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.

BACKGROUND AND OBJECTIVES:Peritoneal dialysis (PD) patients may be overhydrated especially when inflammation is present. We hypothesized that patients with a plasma albumin below the median value would have measurable overhydration without a proportional increase in plasma volume (PV). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:We investigated a cross-sectional sample of 46 prevalent PD patients powered to detect a proportional increase in PV associated with whole body overhydration and hypoalbuminemia. PV was determined from (125)I-labeled albumin dilution, absolute total body water from D dilution (TBW(D)), and relative hydration from multifrequency bioimpedance analysis (BIA; Xitron 4200) expressed as the extracellular water (ECW):TBW(BIA) ratio. RESULTS:Whereas patients with plasma albumin below the median (31.4 g/dl) were overhydrated as determined both by BIA alone (ECW:TBW(BIA) 0.49 versus 0.47, P < 0.036) and the difference between estimated TBW(BIA) and measured TBW(D) (3.55 versus 0.94 L, P = 0.012), corrected PV was not different (1463 versus 1482 ml/m(2), NS). Mean PV was not different from predicted, and its variance did not correlate with any other clinical measures. Multivariate analysis showed that the only independent predictor of whole body overhydration was reduced plasma albumin. CONCLUSIONS:Hypoalbuminemia is an important determinant of tissue overhydration in PD patients. This overhydration is not associated with an increased plasma volume. Attempts to normalize the ECW:TBW ratio in hypoalbuminemic, inflamed PD patients may lead to hypovolemia and loss of residual renal function.

Encapsulating peritoneal sclerosis (EPS) is a serious condition whose frequency is increasing the longer the duration of peritoneal dialysis. To identify prognostic indicators of EPS, we studied here longitudinal changes in peritoneal membrane function of patients who later developed this complication. We identified all patients with an unequivocal diagnosis of EPS who began their peritoneal dialysis in our unit over a 20-year period and matched each of them for dialysis duration and age with four control patients who completed their dialysis. The dialysate/plasma creatinine ratio increased with time in both groups but was significantly higher in the patients with EPS only at the time their dialysis was discontinued. The ultrafiltration capacity was significantly worse for at least 2 years before stopping dialysis, diverging further at the time dialysis ceased, suggesting reduced osmotic conductance in the EPS patients. Both the glucose exposure rate for the 5 years preceding stoppage of dialysis and exposure to the osmotic agent icodextrin were significantly higher. Residual renal function was less in the EPS group, but there was no significant difference in the rates of peritonitis compared to the control group. The 24 h peritoneal protein clearance was not significantly different in EPS patients, possibly due to a greater fibrous matrix. Thus, our study shows that regular peritoneal membrane function tests can identify most patients at high risk of developing EPS before its occurrence.

The rate of transport of small solutes across the peritoneal membrane is one of the most important measurements in PD patients. Significant between-patient variability is associated with an impact on small solute clearance, ultrafiltration and even survival. Cross-sectional and longitudinal studies show that solute transport generally increases with time on treatment although this is again highly variable between individuals and is likely to represent an increased vascularity of the membrane. Initially, there is a coupled decrease in the ultrafiltration capacity of the membrane that can be explained by the earlier loss of the osmotic gradient leading predominantly to reduced free water transport via aquaporins combined with more fluid reabsorption once the osmotic gradient has dissipated. Subsequently, in some patients a further disproportionate fall in ultrafiltration occurs due to uncoupling of fluid transport from solute transport as a result of a reduction in the osmotic conductance of the membrane. Drivers of this damage appear to be peritonitis, glucose exposure and early loss of residual renal function. Cytokines and growth factors appear to be involved in this process and may prove useful biomarkers of membrane injury in the future.

BACKGROUND AND OBJECTIVESFast peritoneal membrane transport status may be due to inflammation or increased peritoneal membrane surface area. We evaluated the ability of peritoneal protein clearance (Pcl) to distinguish fast peritoneal membrane transport status as a consequence of peritoneal membrane inflammation and assess its impact on patient survival.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSPatients who initiated peritoneal dialysis at our center since January 1998 and had a baseline peritoneal equilibration test, measurement of dialysis adequacy, and 24-h dialysate Pcl were included. Demography, comorbidities, and biochemical data were prospectively collected. Follow-up was until death or the end of the period studied. Multivariate regression analysis identified factors that were associated with Pcl. A Cox proportional hazards model was used to identify factors that were associated with survival.RESULTSA total of 192 patients (56% men, mean age 54.3 +/- 15.3; 32% with diabetes) were included. On univariate analysis, Pcl was negatively correlated with serum albumin and positively correlated with age, dialysate/plasma creatinine ratio (D/Pcr), the presence of peripheral vascular disease, and urine volume. On multivariate analysis, serum albumin, D/Pcr, urine volume, and peripheral vascular disease remained significant. Predictors of mortality were age, comorbidity grade, and Pcl but not D/Pcr.CONCLUSIONSIn this cohort, peritoneal transport status no longer predicted survival, whereas Pcl remained a predictor. Increased large-pore protein loss may reflect the severity of underlying cardiovascular disease, portending a poor prognosis for these patients.

Failed transplantation is an increasingly common cause for starting dialysis treatment. As with all patients approaching dialysis there is a need for adequate physical and psychological preparation and yet whilst by definition these individuals are known to health professionals this is not always achieved. It is likely that given adequate information, a significant proportion of these patients would prefer PD on lifestyle grounds. There is increasingly strong evidence that patients commencing PD after transplant failure enjoy overall survival and technique survival that is no different to those new to dialysis, even when other risk factors such as age, comorbidity, race, gender and membrane function are taken into account. The risk of peritonitis is also not different. These patients tend to lose residual renal function more rapidly but this does not translate into worse outcomes. The role and benefit in modulating immune suppressive drugs before and after commencing PD is not clear.