Assessment of body cell mass at bedside in critically ill patients

Critical illness affects body composition profoundly, especially body cell mass (BCM). BCM loss reflects lean tissue wasting and could be a nutritional marker in critically ill patients. However, BCM assessment with usual isotopic or tracer methods is impractical in intensive care units (ICUs). We aimed to modelize the BCM of critically ill patients using variables available at bedside. Fat-free mass (FFM), bone mineral (Mo), and extracellular water (ECW) of 49 critically ill patients were measured prospectively by dual-energy X-ray absorptiometry and multifrequency bioimpedance. BCM was estimated according to the four-compartment cellular level: BCM = FFM - (ECW/0.98) - (0.73 × Mo). Variables that might influence the BCM were assessed, and multivariable analysis using fractional polynomials was conducted to determine the relations between BCM and these data. Bootstrap resampling was then used to estimate the most stable model predicting BCM. BCM was 22.7 ± 5.4 kg. The most frequent model included height (cm), leg circumference (cm), weight shift (Δ) between ICU admission and body composition assessment (kg), and trunk length (cm) as a linear function: BCM (kg) = 0.266 × height + 0.287 × leg circumference + 0.305 × Δweight - 0.406 × trunk length - 13.52. The fraction of variance explained by this model (adjusted r(2)) was 46%. Including bioelectrical impedance analysis variables in the model did not improve BCM prediction. In summary, our results suggest that BCM can be estimated at bedside, with an error lower than ±20% in 90% subjects, on the basis of static (height, trunk length), less stable (leg circumference), and dynamic biometric variables (Δweight) for critically ill patients.     

Contribution of genetic and environmental factors to variation in body compartments--a twin study in adults

This study aimed at analyzing the contribution of genetic and environmental factors on phenotypic variation of various traits of body composition. Subjects were 30 same-sexed pairs of twins including 20 monozygous (MZ) and 10 dizygous (DZ) pairs, aged 19-62 years. Zygosity was determined by DNA typing and morphological diagnosis. Body composition parameters (fat mass FM, lean body mass LBM, body cell mass BCM, extracellular mass ECM, total body water TBW, extracellular water ECW, and intracellular water ICW) were estimated by tetrapolar bioelectrical impedance analysis. Potential environmental factors influencing body composition (number of children, sporting activity and smoking behaviour) were determined by questionnaires. Heritabilities for traits of body composition were calculated by use of the twin method. Intraclass correlation is > 0.80 for the variation of LBM, BCM, ECM, TBW, ECW, and ICW in both MZ and DZ twins. Estimated heritability (h2) for FM, LBM, BCM, ECW, TBW, ECW, and ICW is 65%, 77%, 79%, 83%, 76%, 68%, and 82%, respectively. The h2 values for FM and LBM are consistent with those reported in other twin studies. For BCM, ECM, ECW and ICW, no comparative h2 estimates exist. Within-pair differences in body compartments do not change with increasing age in MZ and DZ twin pairs (p > 0.05). Stepwise multiple regression analyses indicate that zygosity, age, sex, number of children, sporting level and smoking behaviour do not significantly predict within-pair differences for weight, BMI, FM, LBM, TBW, ECW and ICW (each, p > 0.05). In contrast, sex and the number of children explain together 27% of observed within-pair differences for BCM. Zygosity is the only significant predictor of within-pair differences for ECM and height, explaining 20% (p = 0.008) and 36% of variance, respectively (p < 0.0001). Results indicate that genetic factors exert stronger influences on body composition than the considered environmental traits.     

The importance of body composition and dry weight assessments in patients with chronic kidney disease

Chronic volume overload is the major cause of hypertension and other cardiovascular morbidity in dialysis patients. One of the most important goals of physicians who take care of patients with chronic renal failure is to obtain near euvolemia or "dry body weight" in order to maintain or normalize blood pressure and prevent further cardiovascular events. In clinical practice, exact estimation of dry weight in hemodialysis patients remains a major challenge. Alterations in body composition, particularly malnutrition, are common in patients receiving long-term hemodialysis and contribute to a high mortality rate. In contrast, obesity - a known risk factor for cardiovascular morbidity and mortality - is prevalent amongst kidney allograft recipients in - long term after renal transplantation. Several technological tools and biochemical markers for estimation of plasma volume and body composition are available for clinical use. Our aim was to highlight the importance of control of body fluid volume and body composition in patients with chronic kidney disease and to describe the different methods available for such measurements.     

