Paul Chamney

The mortality risk of overhydration in haemodialysis patients

Background. While cardiovascular events remain the primary form of mortality in haemodialysis (HD) patients, few centres are aware of the impact of the hydration status (HS). The aim of this study was to investigate how the magnitude of the prevailing overhydration influences long-term survival. Methods. We measured the hydration status in 269 prevalent HD patients (28% diabetics, dialysis vintage = 41.2 ± 70 months) in three European centres with a body composition monitor (BCM) that enables quantitative assessment of hydration status and body composition. The survival of these patients was ascertained after a follow-up period of 3.5 years. The cut off threshold for the definition of hyperhydration was set to 15% relative to the extracellular water (ECW), which represents an excess of ECW of ∼2.5 l. Cox-proportional hazard models were used to compare survival according to the baseline hydration status for a set of demographic data, comorbid conditions and other predictors. Results. The median hydration state (HS) before the HD treatment (ΔHSpre) for all patients was 8.6 ± 8.9%. The unadjusted gross annual mortality of all patients was 8.5%. The hyperhydrated subgroup (n = 58) presented ΔHSpre = 19.9 ± 5.3% and a gross mortality of 14.7%. The Cox adjusted hazard ratios (HRs) revealed that age (HRage = 1.05, 1/year; P < 0.001), systolic blood pressure (BPsys) (HRBPsys = 0.986 1/mmHg; P = 0.014), diabetes (HRDia = 2.766; P < 0.001), peripheral vascular disease (PVD) (HRPVD = 1.68; P = 0.045) and relative hydration status (ΔHSpre) (HRΔHSpre = 2.102 P = 0.003) were the only significant predictors of mortality in our patient population. Conclusion. The results of our study indicate that the hydration state is an important and independent predictor of mortality in chronic HD patients secondary only to the presence of diabetes. We believe that it is essential to measure the hydration status objectively and quantitatively in order to obtain a more clearly defined assessment of the prognosis of haemodialysis patients.

Body fluid volume determination via body composition spectroscopy in health and disease

The assessment of extra-, intracellular and total body water (ECW, ICW, TBW) is important in many clinical situations. Bioimpedance spectroscopy (BIS) has advantages over dilution methods in terms of usability and reproducibility, but a careful analysis reveals systematic deviations in extremes of body composition and morbid states. Recent publications stress the need to set up and validate BIS equations in a wide variety of healthy subjects and patients with fluid imbalance. This paper presents two new equations for determination of ECW and ICW (referred to as body composition spectroscopy, BCS) based on Hanai mixture theory but corrected for body mass index (BMI). The equations were set up by means of cross validation using data of 152 subjects (120 healthy subjects, 32 dialysis patients) from three different centers. Validation was performed against bromide/deuterium dilution (NaBr, D2O) for ECW/TBW and total body potassium (TBK) for ICW. Agreement between BCS and the references (all subjects) was -0.4 +/- 1.4 L (mean +/- SD) for ECW, 0.2 +/- 2.0 L for ICW and -0.2 +/- 2.3 L for TBW. The ECW agreement between three independent reference methods (NaBr versus D2O-TBK) was -0.1 +/- 1.8 L for 74 subjects from two centers. Comparing the new BCS equations with the standard Hanai approach revealed an improvement in SEE for ICW and TBW by 0.6 L (24%) for all subjects, and by 1.2 L (48%) for 24 subjects with extreme BMIs (<20 and >30). BCS may be an appropriate method for body fluid volume determination over a wide range of body compositions in different states of health and disease.

Importance of Whole-Body Bioimpedance Spectroscopy for the Management of Fluid Balance

Introduction: Achieving normohydration remains a non-trivial issue in haemodialysis therapy. Preventing the deleterious effects of fluid overload and dehydration is difficult to achieve. Objective and clinically applicable methods for the determination of a target representing normohydration are needed. Methods: Whole-body bioimpedance spectroscopy (50 frequencies, 5–1,000 kHz) in combination with a physiologic tissue model can provide an objective target for normohydration based on the concept of excess extracellular volume. We review the efficacy of this approach in a number of recent clinical applications. The accuracy to determine fluid volumes (e.g. extracellular water), body composition (e.g. fat mass) and fluid overload was evaluated in more than 1,000 healthy individuals and patients against available gold standard reference methods (e.g. bromide, deuterium, dual-energy X-ray absorptiometry, air displacement plethysmography, clinical assessment). Results: The comparison with gold standard methods showed excellent accordance [e.g. R2 (total body water) = 0.88; median ± SD (total body water) = –0.17 ± 2.7 litres]. Agreement with high-quality clinical assessment of fluid status was demonstrated in several hundred patients (median ± SD = –0.23 ± 1.5 litres). The association between ultrafiltration volume and change in fluid overload was reflected well by the method (median ± SD = 0.015 ± 0.8 litres). The predictive value of fluid overload on mortality underlines forcefully the clinical relevance of the normohydration target, being secondary only to the presence of diabetes. The objective normohydration target could be achieved in prevalent haemodialysis patients leading to an improvement in hypertension and reduction of adverse events. Conclusion: Whole-body bioimpedance spectroscopy in combination with a physiologic tissue model provides for the first time an objective and relevant target for clinical dry weight assessment.

