What are the Consequences of Volume Expansion in Chronic Dialysis Patients?

In the saga of clinical nephrology, ﬂuid overloadappears as one of the most important modiﬁablerisk factors for mortality in dialysis patients, poten-tially even more fundamental than poor nutrition.The present review article aims at providing opin-ion-based answers to three questions on ﬂuidoverload, namely: (i) ﬂuid overload: Why bother? (ii) what is ﬂuid overload and how can it be mea-sured? (iii) what have we learned from bioimped-ance-based measurements of ﬂuid overload? Fluid Overload: Why Bother? Datasets on hemodialysis patients have evolvedfrom early local registries, through nationwidesurveys (including the United States Renal DataSystem (1)) to international studies (2,3). This gath-ering of information is aimed at improving dialysiscare and, ultimately, cardiovascular disease mortal-ity, which is 10–30 times higher in dialysis patientsthan in the general population (4,5). Among theirprimary risk factors are higher age, presence ofdiabetes, and other comorbidities (6,7), but thesefactors are not modiﬁable. Traditional, modiﬁablerisk factors include central vein catheters, an inade-quate dialysis prescription (lower treatment timeand Kt/V), and poor nutrition (8). A previousanalysis of an observational dataset suggested that,of the principal, modiﬁable risk factors, a serumalbumin <3.5 g/dl (relative risk = 1.38, p < 0.0001)was associated with the highest relative risk ofmortality (9). Fluid overload is another modiﬁable risk factor.To the best of our knowledge, three analyses havebeen published to date regarding the mortality riskassociated with quantiﬁed ﬂuid overload:(i) In a blinded study of 269 patients, those withpredialysis ﬂuid overload surpassing 15% oftheir extracellular volume had an adjusted haz-ard ratio for all-cause mortality of 2.10 (90%CI 1.39–3.18), compared to those with ﬂuidoverload below 15% of their extracellular vol-ume (reference) (10). (ii) In comparison to a positively selected reference pop-ulation comprising 50 “normohydrated” patientsfrom the “long, slow dialysis” center in Tassin/France (11), 35 ﬂuid overloaded patients fromanother unit (an excess of 3.5 1.2 l predialysis,equivalent to 20.2 4.8% of their extracellular vol-ume) had an adjusted hazard ratio for all-causemortality of 3.41 (90% CI 1.62 –7.17) (12). (iii) In a study of 309 patients using a plasma vol-ume monitor, those with rapid plasma reﬁlling(a slope below the median of 1.39% per hour),an indicator of ﬂuid overload, had a hazardratio for mortality of 1.72 (95% CI 1.14–2.58)compared to patients with steeper slopes (13). The results derived from these relatively small threedatasets (10–12) cannot be readily compared withthose obtained from the large observational studiesmentioned before. Nevertheless, hazard ratios formortality between 1.72 and 3.41 are big risks, com-pared with the relative risk of 1.38 associated with aserum albumin concentration of <3.5 g/dl (9). Fluidoverload may thus be the most important modiﬁablerisk factor for mortality in dialysis patients.What is Fluid Overload/How Can FluidOverload Be Measured? Fluid overload is a widely used medical term withan International Classiﬁcation of Diseases (ICD)