Breath Analysis and the Measurement of Total Body Water Using Isotope Dilution - Applications in the Dialysis Clinic

Determination of fluid status in patients suffering from kidney failure presents particular challenges. In addition to the failure of homeostatic mechanisms controlling fluid status their chronic disease and associated comorbid conditions disturb body composition, for example by causing muscle wasting or obesity. Accurate assessment of fluid status at the bedside would likely inform better clinical decision making. To facilitate this, a near patient method for determining the total body water (TBW) was developed. Following ingestion of a known amount of D2O, which equilibrates as HDO the TBWD is determined using the dilution principle. Flowing afterglow mass spectrometry accurately measures the concentration of HDO in either breath or the headspace of fluids (e.g. dialysate) enabling immediate calculation of TBW without the need for laboratory measurements. A series of clinical studies was undertaken to establish the validity of the method, especially for longitudinal measurements and in the context of other bed-side methods such as bioimpedance analysis (BIA), its feasibility and acceptability in the dialysis clinic. Compared to healthy volunteers dialysis patients had much less stable body composition and the combination of absolute TBWD and the fraction of lean body mass using BIA demonstrated that longitudinal changes were influenced by comorbidity. As a research tool TBWD combined with BIA has facilitated investigation of the mechanisms of over-hydration, e.g. hypoalbuminaemia and the impact of dialysis solutions designed to improve fluid status. Current research is focussing on determining the added value of bedside body composition analysis in the routine clinical management of dialysis patients.