Acute Kidney Injury is Associated with Elevated Urinary Endotrophin

Background: Acute Kidney Injury (AKI) is prevalent among hospitalized patients. Novel biomarkers are needed to diagnose AKI and target therapies. Endotrophin (ETP) is a molecule released during collagen type VI formation that may promote injury and fibrosis. While serum ETP elevation has been associated with adverse outcomes in AKI, urinary ETP has not been assessed in AKI nor has ETP been evaluated in a pediatric population. Methods: Urine samples were collected from a tertiary children’s hospital. Medical records were reviewed and patients who met criteria were sorted into 3 categories: 1. AKI; 2. Hospitalized controls; and 3. Outpatient controls. ETP was measured using ELISA, and results were corrected to urine creatinine (uETP:Cre). A multivariate linear regression assessed whether demographic variables independently associated with uETP:Cre. Odds of AKI were assessed in serial uETP:Cre tertiles using a multivariate logistic regression model that adjusted for patient variables. Results: uETP:Cre was elevated in patients with AKI compared to hospitalized patients without AKI (p<0.05) and outpatient controls (p<0.0001). Multivariate analysis revealed that age, but not sex, race, or ethnicity independently correlated with uETP:Cre. After adjustment for these variables, the odds ratio for AKI increased with serial uETP:Cre tertiles. Conclusions: Non-invasive measurement of uETP may deliver meaningful information to aid AKI diagnosis. Given that ETP may be both a biomarker and a clinically actionable stimulus of inflammation and fibrosis, future studies are needed to understand the role of elevated ETP in AKI and if existing ETP neutralizing antibodies could represent a new avenue of AKI therapy.