Salt and Water Retention Is Associated with Microinflammation and Endothelial Injury in Chronic Kidney Disease.

BACKGROUND: Progressive chronic kidney disease (CKD) inevitably leads to salt and water retention and disturbances in the macro-and microcirculation. OBJECTIVES: We hypothesize that salt and water dysregulation in advanced CKD may be linked to inflammation and microvascular injury pathways. METHODS: We studied 23 CKD stage 5 patients and 11 healthy controls (HC). Tissue sodium concentration was assessed using 23Sodium magnetic resonance (MR) imaging. Hydration status was evaluated using bioimpedance spectroscopy. A panel of inflammatory and endothelial biomarkers was also measured. RESULTS: CKD patients had fluid overload (FO) when compared to HC (overhydration index: CKD = 0.5 ± 1.9 L vs. HC = -0.5 ± 1.0 L; p = 0.03). MR-derived tissue sodium concentrations were predominantly higher in the subcutaneous (SC) compartment (median [interquartile range] CKD = 22.4 mmol/L [19.4-31.3] vs. HC = 18.4 mmol/L [16.6-21.3]; p = 0.03), but not the muscle (CKD = 24.9 ± 5.5 mmol/L vs. HC = 22.8 ± 2.5 mmol/L; p = 0.26). Tissue sodium in both compartments correlated to FO (muscle: r = 0.63, p < 0.01; SC: rs = 0.63, p < 0.01). CKD subjects had elevated levels of vascular cell adhesion molecule (p < 0.05), tumor necrosis factor-alpha (p < 0.01), and interleukin (IL)-6 (p = 0.01) and lower levels of vascular endothelial growth factor-C (p = 0.04). FO in CKD was linked to higher IL-8 (r = 0.51, p < 0.05) and inversely associated to E-selectin (r = -0.52, p = 0.01). Higher SC sodium was linked to higher intracellular adhesion molecule (ICAM; rs = 0.54, p = 0.02). CONCLUSION: Salt and water accumulation in CKD appears to be linked with inflammation and endothelial activation pathways. Specifically IL-8, E-Selectin (in FO), and ICAM (in salt accumulation) may be implicated in the pathophysiology of FO and merit further investigation.

A multidisciplinary consensus on dehydration: definitions, diagnostic methods and clinical implications.

Background: Dehydration appears prevalent, costly and associated with adverse outcomes. We sought to generate consensus on such key issues and elucidate need for further scientific enquiry. Materials and methods: A modified Delphi process combined expert opinion and evidence appraisal. Twelve relevant experts addressed dehydration's definition, objective markers and impact on physiology and outcome. Results: Fifteen consensus statements and seven research recommendations were generated. Key findings, evidenced in detail, were that there is no universally accepted definition for dehydration; hydration assessment is complex and requires combining physiological and laboratory variables; "dehydration" and "hypovolaemia" are incorrectly used interchangeably; abnormal hydration status includes relative and/or absolute abnormalities in body water and serum/plasma osmolality (pOsm); raised pOsm usually indicates dehydration; direct measurement of pOsm is the gold standard for determining dehydration; pOsm >300 and ≤280 mOsm/kg classifies a person as hyper or hypo-osmolar; outside extremes, signs of adult dehydration are subtle and unreliable; dehydration is common in hospitals and care homes and associated with poorer outcomes. Discussion: Dehydration poses risk to public health. Dehydration is under-recognized and poorly managed in hospital and community-based care. Further research is required to improve assessment and management of dehydration and the authors have made recommendations to focus academic endeavours. Key messages Dehydration assessment is a major clinical challenge due to a complex, varying pathophysiology, non-specific clinical presentations and the lack of international consensus on definition and diagnosis. Plasma osmolality represents a valuable, objective surrogate marker of hypertonic dehydration which is underutilized in clinical practice. Dehydration is prevalent within the healthcare setting and in the community, and appears associated with increased morbidity and mortality.

The influence of radio frequency ablation on intra-articular fluid temperature in the ankle joint - a cadaver study.

