrhea because they had no caloric reserves from which to draw during a period of decreased food assimilation. Malnourished infants were subject to death from sudden hypoglycemia resulting in respiratory paralysis.

title: Relationship between muscle potassium and total body potassium in infants with malnutrition.
abstract: Specimens of muscle were obtained with a biopsy needle from 23 Jamaican children who were recovering from malnutrition. The samples were analyzed for water, fat, nitrogen, and potassium; total body potassium was also measured. Muscle water is increased, but potassium concentration declines in malnutrition. A significant relationship exists between the depletions of muscle potassium and of total body potassium in malnourished infants. Analysis of muscle biopsy samples may lead to a better understanding of the response of tissue to protein depletion at the cellular level.

title: Total body water in malnutrition: the possible role of energy intake.
abstract: 1. Total body water (TBW) was measured using tritiated water in sixty-five children. The measurements were distributed throughout rehabilitation in order to define the effect of changing energy intakes. 2. Oedematous children had a high TBW which decreased to the normal range during loss of oedema providing they were not receiving more than maintenance amounts of energy during this period. 3. Marasmic children who had not received greater than maintenance amounts of energy had a normal TBW. 4. Treatment with a high-energy diet was associated with an initial increase in TBW. 5. The possible mechanisms for this phenomenon are discussed.

title: Na+/K+ pump inhibition induces cell shrinkage in cultured chick cardiac myocytes
abstract: SummaryMyocardial cell swelling occurs in ischemia and in reperfusion injury before the onset of irreversible injury. Swelling has been attributed to failure of the Na+/K+ pump and the accumulation of intracellular Na+. To evaluate the role of the pump-leak model of cell volume maintenance, short term changes in cell volume in response to Na+/K+ pump inhibition were studied in aggregates of cultured embryonic chick cardiac myocytes using optical and biochemical methods. Exposure to 100 μM ouabain over 20 min induced cell shrinkage of approximately 10%. Cell water was also decreased by Na+/K+ pump inhibition; incubation for 1 hr either in the presence of 100 μM ouaain or in K+-free solution reduced cell water by 18.4% and 28.4% respectively. When exposed to ouabain in the absence of extracellular Ca2+, the aggregates swelled by approximately 15%, indicating that extracellular Ca2+ was required for the ouabain-induced shrinkage to occur. Ouabain still caused shrinkage, however, in the presence of the Ca2+ channel blockers verapamil (10 μM) and nifedipine (10 μM), suggesting that Na+/Ca2+ exchange, rather than Ca2+ channels, is the route for Ca2+ influx during Na+/K+ pump inhibition. Efflux of amino acids (taurine, aspartate, glutamate, glycine and alanine) from confluent monolayers of chick heart cells exposed to ouabain for 20 min was nearly double that observed in control solution. These results suggest that, during Na+/K+ pump inhibition, chick heart cells can limit accumulation of intracellular sodium by means of Na+/Ca2+ exchange, and that a rise in intracellular [Ca2+], also mediated by Na+/Ca2+ exchange, promotes the loss of amino acids and ions to cause cell shrinkage. Therefore, swelling during ischemic injury may not result from Na+/K+ pump failure alone, but may reflect the exhaustion of alternative volume regulatory transport mechanisms.

title: Use of the Body Composition Monitor for Fluid Status Measurements in Elderly Malnourished Subjects
abstract: Most hemodialysis (HD) patients are able to finish dialysis at or below the normally hydrated weight determined using the body composition monitor (BCM). However, a minority become symptomatic when they are still fluid overloaded based on BCM-measured overhydration (OH). Malnourished patients frequently fall into this group, suggesting that they may have OH that is inaccessible to ultrafiltration. To isolate any effect of malnutrition on BCM-measured OH from those relating to renal failure, OH measurements for 20 elderly subjects with normal renal function who were classified as malnourished were compared with an age-matched cohort with no known nutritional issues. Body composition monitor measurements were also made on five malnourished HD patients. Mean OH for malnourished subjects with normal renal function was not significantly different from an age-matched cohort without known nutritional deficiencies (1.3 and 1.1 L, respectively; p = 0.5). Post-dialysis OH for HD patients ranged from −0.1 to +4.5 L. A slightly elevated BCM-measured OH appears to be common in elderly subjects and may be explained by changes in the composition of adipose tissue. The effect of malnutrition could not be isolated from sarcopenia, but this study supports the need for caution when reducing target weight in vulnerable patients.

