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.