Towards improved cardiovascular management: the necessity of combining blood pressure and fluid overload

BACKGROUND Hypertension and fluid overload (FO) are well-recognized problems in the chronic kidney disease (CKD) population. While the prevalence of hypertension is well documented, little is known about the severity of FO in this population. METHODS A new bioimpedance spectroscopy device (BCM-Body Composition Monitor) was selected that allows quantitative determination of the deviation in hydration status from normal ranges (DeltaHS). Pre-dialysis systolic blood pressure (BPsys) and DeltaHS was analysed in 500 haemodialysis patients from eight dialysis centres. A graphical tool (HRP-hydration reference plot) was devised allowing DeltaHS to be combined with measurements of BPsys enabling comparison with a matched healthy population (n = 1244). RESULTS Nineteen percent of patients (n = 95) were found to have normal BPsys and DeltaHS in the normal range. Approximately one-third of patients (n = 133) exhibited reasonable control of BPsys and fluids (BPsys <150 mmHg and DeltaHS <2.5 L). In only 15% of patients (n = 74) was hypertension observed (BPsys >150 mmHg) with a concomitant DeltaHS >2.5 L (possible volume-dependent hypertension). In contrast, 13% of patients (n = 69) were hypertensive with DeltaHS <1.1 L (possible essential hypertension). In 10% of patients (n = 52), BPsys <140 mmHg was recorded despite DeltaHS exceeding 2.5 L. CONCLUSION Our study illustrated the wide variability in BPsys regardless of the degree of DeltaHS. The HRP provides an invaluable tool for classifying patients in terms of BPsys and DeltaHS and the proximity of these parameters to reference ranges. This represents an important step towards more objective choice of strategies for the optimal treatment of hypertension and FO. Further studies are required to assess the prognostic and therapeutic role of the HRP.

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.

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.

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.

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.

Use of the Body Composition Monitor for Fluid Status Measurements in Subjects with High Body Mass Index

Background: Fluid management is a central aspect of haemodialysis (HD). Body composition monitor (BCM)-measured overhydration (OH) can improve fluid management strategies, but there remains uncertainty about its use in subjects with high body mass index (BMI). This study explored whether the observed tendency for HD patients with high BMI to complete dialysis fluid depleted according to BCM is associated with an artefact in the BCM models, or with systematic differences in the prescription and delivery of treatment. Methods: To isolate the effect of BMI from effects relating to treatment, BCM measurements were made on 20 healthy subjects with high BMI. Mean OH was compared with a previously reported cohort of healthy subjects with normal BMI. To further explore BCM-measured OH in HD patients, measurements were made pre- and post-dialysis on 10 patients with high BMI alongside relative blood volume monitoring. Body shape was classified to assess associations between shape and OH. Results: The mean OH for healthy subjects with high BMI was -0.1 litres, which was not different from that of healthy subjects with normal BMI. Median BCM-measured OH for HD patients was 1.8 and -1.8 litres pre- and post-dialysis respectively, while blood volume and blood pressure were maintained. Body shape correlated with OH in control subjects but not HD patients. Conclusions: We found no evidence of systematic bias in BCM-measured OH with high BMI in healthy subjects. BCM-measured post-dialysis fluid depletion in asymptomatic patients with high BMI appears to result from greater tolerance of ultrafiltration and ability to maintain blood volume.

Reconstruction of venous pressure in haemodialysis patients

Blood pressure instability is the most frequent complication of haemodialysis treatments, Individualised control of fluid removal that takes into account impaired physiological responses, is the key to improved stability. The cardiopulmonary reflex, the first line of defence to prevent hypotension caused by hypovolaemia, is mainly dependant on the central venous pressure (CVP). Until now only invasive methods are available for the measurement of CVP. A system for observing the venous pressure based on cardiac output, blood pressure and heart rate measurements combined with additional information about the patients heart condition (hypertrophy and contractility) was developed, The core of this system is an inverted non-pulsatile model of the heart which enables the reconstruction of the venous pressure. A cross cheek of the calculated venous pressure values by using relative blood volume measurements was applied to 12 different patients. The reconstructed venous pressure is linearly volume dependent and stays inside the known physiological range. It decreases during the dialysis treatment from very high values (12 mmHg) in the heavily fluid overloaded stage, towards near normal values (3 mmHg) when reaching dry weight. The results are reproducible and patient specific. The venous pressure can be used as a much better indicator for oncoming hypotension episodes then the mean arterial pressure.