Use of body composition measurements to guide the assessment of dry weight in anuric dialysis patients: improvements in blood pressure control

PurposeFluid management using a body composition monitor (BCM) based on bioimpedance spectroscopy has been found to be beneficial for maintenance hemodialysis (MHD) patients. Our purpose was to provide a management procedure for the adjustment of post-dialysis overhydration (OH_post) and to evaluate whether this approach could improve blood pressure.MethodsPost-dialysis fluid status was assessed weekly using the BCM. The reference value of OH_post and the flow procedure for post-dialysis target weight (PDTW) adjustment were established via measurements of OH_post in 60 normotensive MHD patients. In the interventional study, we adjusted the PDTW of hypertensive patients to the optimal OH_post range, with a 0.2–0.5 kg change in PDTW per week.ResultsThis observational study included 130 anuric MHD patients, of whom 60 were in the pre-dialysis systolic blood pressure (sBP_pre) < 140 mmHg group. On multivariate logistic regression analysis, we found that only OH_post was significantly associated with sBP_pre ≥ 140 mmHg (odds ratio = 2.293, p = 0.000). Patients in the OH_post < ?1.8 L group were mainly male and younger, and had higher post-dialysis diastolic blood pressure, ultrafiltration volume, levels of nutrition markers (serum albumin and creatinine), body mass index, and lean tissue index (LTI). On multiple stepwise regression analysis, only the change in LTI was found to be an independent predictor of OH_post [R² 0.208, β = ?0.196, 95% CI (?0.296, ?0.095), p < 0.001]. The reference value of OH_post was found to deviate by ? 2.5–0.5 L from that of normotensive patients. At the end of the study, the systolic blood pressure of 38 patients was less than 140 mmHg after PDTW adjustment. The changes in OH_post from the initial to last adjustment were significant (t = 5.431, p < 0.001), with a substantial decrease in the sBP_pre (t = 11.208, p < 0.001).ConclusionsAssessment of OH_post and LTI using a BCM with a patient-specific optimal PDTW adjustment flow can lead to significantly better control of hypertension in anuric MHD patients.     

Effect of subclinical hypothyroidism on body fluid compartments.

OBJECTIVE: The present study was aimed to assess the effects of subclinical hypothyroidism on body composition (BC). SUBJECTS: Thirty-one women (age: 37 +/- 9.9 years) with a wide range of body mass index (BMI) were studied. Subclinical hypothyroidism was defined by a basal TSH > or = 4 mU/L and/or TRH stimulated peak > or = 30 mU/L. MEASUREMENTS: For each subject, weight, height, BMI, multifrequency bioelectrical impedance spectroscopy (BIS) and D2O and NaBr dilution tests were performed to assessed total body water (TBW) and extracellular water (ECW). Thyroid function (basal and TRH stimulated TSH, free T3, and free T4) were determined from fasting blood samples for all subjects. Total body dual energy X-ray absorptiometry (DXA) were used to measure fat mass (FM) and lean mass (Lean). RESULTS: The results of BIS were compared with the TBW and ECW estimated by the dilution techniques on the same individuals. The correlation was R2 = 0.65 for impedance at 5 kHz and ECW by NaBr and R2 = 0.72 for impedance at 100 kHz and TBW by D2O. Intracellular water (ICW) was calculated as differences between TBW and ECW measured by dilution methods. Percent of ECW and ICW were related to BMI (ANOVA, p < 0.001). No difference in TBW, body water distribution and body composition related to thyroid function was demonstrated. CONCLUSIONS: In our patients affected with subclinical hypothyroidism, with or without obesity, only obesity appeared related to TBW, ECW and ICW; the subclinical hypothyroidism, on the contrary, had no effect on compartments of body fluids. Bioimpedance is a valid tool to assess body fluid distribution in subclinical hypothyroidism.     

Extracellular water: greater expansion with age in African Americans.