BACKGROUND: Radio frequency ablation devices have found a widespread application in arthroscopic surgery. However, recent publications report about elevated temperatures, which may cause damage to the capsular tissue and especially to chondrocytes. The purpose of this study was the investigation of the maximum temperatures that occur in the ankle joint with the use of a commercially available radio frequency ablation device. METHODS: Six formalin-fixed cadaver ankle specimens were used for this study. The radio frequency device was applied for 120 s to remove tissue. Intra-articular temperatures were logged every second for 120 s at a distance of 3, 5 and 10 mm from the tip of the radio frequency device. The irrigation fluid flow was controlled by setting the inflow pressure to 10 mmHg, 25 mmHg, 50 mmHg and 100 mmHg, respectively. The controller unit voltage setting was set to 1, 5 and 9. RESULTS: Maximum temperatures exceeding 50 °C/122 °F were observed for all combinations of parameters, except for those with a pressure of 100 mmHg pressure. The main critical variable is the pressure setting, which is highly significant. The controller unit voltage setting showed no effect on the temperature measurements. The highest temperature was 102.7 °C/215.6 °F measured for an irrigation flow of 10 mmHg. The shortest time span to exceed 50 °C/122 °F was 3 s. CONCLUSION: In order to avoid temperatures exceeding 50 °C/122 °F in the use of radio frequency devices in arthroscopic surgeries of the ankle joint, it is recommended to use a high irrigation flow by setting the pressure difference across the ankle joint as high as feasible. Even short intervals of a low irrigation flow may lead to critical temperatures above 50 °C/122 °F. LEVEL OF EVIDENCE: Level II, diagnostic study.

Intermittent bolus feeding promotes greater lean growth than continuous feeding in a neonatal piglet model.

Background: Orogastric tube feeding is indicated in neonates with an impaired ability to ingest food normally and can be administered with an intermittent bolus or continuous feeding schedule. Objectives: The objectives were to 1) compare the long-term effect of continuous with intermittent feeding on growth using the newborn pig as a model, 2) determine whether feeding frequency alters lean tissue and fat mass gain, and 3) identify the signaling mechanisms by which protein deposition is controlled in skeletal muscle in response to feeding frequency. Design: Neonatal pigs were fed the same amount of a balanced formula by orogastric tube either as an intermittent bolus meal every 4 h (INT) or as a continuous infusion (CON). Body composition was assessed at the start and end of the study by dual-energy X-ray absorptiometry, and hormone and substrate profiles, muscle mass, protein synthesis, and indexes of nutrient and insulin signaling were measured after 21 d. Results: Body weight, lean mass, spine length, and skeletal muscle mass were greater in the INT group than in the CON group. Skeletal muscle fractional protein synthesis rates were greater in the INT group after a meal than in the CON group and were associated with higher circulating branched-chain amino acid and insulin concentrations. Skeletal muscle protein kinase B (PKB) and ribosomal protein S6 kinase phosphorylation and eukaryotic initiation factor (eIF) 4E-eIF4G complex formation were higher, whereas eIF2α phosphorylation was lower in the INT group than in the CON group, indicating enhanced activation of insulin and amino acid signaling to translation initiation. Conclusions: These results suggest that when neonates are fed the same amounts of nutrients as intermittent meals rather than continuously there is greater lean growth. This response can be ascribed, in part, to the pulsatile pattern of amino acids, insulin, or both induced by INT, which enables the responsiveness of anabolic pathways to feeding to be sustained chronically in skeletal muscle.

Extracellular Acid-Base Balance and Ion Transport Between Body Fluid Compartments.

Clinical assessment of acid-base disorders depends on measurements made in the blood, part of the extracellular compartment. Yet much of the metabolic importance of these disorders concerns intracellular events. Intracellular and interstitial compartment acid-base balance is complex and heterogeneous. This review considers the determinants of the extracellular fluid pH related to the ion transport processes at the interface of cells and the interstitial fluid, and between epithelial cells lining the transcellular contents of the gastrointestinal and urinary tracts that open to the external environment. The generation of acid-base disorders and the associated disruption of electrolyte balance are considered in the context of these membrane transporters. This review suggests a process of internal and external balance for pH regulation, similar to that of potassium. The role of secretory gastrointestinal epithelia and renal epithelia with respect to normal pH homeostasis and clinical disorders are considered. Electroneutrality of electrolytes in the ECF is discussed in the context of reciprocal changes in Cl- or non Cl- anions and [Formula: see text].

Estimation of Fat-free Mass at Discharge in Preterm Infants Fed With Optimized Feeding Regimen.

