Hyponatraemia and fluid overload are associated with higher risk of mortality in dialysis patients.

BACKGROUND: The 5-year mortality rate for haemodialysis patients is over 50%. Acute and chronic disturbances in salt and fluid homeostasis contribute to poor survival and are established as individual mortality risk factors. However, their interaction in relation to mortality is unclear. METHODS: We used the European Clinical Database 5 to investigate in a retrospective cohort analysis the relationship between transient hypo- and hypernatremia, fluid status and mortality risk of 72 163 haemodialysis patients from 25 countries. Incident haemodialysis patients with at least one valid measurement of bioimpedance spectroscopy were followed until death or administrative censoring from 1 January 2010 to 4 December 2019. Fluid overload and depletion were defined as >2.5 L above, and -1.1 L below normal fluid status, respectively. N = 2 272 041 recorded plasma sodium and fluid status measurements were available over a monthly time grid and analysed in a Cox regression model for time-to-death. RESULTS: Mortality risk of hyponatremia (plasma sodium <135 mmol/L) was slightly increased when fluid status was normal [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.18-1.35], increased by half when patients were fluid depleted (HR 1.56, 95% CI 1.27-1.93) and accelerated during fluid overload (HR 1.97, 95% CI 1.82-2.12). CONCLUSIONS: Plasma sodium and fluid status act independently as risk factors on mortality. Patient surveillance of fluid status is especially important in the high-risk subpopulation of patients with hyponatremia. Prospective patient-level studies should examine the effects of chronic hypo- and hypernatremia, risk determinants, and their outcome risk.

Prevalence of fluid overload in an urban US hemodialysis population: A cross-sectional study.

INTRODUCTION: Inadequate fluid status remains a key driver of cardiovascular morbidity and mortality in chronic hemodialysis (HD) patients. Quantification of fluid overload (FO) using bioimpedance spectroscopy (BIS) has become standard in many countries. To date, no BIS device has been approved in the United States for fluid status assessment in kidney patients. Therefore, no previous quantification of fluid status in US kidney patients using BIS has been reported. Our aim was to conduct a cross-sectional BIS-based assessment of fluid status in an urban US HD population. METHODS: We determined fluid status in chronic HD patients using whole body BIS (Body Composition Monitor, BCM). The BCM reports FO in liters; negative FO denotes fluid depletion. Measurements were performed before dialysis. Post-HD FO was estimated by subtracting the intradialytic weight loss from the pre-HD FO. FINDINGS: We studied 170 urban HD patients (age 61 ± 14 years, 60% male). Pre- and post-HD FO (mean ± SD), were 2.2 ± 2.4 and -0.2 ± 2.7 L, respectively. Pre-HD, 43% of patients were fluid overloaded, 53% normally hydrated, and 4% fluid depleted. Post-HD, 12% were fluid overloaded, 55% normohydrated and 32% fluid depleted. Only 48% of fluid overloaded patients were hypertensive, while 38% were normotensive and 14% hypotensive. Fluid status did not differ significantly between African Americans (N = 90) and Caucasians (N = 61). DISCUSSION: While about half of the patients had normal fluid status pre-HD, a considerable proportion of patients was either fluid overloaded or depleted, indicating the need for tools to objectively quantify fluid status.

Sodium, volume and pressure control in haemodialysis patients for improved cardiovascular outcomes.

Chronic volume overload is pervasive in patients on chronic haemodialysis and substantially increases the risk of cardiovascular death. The rediscovery of the three-compartment model in sodium metabolism revolutionizes our understanding of sodium (patho-)physiology and is an effect modifier that still needs to be understood in the context of hypertension and end-stage kidney disease. Assessment of fluid overload in haemodialysis patients is central yet difficult to achieve, because traditional clinical signs of volume overload lack sensitivity and specificity. The highest all-cause mortality risk may be found in haemodialysis patients presenting with high fluid overload but low blood pressure before haemodialysis treatment. The second highest risk may be found in patients with both high blood pressure and fluid overload, while high blood pressure but normal fluid overload may only relate to moderate risk. Optimization of fluid overload in haemodialysis patients should be guided by combining the traditional clinical evaluation with objective measurements such as bioimpedance spectroscopy in assessing the risk of fluid overload. To overcome the tide of extracellular fluid, the concept of time-averaged fluid overload during the interdialytic period has been established and requires possible readjustment of a negative target post-dialysis weight. 23Na-magnetic resonance imaging studies will help to quantitate sodium accumulation and keep prescribed haemodialytic sodium mass balance on the radar. Cluster-randomization trials (e.g. on sodium removal) are underway to improve our therapeutic approach to cardioprotective haemodialysis management.