Aging is associated with the onset of chronic diseases that lead to pathological expansion of the extracellular water (ECW) compartment. Healthy aging, in the absence of disease, is also reportedly accompanied by a relative expansion of the ECW compartment, although the studies on which this observation is based are few in number, applied different ECW measurement methods, included small ethnically homogeneous subject samples, and failed to adjust ECW for non-age-related influencing factors. The aim of the current study was to examine, in a large (n = 1,538) ethnically diverse [African American (AA), Asian, Caucasian, Hispanic] subject group the cross-sectional relationships between ECW and age after controlling first for other potential factors that may influence fluid distribution. ECW and intracellular water (ICW) were derived from measured total body water (isotope dilution) and potassium (40K whole body counting). The cross-sectional relationships between ECW, ICW, and ECW/ICW (E/I), and age were developed using multiple regression modelling methods. Body weight, weight squared, height, age, sex, race, and interactions were all significant ECW predictors. The slope of the observed race x age interaction was significantly greater in AA (beta = 0.0005, P = 0.005) than in the three other race groups. Race, sex, and age differences in fluid distribution persisted after adjusting for body composition in a subgroup (n = 994) with dual-energy X-ray absorptiometry lean soft tissue and fat measurements. A relative ECW expansion (i.e., E/I) was present with greater age in most sex-race groups, although the effect was not significantly larger in AA males (P > 0.05) compared with the other race groups, except Asians (P < 0.05). For females, a larger E/I-age effect was found in AA compared with the other race groups, but only the comparison against Hispanics was significant (P < 0.05). The ECW compartment and E/I are thus variably larger, according to race, in healthy older subjects independent of sex, lean soft tissue, and fat mass.     

血清D-二聚体、尿素氮与肌酐比值联合C反应蛋白与白蛋白比值对重症肺炎患者院内死亡的评估价值

摘要 目的：探讨血清D-二聚体（D-D）、尿素氮与肌酐比值（UCR）联合C反应蛋白与白蛋白比值（CAR）对重症肺炎（SP）患者院内死亡的评估价值。方法：选取2019年6月～2022年6月我院收治的101例SP患者,根据是否发生院内死亡分为死亡组和存活组。检测血清D-D和计算UCR、CAR。分析SP患者院内死亡的影响因素,受试者工作特征（ROC）曲线分析血清D-D、UCR、CAR对SP患者院内死亡的评估价值。结果：101例SP患者院内死亡率40.59％（41/101）。死亡组血清D-D、UCR、CAR高于存活组（P均＜0.05）。多因素Logistic回归分析显示,年龄增加、肺外并发症≥2个和D-D、UCR、CAR升高为SP患者院内死亡的独立危险因素（P均＜0.05）。ROC曲线分析显示,血清D-D、UCR、CAR单独与联合评估SP患者院内死亡的曲线下面积分别为0.781、0.798、0.793、0.929,血清D-D、UCR联合CAR评估SP患者院内死亡的AUC大于各指标单独评估。结论：血清D-D、UCR、CAR升高为SP患者院内死亡的独立危险因素,D-D、UCR联合CAR对SP患者院内死亡的评估价值较高。     

Myeloperoxidase-catalyzed 3-chlorotyrosine formation in dialysis patients.

Oxidative stress has been implicated in the cardiovascular complications that affect chronic renal failure patients on hemodialysis, though the physiologically relevant pathways mediating oxidative damage are poorly understood. It is known, however, that hemodialysis activates neutrophils, a well-characterized source of hydrogen peroxide and myeloperoxidase. The phagocyte-derived myeloperoxidase-hydrogen peroxide-chloride system generates hypochlorous acid, which reacts with tyrosine residues of proteins to form 3-chlorotyrosine. To explore the role of activated phagocytes in oxidative stress in chronic renal failure, we used 3-chlorotyrosine as a specific marker of myeloperoxidase activity. Utilizing isotope dilution gas chromatography-mass spectrometry, we compared 3-chlorotyrosine levels in plasma proteins of five patients on chronic hemodialysis therapy with those of age- and sex-matched healthy controls. The oxidized amino acid was present in the plasma proteins of 4 of the hemodialysis patients (3.5 +/- 0.8 micromol per mol tyrosine) but was undetectable in the healthy subjects. Therefore, one pathway for oxidative stress in hemodialysis patients appears to involve hypochlorous acid generated by the myeloperoxidase system of activated phagocytes. We also examined intradialytic 3-chlorotyrosine levels using membranes that activate white blood cells and the alternative pathway of complement. Hemodialysis increased plasma myeloperoxidase and the expression of CD11b/CD18 by circulating phagocytes, but failed to demonstrably increase 3-chlorotyrosine levels. 3-chlorotyrosine was detectable in 12 of 19 samples in total, with significant intrasubject variability. Our observations suggest that oxidants generated by myeloperoxidase contribute to the increased oxidative stress observed in renal-failure patients but do not damage plasma proteins during the hemodialysis procedure itself.     

