Fluid volume management in hemodialysis: never give up!

Every hemodialysis session starts with the question of how much fluid should be removed, which can currently not be answered precisely. Herein, we first revisit the "probing-dry-weight" concept, using the historical example of Tassin/France (practicing also "long, slow dialysis"): Mortality outcomes were, in the 1980s, better than registry data, but are nowadays similar to European average. In view of the negative primary end point in a recent trial on dry weight assessment, based on lung ultrasound-guided evaluation of fluid excess in the lungs, and a meta-analysis of prospective studies failing to show that bioimpedance-based interventions for correction of volume overload had a direct effect on all-cause mortality, we ask how to ever move forward. Clinical reasoning demands that as much information as possible should be gathered on the fluid status of patients undergoing dialysis. Besides body weight and blood pressure, measurements of bioimpedance and dialysate bolus-derived absolute blood volume can in principle be automatized, whereas lung ultrasound can be obtained routinely. In the era of machine learning, fluid management could consist of flexible target weight prescriptions, adjusted on a daily basis and accounting even for fluctuations in fluid-free body mass. In view of all the negative prospective results surrounding fluid management in hemodialysis, we propose this as a "never-give-up" approach.

An analysis of the impact of fluid overload and fluid depletion for all-cause and cardiovascular mortality.

BACKGROUND: Both baseline fluid overload (FO) and fluid depletion are associated with increased mortality risk and cardiovascular complications in haemodialysis patients. Fluid status may vary substantially over time, and this variability could also be associated with poor outcomes. METHODS: In our retrospective cohort study, including 4114 haemodialysis patients from 34 Romanian dialysis units, we investigated both all-cause and cardiovascular mortality risk according to baseline pre- and post-dialysis volume status, changes in pre- and post-dialysis fluid status during follow-up (time-varying survival analysis), pre-post changes in volume status during dialysis and pre-dialysis fluid status variability during the first 6 months of evaluation. RESULTS: According to their pre-dialysis fluid status, patients were stratified in the following groups: normovolaemic with an absolute FO (AFO) compartment between -1.1 and 1.1 L, fluid depletion with an AFO below -1.1 L, moderate FO with an AFO compartment >1.1 but <2.5 L and severe FO with the AFO compartment >2.5 L. Baseline pre-dialysis FO and fluid depletion patients had a significantly elevated risk of all-cause mortality risk {hazard ratio [HR] 1.53 [95% confidence interval (CI) 1.22-1.93], HR 2.04 (95% CI 1.59-2.60) and HR 1.88 (95% CI 1.07-3.39) for moderate FO, severe FO and fluid depletion, respectively}. In contrast, post-dialysis fluid depletion was associated with better survival [HR 0.71 (95% CI 0.57-0.89)]. Similar results were found when using changes in pre- or post-dialysis fluid status during follow-up (time-varying values): FO patients had an increased risk of all-cause [moderate FO: HR 1.39 (95% CI 1.11-1.75); severe FO: HR 2.29 (95% CI 2.01-3.31] and cardiovascular (CV) mortality [moderate FO: HR 1.34 (95% CI 1.05-1.70); severe FO: HR 2.34 (95% CI 1.67-3.28)] as compared with normohydrated patients. Using pre-post changes in volume status during dialysis, we categorized the patients into six groups: Group 1, AFO <-1.1 L pre- and post-dialysis; Group 2, AFO between -1.1 and 1.1 L pre-dialysis and <-1.1 L post-dialysis (the reference group); Group 3, AFO between -1.1 and 1.1 L pre- and post-dialysis; Group 4, AFO >1.1 L pre-dialysis and <-1.1 L post-dialysis; Group 5, AFO >1.1 L pre-dialysis and between -1.1 and 1.1 L post-dialysis; Group 6, AFO >1.1 L pre- and post-dialysis. Using the baseline values, only patients in Groups 1, 5 and 6 maintained an increased risk for all-cause mortality as compared with the reference group. Additionally, CV mortality risk was significantly higher for patients in Groups 5 and 6. When we applied the time-varying analysis, patients in Groups 1, 5 and 6 had a significantly higher risk for both all-cause and CV mortality risk. In the last approach, the highest risk for the all-cause mortality outcome was observed for patients with high-amplitude fluctuation during the first 6 months of evaluation [HR 2.75 (95% CI 1.29-5.84)]. CONCLUSION: We reconfirm the association between baseline pre- and post-dialysis volume status and mortality in dialysis patients; additionally, we showed that greater fluid status variability is independently associated with higher mortality.

