Ultrafiltration Rate and Mortality in Maintenance Hemodialysis Patients

Abstract

Background: Observational data have demonstrated an association between higher ultrafiltration rates and greater mortality among hemodialysis patients. Prior studies were small and did not consider potential differences in the association across body sizes and other related subgroups. No study has investigated ultrafiltration rates normalized to anthropometric measures beyond body weight. Also, potential methodological shortcomings in prior studies have led to questions about the veracity of the ultrafiltration rate-mortality association.

Study design: Retrospective cohort.

Setting & participants: 118,394 hemodialysis patients dialyzing in a large dialysis organization, 2008 to 2012.

Predictors: Mean 30-day ultrafiltration rates were dichotomized at 13 and 10mL/h/kg, separately and categorized using various cutoff points. Ultrafiltration rates normalized to body weight, body mass index, and body surface area were investigated.

Outcomes: All-cause mortality.

Measurements: Multivariable survival models were used to estimate the association between ultrafiltration rate and all-cause mortality.

Results: At baseline, 21,735 (18.4%) individuals had ultrafiltration rates > 13mL/h/kg and 48,529 (41.0%) had ultrafiltration rates > 10mL/h/kg. Median follow-up was 2.3 years, and the mortality rate was 15.3 deaths/100 patient-years. Compared with ultrafiltration rates ≤ 13mL/h/kg, ultrafiltration rates > 13mL/h/kg were associated with greater mortality (adjusted HR, 1.31; 95% CI, 1.28-1.34). Compared with ultrafiltration rates ≤ 10mL/h/kg, ultrafiltration rates > 10mL/h/kg were associated with greater mortality (adjusted HR, 1.22; 95% CI, 1.20-1.24). Findings were consistent across subgroups of sex, race, dialysis vintage, session duration, and body size. Higher ultrafiltration rates were associated with greater mortality when normalized to body weight, body mass index, and body surface area.

Limitations: Residual confounding cannot be excluded given the observational study design.

Conclusions: Regardless of the threshold implemented, higher ultrafiltration rate was associated with greater mortality in the overall study population and across key subgroups. Randomized controlled trials are needed to investigate whether ultrafiltration rate reduction improves clinical outcomes.

Keywords: Hemodialysis; anthropometric measures; body mass index (BMI); body size; body surface area (BSA); body weight; end-stage renal disease (ESRD); metabolic mass; mortality; rapid fluid removal; ultrafiltration rate (UFR).

Figure 1. Study design schematic

^a Source cohort consisted of 337,863 in-center hemodialysis patients with complete age, sex, race and ethnicity data.

Figure 2

Flow-chart of cohort selection.

Figure 3. Associations between prescribed ultrafiltration rate and mortality by percentile of post-dialysis weight, body mass index and body surface area

Fine and Gray proportional subdistribution hazards regression models with kidney transplantation and dialysis modality change treated as competing risks were used to estimate the ultrafiltration rate and all-cause mortality association comparing mean UF rates >13 mL/h/kg to those ≤13 mL/h/kg within strata of body weight, BMI and BSA (separately). Models were adjusted for age (continuous), sex (female vs. male), race (black vs. non-black), ethnicity (Hispanic vs. non-Hispanic), dialysis vintage (1–2, 3–4, ≥5 vs. <1 year), vascular access (graft, fistula vs. catheter), history of heart failure (yes vs. no), history of cardiovascular disease (yes vs. no), history of diabetes (yes vs. no), albumin (3.1–3.5, 3.6–4.0, >4.0 vs. ≤3.0 g/dL), creatinine (continuous), phosphorous (4.1–5.0, 5.1–6.0, >6.0 vs. ≤4.0 mg/dL), hemoglobin (10.0–11.9, ≥12.0 vs. <10.0 g/dL), urea reduction ratio (continuous), pre-HD systolic blood pressure (131–150, 151–170, >170 vs. ≤130 mmHg), and missed sessions (≥3 vs. <3). Post-dialysis weight was used to calculate normalized UF rates for weight, BMI and BSA. 20^th/80^th percentile for post-weight = 60.9/95.3 kg; 21.8/32.8 kg/m² for BMI; 1.66/2.10 m² for BSA. 80^th percentile for UF rate normalized to BMI = 37 mL/h/(kg/m²); UF rate normalized to BSA = 500 mL/h/m². 80^th percentile selected for BMI and BSA based on 13 mL/h/kg being the 80^th percentile of UF rate when normalized to post-HD weight. Abbreviations: HR=hazard ratio, CI=confidence interval, HD=hemodialysis