Bio-impedance spectroscopy added to a fluid management protocol does not improve preservation of residual kidney function in incident hemodialysis patients in a randomized controlled trial.

Avoiding excessive dialysis-associated volume depletion may help preserve residual kidney function (RKF). To establish whether knowledge of the estimated normally hydrated weight from bioimpedance measurements (BI-NHW) when setting the post-hemodialysis target weight (TW) might mitigate rate of loss of RKF, we undertook an open label, randomized controlled trial in incident patients receiving HD, with clinicians and patients blinded to bioimpedance readings in controls. A total of 439 patients with over 500 ml urine/day or residual GFR exceeding 3 ml/min/1.73m2 were recruited from 34 United Kingdom centers and randomized 1:1, stratified by center. Fluid assessments were made for up to 24 months using a standardized proforma in both groups, supplemented by availability of BI-NHW in the intervention group. Primary outcome was time to anuria, analyzed using competing-risk survival models adjusted for baseline characteristics, by intention to treat. Secondary outcomes included rate of RKF decline (mean urea and creatinine clearance), blood pressure and patient-reported outcomes. There were no group differences in cause-specific hazard rates of anuria (0.751; 95% confidence interval (0.459, 1.229)) or sub-distribution hazard rates (0.742 (0.453, 1.215)). RKF decline was markedly slower than anticipated, pooled linear rates in year 1: -0.178 (-0.196, -0.159)), year 2: -0.061 (-0.086, -0.036)) ml/min/1.73m2/month. Blood pressure and patient-reported outcomes did not differ by group. The mean difference agreement between TW and BI-NHW was similar for both groups, Bioimpedance: -0.04 kg; Control: -0.25 kg. Thus, use of a standardized clinical protocol for fluid assessment when setting TW is associated with excellent preservation of RKF. Hence, bioimpedance measurements are not necessary to achieve this.

Patient perspectives of target weight management and ultrafiltration in haemodialysis: a multi-center survey.

BACKGROUND: Decisions around planned ultrafiltration volumes are the only part of the haemodialysis prescription decided upon at every session. Removing too much fluid or too little is associated with both acute symptoms and long-term outcomes. The degree to which patients engage with or influence decision-making is not clear. We explored patient perspectives of prescribing ultrafiltration volumes, their understanding of the process and engagement with it. METHODS: A questionnaire developed for this study was administered to 1077 patients across 10 UK Renal Units. Factor analysis reduced the dataset into factors representing common themes. Relationships between survey results and factors were investigated using regression models. ANCOVA was used to explore differences between Renal Units. RESULTS: Patients generally felt in control of their fluid management and that they were given the final say on planned ultrafiltration volumes. Around half of the respondents reported they take an active role in their treatment. However, respondents were largely unable to relate signs and symptoms to fluid management practice and a third said they would not report common signs and symptoms to clinicians. A fifth of patients reported not to know how ultrafiltration volumes were calculated. Patients responded positively to questions relating to healthcare staff, though with significant variation between units, highlighting differences in perception of care. CONCLUSIONS: Despite a lack of formal acknowledgement in fluid management protocols, patients have significant involvement in decisions regarding fluid removal during dialysis. Furthermore, substantial gaps remain in patient knowledge and engagement. Formalizing the role of patients in these decisions, including patient education, may improve prescription and achievement of target weights.

Blood pressure and volume management in dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Blood pressure (BP) and volume control are critical components of dialysis care and have substantial impacts on patient symptoms, quality of life, and cardiovascular complications. Yet, developing consensus best practices for BP and volume control have been challenging, given the absence of objective measures of extracellular volume status and the lack of high-quality evidence for many therapeutic interventions. In February of 2019, Kidney Disease: Improving Global Outcomes (KDIGO) held a Controversies Conference titled Blood Pressure and Volume Management in Dialysis to assess the current state of knowledge related to BP and volume management and identify opportunities to improve clinical and patient-reported outcomes among individuals receiving maintenance dialysis. Four major topics were addressed: BP measurement, BP targets, and pharmacologic management of suboptimal BP; dialysis prescriptions as they relate to BP and volume; extracellular volume assessment and management with a focus on technology-based solutions; and volume-related patient symptoms and experiences. The overarching theme resulting from presentations and discussions was that managing BP and volume in dialysis involves weighing multiple clinical factors and risk considerations as well as patient lifestyle and preferences, all within a narrow therapeutic window for avoiding acute or chronic volume-related complications. Striking this challenging balance requires individualizing the dialysis prescription by incorporating comorbid health conditions, treatment hemodynamic patterns, clinical judgment, and patient preferences into decision-making, all within local resource constraints.