Elevated tissue sodium deposition in patients with type 2 diabetes on hemodialysis detected by 23Na magnetic resonance imaging.

Long-term elevated blood sugar levels result in tissue matrix compositional changes in patients with diabetes mellitus type 2 (T2DM). We hypothesized that hemodialysis patients with T2DM might accumulate more tissue sodium than control hemodialysis patients. To test this, 23Na magnetic resonance imaging (23Na MRI) was used to estimate sodium in skin and muscle tissue in hemodialysis patients with or without T2DM. Muscle fat content was estimated by 1H MRI and tissue sodium content by 23Na MRI pre- and post-hemodialysis in ten hemodialysis patients with T2DM and in 30 matched control hemodialysis patients. We also assessed body fluid distribution with the Body Composition Monitor. 1H MRI indicated a tendency to higher muscle fat content in hemodialysis patients with T2DM compared to non-diabetic hemodialysis patients. 23Na MRI indicated increased sodium content in muscle and skin tissue of hemodialysis patients with T2DM compared to control hemodialysis patients. Multi-frequency bioimpedance was used to estimate extracellular water (ECW), and excess ECW in T2DM hemodialysis patients correlated with HbA1c levels. Sodium mobilization during hemodialysis lowered muscle sodium content post-dialysis to a greater degree in T2DM hemodialysis patients than in control hemodialysis patients. Thus, our findings provide evidence that increased sodium accumulation occurs in hemodialysis patients with T2DM and that impaired serum glucose metabolism is associated with disturbances in tissue sodium and water content.

Greater fluid overload and lower interdialytic weight gain are independently associated with mortality in a large international hemodialysis population.

Background: Fluid overload and interdialytic weight gain (IDWG) are discrete components of the dynamic fluid balance in haemodialysis patients. We aimed to disentangle their relationship, and the prognostic importance of two clinically distinct, bioimpedance spectroscopy (BIS)-derived measures, pre-dialysis and post-dialysis fluid overload (FOpre and FOpost) versus IDWG. Methods: We conducted a retrospective cohort study on 38 614 incident patients with one or more BIS measurement within 90 days of haemodialysis initiation (1 October 2010 through 28 February 2015). We used fractional polynomial regression to determine the association pattern between FOpre, FOpost and IDWG, and multivariate adjusted Cox models with FO and/or IDWG as longitudinal and time-varying predictors to determine all-cause mortality risk. Results: In analyses using 1-month averages, patients in quartiles 3 and 4 (Q3 and Q4) of FO had an incrementally higher adjusted mortality risk compared with reference Q2, and patients in Q1 of IDWG had higher adjusted mortality compared with Q2. The highest adjusted mortality risk was observed for patients in Q4 of FOpre combined with Q1 of IDWG [hazard ratio (HR) = 2.66 (95% confidence interval 2.21-3.20), compared with FOpre-Q2/IDWG-Q2 (reference)]. Using longitudinal means of FO and IDWG only slightly altered all HRs. IDWG associated positively with FOpre, but negatively with FOpost, suggesting a link with post-dialysis extracellular volume depletion. Conclusions: FOpre and FOpost were consistently positive risk factors for mortality. Low IDWG was associated with short-term mortality, suggesting perhaps an effect of protein-energy wasting. FOpost reflected the volume status without IDWG, which implies that this fluid marker is clinically most intuitive and may be best suited to guide volume management in haemodialysis patients.

Validating the use of bioimpedance spectroscopy for assessment of fluid status in children.