Controlled trial of enalapril in patients with chronic fluid overload undergoing dialysis

About one third of patients receiving dialysis for end stage renal failure have chronic fluid overload despite advice to restrict their oral fluid intake. To investigate the potential of an angiotensin converting enzyme inhibitor in reducing the urge to drink and consequent gain in weight, a double blind, placebo controlled crossover trial of enalapril was conducted in 25 patients receiving dialysis who had fluid overload. The trial comprised a baseline period of four weeks; two periods of treatment, each of four weeks, during which patients received either placebo or enalapril 5 mg twice each week; and a follow up period of four weeks. Five patients withdrew from the trial, one because of an adverse drug reaction to enalapril. A range of biochemical and behavioural variables was measured during the baseline period, at the completion of periods 1 and 2, and during follow up. These variables included gain in weight between dialysis sessions; blood pressure; plasma concentrations of sodium, angiotensin II, and vasopressin; plasma renin and angiotensin converting enzyme activities; osmolality; and estimations of thirst, intake of fluid, and control of drinking. Enalapril caused a significant reduction in gain in weight between dialysis sessions, thirst, and oral intake of fluid in parallel with significantly increased renin activity, significantly decreased angiotensin converting enzyme activity, and decreased concentrations of angiotensin II. Gain in weight and angiotensin converting enzyme activity returned to baseline values once patients stopped taking enalapril.These results suggest that enalapril may act on the renin-angiotensin system and reduce intake of fluid by inhibiting angiotensin converting enzyme.     

Fluid compartmentation in skeletal muscle and carcass of Mus musculus acclimated to water scarcity

1. Total water (TW), and extracellular water (ECW) (as sodium and chloride space) were determined in skeletal muscle and carcass of Mus musculus acclimated to long-term water shortage. 2. The presence of fat in control mice and those in early stages of acclimation resulted in an apparent increase in TW and ECW as acclimation proceeded. 3. In contrast, fluid volumes per fat-free weight were either unchanged from controls or reduced. 4. Sodium space exceeded chloride space. 5. Muscle and carcass had essentially the same pattern of fluid shifts. 6. We conclude that ECW maintenance is a preeminent component of the acclimation process in this species.     

Four‐Compartment Cellular Level Body Composition Model: Comparison of Two Approaches**

Objective: The aim of this study was to develop and compare two DXA‐based four‐compartment [body weight = body cell mass (BCM) + extracellular fluid (ECF) + extracellular solids (ECS) + fat] cellular level models. Research Methods and Procedures: Total body potassium (TBK) model: BCM from TBK by whole‐body counting—ECF_TBK = LST ? [BCM_TBK + 0.73 × osseous mineral (Mo)]. Bromide model: ECF from sodium bromide dilution—BCM_BROMIDE = LST ? (ECF_BROMIDE + 0.73 × Mo); Mo and LST measurements came from DXA. The two approaches were evaluated in 99 healthy men and 118 women. Results: BCM estimates were highly correlated (r = 0.97, p < 0.001), as were ECF estimates (r = 0.87, p < 0.001); a small statistically significant mean difference was present (mean ± SD; BCM_TBK model, 30.4 ± 8.9 kg; BCM_BROMIDE, 31.4 ± 9.3 kg; Δ = 1.0 ± 2.8 kg; p < 0.001; ECF_TBK, 18.5 ± 4.2 kg; ECF_BROMIDE, 17.5 ± 3.6 kg; Δ = 1.0 ± 2.8 kg; p < 0.001). A high correlation (r = 0.97, p < 0.001) and good agreement (38.9 ± 9.5 vs. 38.9 ± 9.5 kg; Δ = 0.0 ± 2.4 kg; p = 0.39) were present between TBW, derived as the sum of intracellular water from TBK and ECW from bromide, and measured TBW by ²H₂O dilution. Discussion: Two developed four‐compartment cellular level DXA models, one of which is appropriate for use in most clinical and research settings, provide comparable results and are applicable for BCM and ECF estimation of subject groups with hydration disturbances.     