title: Body composition in chronic undernutrition.
abstract: Anthropometric (height, weight, and skinfolds), biochemical (serum proteins, albumin, and cholesterol), metabolic (nitrogen balance and creatinine excretion), hematological (plasma volume, hemoglobin, hematocrit, bone marrow hemosiderin, percent transferrin saturation, vitamin B12, and folic acid) variables and body water compartments (total and extracellular) have been measured in 49 adult male subjects who exhibited a wide range of nutritional states from normal to severely undernourished. Changes in body composition associated with moderate degrees of nutritional compromise were related principally to decreases in body cell mass (-15%). Body fat was normal. With severe nutritional involvement, both fat depots (-29%) and body cell mass (-29%) were significantly diminished. Muscle cell mass was more affected than other cells in the body (-41%). These data could indicate that in the group with moderate compromise, energy reserves (and hence energy balance) were maintained but dietary protein deficiencies were not compensated for. Both calorie and protein deficiencies were evident in the subjects with severe undernutrition. Multiple regression equations (r greater than 0.8) were developed that allow prediction of muscle cell mass, fat-free weight, and body cell mass from simple anthropometry and serum albumin levels. Decreases in serum albumin concentration were best related to deficits in muscle mass (r = 0.77).

title: The Plasma Level of Brain Natriuretic Peptide Is Increased in Malnourished Hemodialysis Patients
abstract: In hemodialysis (HD) patients, the plasma brain natriuretic peptide (BNP) level is associated with left ventricular dysfunction and patients’ survival. Malnutrition is common in HD patients, it is associated with inflammation and contributes to the high incidence of cardiovascular (CV) disease in this setting (malnutrition-inflammation-atherosclerosis syndrome). In a cross-sectional study, we assessed the relationship between predialysis plasma BNP level and nutritional markers in chronic HD patients.  Of 210 patients receiving HD treatment in our unit, 51 patients who were treated with three times weekly long-hour HD (5–8 h/session) for at least 6 months (mean age 65.8 ± 15.0 years; F/M ratio 23/28; vintage 71.3 ± 71.9 months; BMI 24.9 ± 5.9; session time 6.9 ± 1.3 h; percentage of diabetic patients 31%) were studied before a mid-week HD session for nutritional markers (plasma albumin 35.3 ± 3.7 g/l; prealbumin 0.36 ± 0.09 g/l; CRP 15.3 ± 14.7 mg/l; nPNA 1.29 ± 0.29 g/kg/day) and plasma BNP (246.9 ± 252.2 ng/l, normal <100 ng/l, Bayer® kit). The interdialytic weight gain was 2.1 ± 1.0 kg. In the last 3 months prior to the commencement of the study, the patients’ dry weight varied by +0.17 ± 1.9 kg.  Predialysis plasma BNP levels did not differ according to gender and the presence of diabetes. It was not correlated with age and vintage but was found to be negatively associated with the session time (r = –0.34, p = 0.018). Several nutritional markers were negatively correlated with BNP levels: prealbumin (r = –0.46, p = 0.001), BMI (r = –0.33, p = 0.018), nPNA (r = –0.46, p = 0.002). The plasma albumin relationship with the BNP level was close to significance (p = –0.26, p = 0.070). The 3-month dry weight variation was also negatively correlated with BNP levels (r = –0.34, p = 0.018). With multiple stepwise regression analysis, prealbumin and session time remained significant (respectively p = 0.004 and 0.01). BNP levels were higher in a subgroup of malnourished patients (n = 12) (400 ± 405 vs. 202 ± 166 ng/l, p = 0.03) than in patients who did not meet the malnutrition criteria (34 patients). They were not correlated with CRP levels, interdialytic weight gain, or predialysis MAP.  Hence, the plasma BNP level was found to be associated with malnutrition but not with inflammation. This underlines the relationship between nutrition and the CV system in HD patients. The body weight variations associated with malnutrition and the difficulties in assessing and adjusting dry weight may lead to fluid overload, which could explain, in part, these correlations.