Renal Association Clinical Practice Guideline on Haemodialysis.

This guideline is written primarily for doctors and nurses working in dialysis units and related areas of medicine in the UK, and is an update of a previous version written in 2009. It aims to provide guidance on how to look after patients and how to run dialysis units, and provides standards which units should in general aim to achieve. We would not advise patients to interpret the guideline as a rulebook, but perhaps to answer the question: "what does good quality haemodialysis look like?"The guideline is split into sections: each begins with a few statements which are graded by strength (1 is a firm recommendation, 2 is more like a sensible suggestion), and the type of research available to back up the statement, ranging from A (good quality trials so we are pretty sure this is right) to D (more like the opinion of experts than known for sure). After the statements there is a short summary explaining why we think this, often including a discussion of some of the most helpful research. There is then a list of the most important medical articles so that you can read further if you want to - most of this is freely available online, at least in summary form.A few notes on the individual sections: 1. This section is about how much dialysis a patient should have. The effectiveness of dialysis varies between patients because of differences in body size and age etc., so different people need different amounts, and this section gives guidance on what defines "enough" dialysis and how to make sure each person is getting that. Quite a bit of this section is very technical, for example, the term "eKt/V" is often used: this is a calculation based on blood tests before and after dialysis, which measures the effectiveness of a single dialysis session in a particular patient. 2. This section deals with "non-standard" dialysis, which basically means anything other than 3 times per week. For example, a few people need 4 or more sessions per week to keep healthy, and some people are fine with only 2 sessions per week - this is usually people who are older, or those who have only just started dialysis. Special considerations for children and pregnant patients are also covered here. 3. This section deals with membranes (the type of "filter" used in the dialysis machine) and "HDF" (haemodiafiltration) which is a more complex kind of dialysis which some doctors think is better. Studies are still being done, but at the moment we think it's as good as but not better than regular dialysis. 4. This section deals with fluid removal during dialysis sessions: how to remove enough fluid without causing cramps and low blood pressure. Amongst other recommendations we advise close collaboration with patients over this. 5. This section deals with dialysate, which is the fluid used to "pull" toxins out of the blood (it is sometimes called the "bath"). The level of things like potassium in the dialysate is important, otherwise too much or too little may be removed. There is a section on dialysate buffer (bicarbonate) and also a section on phosphate, which occasionally needs to be added into the dialysate. 6. This section is about anticoagulation (blood thinning) which is needed to stop the circuit from clotting, but sometimes causes side effects. 7. This section is about certain safety aspects of dialysis, not seeking to replace well-established local protocols, but focussing on just a few where we thought some national-level guidance would be useful. 8. This section draws together a few aspects of dialysis which don't easily fit elsewhere, and which impact on how dialysis feels to patients, rather than the medical outcome, though of course these are linked. This is where home haemodialysis and exercise are covered. There is an appendix at the end which covers a few aspects in more detail, especially the mathematical ideas. Several aspects of dialysis are not included in this guideline since they are covered elsewhere, often because they are aspects which affect non-dialysis patients too. This includes: anaemia, calcium and bone health, high blood pressure, nutrition, infection control, vascular access, transplant planning, and when dialysis should be started.

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.

Dialysis modality choice in elderly patients with end-stage renal disease: a narrative review of the available evidence.