Using Bioimpedance Spectroscopy to Assess Volume Status in Dialysis Patients.

The aim of the paper is to reflect on the current status of bioimpedance spectroscopy (BIS) in fluid management in dialysis patients. BIS identifies fluid overload (FO) as a virtual (overhydration) compartment, which is calculated from the difference between the measured extracellular volume and the predicted values based on a fixed hydration of lean and adipose tissue mass. FO is highly prevalent in both hemodialysis (HD) and peritoneal dialysis (PD) patients, while levels of FO are at a population level comparable between PD patients and HD patients when measured before the dialysis treatment. Even mild levels of FO are independently related to outcome in patients on HD, PD as well as in nondialysis patients with advanced chronic kidney disease. FO is not only related to left ventricular hypertrophy (LVH) but also forms part of a multidimensional spectrum with noncardiovascular risk factors such as malnutrition and inflammation. Even after multiple adjustments, FO remains an independent predictor of mortality. BIS-assisted adjustment of dry weight in HD patients has been shown to improve hypertension control and LVH and has resulted in a decline in intradialytic symptomatology. On the other hand, with increased fluid removal, target weight may not always be reached due to an increase in intradialytic symptomatology, and care should be applied in target weight adjustment in fluid overloaded patients with severe malnutrition and/or inflammation. Although a reduction in hospitalization rate was suggested, the effect of BIS-guided dry weight adjustment on mortality has not yet been shown, however, although available studies are underpowered. In PD patients, results have been more equivocal, which may be partly related to differences in treatment protocols or study populations. Future large-scale studies are needed to assess the full potential of BIS.

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.

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.

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.

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.

Identificar situaciones de riesgo para los pacientes en hemodiálisis mediante la adecuada valoración de su composición corporal / Risk identification in haemodialysis patients by appropriate body composition assessment

Introducción Circunstancias como el género, la edad, la presencia de diabetes mellitus (DM) y la insuficiencia renal tienen impacto sobre la composición corporal de los pacientes. Sin embargo, a la hora de evaluar parámetros nutricionales como el tejido magro y graso de los pacientes en hemodiálisis (HD) se emplean valores de referencia provenientes de población sana. Objetivos: Analizar la composición corporal mediante bioimpedancia espectroscópica (BIS) de 6.395 pacientes en HD para obtener valores de referencia de índice de tejido magro (ITM) y de índice de tejido graso (ITG) procedentes de pacientes en HD y confirmar su validez al demostrar que aquellos con un ITM por debajo del percentil 10 calculado para su grupo tienen mayor riesgo de muerte. Material y métodos Usamos la BIS para determinar el ITM e ITG de nuestra cohorte de pacientes en HD en España. Calculamos el percentil 10 y el percentil 90 del ITM e ITG en cada decil de edad de pacientes, agrupados según su género y presencia de DM. Recogemos parámetros clínicos, analíticos y demográficos. Resultados: Objetivamos que los valores del percentil 10 y del 90 de ITM/ITG varían en función del grupo (edad, género y presencia de DM) y que, tras ajustar por otros factores de riesgo como la sobrehidratación, los pacientes con ITM inferior al percentil 10 tienen mayor riesgo relativo de muerte (OR 1,57) que aquellos con valores superiores. Conclusiones: Monitorizar el ITM e ITG de los pacientes en HD CON adecuados valores de referencia puede ser útil para identificar situaciones de riesgo en los pacientes en HD (AU)

Introduction: Circumstances such as gender, age, diabetes mellitus (DM) and renal failure impact on the body composition of patients. However, we use nutritional parameters such as lean and fat tissue with reference values from healthy subjects to assess the nutritional status of haemodialysis (HD) patients. Aims: To analyse body composition by bioimpedance spectroscopy (BIS) of 6395 HD patients in order to obtain reference values of lean tissue index (LTI) and fat tissue index (FTI) from HD patients; and to confirm its validity by showing that those patients with LTI below the 10th percentile calculated for their group have greatest risk of death. Material and methods: We used the BIS to determine the LTI and FTI in our cohort of HD patients in Spain. We calculated the 10th percentile and 90th percentile of LTI and FTI in each age decile for patients grouped by gender and presence of DM. We collected clinical, laboratory and demographic parameters. Results: The LTI/FTI 10 and 90 percentile values varied by group (age, gender and presence of DM) and, after adjusting for other risk factors such as fluid overload, those patients with LTI lower than percentile 10 had a higher relative risk of death (OR 1.57) than those patients with higher values. Conclusions: Monitoring the LTI and FTI of patients on HD using suitable reference values may help to identify risk in this patient population (AU)

Ultra-long-term human salt balance studies reveal interrelations between sodium, potassium, and chloride intake and excretion.