BACKGROUND: Bioimpedance spectroscopy (BIS) with a whole-body model to distinguish excess fluid from major body tissue hydration can provide objective assessment of fluid status. BIS is integrated into the Body Composition Monitor (BCM) and is validated in adults, but not children. This study aimed to (1) assess agreement between BCM-measured total body water (TBW) and a gold standard technique in healthy children, (2) compare TBW_BCM with TBW from Urea Kinetic Modelling (UKM) in haemodialysis children and (3) investigate systematic deviation from zero in measured excess fluid in healthy children across paediatric age range. METHODS: TBW_BCM and excess fluid was determined from standard wrist-to-ankle BCM measurement. TBW_D2O was determined from deuterium concentration decline in serial urine samples over 5 days in healthy children. UKM was used to measure body water in children receiving haemodialysis. Agreement between methods was analysed using paired t test and Bland-Altman method comparison. RESULTS: In 61 healthy children (6-14 years, 32 male), mean TBW_BCM and TBW_D2O were 21.1 ± 5.6 and 20.5 ± 5.8 L respectively. There was good agreement between TBW_BCM and TBW_D2O (R2 = 0.97). In six haemodialysis children (4-13 years, 4 male), 45 concomitant measurements over 8 months showed good TBW_BCM and TBW_UKM agreement (mean difference - 0.4 L, 2SD = ± 3.0 L). In 634 healthy children (2-17 years, 300 male), BCM-measured overhydration was - 0.1 ± 0.7 L (10-90th percentile - 0.8 to + 0.6 L). There was no correlation between age and OH (p = 0.28). CONCLUSIONS: These results suggest BCM can be used in children as young as 2 years to measure normally hydrated weight and assess fluid status.

Chronic Fluid Overload and Mortality in ESRD.

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.

Magnetic resonance-determined sodium removal from tissue stores in hemodialysis patients.

We have previously reported that sodium is stored in skin and muscle. The amounts stored in hemodialysis (HD) patients are unknown. We determined whether (23)Na magnetic resonance imaging (sodium-MRI) allows assessment of tissue sodium and its removal in 24 HD patients and 27 age-matched healthy controls. We also studied 20 HD patients before and shortly after HD with a batch dialysis system with direct measurement of sodium in dialysate and ultrafiltrate. Age was associated with higher tissue sodium content in controls. This increase was paralleled by an age-dependent decrease of circulating levels of vascular endothelial growth factor-C (VEGF-C). Older (>60 years) HD patients showed increased sodium and water in skin and muscle and lower VEGF-C levels compared with age-matched controls. After HD, patients with low VEGF-C levels had significantly higher skin sodium content compared with patients with high VEGF-C levels (low VEGF-C: 2.3 ng/ml and skin sodium: 24.3 mmol/l; high VEGF-C: 4.1 ng/ml and skin sodium: 18.2 mmol/l). Thus, sodium-MRI quantitatively detects sodium stored in skin and muscle in humans and allows studying sodium storage reduction in ESRD patients. Age and VEGF-C-related local tissue-specific clearance mechanisms may determine the efficacy of tissue sodium removal with HD. Prospective trials on the relationship between tissue sodium content and hard end points could provide new insights into sodium homeostasis, and clarify whether increased sodium storage is a cardiovascular risk factor.

Baseline hydration status in incident peritoneal dialysis patients: the initiative of patient outcomes in dialysis (IPOD-PD study)†.

BACKGROUND: Non-euvolaemia in peritoneal dialysis (PD) patients is associated with elevated mortality risk. There is an urgent need to collect data to help us understand the association between clinical practices and hydration and nutritional status, and their effects on patient outcome. METHODS: The aim of this prospective international, longitudinal observational cohort study is to follow up the hydration and nutritional status, as measured by bioimpedance spectroscopy using the body composition monitor (BCM) of incident PD patients for up to 5 years. Measures of hydration and nutritional status and of clinical, biochemical and therapy-related data are collected directly before start of PD treatment, at 1 and 3 months, and then every 3 months. This paper presents the protocol and a pre-specified analysis of baseline data of the cohort. RESULTS: A total of 1092 patients (58.1% male, 58.0 ± 15.3 years) from 135 centres in 32 countries were included. Median fluid overload (FO) was 2.0 L (males) and 0.9 L (females). Less than half of the patients were normohydrated (38.7%), whereas FO > 1.1 L was seen in 56.5%. Systolic and diastolic blood pressure were 139.5 ± 21.8 and 80.0 ± 12.8 mmHg, respectively, and 25.1% of patients had congestive heart failure [New York Heart Association (NYHA) 1 or higher]. A substantial number of patients judged to be not overhydrated on clinical judgement appeared to be overhydrated by BCM measurement. Overhydration at baseline was independently associated with male gender and diabetic status. CONCLUSIONS: The majority of patients starting on PD are overhydrated already at start of PD. This may have important consequences on clinical outcomes and preservation of residual renal function. Substantial reclassification of hydration status by BCM versus on a clinical basis was necessary, especially in patients who were not overtly overhydrated. Both clinical appreciation and bioimpedance should be combined in clinical decision-making on hydration status.

