Urinary Netrin-1 Is an Early Predictive Biomarker of Acute Kidney Injury after Cardiac Surgery

Background and objectives: Netrin-1, a laminin-related axon guidance molecule, is highly induced and excreted in the urine after acute kidney injury (AKI) in animals. Here, we determined the utility of urinary netrin-1 levels to predict AKI in humans undergoing cardiopulmonary bypass (CPB). Design, setting, participants, & measurements: Serial urine samples were analyzed by enzyme-linked immunosorbent assay for netrin-1 in 26 patients who developed AKI (defined as a 50%, or greater increase in serum creatinine after CPB) and 34 controls (patients who did not develop AKI after CPB). Results: Using serum creatinine, AKI was detected on average only 48 hours after CPB. In contrast, urine netrin-1 increased at 2 hours after CPB, peaked at 6 hours (2462 +/- 370 pg/mg creatinine), and remained elevated up to 48 hours after CPB. The predictive power of netrin-1 as demonstrated by area under the receiver-operating characteristics curve for diagnosis of AKI at 2, 6, and 12 hours after CPB was 0.74, 0.86, and 0.89, respectively. The 6-hour urine netrin-1 measurement strongly correlated with duration and severity of AKI, as well as length of hospital stay (all P < 0.05). Adjusting for CPB time, the 6-hour netrin-1 remained a powerful independent predictor of AKI, with an odds ratio of 1.20 (95%) confidence interval: 1.08 to 1.41; P = 0.006). Conclusion: Our results suggest that netrin-1 is an early, predictive biomarker of AKI after CPB and may allow for the reliable early diagnosis and prognosis of AKI after CPB, before the rise in serum creatinine. Clin J Am Soc Nephrol 5: 395-401, 2010. doi: 10.2215/CJN.05140709