title: Fat tissue and inflammation in patients undergoing peritoneal dialysis
abstract: Body weight has been increasing in the general population and is an established risk factor for hypertension, diabetes, and all-cause and cardiovascular mortality. Patients undergoing peritoneal dialysis (PD) gain weight, mainly during the first months of treatment. The aim of this study was to assess the relationship between body composition and metabolic and inflammatory status in patients undergoing PD.  This was a prospective, non-interventional study of prevalent patients receiving PD. Body composition was studied every 3 months using bioelectrical impedance (BCM®). We performed linear regression for each patient, including all BCM® measurements, to calculate annual changes in body composition. Thirty-one patients in our PD unit met the inclusion criteria.  Median follow-up was 26 (range 17–27) months. Mean increase in weight was 1.8 ± 2.8 kg/year. However, BCM® analysis revealed a mean increase in fat mass of 3.0 ± 3.2 kg/year with a loss of lean mass of 2.3 ± 4.1 kg/year during follow-up. The increase in fat mass was associated with the conicity index, suggesting that increases in fat mass are based mainly on abdominal adipose tissue. Changes in fat mass were directly associated with inflammation parameters such as C-reactive protein (r = 0.382, P = 0.045) and inversely associated with high-density lipoprotein cholesterol (r=−0.50, P = 0.008).  Follow-up of weight and body mass index can underestimate the fat mass increase and miss lean mass loss. The increase in fat mass is associated with proinflammatory state and alteration in lipid profile.

title: Associations of Body Mass Index and Body Fat With Markers of Inflammation and Nutrition Among Patients Receiving Hemodialysis.
abstract: Understanding the extent to which visceral and subcutaneous body fat are associated with markers of nutrition and inflammation in patients on dialysis therapy could shed light on the obesity paradox and the biology of subcutaneous fat.



Cross-sectional.



609 adults receiving hemodialysis who participated in the ACTIVE/ADIPOSE Study.



Body mass index (BMI), waist circumference, and bioelectrical impedance spectroscopy-derived estimates of percent body fat.



C-Reactive protein (CRP), interleukin 6 (IL-6), prealbumin, albumin, leptin, and adiponectin concentrations.



We performed linear regression analyses to examine the extent to which proxies of visceral and subcutaneous fat were associated with inflammation, nutrition, and adiposity-related hormones.



BMI was directly associated with markers of inflammation (standardized estimate for ln[CRP in mg/L]: 0.30 [95% CI, 0.22-0.38] per 10kg/m2; for ln[IL-6 in pg/mL]: 0.10 [95% CI, 0.02-0.18] per 10kg/m2), but was not associated with markers of nutrition. BMI was also inversely associated with adiponectin and directly associated with leptin. With waist circumference and percent body fat (as a proxy of visceral and subcutaneous fat, respectively) modeled together, waist circumference was associated with markers of inflammation (standardized estimate for ln[CRP in mg/L]: 0.21 [95% CI, 0.09-0.34] per 10cm; for ln[IL-6 in pg/mL]: 0.18 [95% CI, 0.07-0.29] per 10cm), whereas percent body fat was not associated with CRP (standardized estimate for ln[CRP in mg/L]: 0.03 [95% CI, -0.10 to 0.15] per 1%) and was inversely associated with IL-6 (standardized estimate for ln[IL-6 in pg/mL]: -0.15 [95% CI, -0.27 to -0.02] per 1%). In addition, waist circumference was inversely associated with prealbumin and albumin (standardized estimates of -0.12 [95% CI, -0.23 to -0.02] mg/dL per 10cm and -0.17 [95% CI, -0.28 to -0.06] g/dL per 10cm, respectively), and percent body fat was directly associated with prealbumin and albumin (0.20 [95% CI, 0.07-0.32] mg/dL and 0.15 [95% CI, 0.02-0.28] g/dL per 1%, respectively). Higher waist circumference was associated indirectly with adiponectin and directly with leptin concentrations.