Body composition in dialysis patients: a functional assessment of bioimpedance using different prediction models.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Assessment of bioimpedance spectroscopy devices: a comparative study and error analysis of gold-plated copper electrodes.

Objective. Bioimpedance spectroscopy (BIS) is a non-invasive diagnostic tool to derive fluid volume compartments from frequency dependent voltage drops in alternating currents by extrapolating to the extracellular resistance (R0) and intracellular resistance (Ri). Here we tested whether a novel BIS device with reusable and adhesive single-use electrodes produces results which are (in various body positions) equivalent to an established system employing only single-use adhesive electrodes.Approach. Two BIS devices ('Cella' and the 'Body Composition Monitor' [BCM]) were compared using four dedicated resistance testboxes and by measuring 40 healthy volunteers.Invivocomparisons included supine wrist-to-ankle (WA) reference measurements and wrist-to-wrist (WW) measurements with pre-gelled silver/silver-chloride (Ag/AgCl) electrodes and WW measurements with reusable gold-plated copper electrodes.Main results. Coefficient of variation were <1% for all testbox measurements with both BIS devices. Accuracy was within ±1% of true resistance variability, a threshold which was only exceeded by the Cella device for all resistances in a testbox designed with a lowR0/Riratio.Invivo, WA-BIS differed significantly between BIS devices (p< 0.001). Reusable WW electrodes exhibited larger resistances than WW-BIS with Ag/AgCl electrodes (R0: 738.36 and 628.69 Ω;Ri: 1508.18 and 1390 Ω) and the relative error varied from 7.6% to 31.1% (R0) and -15.6% to 37.3% (Ri).Significance. Both BIS devices produced equivalent resistances measurements but different estimates of body composition bothinsilicoand in WA setupsinvivo, suggesting that the devices should not be used interchangeably. Employing WW reusable electrodes as opposed to WA and WW measurement setups with pre-gelled Ag/AgCl electrodes seems to be associated with measurement variations that are too large for safe clinical use. We recommend further investigations of measurement errors originating from electrode material and current path.

Effect of fluid management guided by bioimpedance spectroscopy on cardiovascular parameters in hemodialysis patients: a randomized controlled trial.

BACKGROUND: 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. STUDY DESIGN: Prospective, randomized, and controlled study. SETTING & PARTICIPANTS: 156 hemodialysis patients from 2 centers were randomly assigned to 2 groups. INTERVENTION: 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. OUTCOMES: 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. MEASUREMENTS: 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. RESULTS: 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. LIMITATIONS: Ambulatory blood pressure data were not available for all patients. CONCLUSIONS: 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.

Significance of interdialytic weight gain versus chronic volume overload: consensus opinion.

Predialysis volume overload is the sum of interdialytic weight gain (IDWG) and residual postdialysis volume overload. It results mostly from failure to achieve an adequate volume status at the end of the dialysis session. Recent developments in bioimpedance spectroscopy and possibly relative plasma volume monitoring permit noninvasive volume status assessment in hemodialysis patients. A large proportion of patients have previously been shown to be chronically volume overloaded predialysis (defined as >15% above 'normal' extracellular fluid volume, equivalent to >2.5 liters on average), and to exhibit a more than twofold increased mortality risk. By contrast, the magnitude of the mortality risk associated with IDWG is much smaller and only evident with very large weight gains. Here we review the available evidence on volume overload and IDWG, and question the use of IDWG as an indicator of 'nonadherence' by describing its association with postdialysis volume depletion. We also demonstrate the relationship between IDWG, volume overload and predialysis serum sodium concentration, and comment on salt intake. Discriminating between volume overload and IDWG will likely lead to a more appropriate management of fluid withdrawal during dialysis. Consensually, the present authors agree that this discrimination should be among the primary goals for dialysis caretakers today. In consequence, we recommend objective measures of volume status beyond mere evaluations of IDWG.

A multicentric, international matched pair analysis of body composition in peritoneal dialysis versus haemodialysis patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Ultrafiltration-induced decrease in relative blood volume is larger in hemodialysis patients with low specific blood volume: Results from a dialysate bolus administration study.

