(20) Assessing the correlation of urinary proteomic biomarkers with acute kidney injury and kidney hypoxia in preterm neonates < 32 weeks gestation

Background: Current methods of diagnosing preterm neonatal acute kidney injury (AKI) are unreliable, leading to delays in diagnosis and increased morbidity and mortality. The use of near-infrared spectroscopy (NIRS) to monitor kidney oxygenation and the role of urinary biomarkers are both alternative, noninvasive methods of early detection and diagnosis of AKI. However, the correlation between AKI, kidney oxygenation, and urinary proteomic biomarkers has not been evaluated.

Objectives: To evaluate how urinary levels of Beta 2-Microglobulin (B2M), Cystatin C (cysC), and Neutrophil gelatinase associated lipocalin (NGAL) correlate with AKI and kidney hypoxia.

Design/Methods: A prospective observational study of preterm neonates born < 32 weeks gestational age was performed from 2021-2023. Invos NIRS neonatal sensors were applied from days 4 to 14 days of age. Kidney hypoxia was summarized as the proportion of time < 50%. Every 6-hour urine output and all clinically obtained serum creatinine (SCr) values were collected to stage participants for AKI using the modified neonatal KDIGO definition. Urine samples were obtained every 6 hours via cotton in the diaper and B2M, cysC, NGAL and urinary creatinine were measured. Median biomarker values were compared to AKI status as well as hypoxia status (low, medium, and high). A receiver operator curve (ROC) was generated for each biomarker prior to AKI onset vs. participants without AKI.

Results: Of the 40 enrolled participants with median birth weight 1.25 kg (IQR 1.02-1.45) and gestational age of 29 weeks (IQR 27-30), 999 urine samples were analyzed from 32 participants. Five developed AKI, four with stage 1 and one with stage 2 injury. For B2M and NGAL, there were no differences by either AKI or hypoxia status (Table 1 and 2). CysC levels were significantly higher among participants with AKI (1.5 vs. 0.5 mg/L, p=0.05). CysC levels were also highest among participants with the most kidney hypoxia (1.5 vs. 0.4 mg/L, p< 0.01). ROC analysis showed significance for all biomarkers, with cysC having the highest area under the curve (0.63, p< 0.01, Figure 1). There was a significant negative correlation between increasing gestational age and cysC and NGAL but not B2M (Figure 2).

Conclusion: Preterm neonates with AKI and those with the most kidney hypoxia have significantly higher levels of the urinary proteomic biomarker Cystatin C.