Increased extracellular water compartment, relative to intracellular water compartment, after weight reduction.

The hydration of fat free mass (FFM) and extracellular (ECW) and intracellular water (ICW) compartments were studied in 30 obese premenopausal women before and after a 3-mo weight-reduction program and again after a 9-mo weight-maintenance program. Body fat was determined by a four-compartment model. Total body water and ECW were determined by deuterium dilution and bromide dilution, respectively. After the weight-reduction period, mean weight loss was 12.8 kg, and body fat was reduced on average by 10.9 kg. During weight maintenance, changes in body mass and body fat were not significant. Before weight reduction, mean ECW/ICW ratio was relatively high (0.78 +/- 0.10). During the the study, total body water and ICW did not change significantly. ECW did not change significantly after weight reduction, but 12 mo after the start ECW was significantly increased by 1 liter. The ECW/ICW ratio increased to 0.87 +/- 0.12 (month 12). The hydration of the FFM increased from 74 +/- 1 to 77 +/- 2% during the weight reduction and remained elevated during weight maintenance. In conclusion, the ECW/ICW ratio and the hydration of the FFM, did not normalize during weight reduction and weight maintenance.     

Atrial natriuretic hormone secretion in patients with renal failure

To study the effects of volume overload and renal failure on plasma levels of immunoreactive atrial natriuretic hormone (IR-ANH), we measured levels of this hormone in normal subjects, in patients with advanced chronic renal failure (CRF) with and without clinically evident volume overload, and in patients with end-stage renal disease (ESRD) treated with chronic hemodialysis. The levels were 13 +/- 2 pmol/l in normal volunteers, 77 +/- 24 pmol/l in patients with CRF without volume overload, and 219 +/- 50 pmol/l in patients with CRF and clinically evident volume overload (analysis of variance, p less than 0.001, alpha = 0.05 compared to normals). In patients with ESRD, the levels of IR-ANH were 145 +/- 46 pmol/l before dialysis and decreased to 87 +/- 31 after dialysis (p less than 0.025). No correlation was found between the decrease in IR-ANH levels and the decrease in weight during dialysis. A significant positive correlation was found between the IR-ANH levels and blood urea nitrogen in patients with CRF (r = 0.658, p less than 0.01). Volume overload appears to be the most important stimulatory factor for ANH secretion in renal failure patients but other mechanisms, especially a decrease in metabolic clearance, may also contribute to elevated plasma levels. The increased secretion of ANH in patients with renal failure may be an important adaptive response to volume overload and hypertension.     

Bioimpedance Spectroscopy for Assessment of Volume Status in Patients before and after General Anaesthesia

BackgroundTechnically assisted assessment of volume status before surgery may be useful to direct intraoperative fluid administration. We therefore tested a recently developed whole-body bioimpedance spectroscopy device to determine pre- to postoperative fluid distribution.MethodsUsing a three-compartment physiologic tissue model, the body composition monitor (BCM, Fresenius Medical Care, Germany) measures total body fluid volume, extracellular volume, intracellular volume and fluid overload as surplus or deficit of ‘normal’ extracellular volume. BCM-measurements were performed before and after standardized general anaesthesia for gynaecological procedures (laparotomies, laparoscopies and vaginal surgeries). BCM results were blinded to the attending anaesthesiologist and data analysed using the 2-sided, paired Student’s t-test and multiple linear regression.ResultsIn 71 females aged 45±15 years with body weight 67±13 kg and duration of anaesthesia 154±68 min, pre- to postoperative fluid overload increased from −0.7±1.1 L to 0.1±1.0 L, corresponding to −5.1±7.5% and 0.8±6.7% of normal extracellular volume, respectively (both p<0.001), after patients had received 1.9±0.9 L intravenous crystalloid fluid. Perioperative urinary excretion was 0.4±0.3 L. The increase in extracellular volume was paralleled by an increase in total body fluid volume, while intracellular volume increased only slightly and without reaching statistical significance (p = 0.15). Net perioperative fluid balance (administered fluid volume minus urinary excretion) was significantly associated with change in extracellular volume (r² = 0.65), but was not associated with change in intracellular volume (r² = 0.01).ConclusionsRoutine intraoperative fluid administration results in a significant, and clinically meaningful increase in the extracellular compartment. BCM-measurements yielded plausible results and may become useful to guide intraoperative fluid therapy in future studies.     