INTRODUCTION: Prescribing the ultrafiltration in hemodialysis patients remains challenging and might benefit from the information on absolute blood volume, estimated by intradialytic dialysate bolus administration. Here, we aimed at determining the relationship between absolute blood volume, normalized for body mass (specific blood volume, Vs), and ultrafiltration-induced decrease in relative blood volume (∆RBV) as well as clinical parameters including body mass index (BMI). METHODS: This retrospective analysis comprised 77 patients who had their dialysate bolus-based absolute blood volume extracted routinely with an automated method. Patient-specific characteristics and ∆RBV were analyzed as a function of Vs, dichotomizing the data above or below a previously proposed threshold of 65 ml/kg for Vs. Statistical methodology comprised descriptive analyses, two-group comparisons, and correlation analyses. FINDINGS: Median Vs was 68.6 ml/kg (54.9 ml/kg [Quartile 1], 83.4 ml/kg [Quartile 3]). Relative blood volume decreased by 6.3% (2.6%, 12.2%) over the entire hemodialysis session. Vs correlated inversely with BMI (rs  = -0.688, p < 0.001). ∆RBV was 9.8% in the group of patients with Vs <65 ml/kg versus 6.0% in the group of patients with Vs ≥65 ml/kg (p = 0.024). The two groups did not differ significantly regarding their specific ultrafiltration volume, normalized for body mass, which amounted to 34.1 ml/kg and 36.0 ml/kg in both groups, respectively (p = 0.630). ∆RBV correlated inversely with Vs (rs  = -0.299, p = 0.008). DISCUSSION: The present study suggests that patients with higher BMI and lower Vs experience larger blood volume changes, despite similar ultrafiltration requirements. These results underline the clinical plausibility and importance of dialysate bolus-based absolute blood volume determination in the assessment of target weight, especially in view of a previous study where intradialytic morbid events could be decreased when the target weight was adjusted, based on Vs.

Importance of normohydration for the long-term survival of haemodialysis patients.

BACKGROUND: Fluid overload and hypertension are among the most important risk factors for haemodialysis (HD) patients. The aim of this study was to analyse the impact of fluid overload for the survival of HD patients by using a selected reference population from Tassin. METHODS: A positively selected HD population (n = 50) from Tassin (Lyon-France) was used as a reference for fluid status and all-cause mortality. This population was compared to one dialysis centre from Giessen (Germany) which was separated into a non-hyperhydrated (n = 123) and a hyperhydrated (n = 35) patient group. The hydration status (ΔHS) of all patients was objectively measured with whole-body bioimpedance spectroscopy in 2003. All-cause mortality was analysed after a 6.5-year follow-up. RESULTS: Most of the reference patients from Tassin were normohydrated (ΔHS = 0.25 ± 1.15 L) at the start of the HD session. The hydration status of the Tassin patients was not different to the non-hyperhydrated Giessen patients (ΔHS = 0.8 ± 1.1 L) but significantly lower than in the hyperhydrated Giessen group (ΔHS = 3.5 ± 1.2 L). Multivariate adjusted all-cause mortality was significantly increased in the hyperhydrated patient group (hazard ratio = 3.41)- no difference in mortality could be observed between the Tassin and the non-hyperhydrated group from Giessen-even considering the fact that Tassin patients presented a significantly lower blood pressure. CONCLUSIONS: Fluid overload has a very high predictive value for all-cause mortality and seems to be one of the major killers in the HD population. Patients might strongly benefit from active management of fluid overload.

Determination of fluid status in haemodialysis patients with whole body and calf bioimpedance techniques.

AIM: The aim of this study was to demonstrate the ability of widely used bioimpedance techniques to assess dry weight (DW) and to predict a state of normal hydration in haemodialysis patients whose post-dialysis weight had been gradually reduced from baseline in successive treatments over time. METHODS: Calf bioimpedance spectroscopy (cBIS) was employed to determine DW (DW(cBIS) ) as defined by flattening of an intradialytic continuously measured resistance curve and by normalized resistivity (nRho) being in the gender-specific normal range. The wECV/TBW ratio was determined by 'classical' wrist-to-ankle whole body bioimpedance spectroscopy (wBIS); in addition, a novel whole body model (WBM) based on wBIS was used to predict normal hydration weight (NHW(WBM) ). RESULTS: Twenty-one haemodialysis patients were studied; 11 ± 6 measurements were performed per patient. Nine patients reached DW(cBIS) (DW(cBIS) group), while 12 patients remained fluid-overloaded (non-DW(cBIS) group). Change in wECV as measured by wBIS accounted for 46 ± 23% in DW(cBIS) group, which was higher than in non-DW(cBIS) group (33 ± 48%, P < 0.05) of actual weight loss at the end of study. In both groups the wECV/TBW ratio did not change significantly between baseline and study end. Mean predicted NHW(WBM) at baseline was 3.55 ± 1.6 kg higher than DW(cBIS) . The difference in DW(cBIS) and NHW(WBM) was 1.97 ± 1.0 kg at study end. CONCLUSION: WBM could be useful to predict a target range of normal hydration weight particularly for patients with substantial fluid overload. The cBIS provides an accurate reference for the estimation of DW so that combined use of cBIS and WBM is promising and warrants further studies.