OBJECTIVES: The purpose of the present study was to validate a previously calculated equation (E1) that estimates infant fat-free mass (FFM) at discharge using data from a population of preterm infants receiving an optimized feeding regimen. METHODS: Preterm infants born before 33 weeks of gestation between April 2014 and November 2015 in the tertiary care unit of Croix-Rousse Hospital in Lyon, France, were included in the study. At discharge, FFM was assessed by air displacement plethysmography (PEA POD) and was compared with FFM estimated by E1. FFM was estimated using a multiple linear regression model. RESULTS: Data on 155 preterm infants were collected. There was a strong correlation between the FFM estimated by E1 and FFM assessed by the PEA POD (r = 0.939). E1, however, underestimated the FFM (average difference: -197 g), and this underestimation increased as FFM increased. A new, more predictive equation is proposed (r = 0.950, average difference: -12 g). CONCLUSIONS: Although previous estimation methods were useful for estimating FFM at discharge, an equation adapted to present populations of preterm infants with "modern" neonatal care and nutritional practices is required for accuracy.

Hand-to-Hand Model for Bioelectrical Impedance Analysis to Estimate Fat Free Mass in a Healthy Population.

This study aimed to establish a hand-to-hand (HH) model for bioelectrical impedance analysis (BIA) fat free mass (FFM) estimation by comparing with a standing position hand-to-foot (HF) BIA model and dual energy X-ray absorptiometry (DXA); we also verified the reliability of the newly developed model. A total of 704 healthy Chinese individuals (403 men and 301 women) participated. FFM (FFMDXA) reference variables were measured using DXA and segmental BIA. Further, regression analysis, Bland-Altman plots, and cross-validation (2/3 participants as the modeling group, 1/3 as the validation group; three turns were repeated for validation grouping) were conducted to compare tests of agreement with FFMDXA reference variables. In male participants, the hand-to-hand BIA model estimation equation was calculated as follows: FFMmHH = 0.537 h²/ZHH - 0.126 year + 0.217 weight + 18.235 (r² = 0.919, standard estimate of error (SEE) = 2.164 kg, n = 269). The mean validated correlation coefficients and limits of agreement (LOAs) of the Bland-Altman analysis of the calculated values for FFMmHH and FFMDXA were 0.958 and -4.369-4.343 kg, respectively, for hand-to-foot BIA model measurements for men; the FFM (FFMmHF) and FFMDXA were 0.958 and -4.356-4.375 kg, respectively. The hand-to-hand BIA model estimating equation for female participants was FFMFHH = 0.615 h²/ZHH - 0.144 year + 0.132 weight + 16.507 (r² = 0.870, SEE = 1.884 kg, n = 201); the three mean validated correlation coefficient and LOA for the hand-to-foot BIA model measurements for female participants (FFMFHH and FFMDXA) were 0.929 and -3.880-3.886 kg, respectively. The FFMHF and FFMDXA were 0.942 and -3.511-3.489 kg, respectively. The results of both hand-to-hand and hand-to-foot BIA models demonstrated similar reliability, and the hand-to-hand BIA models are practical for assessing FFM.

A note regarding the mathematical treatment of a class of steady-state compartmental models of the circulation.

A class of steady-state compartmental models of the circulation is examined and it is shown that the mathematical problem for this model class involves a single nonlinear equation. In an important subclass and with certain assumptions regarding the form of the Starling-type cardiac function curves, the single equation is of the form Z = µ + λ log[(1 - Z)/Z] where µ and λ are mathematical parameters related to the physiological parameters of the system and Z is proportional to the cardiac output. This result holds regardless of the number and arrangement of compartments within the model itself or of the number of physiological parameters the model contains. An example of this class with 25 physiological parameters is presented to illustrate this approach.

Comparison of NIRS, serum biomarkers, and muscle damage in a porcine balloon compression model of acute compartment syndrome.