Intra-Abdominal Pressure Correlates with Extracellular Water Content

Background

Secondary increase in intra-abdominal pressure (IAP) may result from extra-abdominal pathology, such as massive fluid resuscitation, capillary leak or sepsis. All these conditions increase the extravascular water content. The aim of this study was to analyze the relationship between IAP and body water volume.

Material and Methods

Adult patients treated for sepsis or septic shock with acute kidney injury (AKI) and patients undergoing elective pharyngolaryngeal or orthopedic surgery were enrolled. IAP was measured in the urinary bladder. Total body water (TBW), extracellular water content (ECW) and volume excess (VE) were measured by whole body bioimpedance. Among critically ill patients, all parameters were analyzed over three consecutive days, and parameters were evaluated perioperatively in surgical patients.

Results

One hundred twenty patients were studied. Taken together, the correlations between IAP and VE, TBW, and ECW were measured at 408 time points. In all participants, IAP strongly correlated with ECW and VE. In critically ill patients, IAP correlated with ECW and VE. In surgical patients, IAP correlated with ECW and TBW. IAP strongly correlated with ECW and VE in the mixed population. IAP also correlated with VE in critically ill patients. ROC curve analysis showed that ECW and VE might be discriminative parameters of risk for increased IAP.

Conclusion

IAP strongly correlates with ECW.     

Short and Long-Term Effects of the Angiotensin II Receptor Blocker Irbesartan on Intradialytic Central Hemodynamics: A Randomized Double-Blind Placebo-Controlled One-Year Intervention Trial (the SAFIR Study)

Background and Aim

Little is known about the tolerability of antihypertensive drugs during hemodialysis treatment. The present study evaluated the use of the angiotensin II receptor blocker (ARB) irbesartan.

Design

Randomized, double-blind, placebo-controlled, one-year intervention trial.

Setting and Participants

Eighty-two hemodialysis patients with urine output >300 mL/day and dialysis vintage <1 year.

Intervention

Irbesartan/placebo 300 mg/day for 12 months administered as add-on to antihypertensive treatment using a predialytic systolic blood pressure target of 140 mmHg in all patients.

Outcomes and Measurements

Cardiac output, stroke volume, central blood volume, total peripheral resistance, mean arterial blood pressure, and frequency of intradialytic hypotension.

Results

At baseline, the groups were similar regarding age, comorbidity, blood pressure, antihypertensive medication, ultrafiltration volume, and dialysis parameters. Over the one-year period, predialytic systolic blood pressure decreased significantly, but similarly in both groups. Mean start and mean end cardiac output, stroke volume, total peripheral resistance, heart rate, and mean arterial pressure were stable and similar in the two groups, whereas central blood volume increased slightly but similarly over time. The mean hemodynamic response observed during a dialysis session was a drop in cardiac output, in stroke volume, in mean arterial pressure, and in central blood volume, whereas heart rate increased. Total peripheral resistance did not change significantly. Overall, this pattern remained stable over time in both groups and was uninfluenced by ARB treatment. The total number of intradialytic hypotensive episodes was (placebo/ARB) 50/63 (P = 0.4). Ultrafiltration volume, left ventricular mass index, plasma albumin, and change in intradialytic total peripheral resistance were significantly associated with intradialytic hypotension in a multivariate logistic regression analysis based on baseline parameters.

Conclusion

Use of the ARB irbesartan as an add-on to other antihypertensive therapy did not significantly affect intradialytic hemodynamics, neither in short nor long-term, and no significant increase in hypotensive episodes was seen.

Trial registration

Clinicaltrials.gov NCT00791830     

Effect of Isovolemic,Isothermic Hemodialysis on Cerebral Perfusion and Vascular Stiffness Using Contrast Computed Tomography and Pulse Wave Velocity

Background

Patients undergoing hemodialysis treatment have a six-fold increased risk for stroke relative to the general population. However, the effect of hemodialysis on cerebral blood flow is poorly studied and confounding factors like blood pressure and ultrafiltration as well as temperature changes have rarely been accounted for. The aim of our study was to use state-of-the-art technology to evaluate the effect of a single dialysis session on cerebral perfusion as well as on vascular stiffness.

