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    Original Investigation
    Critical Care Medicine
    June 7, 2019

    Association of Net Ultrafiltration Rate With Mortality Among Critically Ill Adults With Acute Kidney Injury Receiving Continuous Venovenous Hemodiafiltration: A Secondary Analysis of the Randomized Evaluation of Normal vs Augmented Level (RENAL) of Renal Replacement Therapy Trial

    Author Affiliations
    • 1The Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
    • 2The Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
    • 3Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
    • 4Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
    • 5The George Institute for Global Health and University of Sydney, Sydney, New South Wales, Australia
    • 6Renal Section, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania
    • 7Department of Intensive Care Medicine, Austin Hospital, The University of Melbourne, Melbourne, Victoria, Australia
    JAMA Netw Open. 2019;2(6):e195418. doi:10.1001/jamanetworkopen.2019.5418
    Key Points español 中文 (chinese)

    Question  Is the net ultrafiltration (ie, fluid removal) rate associated with survival among critically ill patients with acute kidney injury?

    Findings  In this secondary analysis of a randomized clinical trial involving 1434 critically ill patients treated with continuous venovenous hemodiafiltration, a net ultrafiltration rate greater than 1.75 mL/kg/h compared with a net ultrafiltration rate less than 1.01 mL/kg/h was significantly associated with lower 90-day risk-adjusted survival.

    Meaning  Among critically ill patients with acute kidney injury being treated with continuous venovenous hemodiafiltration, net ultrafiltration rates greater than 1.75 mL/kg/h were associated with increased mortality.

    Abstract

    Importance  Net ultrafiltration (NUF) is frequently used to treat fluid overload among critically ill patients, but whether the rate of NUF affects outcomes is unclear.

    Objective  To examine the association of NUF with survival among critically ill patients with acute kidney injury being treated with continuous venovenous hemodiafiltration.

    Design, Setting, and Participants  The Randomized Evaluation of Normal vs Augmented Level (RENAL) of Renal Replacement Therapy trial was conducted between December 30, 2005, and November 28, 2008, at 35 intensive care units in Australia and New Zealand among critically ill adults with acute kidney injury who were being treated with continuous venovenous hemodiafiltration. This secondary analysis began in May 2018 and concluded in January 2019.

    Exposures  Net ultrafiltration rate, defined as the volume of fluid removed per hour adjusted for patient body weight.

    Main Outcomes and Measures  Risk-adjusted 90-day survival.

    Results  Of 1434 patients, the median (interquartile range) age was 67.3 (56.9-76.3) years; 924 participants (64.4%) were male; median (interquartile range) Acute Physiology and Chronic Health Evaluation III score was 100 (84-118); and 634 patients (44.2%) died. Using tertiles, 3 groups were defined: high, NUF rate greater than 1.75 mL/kg/h; middle, NUF rate from 1.01 to 1.75 mL/kg/h; and low, NUF rate less than 1.01 mL/kg/h. The high-tertile group compared with the low-tertile group was not associated with death from day 0 to 6. However, death occurred in 51 patients (14.7%) in the high-tertile group vs 30 patients (8.6%) in the low-tertile group from day 7 to 12 (adjusted hazard ratio [aHR], 1.51; 95% CI, 1.13-2.02); 45 patients (15.3%) in the high-tertile group vs 25 patients (7.9%) in the low-tertile group from day 13 to 26 (aHR, 1.52; 95% CI, 1.11-2.07); and 48 patients (19.2%) in the high-tertile group vs 29 patients (9.9%) in the low-tertile group from day 27 to 90 (aHR, 1.66; 95% CI, 1.16-2.39). Every 0.5-mL/kg/h increase in NUF rate was associated with increased mortality (3-6 days: aHR, 1.05; 95% CI, 1.00-1.11; 7-12 days: aHR, 1.08; 95% CI, 1.02-1.15; 13-26 days: aHR, 1.11; 95% CI, 1.04-1.18; 27-90 days: aHR, 1.13; 95% CI, 1.05-1.22). Using longitudinal analyses, increase in NUF rate was associated with lower survival (β = .056; P < .001). Hypophosphatemia was more frequent among patients in the high-tertile group compared with patients in the middle-tertile group and patients in the low-tertile group (high: 308 of 477 patients at risk [64.6%]; middle: 293 of 472 patients at risk [62.1%]; low: 247 of 466 patients at risk [53.0%]; P < .001). Cardiac arrhythmias requiring treatment occurred among all groups: high, 176 patients (36.8%); middle: 175 patients (36.5%); and low: 147 patients (30.8%) (P = .08).

    Conclusions and Relevance  Among critically ill patients, NUF rates greater than 1.75 mL/kg/h compared with NUF rates less than 1.01 mL/kg/h were associated with lower survival. Residual confounding may be present from unmeasured risk factors, and randomized clinical trials are required to confirm these findings.

    Trial Registration  ClinicalTrials.gov identifier: NCT00221013

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