Although the observed associations implicate visceral fat as the cause of inflammation, it cannot be determined in this cross-sectional study.



Proxies of visceral and subcutaneous fat appear to have opposing associations with biomarkers of inflammation and nutrition. Subcutaneous fat may be an indicator of nutritional status, and visceral fat, an indicator of inflammation.

title: Pro- and anti-inflammatory cytokine gene expression in subcutaneous and visceral fat in severe obesity.
abstract: Pro-inflammatory molecules produced by adipose tissue have been implicated in the risk of cardiovascular (CV) disease in obesity. We investigated the expression profile of 19 pro-inflammatory and seven anti-inflammatory genes in subcutaneous adipose tissue (SAT) and in visceral adipose tissue (VAT) in 44 severely obese individuals who underwent bariatric surgery.



SAT and VAT expressed an identical series of pro-inflammatory genes. Among these genes, 12 were significantly more expressed in SAT than in VAT while just one (IL18) was more expressed in VAT. The remaining genes were equally expressed. Among pro-inflammatory cytokines, both IL6 and IL8 were about 20 times more intensively expressed in SAT than in VAT. The expression of nine genes was highly associated in SAT and VAT. Only for three pro-inflammatory cytokines (IL8, IL18, SAA1) in SAT the gene expression in adipose tissue associated with the circulating levels of the corresponding gene products while no such an association was found as for VAT.



The expression of critical pro-inflammatory genes is substantially higher in SAT than in VAT in individuals with morbid obesity. The variability in circulating levels of pro-inflammatory cytokines is, in small part and just for three pro-inflammatory cytokines, explained by underlying gene expression in SAT but not in VAT. These results point to a compartment-specific adipose tissue contribution to inflammation in obesity and indicate that abdominal SAT contributes more than VAT to the pro-inflammatory milieu associated with severe obesity.

title: Effect of an intradialytic protein-rich meal intake in nutritional and body composition parameters on hemodialysis patients.
abstract: Protein intake is a key point to maintain an adequate nutritional status in hemodialysis (HD) patients. There are some studies that confirm the positive influence of intradialytic oral nutritional supplementation in several nutritional parameters in HD patients. The aim of this study was to evaluate the effect of an intradialytic protein rich meal in nutritional and body composition parameters on HD patients.



This was a 6-months single center non-randomized study with 99 patients in HD from one Nephrocare dialysis unit in Portugal. Patients in the intervention group (IG) presented one albumin value ≤ 3.8 g/dL in the two measurements prior to the beginning of the study. The IG ate a protein rich meal during each treatment. The control group (CG) continued to eat their usual snack brought from home. Albumin, nPCR, potassium, phosphorus, C-reactive protein (CRP), dry weight and body composition were measured at baseline and at the end of the study.



Patient's mean age was 69.9 ± 12.9 years and HD vintage, 60.0 ± 50.5 months. Both groups were similar at the start of the study, except in albumin (p = 0.019). After the intervention, protein intake increased in the IG (p = 0.001). Albumin decreased in both groups but this difference was higher and only statistically significant in the CG (p = 0.039). Regarding body composition, in the CG, the fat tissue index (FTI) (p = 0.022) and the lean tissue index (LTI) (p = 0.003) diminished after the 6 months of the follow-up. However, in the IG the LTI value also reduced (p = 0.008) but FTI increased (p = <0.001) at the end of the study. There were no statistically significant differences on dry weight, potassium, phosphorus, and CRP.



Apart from the effect on protein intake, the importance of this study relies on the positive changes in regard to patient's body composition obtained after 6 months of an intradialytic intake of a protein rich meal during the HD treatment. This type of intervention can contribute to ameliorate patient's nutritional status without a negative effect on other parameters.

title: The effect of high-volume online haemodiafiltration on nutritional status and body composition: the ProtEin Stores prEservaTion (PESET) study
abstract: Compared with conventional haemodialysis (HD), online haemodiafiltration (OL-HDF) achieves a more efficient removal of uraemic toxins and reduces inflammation, which could favourably affect nutritional status. We evaluate the effect of OL-HDF on body composition and nutritional status in prevalent high-flux HD (HF-HD) patients.



