Netrin-1: A Novel Universal Biomarker of Human Kidney Injury

Currently available diagnostic markers representing kidney injury or function such as serum creatinine and blood urea nitrogen are insensitive and often increased late in the disease process. Netrin-1 protein, a laminin-related secreted molecule, is minimally or not expressed in tubular epithelial cells of normal kidneys. However, it is highly expressed in injured kidneys. Netrin-1 protein has been shown to be detected in urine from mice with acute kidney injury. The current study was carried out to evaluate whether netrin-1 is also induced in human acute kidney injury (AKI) and can serve as a urinary biomarker of the condition. We analyzed netrin-1 levels by sandwich enzyme-linked immunosorbent assay in urine samples from 10 healthy controls, 22 recipients of a renal allograft, 11 patients with ischemic AKI, 13 with AKI associated with sepsis, 9 with radiocontrast-induced AKI, and 8 with drug-induced AKI. Urinary netrin-1 levels normalized for urinary creatinine were significantly higher in all subject groups. The highest values were observed in patients with sepsis and in transplant patients immediately postoperatively. The level of NGAL was similarly increased in transplant patients. In conclusion, urinary netrin-1 levels are increased in patients with various forms of AKI/ATN and may serve as a universal biomarker for AKI.