Acute Kidney Injury in Critically Ill Children: Epidemiology, Risk Factors, and Outcomes

• Author / Creator

  Alobaidi, Rashid

• Background:
  Acute kidney injury (AKI) is common in critically ill children. The development of AKI is not a trivial complication. Accumulating data show suboptimal short-term and poor long-term outcomes after an episode of AKI. Understanding the epidemiology of AKI in the pediatric population and identification of those at greatest risk is critical. The current evidence base is limited by number of factors: 1) The population-based incidence of AKI in critically ill children has not been examined. The majority of AKI studies in pediatric populations have been single center with relatively small numbers necessitating validation using larger cohorts. 2) Existing pediatric studies have used diverse AKI definitions. There are limited pediatric studies that have applied the KDIGO consensus criteria to describe the epidemiology and outcome of AKI in PICU. 3) Existing evidence suggest fluid overload plays an important role in the pathophysiology of AKI and have significant potential to modify outcomes. However, this relationship has not been thoroughly evaluated in the pediatric population. 4) Finally, the methods to assess fluid balance and define fluid overload are inconsistently described in the literature.

  Methods:
  In order to address these knowledge gaps, two methods were used in this thesis. First, I conducted a population-based multicentre cohort study to evaluate the epidemiology of AKI, associated risk factors and outcomes. All children admitted to three pediatric intensive care units (PICU) in Alberta, Canada between January 1 to December 31, 2015, utilizing prospectively collected data from a bedside clinical information system and data repository, were included.

        Second, I performed a systematic review and meta-analysis to describe the methods used to measure fluid balance, define fluid overload, and evaluate the association between fluid balance and outcomes in critically ill children.
  

  Results:
  In the first part of the thesis, a total of 1017 patients were included. AKI developed in 308 patients (30.3%; 95% CI, 28.1% to 33.8%) and severe AKI (KDIGO stage 2 and 3) developed in 124 patients (12.2%; 95% CI, 10.3% to 14.4%). Incidence rates for critical illness-associated AKI and severe AKI were 34 (95% CI, 30.3 to 38.0) and 14 (95% CI, 11.38 to 16.38) per 100,000 children-year, respectively. Thirty-two patients (3.1%) did not survive to PICU discharge. The AKI-associated PICU mortality rate was 2.3 (95% CI, 1.4 to 3.5) per 100,000 children-year. After adjustment for weight, case-mix, illness acuity (Pediatric Index of Mortality 3) and PICU site, severe AKI was associated with greater PICU mortality (odds ratio [OR] 11.93; 95% CI, 4.68 to 30.42) and 1-year mortality (OR 5.50, 95% CI, 2.76 to 10.96). Severe AKI was further associated with greater duration of mechanical ventilation, duration of vasoactive support and lengths of PICU and hospital stay.

          In the second part, the systematic review and meta-analysis, a total of 44 studies (7507 children) were included. Fluid overload, however defined, was associated with increased in-hospital mortality (17 studies [n = 2853]; odds ratio [OR], 4.34 [95% CI, 3.01-6.26]; I2 = 61%). Survivors had lower percentage fluid overload than non-survivors (22 studies [n = 2848]; mean difference, −5.62 [95% CI, −7.28 to −3.97]; I2 = 76%). After adjustment for illness severity, there was a 6% increase in odds of mortality for every 1% increase in percentage fluid overload (11 studies [n = 3200]; adjusted OR, 1.06 [95% CI, 1.03-1.10]; I2 = 66%). Fluid overload was associated with increased risk for prolonged mechanical ventilation (>48 hours) (3 studies [n = 631]; OR, 2.14 [95% CI, 1.25-3.66]; I2 = 0%) and acute kidney injury (7 studies [n = 1833]; OR, 2.36 [95% CI, 1.27-4.38]; I2 = 78%).
  

  Conclusion
  The population-level burden of AKI and its attributable risks, including greater mortality and health services use, are considerable among critically ill children. These findings emphasize the need for enhanced surveillance for AKI, identification of modifiable risks and evaluation of interventional strategies. Fluid overload could represent a modifiable risk factor and a target for intervention in critically ill children, particularly for those with or at risk of AKI. The findings suggest fluid overload is associated with substantial morbidity and mortality in this population. Additional research should now ideally focus on interventions aimed to mitigate the potential for harm associated with fluid overload.

• Subjects / Keywords

  • acute kidney injury
  • fluid balance
  • critically ill children
  • kidney failure
  • fluid overload

• Graduation date

  Fall 2019

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-cd1f-nx16

• License

  Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.