Feasibility of Dialysate Bolus-Based Absolute Blood Volume Estimation in Maintenance Hemodialysis Patients.

BACKGROUND: Absolute blood volume (ABV) is a critical component of fluid status, which may inform target weight prescriptions and hemodynamic vulnerability of dialysis patients. Here, we utilized the changes in relative blood volume (RBV), monitored by ultrasound (BVM) upon intradialytic 240 mL dialysate fluid bolus-infusion 1 h after hemodialysis start, to calculate the session-specific ABV. With the main goal of assessing clinical feasibility, our sub-aims were to (i) standardize the BVM-data read-out; (ii) determine optimal time-points for ABV-calculation, "before-" and "after-bolus"; (iii) assess ABV-variation. METHODS: We used high-level programming language and basic descriptive statistics in a retrospective study of routinely measured BVM-data from 274 hemodialysis sessions in 98 patients. RESULTS: Regarding (i) and (ii), we automatized the processing of RBV-data, and determined an algorithm to select the adequate RBV-data points for ABV-calculations. Regarding (iii), we found in 144 BVM-curves from 75 patients, that the average ABV ± standard deviation was 5.2 ± 1.5 L and that among those 51 patients who still had ≥2 valid estimates, the average intra-patient standard deviation in ABV was 0.8 L. Twenty-seven of these patients had an average intra-patient standard deviation in ABV <0.5 L. CONCLUSIONS: We demonstrate feasibility of ABV-calculation by an automated algorithm after dialysate bolus-administration, based on the BVM-curve. Based on our results from this simple "abridged" calculation approach with routine clinical measurements, we encourage the use of multi-compartment modeling and comparison with reference methods of ABV-determination. Hopes are high that clinicians will be able to use ABV to inform target weight prescription, improving hemodynamic stability.

Guided optimization of fluid status in haemodialysis patients.

BACKGROUND: Achieving normohydration remains a non-trivial issue in haemodialysis therapy. Guiding the haemodialysis patient on the path between fluid overload and dehydration should be the clinical target, although it can be difficult to achieve this target in practice. Objective and clinically applicable methods for the determination of the normohydration status on an individual basis are needed to help in the identification of an appropriate target weight. METHODS: The aim of this prospective trial was to guide the patient population of a complete dialysis centre towards normohydration over the course of approximately 1 year. Fluid status was assessed frequently (at least monthly) in haemodialysis patients (n = 52) with the body composition monitor (BCM), which is based on whole body bioimpedance spectroscopy. The BCM provides the clinician with an objective target for normohydration. The patient population was divided into three groups: the hyperhydrated group (relative fluid overload >15% of extracellular water (ECW); n = 13; Group A), the adverse event group (patients with more than two adverse events in the last 4 weeks; n = 12; Group B) and the remaining patients (n = 27; Group C). RESULTS: In the hyperhydrated group (Group A), fluid overload was reduced by 2.0 L (P < 0.001) without increasing the occurrence of intradialytic adverse events. This resulted in a reduction in systolic blood pressure of 25 mmHg (P = 0.012). Additionally, a 35% reduction in antihypertensive medication (P = 0.031) was achieved. In the adverse event group (Group B), the fluid status was increased by 1.3 L (P = 0.004) resulting in a 73% reduction in intradialytic adverse events (P < 0.001) without significantly increasing the blood pressure. CONCLUSION: The BCM provides an objective assessment of normohydration that is clinically applicable. Guiding the patients towards this target of normohydration leads to better control of hypertension in hyperhydrated patients, less intradialytic adverse events and improved cardiac function.