#5359 DETECTING NEONATAL AKI BY SERUM CYSTATIN-C

Abstract Background and Aims Serum creatinine is not a sensitive biomarker for acute kidney injury (AKI) in neonates. Unlike creatinine, cystatin-C (Cys-C) does not cross the blood placental barrier and the serum level in the neonates is not significantly impacted by the gestation age, birthweight, and the age during the first four weeks after birth. Therefore, serum Cys-C may be a better marker neonatal AKI than serum creatinine. We aimed to assess the performance of serum Cys-C as an alternative biomarker for detecting neonatal AKI. Method This is a large multicenter cohort study including 52,333 hospitalized neonates. First, we assess the impacts of gestational age, birthweight, and days after birth on the level of Cys-C, and estimated the upper normal limit (UNL) and the reference change value RCV of serum Cys-C in neonates. Then, we proposed a Cys-C based criteria (CyNA) for detecting neonatal AKI based on both Cys-C level and the change in Cys-C using UNL and RCV as the cutoffs, respectively. Finally, we assessed the performance of CyNA in detecting neonatal AKI and the association of CyNA-detected AKI with the risk of in-hospital death, and compared the performance with that using the KDIGO creatinine criteria. Results Cys-C level in neonates did not vary with gestational age and birthweight, and remained relatively stable during the neonatal period (Figure 1). The UNL of Cys-C was 2.2 mg/L and the RCV (for Cys-C ratio) was 1.25. CyNA criteria defines AKI by a serum Cys-C of ≥2.2 mg/L (UNL) or an increase in Cys-C of ≥25% (RCV) during the neonatal period. Among 52,333 neonates 6,336 (12.1%) AKI cases were detected by CyNA criteria, of whom 96 (1.5%) died. In comparison, 202 (0.44%) death events occurred in 45,997 neonates who did not have AKI. After adjusting all comorbidities, CYNA-detected AKI was associated with a significantly increased risk of in-hospital mortality (adjusted HR 2.91, 95% confidence interval, 2.24 to 3.78). Among 45,839 neonates that had measurement of both Cys-C and SCr, 4,513 (9.8%) had AKI detected by CyNA only, 373 (0.8%) by KDIGO only, and 381 (0.8%) by both criteria (Table 1). After adjusting admission to ICU and comorbidities, AKI detected by CyNA only (C+/K-) was associated with a significantly increased risk of in-hospital mortality compared with those without AKI by both criteria (C-/K-), with an adjusted hazard ratio of 2.86 (95% CI, 2.02 to 4.04). In comparison, the HR for those detected by KDIGO only (C-/K+) was lower at 2.15 (95% CI, 0.96 to 4.81). Neonates with AKI detected by both criteria (C+/K+) had the highest risk of in-hospital mortality (HR 4.86, 95% confidence interval, 2.84 to 8.29). Conclusion Serum Cys-C is a robust and sensitive biomarker for detecting neonatal AKI. CyNA is 5.5 times more sensitive than the modified KDIGO in detecting neonates who are at an elevated risk of in-hospital mortality.