Comparative analysis of urinary biomarkers for early detection of acute kidney injury following cardiopulmonary bypass

Abstract

The purpose of this study was to compare the performance of six candidate urinary biomarkers, kidney injury molecule (KIM)-1, N-acetyl-β-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL), interleukin (IL)-18, cystatin C and α-1 microglobulin, measured 2 h following cardiopulmonary bypass (CPB) for the early detection of acute kidney injury (AKI) in a prospective cohort of patients undergoing cardiac surgery. A total of 103 subjects were enrolled; AKI developed in 13%. Urinary KIM-1 achieved the highest area under-the-receiver-operator-characteristic curve (AUC 0.78, 95% confidence interval 0.64–0.91), followed by IL-18 and NAG. Only urinary KIM-1 remained independently associated with AKI after adjustment for a preoperative AKI prediction score (Cleveland Clinic Foundation score; p = 0.02), or CPB perfusion time (p = 0.006). In this small pilot cohort, KIM-1 performed best as an early biomarker for AKI. Larger studies are needed to explore further the role of biomarkers for early detection of AKI following cardiac surgery.

Keywords::

• Acute kidney injury
• early detection
• urinary biomarker
• cardiac surgery

Acknowledgements

This study was supported by grants from the Norman Coplon Research Program of Satellite Healthcare, Inc. (to B.L.J.), the American Heart Association (to O.L.), and the Earl P. Charlton Research Program of Tufts University School of Medicine (to O.L.). O.L. is supported by a grant from the American Heart Association (AHA no. 0535367N). B.L.J. is supported by grants from the National Institutes of Health (DK065102 and DK077751). J.V.B. is supported by grants from the National Institutes of Health (DK 39773, DK 074099, DK 072381). W.K.H. is supported by a grant from the National Institutes of Health (DK64075). The authors thank members of the Divisions of Cardio-thoracic Surgery at each participating institution, and Noreen Dolan, RN and Robert W. MacKinnon RN for assistance with enrolment of study participants, and Mary Lou Ganzer, PhD (Siemens Healthcare Diagnostics, Deerfield, IL) for loaning the Behring Nephelometer II System to the Kidney & Dialysis Research Laboratory of Caritas St Elizabeth’s Medical Center, and for providing expert technical advice. This work was presented in part at the 40th Annual Meeting of the American Society of Nephrology, San Francisco, CA, USA, 31 October to 5 November, 2007.

Declaration of interests: The authors alone are responsible for the content and writing of the paper. J.V.B. is a co-inventor on KIM-1 patents (patent numbers 6,664,385 and 7,179,901) that are licensed to Johnson and Johnson.