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Biomarkers for Early Acute Kidney Injury Diagnosis and Severity Prediction: A Pilot Multicenter Canadian Study of Children Admitted to the ICU

Palermo, Jennifer MD1; Dart, Allison B. MD2; De Mello, Alanna BSc3; Devarajan, Prasad MD4; Gottesman, Ronald MD1; Garcia Guerra, Gonzalo MD, MSc5; Hansen, Greg MD6; Joffe, Ari R. MD5; Mammen, Cherry MD3; Majesic, Nick BSc7; Morgan, Catherine MD7; Skippen, Peter MD8; Pizzi, Michael BSc1; Palijan, Ana PhD1; Zappitelli, Michael MD1

Pediatric Critical Care Medicine: June 2017 - Volume 18 - Issue 6 - p e235–e244
doi: 10.1097/PCC.0000000000001183
Online Clinical Investigations
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Objective: Acute kidney injury occurs early in PICU admission and increases risks for poor outcomes. We evaluated the feasibility of a multicenter acute kidney injury biomarker urine collection protocol and measured diagnostic characteristics of urine neutrophil gelatinase–associated lipocalin, interleukin-18, and liver fatty acid binding protein to predict acute kidney injury and prolonged acute kidney injury.

Design: Prospective observational pilot cohort study.

Setting: Four Canadian tertiary healthcare PICUs.

Patients: Eighty-one children 1 month to 18 years old. Exclusion criteria were as follows: cardiac surgery, baseline severe kidney disease, and inadequate urine or serum for PICU days 1–3.

Interventions: PICUs performed standardized urine collection protocol to obtain early PICU admission urine samples, with deferred consent.

Measurements and Main Results: Study barriers and facilitators were recorded. Acute kidney injury was defined based on Kidney Disease: Improving Global Outcomes serum creatinine criteria (acute kidney injuryserum creatinine) and by serum creatinine and urine output criteria (acute kidney injuryserum creatinine+urine output) Prolonged acute kidney injury was defined as acute kidney injury duration of 48 hours or more. PICU days 1–3 neutrophil gelatinase–associated lipocalin, interleukin-18, and liver fatty acid binding protein were evaluated for acute kidney injury prediction (area under the curve). Biomarkers on the first day of acute kidney injury attainment (day 1 acute kidney injury) were evaluated for predicting prolonged acute kidney injury. Eighty-two to 95% of subjects had urine collected from PICU days 1–3. Acute kidney injuryserum creatinine developed in 16 subjects (20%); acute kidney injuryserum creatinine+urine output developed in 38 (47%). On PICU day 1, interleukin-18 predicted acute kidney injuryserum creatinine with area under the curve=0.82, but neutrophil gelatinase–associated lipocalin and liver fatty acid binding protein predicted acute kidney injuryserum creatinine with area under the curve of less than or equal to 0.69; on PICU day 2, area under the curve was higher (not shown). Interleukin-18 and liver fatty acid binding protein on day 1 acute kidney injury predicted prolonged acute kidney injuryserum creatinine (area under the curve=0.74 and 0.83, respectively). When acute kidney injuryserum creatinine+urine output was used to define acute kidney injury, biomarker area under the curves were globally lower.

Conclusions: Protocol urine collection to procure early admission samples is feasible. Individual biomarker acute kidney injury prediction performance is highly variable and modest. Larger studies should evaluate utility and cost effectiveness of using early acute kidney injury biomarkers.

Supplemental Digital Content is available in the text.

1Divisions of Nephrology and Pediatric Critical Care Medicine, Department of Pediatrics, Montreal Children’s Hospital, McGill University Health Centre, Montreal, Quebec, Canada.

2Section of Nephrology, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada

3Division of Nephrology, British Columbia Children’s Hospital, University of British Columbia, Vancouver, BC, Canada.

4Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH.

5Department of Pediatrics, University of Alberta, Women and Children’s Health Research Institute, Edmonton, AL, Canada.

6Section of Pediatric Intensive Care, Department of Pediatrics and Child Health, University of Manitoba, Children’s Hospital, Winnipeg, Manitoba, Canada.

7Division of Nephrology, Department of Pediatrics, University of Alberta, Edmonton, AL, Canada.

8Pediatric Intensive Care Unit, Children’s Heart Centre, British Columbia Children’s Hospital, Vancouver, BC, Canada.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/pccmjournal).

Dr. Palermo received funding from the McGill University Research Bursary Program. Dr. Dart disclosed other support in the form of operating funds that were provided to perform the study at her site. Dr. Devarajan received support for article research from the National Institutes of Health (NIH; P50DK096418). He is a co-inventor on patents submitted for the use of neutrophil gelatinase–associated lipocalin as a biomarker of kidney injury. Dr. Gottesman received support for article research from the Canadian Institutes of Health Research (CIHR), and his institution received fund from the CIHR. Dr. Majesic received funding from Dr. Morgan. Dr. Zappitelli received a research salary award from the Fonds de Recherches du Quebec-Sante. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: Michele.zappitelli@mcgill.ca

©2017The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies