Fluid retention is associated with cardiovascular mortality in patients undergoing long-term hemodialysis

Abstract

Background: Patients with chronic kidney disease (stage 5) who undergo hemodialysis treatment have similarities to heart failure patients in that both populations retain fluid frequently and have excessively high mortality. Volume overload in heart failure is associated with worse outcomes. We hypothesized that in hemodialysis patients, greater interdialytic fluid gain is associated with poor all-cause and cardiovascular survival.

Methods and results: We examined 2-year (July 2001 to June 2003) mortality in 34,107 hemodialysis patients across the United States who had an average weight gain of at least 0.5 kg above their end-dialysis dry weight by the time the subsequent hemodialysis treatment started. The 3-month averaged interdialytic weight gain was divided into 8 categories of 0.5-kg increments (up to > or =4.0 kg). Eighty-six percent of patients gained >1.5 kg between 2 dialysis sessions. In unadjusted analyses, higher weight gain was associated with better nutritional status (higher protein intake, serum albumin, and body mass index) and tended to be linked to greater survival. However, after multivariate adjustment for demographics (case mix) and surrogates of malnutrition-inflammation complex, higher weight-gain increments were associated with increased risk of all-cause and cardiovascular death. The hazard ratios (95% confidence intervals) of cardiovascular death for weight gain <1.0 kg and > or =4.0 kg (compared with 1.5 to 2.0 kg as the reference) were 0.67 (0.58 to 0.76) and 1.25 (1.12 to 1.39), respectively.

Conclusions: In hemodialysis patients, greater fluid retention between 2 subsequent hemodialysis treatment sessions is associated with higher risk of all-cause and cardiovascular death. The mechanisms by which fluid retention influences cardiovascular survival in hemodialysis may be similar to those in patients with heart failure and warrant further research.

Figure 1

Schematic representation of the bi-diurnal variation of fluid status in chronic hemodialysis patients. Between the two subsequent dialysis treatment sessions, usually 44 hrs apart, patient’s interdialytic weight gain to reflect fluid retention between two consecutive hemodialysis treatments, which will then be removed rather quickly via dialysis ultrafiltration (UF) during a 4-hr dialysis treatment.

Figure 2

All-cause death hazard ratios (and 95% confidence interval error bars) for the entire range of interdialytic fluid gain categories in 34,107 HD patients over 2 years (7/2001-6/2003). Hazard ratios are calculated via time-dependent Cox regression with 3 levels of multivariate adjustment, i.e., minimally adjusted (herewith referred to as “unadjusted” including adjustment for baseline height and weight and calendar quarter), adjusted for “case-mix” (including additional adjustment for age, gender, race/ethnicity, diabetes mellitus and other comorbid states, dialysis vintage, tobacco smoking, primary insurance, marital status, standardized mortality ratio, dialysis dose, dialysis catheter, and residual renal function); and “malnutrition-inflammation-cachexia syndrome” (MICS) surrogates (including 10 laboratory markers, see text). Note that patient population frequency in each group is demonstrated via background bar diagrams in grey.

Figure 3

Cardiovascular death hazard ratios (and 95% confidence interval error bars) for the entire range of interdialytic fluid gain categories in 34,107 HD patients over 2 years (7/2001-6/2003). Hazard ratios are calculated via time-dependent Cox regression with 3 levels of multivariate adjustment, i.e., minimally adjusted (herewith referred to as “unadjusted” including adjustment for baseline height and weight and calendar quarter), adjusted for “case-mix” (including additional adjustment for age, gender, race/ethnicity, diabetes mellitus and other comorbid states, dialysis vintage, tobacco smoking, primary insurance, marital status, standardized mortality ratio, dialysis dose, dialysis catheter, and residual renal function); and “malnutrition-inflammation-cachexia syndrome” (MICS) surrogates (including 10 laboratory markers, see text).

Figure 4

Hazard ratio of all-cause mortality for interdialytic weight gain greater than 1.5 kilograms or liters (vs. <1.5 kilograms or liters) between two subsequent dialysis sessions in 34,107 HD patients adjusted for case-mix and laboratory surrogates of malnutrition and inflammation (time-dependent regression model over 2 year). Error bars indicate 95% confidence intervals. * Dialysis patients with vintage >10 years (<5% of the entire cohort) are excluded to mitigate confounding by number of years of functioning kidney transplant (usually part of the vintage).