The number of elderly patients on maintenance dialysis has rapidly increased in the past few decades, particularly in developed countries, imposing a growing burden on dialysis centres. Hence, many nephrologists and healthcare authorities feel that greater emphasis should be placed on the promotion of home dialysis therapies such as peritoneal dialysis (PD) and home haemodialysis (HD). There is currently no general consensus as to the best dialysis modality for elderly patients with end-stage renal disease. In-centre HD is predominant in most countries, although it is widely recognized that PD has several advantages over HD, including the lack of need for vascular access, continuous slow ultrafiltration, less interference with patients' lifestyle and lower costs. Comparisons of outcomes between elderly patients on PD and HD rely on observational studies, as randomized controlled trials are lacking. The results of these studies are variable. However, most of them suggest that survival rates are largely similar between the two modalities, except for elderly patients with diabetes and/or beyond 1-3 years from dialysis initiation, in which cases HD appears to be superior. An equally important aspect to consider when choosing dialysis modality, particularly in this age group, is the quality of life, and in this regard most studies found no significant differences between PD and HD. In these circumstances, we believe that dialysis modality selection should be guided by patient's preference, based on comprehensive and unbiased information. A multidisciplinary team should review elderly patients starting on dialysis, aiming to identify possible barriers to PD and home HD, including physical, visual, cognitive, psychological and social problems, and to overcome such barriers by adequate care, education, psychological counselling and dialysis assistance.

Rationale and design of BISTRO: a randomized controlled trial to determine whether bioimpedance spectroscopy-guided fluid management maintains residual kidney function in incident haemodialysis patients.

BACKGROUND: Preserved residual kidney function (RKF) and normal fluid status are associated with better patient outcomes in incident haemodialysis patients. The objective of this trial is to determine whether using bioimpedance technology in prescribing the optimal post-dialysis weight can reduce the rate of decline of RKF and potentially improve patient outcomes. METHODS/DESIGN: 516 pateints commencing haemodialysis, aged >18 with RKF of > 3 ml/min/1.73 m2 or a urine volume >500 ml per day or per the shorter inter-dialytic period will be consented and enrolled into a pragmatic, open-label, randomized controlled trial. The intervention is incorporation of bioimpedance spectroscopy (BI) determination of normally hydrated weight to set a post-dialysis target weight that limits volume depletion, compared to current standard practice. Clinicians and participants will be blinded to BI measures in the control group and a standardized record capturing management of fluid status will be used in all participants. Primary outcome is preservation of residual kidney function assessed as time to anuria (≤100 ml/day or ≤200 ml urine volume in the short inter-dialytic period). A sample size of 516 was based upon a cumulative incidence of 30% anuria in the control group and 20% in the treatment group and 11% competing risks (death, transplantation) over 10 months, with up to 2 years follow-up. Secondary outcomes include rate of decline in small solute clearance, significant adverse events, hospitalization, loss of vascular access, cardiovascular events and interventions, dialysis efficacy and safety, dialysis-related symptoms and quality of life. Economic evaluation will be carried out to determine the cost-effectiveness of the intervention. Analyses will be adjusted for patient characteristics and dialysis unit practice patterns relevant to fluid management. DISCUSSION: This trial will establish the added value of undertaking BI measures to support clinical management of fluid status and establish the relationship between fluid status and preservation of residual kidney function in incident haemodialysis patients. TRIAL REGISTRATION: ISCCTN Number: 11342007 , completed 26/04/2016; NIHR Portfolio number: CPMS31766; Sponsor: Keele University.

A randomized controlled trial evaluating the erythropoiesis stimulating agent sparing potential of a vitamin E-bonded polysulfone dialysis membrane.

