METHODS: We conducted a retrospective observational study in our multi-disciplinary Pediatric Intensive Care Unit (ICU) from January 2015 to December 2018. All patients from birth to 16 years of age who were admitted to the pediatric ICU were included. The Kidney Disease Improving Global Outcomes (KDIGO) definition was considered as the reference standard. We compared the incidence data assessed by KDIGO, pediatric risk, injury, failure, loss of kidney function and end- stage renal disease (pRIFLE) and pediatric reference change value optimised for AKI (pROCK).

RESULTS: Out of 7505 patients, 9.2% developed AKI by KDIGO criteria. The majority (59.8%) presented with stage 1 AKI. Recovery from AKI was observed in 70.4% of patients within 7 days from diagnosis. Both pRIFLE and pROCK were less sensitive compared to KDIGO criteria for the classification of AKI. Patients who met all three-KDIGO, pRIFLE and pROCK criteria had a high mortality rate (35.0%).

DESIGN: Single-center retrospective observational study.

SETTING: Thirty-six-bed surgical/medical tertiary PICU.

PATIENTS: Children from birth to less than or equal to 16 years old admitted between 2015 and 2018.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Clinical data were extracted from the PICU clinical information system. Patients with baseline creatinine at admission greater than 20 micromol/L above the calculated normal creatinine level were classified as "high risk of acute kidney injury." Models were created to predict acute kidney injury at admission and on day 1. Out of the 7,505 children admitted during the study period, 738 patients (9.8%) were classified as high risk of acute kidney injury at admission and 690 (9.2%) developed acute kidney injury during PICU admission. Compared to Kidney Disease: Improving Global Outcomes criteria as the reference standard, high risk of acute kidney injury had a lower sensitivity and higher specificity compared with renal angina index greater than or equal to 8 on day 1. For the admission model, the adjusted odds ratio of developing acute kidney injury for high risk of acute kidney injury was 4.2 (95% CI, 3.3-5.2). The adjusted odds ratio in the noncardiac cohort for high risk of acute kidney injury was 7.3 (95% CI, 5.5-9.7). For the day 1 model, odds ratios for high risk of acute kidney injury and renal angina index greater than or equal to 8 were 3.3 (95% CI, 2.6-4.2) and 3.1 (95% CI, 2.4-3.8), respectively.

METHODS: This was a Phase 2 study of the oral RSV fusion protein inhibitor AK0529 in infants aged 1-24 months, hospitalized with RSV infection. In Part 1, patients (n = 24) were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or placebo. In Part 2, patients (n = 48) were randomized 2:1 to receive AK0529 at 0.5, 1, or 2 mg/kg bid or placebo for 5 days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, and respiratory signs and symptoms were assessed daily during treatment.

RESULTS: No safety or tolerability signals were detected for AK0529: grade ≥3 treatment-emergent adverse events occurring in 4.1% of patients in AK0529 and 4.2% in placebo groups, respectively, and none led to death or withdrawal from the study. In Part 2, targeted drug exposure was reached with 2 mg/kg bid. A numerically greater reduction in median viral load with 2 mg/kg bid AK0529 than with placebo at 96 h was observed. A -4.0 (95% CI: -4.51, -2.03) median reduction in Wang Respiratory Score from baseline to 96 h was observed in the 2 mg/kg group compared with -2.0 (95% CI: -3.42, -1.82) in the placebo group.

CONCLUSIONS: AK0529 was well tolerated in hospitalized RSV-infected infant patients. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and Wang Respiratory Score.