Abstract
INTRODUCTION: Critically ill adults with acute kidney injury (AKI) have high morbidity and mortality and lack treatment options. We assessed the association between complement activation (urine Ba fragment levels), and AKI and organ failures. METHODS: A biorepository of critically ill adults was leveraged. AKI staging was based on the Kidney Disease Improving Global Outcomes serum creatinine (sCr) criteria. AKI recovery was defined as sCr reduction to <0.3 mg/dl above baseline within 48 hours after AKI diagnosis. Persistent AKI was defined as need for renal replacement or no sCr recovery. Urine was obtained at intensive care unit (ICU) admission, and at 12 and 24 hours after admission; and urine Ba levels were quantitated via enzyme-linked immunosorbent assay and natural log transformed. Regression analyses were performed to test the association between urine Ba and organ failure outcomes. We adjusted for age and the acute physiology and chronic health evaluation II (APACHE-II) score, which is used to classify ICU severity of illness. RESULTS: A total of 439 patients were included: 252 without AKI, 124 with stage 1 AKI, 43 with stage 2 AKI, and 20 with stage 3 AKI. After adjusting for covariates, urine Ba increased as AKI stage increased. Urine Ba was higher in patients with persistent AKI compared with patients with AKI recovery and without AKI. Increased urine Ba was associated with worse organ failure outcomes (fewer ventilator, ICU, and inotrope-free days, and fewer days alive). CONCLUSION: Urine Ba is increased in patients with severe AKI and discriminates between patients who have AKI recovery and patients who develop persistent AKI. A doubling of urine Ba was associated with a 6.6-fold increased odds of persistent AKI. Future studies to validate these findings and to trial complement factor B inhibition are warranted.