Abstract Rationale Patients with acute respiratory distress syndrome (ARDS) are at risk for higher morbidity and mortality with concurrent acute kidney injury (AKI). AKI diagnosis relies on serum creatinine, which is confounded by fluid overload. Fluid overload-adjusted creatinine (CrFO) can account for accumulated fluid balance and diagnose AKI that would otherwise be missed by standard definitions. It is unknown whether AKI diagnosed by CrFO is biochemically distinct from patients without AKI. Biomarkers indicative of tissue damage and inflammation may correlate with AKI and aid in diagnosis. Angiopoietin-2 (ANGPT-2) and procollagen type III N-terminal peptide (P3NP) have been associated with renal fibrosis and chronic kidney disease, while interleukin 6 and 8 (IL-6, IL-8) and nucleosome proteins have been associated with post-operative and sepsis-associated AKI. Heat shock protein 70 (HSP70) may mediate cell death in ischemic AKI. These biomarkers were evaluated for association with overt and cryptic AKI in ARDS. Methods Secondary analysis of 333 pediatric ARDS (Berlin criteria) patients enrolled 2014 - 2019 at a quaternary pediatric intensive care unit. Fluid intake/output and creatinine were recorded on days 1-7 of ARDS. Plasma biomarkers were collected days 1, 3, and 7 of ARDS. AKI was defined by KDIGO Stage 2/3 at any time days 1-7 of ARDS. For all subjects, CrFO was calculated using (creatinine x 1+net fluid balance/total body water). Patients who only met AKI criteria using CrFO, but not using measured creatinine, were classified as “cryptic AKI.” Biomarker levels and trajectory were compared between patients with no AKI, AKI, and cryptic AKI. Results KDIGO Stage 2/3 AKI was present in 94/333 (28.2%) of patients; cryptic AKI was present in 14/333 (4.2%). Compared to no AKI, AKI and cryptic AKI had higher mortality (10.7% vs 43.6%, 28.6%, p 0.001). Cryptic AKI, relative to no AKI, had higher ANGPT-2, P3NP, HSP70, and nucleosome proteins at all 3 timepoints (all p 0.05). IL-6 and IL-8 were higher on days 1 and 3 (all p0.01). IL-6, IL-8, and HSP70 demonstrated different trajectories between groups. Conclusions ANGPT2, P3NP, IL-6, IL-8, HSP70, and nucleosome proteins were elevated in patients with cryptic AKI compared to patients with no AKI in this pediatric ARDS cohort. Cryptic AKI has a similar biomarker signature to patients with AKI by unadjusted creatinine, suggesting that these biomarkers should be explored as a means of improving identification of clinically relevant AKI, and further describing lung-kidney interactions in critical illness. This abstract is funded by: None
Dixon et al. (Fri,) studied this question.