Plasma Volume,Albumin, and Fluid Status in Peritoneal 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 ¹²⁵I-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/m², 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.Evidence from various sources suggests that in a significant proportion of peritoneal dialysis (PD) patients there is difficulty in achieving euvolemia. Observational studies have found that low levels of salt and water removal, independent of residual renal function, are associated with worse survival (1,2). It is not clear, however, whether this association is causal, with excess tissue hydration or expanded plasma volume (PV) accelerating organ dysfunction, or simply evidence that there are difficulties in achieving euvolemia due to confounding factors such as cardiac dysfunction, inflammation, or poor dietary intake (3–5). Individual variability in peritoneal membrane function may also contribute to this problem, although there is now increasing evidence that poor ultrafiltration associated with high solute transport rates can be avoided by using automated PD and icodextrin (6,7).One of the challenges in establishing cause and effect is the difficulty in measuring volume status in PD patients. Bioimpedance analysis (BIA) has been the most widely applied method and has been the main source of evidence that a significant proportion of PD patients are fluid loaded (8). In particular, the abnormal ratio of reactance (an indicator of body cell mass) to resistance (inversely proportional to the total body water [TBW]) implies patients are overhydrated for a given muscle mass. When extrapolated to actual volumes using commercial algorithms, this is frequently expressed as an abnormally high extracellular water (ECW):TBW ratio. This is clearly a relevant biometric as it predicts survival (9) and detects interventions intended to alter fluid status, (5) but suffers a number of problems. First, the ratio will be affected both by muscle wasting and abnormal tissue hydration, and compared with normal subjects, it is the former that is most abnormal (10). Second, the use of algorithms to estimate TBW volume assumes normal hydration of tissues, and we have recently demonstrated in a cohort of hemodialysis (HD) patients, followed over 12 months, that when combining BIA with absolute measurement of TBW using D dilution, patients with greater degrees of comorbidity have overhydrated tissues (11). Third, BIA fails to distinguish between intravascular and interstitial ECW excess. This is especially relevant in PD patients in whom plasma albumin is frequently depressed due to peritoneal protein losses and inflammation when it is possible to hypothesize that mal-distribution of ECW may occur due to lower plasma oncotic pressure. If so, by attempting to normalize the ECW:TBW in hypoalbuminemic patients, it is possible that PV might be reduced below normal, and there is ample evidence from both observational and intervention studies that volume depletion is a risk factor for loss in residual renal function (5,12,13).The purpose of this study was first to demonstrate that abnormal body composition observed in hypoalbuminemic patients is indeed associated with excess tissue hydration and second to test the hypothesis that this overhydration is not associated with a proportional increase in plasma volume.