Ulrich Moissl

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 approximately 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 (DeltaHSpre) 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 DeltaHSpre = 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 (DeltaHSpre) (HRDeltaHSpre = 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.

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.

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 (&lt;130, 130–160, and &gt;160 mmHg), with nonoverhydrated patients with syst-BP=130–160 mmHg as the reference category; &gt;200,000 FO measurements were performed over follow-up. Baseline FO value predicted excess risk of mortality across syst-BP categories (&lt;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; &gt;160 mmHg: HR, 1.30; 95% CI, 1.19 to 1.42; all P &lt;0.001). However, cumulative 1-year FO exposure predicted a higher death risk ( P &lt;0.001) across all syst-BP categories (&lt;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; &gt;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.

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. R(2) (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.