BACKGROUND: The intake of sodium, chloride, and potassium is considered important to healthy nutrition and cardiovascular disease risk. Estimating the intake of these electrolytes is difficult and usually predicated on urine collections, commonly for 24 h, which are considered the gold standard. We reported on data earlier for sodium but not for potassium or chloride. OBJECTIVE: We were able to test the value of 24-h urine collections in a unique, ultra-long-term balance study conducted during a simulated trip to Mars. DESIGN: Four healthy men were observed while ingesting 12 g salt/d, 9 g salt/d, and 6 g salt/d, while their potassium intake was maintained at 4 g/d for 105 d. Six healthy men were studied while ingesting 12 g salt/d, 9 g salt/d, and 6 g salt/d, with a re-exposure of 12 g/d, while their potassium intake was maintained at 4 g/d for 205 d. Food intake and other constituents were recorded every day for each subject. All urine output was collected daily. RESULTS: Long-term urine recovery rates for all 3 electrolytes were very high. Rather than the expected constant daily excretion related to daily intake, we observed remarkable daily variation in excretion, with a 7-d infradian rhythm at a relatively constant intake. We monitored 24-h aldosterone excretion in these studies and found that aldosterone appeared to be the regulator for all 3 electrolytes. We report Bland-Altman analyses on the value of urine collections to estimate intake. CONCLUSIONS: A single 24-h urine collection cannot predict sodium, potassium, or chloride intake; thus, multiple collections are necessary. This information is important when assessing electrolyte intake in individuals.

Risk identification in haemodialysis patients by appropriate body composition assessment. / Identificar situaciones de riesgo para los pacientes en hemodiálisis mediante la adecuada valoración de su composición corporal.

INTRODUCTION: Circumstances such as gender, age, diabetes mellitus (DM) and renal failure impact on the body composition of patients. However, we use nutritional parameters such as lean and fat tissue with reference values from healthy subjects to assess the nutritional status of haemodialysis (HD) patients. AIMS: To analyse body composition by bioimpedance spectroscopy (BIS) of 6395 HD patients in order to obtain reference values of lean tissue index (LTI) and fat tissue index (FTI) from HD patients; and to confirm its validity by showing that those patients with LTI below the 10th percentile calculated for their group have greatest risk of death. MATERIAL AND METHODS: We used the BIS to determine the LTI and FTI in our cohort of HD patients in Spain. We calculated the 10th percentile and 90th percentile of LTI and FTI in each age decile for patients grouped by gender and presence of DM. We collected clinical, laboratory and demographic parameters. RESULTS: The LTI/FTI 10 and 90 percentile values varied by group (age, gender and presence of DM) and, after adjusting for other risk factors such as fluid overload, those patients with LTI lower than percentile 10 had a higher relative risk of death (OR 1.57) than those patients with higher values. CONCLUSIONS: Monitoring the LTI and FTI of patients on HD using suitable reference values may help to identify risk in this patient population.

The forgotten role of central volume in low frequency oscillations of heart rate variability.

The hypothesis that central volume plays a key role in the source of low frequency (LF) oscillations of heart rate variability (HRV) was tested in a population of end stage renal disease patients undergoing conventional hemodialysis (HD) treatment, and thus subject to large fluid shifts and sympathetic activation. Fluid overload (FO) in 58 chronic HD patients was assessed by whole body bioimpedance measurements before the midweek HD session. Heart Rate Variability (HRV) was measured using 24-hour Holter electrocardiogram recordings starting before the same HD treatment. Time domain and frequency domain analyses were performed on HRV signals. Patients were retrospectively classified in three groups according to tertiles of FO normalized to the extracellular water (FO/ECW%). These groups were also compared after stratification by diabetes mellitus. Patients with the low to medium hydration status before the treatment (i.e. 1st and 2nd FO/ECW% tertiles) showed a significant increase in LF power during last 30 min of HD compared to dialysis begin, while no significant change in LF power was seen in the third group (i.e. those with high pre-treatment hydration values). In conclusion, several mechanisms can generate LF oscillations in the cardiovascular system, including baroreflex feedback loops and central oscillators. However, the current results emphasize the role played by the central volume in determining the power of LF oscillations.

Season affects body composition and estimation of fluid overload in haemodialysis patients: variations in body composition; a survey from the European MONDO database.

