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

Ganesan Ramesh, Catherine D. Krawczeski, Jessica G. Woo, Yu Wang, Prasad Devarajan

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)395-401
Number of pages7
JournalClinical Journal of the American Society of Nephrology
Volume5
Issue number3
DOIs
StatePublished - Mar 1 2010

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Cardiopulmonary Bypass
Acute Kidney Injury
Thoracic Surgery
Biomarkers
Creatinine
Urine
Length of Stay
Serum
netrin-1
Laminin
ROC Curve
Early Diagnosis
Enzyme-Linked Immunosorbent Assay
Odds Ratio
Confidence Intervals

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation

Cite this

Urinary netrin-1 is an early predictive biomarker of acute kidney injury after cardiac surgery. / Ramesh, Ganesan; Krawczeski, Catherine D.; Woo, Jessica G.; Wang, Yu; Devarajan, Prasad.

In: Clinical Journal of the American Society of Nephrology, Vol. 5, No. 3, 01.03.2010, p. 395-401.

Research output: Contribution to journalArticle

Ramesh, Ganesan ; Krawczeski, Catherine D. ; Woo, Jessica G. ; Wang, Yu ; Devarajan, Prasad. / Urinary netrin-1 is an early predictive biomarker of acute kidney injury after cardiac surgery. In: Clinical Journal of the American Society of Nephrology. 2010 ; Vol. 5, No. 3. pp. 395-401.
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abstract = "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.",
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