Methods

Chronic hemodialysis patients (7 male/3 female, mean age 58 years) were recruited. Cerebral blood flow and arterial pulse wave velocity were measured before and immediately after a hemodialysis session. To exclude effects of volume changes we kept ultrafiltration to a minimum, allowing no change in body weight. Isothermic conditions were maintained by using the GENIUS single-pass batch-dialysis system with a high-flux polysulfone dialyser. Cerebral blood flow was measured by contrast-enhanced computed tomography. Pulse wave velocity was measured using the SphygmoCor (AtCor Medical, USA) device by a single operator.

Results

This study shows for the first time that isovolemic, isothermic hemodialysis neither affected blood pressure or heart rate, nor total or regional cerebral perfusion. There was also no change in pulse wave velocity.

Conclusions

Mechanisms other than the dialysis procedure itself might be causative for the high incidence of ischemic strokes in this patient population. Moreover, the sole removal of uremic toxins does not lead to short-term effects on vascular stiffness, underlying the importance of volume control in this patient population.     

Effect of increased convective clearance by on-line hemodiafiltration on all cause and cardiovascular mortality in chronic hemodialysis patients - the Dutch CONvective TRAnsport STudy (CONTRAST): rationale and design of a randomised controlled trial [ISRCTN38365125

BACKGROUND: The high incidence of cardiovascular disease in patients with end stage renal disease (ESRD) is related to the accumulation of uremic toxins in the middle and large-middle molecular weight range. As online hemodiafiltration (HDF) removes these molecules more effectively than standard hemodialysis (HD), it has been suggested that online HDF improves survival and cardiovascular outcome. Thus far, no conclusive data of HDF on target organ damage and cardiovascular morbidity and mortality are available. Therefore, the CONvective TRAnsport STudy (CONTRAST) has been initiated. METHODS: CONTRAST is a Dutch multi-center randomised controlled trial. In this trial, approximately 800 chronic hemodialysis patients will be randomised between online HDF and low-flux HD, and followed for three years. The primary endpoint is all cause mortality. The main secondary outcome variables are fatal and non-fatal cardiovascular events. CONCLUSION: The study is designed to provide conclusive evidence whether online HDF leads to a lower mortality and less cardiovascular events as compared to standard HD.     

Maximal Standard Dose of Parenteral Iron for Hemodialysis Patients: An MRI-Based Decision Tree Learning Analysis

Background and Objectives

Iron overload used to be considered rare among hemodialysis patients after the advent of erythropoesis-stimulating agents, but recent MRI studies have challenged this view. The aim of this study, based on decision-tree learning and on MRI determination of hepatic iron content, was to identify a noxious pattern of parenteral iron administration in hemodialysis patients.

Design, Setting, Participants and Measurements

We performed a prospective cross-sectional study from 31 January 2005 to 31 August 2013 in the dialysis centre of a French community-based private hospital. A cohort of 199 fit hemodialysis patients free of overt inflammation and malnutrition were treated for anemia with parenteral iron-sucrose and an erythropoesis-stimulating agent (darbepoetin), in keeping with current clinical guidelines. Patients had blinded measurements of hepatic iron stores by means of T1 and T2* contrast MRI, without gadolinium, together with CHi-squared Automatic Interaction Detection (CHAID) analysis.

Results

The CHAID algorithm first split the patients according to their monthly infused iron dose, with a single cutoff of 250 mg/month. In the node comprising the 88 hemodialysis patients who received more than 250 mg/month of IV iron, 78 patients had iron overload on MRI (88.6%, 95% CI: 80% to 93%). The odds ratio for hepatic iron overload on MRI was 3.9 (95% CI: 1.81 to 8.4) with >250 mg/month of IV iron as compared to <250 mg/month. Age, gender (female sex) and the hepcidin level also influenced liver iron content on MRI.

Conclusions

The standard maximal amount of iron infused per month should be lowered to 250 mg in order to lessen the risk of dialysis iron overload and to allow safer use of parenteral iron products.