BACKGROUND: Seasonal variations in blood pressure (BP) and inter-dialytic weight gain (IDWG) are well established in dialysis patients. However, no study has assessed changes in body composition (BC) in this population. METHODS: In this survey, seasonal variations in fat mass (FM), lean tissue mass (LTM), extracellular water (ECW) and fluid overload (FO) were assessed in 42 099 dialysis patients (mean age 61.2 years, 58% males) from the Fresenius Medical Care Europe database, as part of the MONitoring Dialysis Outcomes (MONDO) consortium, in relation to other nutritional parameters, IDWG and BP. BC was assessed by a body composition monitor (BCM®, Fresenius Medical Care, Bad Homburg, Germany). RESULTS: FM was highest in winter and lowest in summer (▵FM -1.17 kg; P < 0.001), whereas LTM was lowest during winter and highest in summer (▵LTM 0.86 kg; P < 0.0001). ECW and FO were lowest in winter, and highest in spring (▵ECW: 0.13 L; P < 0.0001, ▵FO: 0.31 L; P < 0.0001) and summer (▵ECW: 0.15 L; P < 0.0001 and ▵FO: 0.2 L; P < 0.0001), despite a higher systolic blood pressure (SBP; 136.7 ± 17.4 mmHg) and IDWG (3.0 ± 1.1 kg) during winter. C-reactive protein (CRP), serum sodium and haemoglobin levels were highest in winter, whereas serum albumin was lowest in fall. Normalized protein catabolic rate (nPCR) was lowest in winter and matched variations in BC only to a minor degree. CONCLUSIONS: BC and hydration state, assessed by bio-impedance spectroscopy, follows a seasonal pattern which may be of relevance for the estimation of target weight, and for the interpretation of longitudinal studies including estimates of BC. Whether these changes should lead to therapeutic interventions could be the focus of future studies.

Effects of fluid overload on heart rate variability in chronic kidney disease patients on hemodialysis.

BACKGROUND: While fluid overload (FO) and alterations in the autonomic nervous system (ANS) such as hypersympathetic activity, are known risk factors for cardiovascular morbidity and mortality in patients on chronic hemodialysis (HD), their relationship has not been thoroughly studied. METHODS: In this observational study involving 69 patients on chronic HD, FO was assessed by whole body bioimpedance measurements before the midweek HD session and ANS activity reflected by Heart Rate Variability (HRV) was measured using 24-hour Holter electrocardiogram recordings starting before the same HD treatment. In total, 13 different HRV indices were analyzed, comprising a mixture of time domain, frequency domain and complexity parameters. A correlation analysis was performed between the HRV indices and hydration status indices. Successively, patients were retrospectively assigned to a high FO (H, FO > 2.5 L) or low FO (L, FO ≤ 2.5 L) group and these were further compared also after stratification by diabetes mellitus. Finally, a small number of patients without diabetes with significant and persistent FO were followed up for 3 months post-study to investigate how normalization of fluid status affects HRV. RESULTS: SDANN, VLF, LZC and HF% parameters significantly correlate with FO (correlation coefficients were respectively r = -0.40, r = -0.37, r = -0.28 and r = 0.26, p-value < 0.05). Furthermore, LF% and LF/HF were inversely correlated with hydration status (correlation coefficients were respectively r = -0.31 and r = -0.33, p-value < 0.05). These results indicate an association between FO and reduced HRV, higher parasympathetic activation and reduced sympathetic response to the HD session. Indeed, group H tended to have lower values of SDANN, VLF and LZC, and higher values of HF% than patients in the L group. Finally, there was a trend towards lower LF% measured during the last 30 minutes of HD for the H group versus the L group. Reduction in FO achieved over 3 months by implementation of a strict fluid management plan resulted in an increase of HRV. CONCLUSIONS: Our results suggest that depressed HRV is associated with fluid overload and that normalization of hydration status is accompanied by improved HRV.

Bioimpedance-guided fluid management in hemodialysis patients.

