Urine Complement Factor Ba is Associated with AKI in Critically Ill Children

Abstract

KEY POINTS: Complement activation, specifically factor B, is implicated in AKI pathogenesis in animal models. Urine Ba (an activation fragment of factor B) was significantly higher in critically ill children with stage 3 AKI and sepsis-AKI. If larger studies show similar association between urine Ba and AKI severity, clinical trials of factor B inhibition are warranted. BACKGROUND:: Critically ill children with AKI have high morbidity and mortality rates and lack treatment options. Complement activation is implicated in AKI pathogenesis, which could be treated with complement-targeted therapeutics. We assessed for an association between urine Ba, an activation fragment of the alternative complement pathway, and AKI in a large cohort of critically ill children. METHODS:: A biorepository of children requiring mechanical ventilation was leveraged. AKI was based on pediatric version of the RIFLE criteria—stage 1: 25% decreased eGFR or urine output (UOP) \u3c0.5ml/kg per hour for 8 hours; stage 2: 50% decreased eGFR or UOP RESULTS:: Seventy-three patients were included, of which 56 had AKI: 26 (46%) stage 1, 16 (29%) stage 2, and 14 (25%) stage 3. Ba was significantly higher in patients with stage 3 AKI compared with all other stages. Ba was higher in sepsis-associated AKI compared with non–sepsis-associated AKI. Multivariate analysis included urine Ba, urine IL-18, urine NGAL, sepsis, and Pediatric Risk of Mortality Scores-II (an estimate of illness severity) and showed a significant association between urine Ba and AKI (odds ratio 1.57, 95% confidence interval, 1.13 to 2.20; CONCLUSION:: Urine Ba is significantly increased in patients with AKI compared with patients without AKI. In patients with similar illness severity, a doubling of urine Ba level was associated with a 57% increase in AKI diagnosis of any stage. Further studies are needed to study complement inhibition in treatment or prevention of AKI in critically ill children