Urinary complement C3 and vitamin D binding protein predict adverse outcomes in patients with acute kidney injury after cardiac surgery.

Introduction: Acute kidney injury is associated with adverse outcomes, including death and dialysis. The goal of this study was to identify prognostic biomarkers of Acute Kidney Injury (AKI) that could be used across multiple phenotypes of AKI, and across different species.

Methods: Liquid chromatography/tandem mass spectrometry analysis of urine samples from three species (human, rat, mouse) and four etiologies of acute kidney injury identified five potential biomarkers; of which two were validated, complement C3 and vitamin D binding protein, in a cohort of 157 patients that developed AKI following cardiothoracic surgery. We studied the relationship between the biomarker's concentration in the urine and the development of a composite primary endpoint (stage 3 acute kidney injury within 10 days or death within 30 days).

Results: Of the153 patients who developed acute kidney injury following cardiovascular surgery; 17 met the combined primary outcome. The median concentration of urine complement C3 adjusted to urine creatinine had the best predictive value and was significantly higher in the primary-outcome group than in the controls. Similarly, the median concentration of vitamin D binding protein was higher in the primary-outcome group.

Conclusions: The studies provide proof in principle that cross-species discovery analyses could be a valuable tool for identifying novel prognostic biomarkers in AKI. Urine complement C3 and vitamin D binding protein could be promising early predictors of adverse outcome in patients who develop AKI after cardiac surgery.