Abstract Body: Background and Objectives:
Post-cardiac arrest syndrome (PCAS), characterized by ischemia-reperfusion injury and systemic inflammation, causes end-organ damage such as acute kidney injury (AKI) which complicates post-arrest care and increases morbidity and mortality. The diagnosis of AKI, which affects over 50% of patients after out-of-hospital cardiac arrest (OHCA), hinges on the delayed rise in serum creatinine thereby impeding timely intervention. This study's objective is to identify early serum biomarkers of renal injury after OHCA to improve AKI diagnosis, predict renal outcomes, and monitor efficacy of OCHA care.

Methods: This is a retrospective analysis of 176 patients (72% males, mean age 53 years) enrolled in the Biorepository of OHCA (BIOHCA) registry at Harborview Medical Center who had serum collected within 12 hours of OHCA. Clinical outcomes were obtained from the electronic medical record and biomarker concentrations (pg/ml) were measured with Meso Scale Discovery (MSD) bioassay kits.

Results: 113 patients (65%) developed AKI, 55% mild (stage 1), 19% moderate (stage 2), and 27% severe (stage 3) of which 14 (47%) developed renal failure requiring KRT. The endothelial damage marker Ang-2, tubular injury markers cystatin-c and Neutrophil gelatinase-associated lipocalin (NGAL), and cytokines IL-18, IL-1β, TNF-α, and IP-10 were significantly higher in those who developed AKI (t-test, p<0.001: Ang-2, cystatin-c, IL-18, IL-1β; NGAL, p=0.006; TNF-α, p=0.002; IP-10, p=0.04), and were associated with AKI severity (Kruskal-Wallis Test, p<0.001: Ang-2, NGAL, IL-18, TNF-α; cystatin-c, p=0.002; IL-1β, p=0.003; IP-10, p=0.05). Ang-2, NGAL, IL-18, and IL-1β were predictive of need for KRT (t-test, NGAL, p=0.019; IL-18, p=0.032; IL-1β, p=0.033). Kidney-injury molecule-1 (KIM-1), IL-6, and MIP-1α were higher in subjects who died compared to survivors (t-test, p<0.001: KIM-1, MIP-1α; IL-6, p=0.013) but were not different between AKI and non-AKI groups.

Conclusions: Several biomarkers associated with the later development of AKI, KRT need, and mortality are elevated within 12 hours of OHCA, demonstrating utility for early AKI diagnosis and clinical prognostication. Ang-2, NGAL, IL-18, and IL-1β; which have previously been implicated in ischemic reperfusion injury, have greater specificity for predicting kidney specific outcomes suggesting that attenuation of PCAS ischemia reperfusion pathways could be a meaningful target to reduce AKI incidence and severity.