Urinary netrin-1 is an early predictive biomarker of acute kidney injury after cardiac surgery.
OBJECTIVE
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).


METHODS
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).


CONCLUSIONS
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.
Ramesh
Ganesan
G
Division of Nephrology, H040, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. gramesh@psu.edu
Krawczeski
Catherine D
CD
Woo
Jessica G
JG
Wang
Yu
Y
Devarajan
Prasad
P
D000208:Acute Disease; D015415:Biomarkers / Q000097:blood / Q000652:urine; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006330:Heart Defects, Congenital / Q000601:surgery*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007674:Kidney Diseases / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000652:urine; D007902:Length of Stay; D016015:Logistic Models; D008297:Male; D009414:Nerve Growth Factors / Q000652:urine*; D000075388:Netrin-1; D016017:Odds Ratio; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000652:urine*; D015854:Up-Regulation
D015415:Biomarkers; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D003404:Creatinine