BACKGROUND: Vitamin E (VE) bonded polysulfone dialysis membranes have putative erythropoiesis stimulating agent (ESA)-sparing and anti-inflammatory properties based on data from a small number of studies. We sought to investigate this in a large, prospective 12-month randomized controlled trial. METHODS: Two-hundred and sixty prevalent haemodialysis (HD) patients were randomized to dialysis with VE-bonded polysulfone membranes or non-VE-bonded equivalents. All ESA-dosing was performed by means of a computer-based anaemia management decision support system. Monthly data were used to calculate the ESA resistance index (ERI) and blood tests were performed at baseline, 6 and 12 months for measurement of C-reactive protein (CRP) levels. RESULTS: Of the 260 patients, 123 were randomized to dialysis with the VE-membrane and 12-month data was available for 220 patients. At the study population level, no beneficial effect of the VE membranes on the ERI or CRP levels was observed. Post hoc analyses indicated that there was a significant fall in ERI for patients with the highest baseline ESA resistance dialysed with the VE (9.28 [7.70-12.5] versus 7.70 [5.34-12.7] IU/week/kg/g/dL Hb, P = 0.01) but not the control membranes (9.45 [7.62-12.3] versus 8.14 [4.44-15.6] IU/week/kg/g/dL Hb, P = 0.41); this was not attributable to changes in CRP levels. CONCLUSIONS: Wholesale switching of all chronic HD patients to dialysis with VE-bonded polysulfone membranes appears not to be associated with improvements in ESA-responsiveness or CRP. These membranes may have utility in patients with heightened ESA resistance.

Use of a standard urine assay for measuring the phosphate content of beverages.

Hyperphosphatemia is strongly associated with cardiovascular morbidity and mortality in patients with chronic kidney disease. Phosphate in beverages is readily absorbed and could have a significant impact on serum phosphate levels. Patients are routinely warned about the phosphoric acid in colas, but information on the phosphate content of other beverages is difficult to find. We have shown that the phosphomolybdate method, which is used in the vast majority of hospital laboratories for measuring phosphate in urine, can give an accurate measurement of the phosphate content of beer, cider, wine, and soft drinks. No change to the standard assay protocol is required. There was considerable variation between different types of wine and beer, probably due to the methods of production. The information the assay provides could enable staff providing dietary advice to compare locally available beverages and help patients to avoid or limit their intake of those with high phosphate content.

Dietary trends and management of hyperphosphatemia among patients with chronic kidney disease: an international survey of renal care professionals.

OBJECTIVE: The objective of this study was to review the opinions and experiences of renal care professionals to examine dietary trends among patients with chronic kidney disease (CKD) and problems associated with the clinical management of hyperphosphatemia. DESIGN: This was an online survey comprising open and closed questions requesting information on patient dietary trends and the clinical management of hyperphosphatemia. The study was conducted in 4 European countries (the Netherlands, Spain, Sweden, and the United Kingdom). SUBJECTS: Participants were 84 renal care professionals. INTERVENTION: This was an online survey. MAIN OUTCOME MEASURE: Responder-reported experiences and perceptions of patient dietary trends and hyperphosphatemia management were assessed. RESULTS: Most survey responders (56%) observed an increase in the consumption of processed convenience food, 48% noticed an increase in the consumption of foods rich in phosphorus-containing additives, and 60% believed that there has been a trend of increasing patient awareness of the phosphorus content of food. Patients undergoing hemodialysis (HD) were most likely to experience difficulties in following advice on dietary phosphorus restriction (38% of responders estimated that 25-50% of their patients experienced difficulties, and 29% estimated that 51-75% experienced difficulties). Maintaining protein intake and restricting dietary phosphorus were perceived as being equally important by at least half of responders for predialysis patients (56%) and for those undergoing peritoneal dialysis and HD (54% and 50%, respectively). There were international variations in dietary trends and hyperphosphatemia management. CONCLUSION: Although most responders have observed a trend of increasing awareness of the phosphorus content of food among patients with CKD, the survey results indicate that many patients continue to experience difficulties when attempting to restrict dietary phosphorus. The survey responses reflect the global trend of increasing consumption of processed convenience foods and phosphorus-containing additives, which has implications for the management of hyperphosphatemia in patients with CKD.

A predictive algorithm for the management of anaemia in haemodialysis patients based on ESA pharmacodynamics: better results for less work.

