Biomarkers for Early Acute Kidney Injury Diagnosis and Severity Prediction: A Pilot Multicenter Canadian Study of Children Admitted to the ICU
Authors: Palermo Jennifer , Dart Allison B. , De Mello Alanna , Devarajan Prasad , Gottesman Ronald , Garcia Guerra Gonzalo , Hansen Greg , Joffe Ari R. , Mammen Cherry , Majesic Nick , Morgan Catherine , Skippen Peter , Pizzi Michael , Palijan Ana , Zappitelli Michael 
Published: April 2017

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.