In all, 33 adults with chronic kidney disease (CKD) Stage 5 undergoing maintenance HF-HD were assigned to post-dilution OL-HDF (n = 17) or to remain on HF-HD (n = 16, control group) for 12 months. The primary outcome was the change in lean tissue mass (LTM), intracellular water (ICW) and body cell mass (BCM) assessed by multifrequency bioimpedance spectroscopy (BIS) at baseline and 4, 8 and 12 months. The rate of change in these parameters was estimated with linear mixed-effects models.



Compared with OL-HDF, patients assigned to HF-HD experienced a gradual reduction in LTM, ICW and BCM. These differences reached statistical significance at Month 12, with a relative difference of 7.31 kg [95% confidence interval (CI) 2.50-12.11; P = 0.003], 2.32 L (95% CI 0.63-4.01; P = 0.008) and 5.20 kg (95% CI 1.74-8.66; P = 0.004) for LTM, ICW and BCM, respectively. The normalized protein appearance increased in the OL-HDF group compared with the HF-HD group [0.26 g/kg/day (95% CI 0.05-0.47); P = 0.002], with a relative reduction in high-sensitive C-reactive protein [-13.31 mg/dL (95% CI -24.63 to -1.98); P = 0.02] at Month 12.



OL-HDF for 1 year compared with HF-HD preserved muscle mass, increased protein intake and reduced the inflammatory state related to uraemia and dialysis, supporting the hypothesis that high convection volume can benefit nutritional status and prevent protein-energy wasting in HD patients.

title: Physical methods for evaluating the nutrition status of hemodialysis patients
abstract: This article aims to provide an overview of the different nutritional markers and the available methodologies for the physical assessment of nutrition status in hemodialysis patients, with special emphasis on early detection of protein energy wasting (PEW). Nutrition status assessment is made on the basis of anamnesis, physical examination, evaluation of nutrient intake, and on a selection of various screening/diagnostic methodologies. These methodologies can be subjective, e.g. the Subjective Global Assessment score (SGA), or objective in nature (e.g. bioimpedance analysis). In addition, certain biochemical tests may be employed (e.g. albumin, pre-albumin). The various subjective-based and objective methodologies provide different insights for the assessment of PEW, particularly regarding their propensity to differentiate between the important body composition compartments—fluid overload, fat mass and muscle mass. This review of currently available methods showed that no single approach and no single marker is able to detect alterations in nutrition status in a timely fashion and to follow such changes over time. The most clinically relevant approach presently appears to be the combination of the SGA method with the bioimpedance spectroscopy technique with physiological model and, additionally, laboratory tests for the detection of micro-nutrient deficiency.

title: A Practical Standardized Composite Nutrition Score Based on Lean Tissue Index: Application in Nutrition Screening and Prediction of Outcome in Hemodialysis Population.
abstract: Rapid screening and monitoring of nutritional status is mandatory in hemodialysis population because of the increasingly encountered nutritional problems. Considering the limitations of previous composite nutrition scores applied in this population, we tried to develop a standardized composite nutrition score (SCNS) using low lean tissue index as a marker of protein wasting to facilitate clinical screening and monitoring and to predict outcome.



This retrospective cohort used 2 databases of dialysis populations from Taiwan between 2011 and 2014. First database consisting of data from 629 maintenance hemodialysis patients was used to develop the SCNS and the second database containing data from 297 maintenance hemodialysis patients was used to validate this developed score.



SCNS containing albumin, creatinine, potassium, and body mass index was developed from the first database using low lean tissue index as a marker of protein wasting. When applying this score in the original database, significantly higher risk of developing protein wasting was found for patients with lower SCNS (odds ratio 1.38 [middle tertile vs highest tertile, P < .0001] and 2.40 [lowest tertile vs middle tertile, P < .0001]). The risk of death was also shown to be higher for patients with lower SCNS (hazard ratio 4.45 [below median level vs above median level, P < .0001]). These results were validated in the second database.