BACKGROUND: Many anaemia management algorithms recommend changes to erythropoiesis-stimulating agent (ESA) doses based on frequent measurement of haemoglobin levels in keeping with the ESA datasheets. We designed a predictive anaemia algorithm based on ESA pharmacodynamics, which we hoped would improve compliance with haemoglobin targets and reduce workload. METHODS: A new algorithm was designed which predicted the 3-month steady-state haemoglobin concentration following a change in ESA dose and only recommended a change if it was outside the range 10.5-12.5 g/dL. Data were collected prospectively for 3 months prior and 15 months subsequent to implementing the algorithm. RESULTS: A total of 214 prevalent dialysis patients were included in the audit. After 12 months, the haemoglobin concentration was 11.4 g/dL, near the midpoint of the target range, with a narrowing of the distribution (SD 1.46 to 1.25 g/dL, P < 0.0001). The proportion of patients with a haemoglobin level in the target range increased from 56% to 66% (P < 0.001) principally due to a reduction in the number of patients with high haemoglobin levels. There was no significant change in the ESA dose over the audit period. The number of prescription changes fell from 1/2.5 months to 1/6.1 months after 12 months (P < 0.001). CONCLUSIONS: Switching prevalent haemodialysis patients to a predictive anaemia management algorithm improved compliance with haemoglobin targets, reduced the number of patients with high haemoglobin levels and reduced the number of ESA dose changes required.

Monitoring residual kidney function in haemodialysis patients using timed urine collections: validation of the use of estimated blood results to calculate GFR.

Objective. With growing recognition of the benefits of preserving residual kidney function (RKF) and use of incremental treatment regimes, the incentive to measure residual clearance in haemodialysis patients is increasing. Interdialytic urine collections used to monitor RKF in research studies are considered impractical in routine care, partly due to the requirement for blood samples before and after the collection. Plasma solute levels can be estimated if patients are in 'steady state', where urea and creatinine concentrations increase at a constant rate between dialysis sessions and are reduced by a constant ratio at each session. Validation of the steady state assumption would allow development of simplified protocols for urine collections in HD patients.Approach. Equations were derived for estimating plasma urea and creatinine at the start or end of the interdialytic interval for patients in steady state. Data collected during the BISTRO study was used to assess the agreement between measured and estimated plasma levels and the effect of using estimated levels on the calculated glomerular filtration rate (GFR).Main results. The mean difference between GFR calculated with estimated plasma levels for the HD session after the collection and a full set of measured levels was 2.0% (95% limits of agreement -10.7% to +14.7%,N = 316). Where plasma levels for the session before the collection were estimated, the mean difference was 1.2% (limits of agreement -10.3% to +7.9%,N = 275).Significance. Using estimated levels for one session led to a clinically significant difference in the calculated GFR for less than 3% of the collections studied. This indicates that the steady state assumption can be used to estimate solute levels when determining GFR from timed urine collections. A pragmatic approach to monitoring RKF in HD would be for patients to collect for approximately 24 h before routine bloods are taken.

A comparison of methods for determining urea distribution volume for routine use in on-line monitoring of haemodialysis adequacy.

BACKGROUND: The availability of haemodialysis machines equipped with on-line clearance monitoring (OCM) allows frequent assessment of dialysis efficiency and adequacy without the need for blood samples. Accurate estimation of the urea distribution volume 'V' is required for Kt/V calculated from OCM to be consistent with conventional blood sample-based methods. METHODS: Ten stable HD patients were monitored monthly for 6 months. Time-averaged OCM clearance (K(OCM)) and pre- and post-dialysis blood samples were collected at each monitored session. The second generation Daugirdas formula was used to calculate the single-pool variable volume Kt/V, (Kt/V)(D). Values of V to allow comparison between OCM and blood-based Kt/V were determined from Watson's formula (V(Watson)), bioimpedance spectroscopy (V(BIS)), classical urea kinetic modelling (V(UKM_C)) and a simple computation of V (V(UKM_S)) from the blood-based Kt/V and K(OCM)t. RESULTS: Comparison of K(OCM)t/V with (Kt/V)(D) shows that using V(Watson) leads to significant systematic underestimation of dialysis dose. K(OCM)t/V(BIS) agrees with (Kt/V)(D) to within +/- 10%. K(OCM)t/V(UKM_S) is, by definition, identical to (Kt/V)(D) when initially calculated. However, if a historical value of V is used, agreement between K(OCM)t/V and (Kt/V)(D) over 6 months varies by 5% for V(BIS) and 10% for V(UKM_S). CONCLUSIONS: When investigating the effect of different treatment strategies on dialysis efficiency, any estimate of V can be used provided it is constant, as K is the relevant parameter. When frequent supervision of actual dialysis dose is required, the greatest consistency between K(OCM)t/V and the reference, Kt/V(D), over time is achieved with V(BIS).