BACKGROUND: Near-infrared spectroscopy (NIRS) has been shown to aid in the diagnosis of extremity acute compartment syndrome (ACS), offering continuous real-time capability to monitor perfusion in extremities. Porcine models of ACS have been developed to attempt to aid in the understanding of the development of ACS and provide better methods of diagnosing ACS. The objective of the present study was to assess and correlate NIRS, tibial intracompartmental pressure (TICP), tibial intracompartmental perfusion pressure (TIPP), serum markers of inflammation and muscle injury in a balloon compression model of ACS. METHODS: Six swine were used. Balloon catheters were inflated below the cranial tibial muscle. Systolic, diastolic, and mean arterial pressures; compartmental pressures; and oximetry were measured before, during, and after balloon inflation/deflation. Cranial tibial muscle was collected for muscle damage scoring. Serum creatine kinase, myoglobin, tumor necrosis factor α, IL-1ß, and IL-6 were measured. Data analysis included comparing differences in TICP, NIRS, and TIPP measurements as well as creatine kinase, myoglobin, tumor necrosis factor α, IL-1ß, and IL-6 levels between time points. Pearson correlations were calculated for muscle degeneration and edema and NIRS. RESULTS: Increases in TICP and decreases in TIPP were found. Near-infrared spectroscopy detected significant changes in tissue oxygenation at all the same time points. Myoglobin significantly increased from 45.7 ± 13.0 ng/mL (baseline) to 219.5 ± 57.3-ng/mL (balloon deflation) and continued to increase over the duration of the study. Creatine kinase significantly increased 2 hours after balloon deflation. Cranial tibial muscle degeneration, necrosis, and edema scores were higher in the test than the control legs. CONCLUSIONS: Near-infrared spectroscopy of the compartment provided a reliable, sensitive measure of both an increase and decrease in TICP and TIPP in this porcine balloon model of ACS. Creatine kinase and myoglobin significantly increased following balloon removal. Significant correlations between muscle degeneration, edema, hemorrhage, and NIRS were found.

Abdominal admittance helps to predict the amount of fluid accumulation in patients with acute heart failure syndromes.

BACKGROUND: Predicting fluid volume that needs to be removed in acute heart failure syndromes (AHFS) patients remains challenging. Thoracic admittance (TA), the reciprocal of thoracic impedance measured by bioelectrical impedance, reflects the amount of fluid in the thorax. Abdominal organs play an important role in AHFS as systemic fluid reservoirs. We investigated the relationship between abdominal admittance (AA) at the time of admission for AHFS and net fluid loss (NFL) during hospitalization. METHODS: Sixty-two consecutive patients hospitalized for AHFS [age 71±10 years, left ventricular ejection fraction (LVEF) 39±17%] were studied. The admittance values, i.e. the reciprocals of the impedance values, were derived using a BioZ(®) (CardioDynamics, San Diego, CA, USA). The change in weight from admission to discharge was used as a surrogate of amount of NFL. RESULTS: At the time of admission, a significant correlation was detected between TA and AA (r=0.46, p=0.0001). TA at admission was significantly correlated with the LV structural variables (end-diastolic dimension and end-systolic dimension), and serum sodium level. AA at admission was significantly correlated with New York Heart Association (NYHA) class and plasma BNP, and also correlated with LVEF and variables related to systemic congestion [minimal inferior vena cava (IVC) diameter and tricuspid regurgitation grade]. Neither TA nor AA values were significantly correlated with weight at admission. During hospitalization, TA and AA declined from 44±8kΩ(-1) to 36±6kΩ(-1) (p<0.0001) and from 74±25kΩ(-1) to 56±17kΩ(-1) (p<0.0001), respectively. Weight fell from 60.1±10.8kg to 54.5±9.4kg (p<0.0001), while NFL was 5.8kg (range, 0.1-17.5kg). In univariate analyses, the admission NYHA class, TA, AA, weight, and IVC diameter correlated with NFL. Multivariate analysis demonstrated that only admission weight [standardized partial regression coefficient (SPRC)=0.596], AA (SPRC=0.529), and NYHA class (SPRC=0.277) were independent predictors of NFL. CONCLUSION: Abdominal admittance measurement helps to predict the amount of fluid volume to be removed in patients with AHFS.

Population pharmacokinetic meta-analysis to bridge ferumoxytol plasma pharmacokinetics across populations.