BACKGROUND AND OBJECTIVES: Achieving and maintaining optimal fluid status remains a major challenge in hemodialysis therapy. The aim of this interventional study was to assess the feasibility and clinical consequences of active fluid management guided by bioimpedance spectroscopy in chronic hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Fluid status was optimized prospectively in 55 chronic hemodialysis patients over 3 months (November 2011 to February 2012). Predialysis fluid overload was measured weekly using the Fresenius Body Composition Monitor. Time-averaged fluid overload was calculated as the average between pre- and postdialysis fluid overload. The study aimed to bring the time-averaged fluid overload of all patients into a target range of 0.5 ± 0.75 L within the first month and maintain optimal fluid status until study end. Postweight was adjusted weekly according to a predefined protocol. RESULTS: Time-averaged fluid overload in the complete study cohort was 0.9 ± 1.6 L at baseline and 0.6 ± 1.1 L at study end. Time-averaged fluid overload decreased by -1.20 ± 1.32 L (P<0.01) in the fluid-overloaded group (n=17), remained unchanged in the normovolemic group (n=26, P=0.59), and increased by 0.59 ± 0.76 L (P=0.02) in the dehydrated group (n=12). Every 1 L change in fluid overload was accompanied by a 9.9 mmHg/L change in predialysis systolic BP (r=0.55, P<0.001). At study end, 76% of all patients were either on time-averaged fluid overload target or at least closer to target than at study start. The number of intradialytic symptoms did not change significantly in any of the subgroups. CONCLUSIONS: Active fluid management guided by bioimpedance spectroscopy was associated with an improvement in overall fluid status and BP.

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.

Long-term space flight simulation reveals infradian rhythmicity in human Na(+) balance.

The steady-state concept of Na(+) homeostasis, based on short-term investigations of responses to high salt intake, maintains that dietary Na(+) is rapidly eliminated into urine, thereby achieving constant total-body Na(+) and water content. We introduced the reverse experimental approach by fixing salt intake of men participating in space flight simulations at 12 g, 9 g, and 6 g/day for months and tested for the predicted constancy in urinary excretion and total-body Na(+) content. At constant salt intake, daily Na(+) excretion exhibited aldosterone-dependent, weekly (circaseptan) rhythms, resulting in periodic Na(+) storage. Changes in total-body Na(+) (±200-400 mmol) exhibited longer infradian rhythm periods (about monthly and longer period lengths) without parallel changes in body weight and extracellular water and were directly related to urinary aldosterone excretion and inversely to urinary cortisol, suggesting rhythmic hormonal control. Our findings define rhythmic Na(+) excretory and retention patterns independent of blood pressure or body water, which occur independent of salt intake.

Optimal fluid control can normalize cardiovascular risk markers and limit left ventricular hypertrophy in thrice weekly dialysis patients.

Increased hemodialysis frequency can make fluid overload easier to treat, although most patients are still treated thrice weekly. Chronic fluid overload is associated with left ventricular hypertrophy and elevated serum cardiac biomarkers, recognized as mortality risk factors. Serum cardiac troponin T (cTnT), N-terminal prohormone brain natriuretic peptide (NT-proBNP), left ventricular mass index by cardiac magnetic imaging, and ambulatory blood pressure was measured in 30 thrice weekly hemodiafiltration patients. Time-averaged fluid overload (TAFO) was quantified by bioimpedance spectroscopy. In the study group, left ventricular hypertrophy was found to be 26% by cardiac magnetic resonance. Ambulatory blood pressure was 130 mmHg (112-151) requiring a low equivalent dose of medication of 0.25 units (0-1). Significantly, lower levels of left ventricular mass index (P < 0.05) were associated in those patients with TAFO <1 L or NT-proBNP <1200 pg/mL or cTnT <0.1 ug/L. In the subgroups, 16 patients had normal cTnT (<0.03 ug/L), 16 patients had NT-proBNP <400 pg/mL, and 20 patients had TAFO <1 L. Nine patients had both cTnT <0.03 ug/L and NT-proBNP <400 pg/mL. Normally hydrated thrice-weekly hemodiafiltration patients can have cardiac biomarker and TAFO levels indistinguishable from the normal healthy population. Obtaining TAFO by bioimpedance monitoring can offer a practical alternative to serum cardiac biomarkers.

Blood pressure variability and cardiovascular autonomic control during hemodialysis in peripheral vascular disease patients.

Hemodialysis (HD) patients with peripheral vascular disease (PVD) are at higher risk of mortality. The main objectives of this work were to investigate the hypothesis of an association between the PVD and an altered control system on peripheral resistance in response to volume depletion induced by HD treatment; and to investigate whether HD induced increase of pulse pressure (PP) is associated with PVD. Continuous blood pressure (BP) was recorded during HD treatment at the beginning and at the end of HD. The overhydration condition was evaluated by means of whole body bioimpedance spectroscopy, measured before each HD treatment. BP variability, heart rate variability and baroreflex sensitivity were then analyzed. Patients affected by PVD reported a prevalence of peripheral local control as shown by higher values of very low frequency in diastolic blood pressure (DBP) variability and a reduced cardiac baroreflex with respect to patients not affected by this pathology. HD treatment induced a significant increase of PP and LF% in DBP series in PVD patients only. Our results suggested that differences in BP variability and PP changes could be related not only to an underlying vascular disease, but also to an alteration in autonomic control.