Reducing sodium intake in hemodialysis patients.

A low salt diet is beneficial for the whole population but has particular advantages for hemodialyis patients because of the role of salt restriction in the management of hypertension and interdialytic weight gain (IDWG). Education on dietary salt intake based on general healthy eating guidelines, such as the "DASH-sodium" diet, should be provided for staff, families, and carers as well as patients. Anuric hemodialysis patients will need to take in approximately 1 l of water for every 8 g salt consumed. Patients who restrict salt intake to <6 g/day, and drink only when thirsty, should gain no more than 0.8 kg/day. Those with significantly greater weight gains, but predialysis serum sodium close to or higher than the dialysate sodium, need further review of their salt intake. Attempts to restrict fluid intake in these patients will be futile. Patients with high interdialytic weight gain (IDWG) and low predialysis sodium should be assessed for other reasons for fluid intake, such as high blood glucose or social drinking. For patients with poor tolerance of fluid removal during dialysis, and those who are hypertensive in the absence of fluid overload, a salt intake 5 g/day or less may be required. Dietary advice for these patients should be customized to ensure that they do not become malnourished.

European best practice quo vadis? From European Best Practice Guidelines (EBPG) to European Renal Best Practice (ERBP).

Although medical guidelines generally are graded according to their evidence level, low evidence 'judgement' are generally perceived as much as absolute truth by the medical community as high evidence 'guidelines' are. Being aware of this bias, a workgroup appointed by the European Renal Association-European Dialysis and Transplantation Association (ERA-EDTA), the members of which are the authors of the current publication, decided that European nephrology guidelines issued by the Association should be published only as 'guidelines' in the case of high-level evidence; otherwise they should be named 'recommendations' or 'position statements' and be published in a different format. Acknowledging that in nephrology, high levels of evidence are often lacking, it was also decided to rename the responsible body from European Best Practice Guidelines (EBPG) to European Renal Best Practice (ERBP). The present publication reviews the arguments based on which this decision was taken.

Time to Reconsider the Role of Relative Blood Volume Monitoring for Fluid Management in Hemodialysis.

Relative blood volume (RBV) monitoring during hemodialysis has been used to help guide fluid management for decades, although with little supporting evidence. The technique relies on the assumption that variation in RBV during fluid removal reflects the capacity for vascular refilling and that efficient refilling is related to fluid overload. This study investigated the relationship between RBV variation and bioimpedance-based fluid overload in 47 patients on stable hemodialysis. Mean treatment ultrafiltration volume (UFV) was 1.7 L and RBV reduction was 3.2%/hour. Relative blood volume slopes were grouped based on trajectory: flatline (no decrease), linear decrease, or linear decrease followed by flatline. Fluid overload was similar (p > 0.05) across groups pre-dialysis (1.0, 2.2, and 1.6 L, respectively) and post-dialysis (-0.8, -0.1, and -0.1 L), whereas UFV was higher in patients with a linear decrease (1.8, 2.5, and 1.6 L; p = 0.02). Specific ultrafiltration rate, but not fluid overload, was associated with RBV change over dialysis. At least half the patients in each group finished dialysis fluid depleted based on bioimpedance, suggesting that the link between refilling and fluid overload is not as straightforward as previously assumed. These results question the assumptions that the absence of an appreciable decrease in RBV indicates fluid overload, and a rapid fall suggests fluid depletion.