BACKGROUND: Ferumoxytol is approved for the treatment of iron-deficiency anaemia (IDA) in adult patients with chronic kidney disease (CKD). Ferumoxytol has recently been investigated for use in all-cause IDA. This analysis was employed to bridge ferumoxytol pharmacokinetics (PK) across populations of healthy subjects and patients with CKD on haemodialysis, and to then make informed inferences regarding the PK behaviour of ferumoxytol in the all-cause IDA population. METHODS: The data analysis was performed using NONMEM. Selected parameters were included for covariate testing. Investigations to determine if changes in volume of distribution during haemodialysis improved the model fit were also conducted. The final model was used to simulate PK in healthy volunteers (HVs) and CKD patients with and without haemodialysis. RESULTS: The final model was a two-compartment model with non-linear elimination. During haemodialysis, the central volume V1 was estimated to be reduced by 0.198 L/h. A positive relationship was identified between initial V1 and observed weight loss during haemodialysis. V1 increased by 0.614 % per kilogram of body weight, and females had an 18.3 % lower V1 than males. Differences between simulated profiles for different populations were marginal: maximum concentration (Cmax) of 209 vs. 204 ng/mL and area under the curve from time zero to infinity (AUCinf) of 5,980 vs. 5,920 ng·h/mL in HVs and CKD non-haemodialysis patients, respectively, for a single dose of 510 mg. CONCLUSIONS: The results indicate that ferumoxytol PK are comparable between HVs and CKD patients. Furthermore, the results are representative of the PK in other populations and can be used to bridge to subjects with general IDA.

Bioelectrical impedance vector analysis in obese women before and after bariatric surgery: changes in body composition.

OBJECTIVE: Because of the inefficacy of standard methods for the evaluation of body composition of grade III obese individuals, it is difficult to analyze the quality of weight loss after bariatric surgery in these patients. Electrical bioimpedance vector analysis and the RXc graph uses crude resistance (R) and reactance (Xc) values, like components of the Z vector, to monitor variations in body fluid and the nutritional status of obese individuals. Using bioelectrical impedance vector analysis (BIVA) and the RXc graph, the objective of the present study was to evaluate long-term changes in weight and body composition of obese women after Roux-en-Y bariatric surgery. METHODS: A study was conducted on 43 grade III obese women submitted to bariatric surgery. Anthropometric and bioimpedance (800 mA-50 kHz) data were obtained during the preoperative period and 1, 2, 3, and 4 y after surgery. BIVA was performed by plotting resistance and reactance values corrected for body height (R/H and Xc/H, Ohm/m) as bivariates on the RXc graph. BIVA software was used to plot the vectors of the RXc plane. RESULTS: Surgery promoted changes in body composition, with a reduction of fat mass and of fat-free mass. During the postoperative period, the vectors demonstrated migration to the right lower quadrant of the graph, corresponding to the classification of cachexia and water retention. CONCLUSION: Weight loss due to surgery results in an important reduction of fat-free mass characterized by the position of most individuals in the cachexia quadrant throughout the postoperative period.

Multi-frequency bioelectrical impedance analysis for assessing fat mass and fat-free mass in stroke or transient ischaemic attack patients.

BACKGROUND/OBJECTIVES: Dual energy X-ray absorptiometry (DEXA) is considered as the reference method in assessing fat-free and fat mass but is costly and not a pragmatic option in daily clinical practice. If devices based on multi-frequency bioelectrical impedance analysis (MF-BIA), which are cheaper and portable, are valid and reliable in measuring body composition, these could be used in routine clinical practice in nutritional management of patients and populations where malnutrition is prevalent. SUBJECTS/METHODS: A study of MF-BIA against DEXA in assessing fat-free and fat mass, and two internal validation studies of MF-BIA were conducted. Bland & Altman analysis to assess comparison against DEXA and Cronbach's α for internal validity were carried out. RESULTS: Ten participants (mean age 66 years; 70% men) with a recent stroke or transient ischaemic attack (TIA) were recruited to assess against DEXA and the first internal validation. The second internal validation was based on 80 pairs of MF-BIA measurements in 40 stroke patients (mean age 70.3 years; 55% men) assessed at hospital admission and on discharge. There was a strong correlation between MF-BIA and DEXA (correlation coefficient was 0.88 for fat-free mass and 0.77 for fat mass). According to Bland & Altman analysis, MF-BIA and DEXA fat-free and fat mass estimates were similar. Internal consistency was high with Cronbach's-α >0.9. CONCLUSION: MF-BIA can be reliably used in stroke and TIA patients. The feasibility, clinical and cost effectiveness of MF-BIA in routine monitoring and management of malnutrition in stroke and TIA patients with high prevalence of nutritional deficits is worthy of further evaluation.