We developed an SCNS consisting of 4 easily available biochemical parameters. This kind of scoring system can be easily applied in different dialysis facilities for screening and monitoring of protein wasting. The wide application of body composition monitor in dialysis population will also facilitate the development of specific nutrition scoring model for individual facility.

title: Frailty and protein-energy wasting in elderly patients with end stage kidney disease.
abstract: Older people constitute an increasingly greater proportion of patients with advanced CKD, including those patients undergoing maintenance dialysis treatment. Frailty is a biologic syndrome of decreased reserve and resistance to stressors that results from cumulative declines across multiple physiologic systems and causes vulnerability to adverse outcomes. Frailty is common in elderly CKD patients, and it may be associated with protein-energy wasting (PEW), sarcopenia, dynapenia, and other complications of CKD. Causes of frailty with or without PEW in the elderly with CKD can be classified into three categories: causes primarily caused by aging per se, advanced CKD per se, or a combination of both conditions. Frailty and PEW in elderly CKD patients are associated with impaired physical performance, disability, poorer quality of life, and reduced survival. Prevention and treatment of these conditions in the elderly CKD patients often require a multifaceted approach. Here, we examine the causes and consequences of these conditions and examine the interplay between frailty and PEW in elderly CKD patients.

title: Physical Activity in End-Stage Renal Disease Patients: The Effects of Starting Dialysis in the First 6 Months after the Transition Period
abstract: Physical inactivity in end-stage renal disease (ESRD) patients is associated with increased mortality, and might be related to abnormalities in body composition (BC) and physical performance. It is uncertain to what extent starting dialysis influences the effects of ESRD on physical activity (PA). This study aimed to compare PA and physical performance between stage 5 chronic kidney disease (CKD-5) non-dialysis and dialysis patients, and healthy controls, to assess alterations in PA during the transition from CKD-5 non-dialysis to dialysis, and to relate PA to BC.  For the cross-sectional analyses 44 CKD-5 non-dialysis patients, 29 dialysis patients, and 20 healthy controls were included. PA was measured by the SenseWear™ pro3. Also, the walking speed and handgrip strength (HGS) were measured. BC was measured by the Body Composition Monitor©. Longitudinally, these parameters were assessed in 42 CKD-5 non-dialysis patients (who were also part of the cross-sectional analysis), before the start of dialysis and 6 months thereafter.  PA was significantly lower in CKD-5 non-dialysis patients as compared to that in healthy controls but not as compared to that in dialysis patients. HGS was significantly lower in dialysis patients as compared to that in healthy controls. Walking speed was significantly lower in CKD-5 non-dialysis patients as compared to that in healthy controls but not as compared to that in dialysis patients. Six months after starting dialysis, activity related energy expenditure (AEE) and walking speed significantly increased.  PA is already lower in CKD-5 non-dialysis patients as compared to that in healthy controls and does not differ from that of dialysis patients. However, the transition phase from CKD-5 non-dialysis to dialysis is associated only with a modest improvement in AEE.

title: Health-related quality of life in end-stage renal disease patients: the effects of starting dialysis in the first year after the transition period
abstract: dialysis patients have low scores of health-related quality of life (HRQOL) which are associated with increased risk of hospitalization and mortality. Also in CKD-5 non-dialysis patients, HRQOL scores seem to be lower as compared with the general population. This study firstly aimed to compare HRQOL between CKD-5 non-dialysis and prevalent dialysis patients in a cross-sectional analysis and to assess longitudinal changes over 1 year after the dialysis initiation. Secondly, the correlation between HRQOL and physical activity (PA) was explored.MethodsCross-sectional 44 CKD-5 non-dialysis, 29 prevalent dialysis, and 20 healthy controls were included. HRQOL was measured by Short Form-36 questionnaires to measure physical and mental domains of health expressed by the physical component summary (PCS) and mental component summary (MCS) scores. PA was measured by a SenseWear™ pro3. Longitudinally, HRQOL was assessed in 38 CKD-5 non-dialysis patients (who were also part of the cross-sectional analysis), before dialysis initiation until 1 year after dialysis initiation.ResultsPCS scores were significantly lower both in CKD-5 non-dialysis patients and in prevalent dialysis patients as compared with healthy controls (p < 0.001). MCS scores were significantly lower in both CKD-5 non-dialysis patients (p = 0.003), and in dialysis patients (p = 0.022), as compared with healthy controls. HRQOL scores did not change significantly from the CKD-5 non-dialysis phase into the first year after dialysis initiation. PA was significantly related to PCS in both CKD-5 non-dialysis patients (r = 0.580; p < 0.001), and dialysis patients (r = 0.476; p = 0.009).ConclusionsHRQOL is already low in the CKD-5 non-dialysis phase. In the first year after dialysis initiation, HRQOL did not change significantly. Given the correlation between PCS score and PA, physical activity programs may be potential tools to improve HRQOL in both CKD-5 non-dialysis as well as in prevalent dialysis patients.

