Posthemodialysis weights and mortality: another narrow range target?

Volumeexcess andcardiac remodelinghavebeen shown in epidemiologic studies to have an association with cardiovascular and all-cause mortality in chronic hemodialysis patients (1–5).However, excessive ultrafiltration and volume depletion can lead to frequent episodes of malaise, weakness, increase risk of falls, episodes of intradialytic hypotension, and brain hypoperfusion, with subsequent white matter degeneration (6). In addition, gastrointestinal ischemia leading to endotoxin exposure is also a plausible clinical consequence of overaggressive ultrafiltration (7). Therefore, the clinical challenge is how best to avoid underaggressive ultrafiltration, which could cause cardiac dysfunction and dyspnea, and overaggressive ultrafiltrationwith its attendant symptoms of fatigue and exercise intolerance, both of which negatively affect quality of life and are equally important from a patient point of view. What is an optimal dry weight? The concept of dry weight is as old as dialysis itself and has been defined various ways (1). An ideal dry weight should be the posthemodialysis weight that results in the (1) shortest postdialysis recovery time; (2) least intradialytic hypotension; (3) longest patient survival; (4) fewest cardiovascular and cerebrovascular events and hospitalizations; (5) fewest hypovolemia-related access thromboses; and (6) fewestpostdialysis falls (8). In2009, SinhaandAgarwal (9) proposed a definition that combines subjective and objective measurements. According to this definition, dry weight is defined as the lowest tolerated postdialysis weight achieved via gradual change in postdialysis weight at which there are minimal signs or symptoms of hypovolemia or hypervolemia. Observational studies support the practice of probing dry weight. Flythe and colleagues reviewed clinical outcomes from a cohort of 14,000 hemodialysis patients (10). The analysis compared outcomes in highversus lowweight gainers (interdialytic weight gains .3 kg versus #3 kg) and for longer versus shorter treatment times (,240 versus $240 minutes) while adjusting for important confounders. This analysis demonstrated a 32% increasedmortality risk inpatientsprescribed,240minutes (compared with those prescribed $240 minutes) and a 29% increased mortality risk associated with higher compared with lower interdialytic weight gains. To study the effect of volume status on mortality, Wizeman et al. (1,11) followed 269 prevalent hemodialysis patients for several years. Theymeasured hydration state using a body composition analyzer. If there was $15% excess of extracellular water (2.5-L volume excess), they classified suchpatients as volumeoverloaded. In a multivariate-adjusted analysis, investigators found that excess hydration was associated with high mortality. The hazard ratio of mortality with excess fluid volume was 2.1 times greater (P50.003) than those without excess fluid volume. A total of 25% of the patients had excess extracellular fluid (ECF) volume. Although the study did not examine reduction in ECF volume with subsequent outcomes, it is quite likely to assume that improvement in ECF volume would be associated with improved survival outcomes if such studies were performed in the future. There are potential hazards related to probing dry weight, including (1) increasedriskof clottedangioaccess, (2) increased rate of attrition in residual renal function, and (3) complications related to intradialytic hypotension. Intradialytic hypotension, in addition to requiring morenursing interventions, can be complicatedby cerebral hypoperfusion, seizures, myocardial dysfunction, and mesenteric ischemia. In this issue of CJASN, Flythe et al. (12) report on the clinical effect of missing target weights (i.e., above and below the prescribed target weight) and clinical outcomes. The authorshypothesized a priori thatpostdialysis weights, above and below the target weight, would be associated with all-cause mortality and that greater frequencies of target weight misses would be related to increased risk of death. Datawere obtained froma national cohort of 12,417 prevalent hemodialysis patients undergoing dialysis between 2005 and 2008 in one of 1263 dialysis clinics affiliated with a single dialysis organization located across the United States. A threshold of 2 kg above and below target weight was chosen to minimize bias from scale error, and the coprimary end points were all-cause andcardiovascularmortality.Mostof thehemodialysis patients were at their target weight at baseline of the observation period (n58527; 79.2%), and only 6.4% (n5682) and 14.4% (n51549) of the cohort were below and above their target weight, respectively. The mean6SD interdialytic weight gain as a percentage of body weight was 2.761.5 and 3.961.5 kg in the below andabove targetweightgroups, respectively.Asexpected, participantswith postdialysis weight.2 kg above target weight were younger, men, had a higher prevalence of heart failure, and on average had been on dialysis Division of Renal Diseases and Hypertension, University of Colorado Denver Anschutz Medical Center, Aurora, Colorado