Urine Quantification Following Furosemide for Severe Acute Kidney Injury Prediction in Critically Ill Children

Abstract

A standardized, quantified assessment of furosemide responsiveness predicts acute kidney injury (AKI) in children after cardiac surgery and AKI progression in critically ill adults. The purpose of this study was to determine if response to furosemide is predictive of severe AKI in critically ill children outside of cardiac surgery. We performed a multicenter retrospective study of critically ill children. Quantification of furosemide response was based on urine flow rate (normalized for weight) measurement 0 to 6 hours after the dose. The primary outcome was presence of creatinine defined severe AKI (Kidney Disease Improving Global Outcomes stage 2 or greater) within 7 days of furosemide administration. Secondary outcomes included mortality, duration of mechanical ventilation and length of stay. A total of 110 patients were analyzed. Severe AKI occurred in 20% ( n = 22). Both 2- and 6-hour urine flow rate were significantly lower in those with severe AKI compared with no AKI ( p = 0.002 and p < 0.001). Cutoffs for 2- and 6-hour urine flow rate for prediction of severe AKI were <4 and <3 mL/kg/hour, respectively. The adjusted odds of developing severe AKI for 2-hour urine flow rate of <4 mL/kg/hour was 4.3 (95% confidence interval [CI]: 1.33-14.15; p = 0.02). The adjusted odds of developing severe AKI for 6-hour urine flow rate of <3 mL/kg/hour was 6.19 (95% CI: 1.85-20.70; p = 0.003). Urine flow rate in response to furosemide is predictive of severe AKI in critically ill children. A prospective assessment of urine flow rate in response to furosemide for predicting subsequent severe AKI is warranted.

Keywords: acute kidney injury; critically ill; furosemide; pediatrics; urine flow rate.

Fig. 1

Consort flow diagram summarizing the total number of patients stratified by acute kidney injury staging at and after furosemide administration.

Fig. 2

Classification of AKI staging at the time of furosemide (T ₀ ) and the maximal stage within 7 days after furosemide dose. ( A ) Of the 98 patients with no AKI on the day of furosemide (T ₀ ), 23 developed AKI. Patients with stage two AKIs had the lowest urine flow rate after furosemide. ( B ) Of the 12 patients with AKI on the day of furosemide (T ₀ ), one recovered function and 11 had persistent AKI. Patients with stage 3 AKI at and after furosemide had the lowest urine flow rate. AKI, acute kidney injury.

Fig. 3

Receiver operating curve including 4 four separate models of urine flow rate for predicting severe acute kidney injury. (1) AUC for 2-hour urine flow rate = 0.70; (2) AUC for 6-hour urine flow rate = 0.76; and (3) AUC for 2-hour urine flow rate adjusting for the covariates of age, PRISM-III score, sepsis diagnosis, and weight-adjusted furosemide dose = 0.87; and (4) AUC for 6-hour urine flow rate adjusting for the covariates of age, PRISM-III score, sepsis diagnosis, and weight adjusted furosemide dose = 0.86. The models with the best performance for predicting severe acute kidney injury are the 2- and 6-hour urine flow rate after adjusting for covariates. AUC, area under the curve; PRISM-III, Pediatric Risk of Mortality Score III.