title: Comparative associations of muscle mass and muscle strength with mortality in dialysis patients.
abstract: Reduced muscle mass and strength are prevalent conditions in dialysis patients. However, muscle strength and muscle mass are not congruent; muscle strength can diminish even though muscle mass is maintained or increased. This study addresses phenotype and mortality associations of these muscle dysfunction entities alone or in combination (i.e., concurrent loss of muscle mass and strength/mobility, here defined as sarcopenia).



This study included 330 incident dialysis patients (203 men, mean age 53±13 years, and mean GFR 7±2 ml/min per 1.73 m(2)) recruited between 1994 and 2010 and followed prospectively for up to 5 years. Low muscle mass (by dual-energy x-ray absorptiometry appendicular mass index) and low muscle strength (by handgrip) were defined against young reference populations according to the European Working Group on Sarcopenia in Older People.



Whereas 20% of patients had sarcopenia, low muscle mass and low muscle strength alone were observed in a further 24% and 15% of patients, respectively. Old age, comorbidities, protein-energy wasting, physical inactivity, low albumin, and inflammation associated with low muscle strength, but not with low muscle mass (multivariate ANOVA interactions). During follow-up, 95 patients (29%) died and both conditions associated with mortality as separate entities. When combined, individuals with low muscle mass alone were not at increased risk of mortality (adjusted hazard ratio [HR], 1.23; 95% confidence interval [95% CI], 0.56 to 2.67). Individuals with low muscle strength were at increased risk, irrespective of their muscle stores being appropriate (HR, 1.98; 95% CI, 1.01 to 3.87) or low (HR, 1.93; 95% CI, 1.01 to 3.71).



Low muscle strength was more strongly associated with aging, protein-energy wasting, physical inactivity, inflammation, and mortality than low muscle mass. Assessment of muscle functionality may provide additional diagnostic and prognostic information to muscle-mass evaluation.

title: A review of sarcopenia: Enhancing awareness of an increasingly prevalent disease.
abstract: Sarcopenia is defined as an age associated decline in skeletal muscle mass. The pathophysiology of sarcopenia is multifactorial, with decreased caloric intake, muscle fiber denervation, intracellular oxidative stress, hormonal decline, and enhanced myostatin signaling all thought to contribute. Prevalence rates are as high as 29% and 33% in elderly community dwelling and long-term care populations, respectively, with advanced age, low body mass index, and low physical activity as significant risk factors. Sarcopenia shares many characteristics with other disease states typically associated with risk of fall and fracture, including osteoporosis, frailty, and obesity. There is no current universally accepted definition of sarcopenia. Diagnosing sarcopenia with contemporary operational definitions requires assessments of muscle mass, muscle strength, and physical performance. Screening is recommended for both elderly patients and those with conditions that noticeably reduce physical function. Sarcopenia is highly prevalent in orthopedic patient populations and correlates with higher hospital costs and rates of falling, fracture, and mortality. As no muscle building agents are currently approved in the United States, resistance training and nutritional supplementation are the primary methods for treating sarcopenia. Trials with various agents, including selective androgen receptor modulators and myostatin inhibitors, show promise as future treatment options. Increased awareness of sarcopenia is of great importance to begin reaching consensus on diagnosis and to contribute to finding a cure for this condition.