Fluid homeostasis in the neonate.

The physiology of the neonate is ideally suited to the transition to extrauterine life followed by a period of rapid growth and development. Intravenous fluids and electrolytes should be prescribed with care in the neonate. Sodium and water requirements in the first few days of life are low and should be increased after the postnatal diuresis. Expansion of the extracellular fluid volume prior to the postnatal diuresis is associated with poor outcomes, particularly in preterm infants. Newborn infants are prone to hypoglycemia and require a source of intravenous glucose if enteral feeds are withheld. Anemia is common, and untreated is associated with poor outcomes. Liberal versus restrictive transfusion practices are controversial, but liberal transfusion practices (accompanied by measures to minimize donor exposure) may be associated with improved long-term outcomes. Intravenous crystalloids are as effective as albumin to treat hypotension, and semi-synthetic colloids cannot be recommended at this time. Inotropes should be used to treat hypotension unresponsive to intravenous fluid, ideally guided by assessment of perfusion rather than blood pressure alone. Noninvasive methods of assessing cardiac output have been validated in neonates. More studies are required to guide fluid management in neonates, particularly in those with sepsis or undergoing surgery. A balanced salt solution such as Hartmann's or Plasmalyte should be used to replace losses during surgery (and blood or coagulation factors as indicated). Excessive fluid administration during surgery should be avoided.

Simple anthropometrics are more correlated with health variables than are estimates of body composition in Yup'ik people.

OBJECTIVES: To (1) evaluate the relationships between several indices of obesity with obesity-related risk factors; (2) compare the accuracy of body composition estimates derived from anthropometry and bioimpedance analysis (BIA) to estimates of body composition assessed by doubly-labeled water (DLW); and (3) establish equations for estimating fat mass (FM), fat-free mass (FFM), and percent body fat (PBF) in Yup'ik people. DESIGN AND METHODS: Participants included 1,056 adult Yup'ik people from 11 communities in Southwestern Alaska. In a sub-study of 30 participants, we developed population-specific linear regression models for estimating FM, FFM, and PBF from anthropometrics, age, sex, and BIA against criterion measures derived from total body water assessed with DLW. These models were then used with the population cohort and we analyzed the relationships between obesity indices and several health-related and disease status variables: (1) fasting plasma lipids, (2) glucose, (3) HbA1c, (4) adiponectin, (5) blood pressure, (6) diabetes (DM), and (7) cerebrocoronary vascular disease (CCVD) which includes stroke and heart disease. RESULTS: The best model for estimating FM in the sub-study used only three variables-sex, waist circumference (WC), and hip circumference and had multiple R(2) = 0.9730. FFM and PBF were calculated from FM and body weight. CONCLUSION: WC and other anthropometrics were more highly correlated with a number of obesity-related risk factors than were direct estimates of body composition. Body composition in Yup'ik people can be accurately estimated from simple anthropometrics.

Evaluation of a dual-scales method to measure weight-bearing through the legs, and effects of weight-bearing inequalities on hip bone mineral density and leg lean tissue mass.

OBJECTIVE: To investigate: the accuracy of measuring relative left/right weight-bearing using two identically calibrated weighing scales; the short-term weight-bearing tendencies in a general population of 9 participants and long-term in 42 females; the effect weight-bearing inequalities on hip bone mineral density and leg lean tissue mass. METHOD: Participants were measured standing astride two scales. Short-term volunteers were measured 10 times on one visit, with repositioning between measurements and the long-term group were measured on three visits at 6 month intervals. Baseline bilateral hip and total body Dual X-ray Absorptiometry scans were performed on the long-term group. RESULTS: The short-term Coefficient of Variation is 5.41% and long-term 7.01%. No significant correlations were found between hip bone density differences and weight-bearing inequalities, although a weak correlation of r = 0.31 (p = 0.047) was found for differences in leg lean tissue mass. CONCLUSION: Left/right weight-bearing measured using two scales is a consistent method for evaluating weight distribution through the legs. The short- and long-term weight-bearing tendencies showed a similar degree of variation. Weight-bearing inequalities were not associated with any significant left/right differences in bone mineral density at the hip, but were weakly associated with left-right differences in leg muscle mass.