title: Functional Impairment, Disability, and Frailty in Adults Aging with HIV-Infection
abstract: The integration of antiretroviral therapy (i.e., ART) into HIV care has dramatically extended the life expectancy of those living with HIV. However, in comparison to similar HIV-uninfected populations, HIV-infected persons experience an excess of morbidity and mortality with an early onset of aging complications including neurocognitive decline, osteoporosis, impaired physical function, frailty, and falls. Recent consensus guidelines encourage clinicians and researchers to consider functional impairment of HIV-infected adults as a measure to understand the impact of aging across a range of abilities. Despite the importance of assessing function in persons aging with HIV infection, a lack of consistent terminology and standardization of assessment tools has limited the application of functional assessments in clinical or research settings. Herein, we distinguish between different approaches used to assess function, describe what is known about function in the aging HIV population, and consider directions for future research.

title: Physical inactivity and protein energy wasting play independent roles in muscle weakness in maintenance haemodialysis patients
abstract: 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.  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.  MVF was 76.1 [58.2–111.7] N.m. and was associated with CI (β = 5.3 [2.2–8.4], p = 0.001), LTI (β = 2.8 [0.6–5.1], p = 0.013), Voorrips score (β = 17.4 [2.9–31.9], p = 0.02) and serum albumin (β = 1.9 [0.5–3.2], p = 0.006). Only serum albumin (β = 0.09 [0.03–0.15], p = 0.003), Voorrips score (β = 0.8 [0.2–1.5], p = 0.005) and CI (β = 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).  Beyond atrophy, physical inactivity and PEW conspire to impair muscle strength and specific torque in CHD patients and could be related to muscle quality.

title: Effect of fluid management guided by bioimpedance spectroscopy on cardiovascular parameters in hemodialysis patients: a randomized controlled trial.
abstract: Fluid overload is the main determinant of hypertension and left ventricular hypertrophy in hemodialysis patients. However, assessment of fluid overload can be difficult in clinical practice. We investigated whether objective measurement of fluid overload with bioimpedance spectroscopy is helpful in optimizing fluid status.



Prospective, randomized, and controlled study.



156 hemodialysis patients from 2 centers were randomly assigned to 2 groups.



Dry weight was assessed by routine clinical practice and fluid overload was assessed by bioimpedance spectroscopy in both groups. In the intervention group (n = 78), fluid overload information was provided to treating physicians and used to adjust fluid removal during dialysis. In the control group (n = 78), fluid overload information was not provided to treating physicians and fluid removal during dialysis was adjusted according to usual clinical practice.



The primary outcome was regression of left ventricular mass index during a 1-year follow-up. Improvement in blood pressure and left atrial volume were the main secondary outcomes. Changes in arterial stiffness parameters were additional outcomes.



Fluid overload was assessed twice monthly in the intervention group and every 3 months in the control group before the mid- or end-week hemodialysis session. Echocardiography, 48-hour ambulatory blood pressure measurement, and pulse wave analysis were performed at baseline and 12 months.



Baseline fluid overload parameters in the intervention and control groups were 1.45 ± 1.11 (SD) and 1.44 ± 1.12 L, respectively (P = 0.7). Time-averaged fluid overload values significantly decreased in the intervention group (mean difference, -0.5 ± 0.8 L), but not in the control group (mean difference, 0.1 ± 1.2 L), and the mean difference between groups was -0.5 L (95% CI, -0.8 to -0.2; P = 0.001). Left ventricular mass index regressed from 131 ± 36 to 116 ± 29 g/m(2) (P < 0.001) in the intervention group, but not in the control group (121 ± 35 to 120 ± 30 g/m(2); P = 0.9); mean difference between groups was -10.2 g/m(2) (95% CI, -19.2 to -1.17 g/m(2); P = 0.04). In addition, values for left atrial volume index, blood pressure, and arterial stiffness parameters decreased in the intervention group, but not in the control group.



Ambulatory blood pressure data were not available for all patients.



Assessment of fluid overload with bioimpedance spectroscopy provides better management of fluid status, leading to regression of left ventricular mass index, decrease in blood pressure, and improvement in arterial stiffness.