Sensitivity and Specificity of a Single Emergency Department Measurement of Urinary Neutrophil Gelatinase–Associated Lipocalin for Diagnosing Acute Kidney Injury

3 June 2008 | Volume 148 Issue 11 | Pages 810-819

Background: A single serum creatinine measurement cannot distinguish acute kidney injury from chronic kidney disease or prerenal azotemia.

Objective: To test the sensitivity and specificity of a single measurement of urinary neutrophil gelatinase–associated lipocalin (NGAL) and other urinary proteins to detect acute kidney injury in a spectrum of patients.

Design: Prospective cohort study.

Setting: Emergency department of Columbia University Medical Center, New York, New York.

Participants: 635 patients admitted to the hospital with acute kidney injury, prerenal azotemia, chronic kidney disease, or normal kidney function.

Measurements: Diagnosis of acute kidney injury was based on the RIFLE (risk, injury, failure, loss, and end-stage) criteria and assigned by researchers who were blinded to experimental measurements. Urinary NGAL was measured by immunoblot, N-acetyl-β-d-glucosaminidase (NAG) by enzyme measurement, ₁-microglobulin and ₁-acid glycoprotein by immunonephelometry, and serum creatinine by Jaffe kinetic reaction. Experimental measurements were not available to treating physicians.

Results: Patients with acute kidney injury had a significantly elevated mean urinary NGAL level compared with the other kidney function groups (416 µg/g creatinine [SD, 387]; P = 0.001). At a cutoff value of 130 µg/g creatinine, sensitivity and specificity of NGAL for detecting acute injury were 0.900 (95% CI, 0.73 to 0.98) and 0.995 (CI, 0.990 to 1.00), respectively, and positive and negative likelihood ratios were 181.5 (CI, 58.33 to 564.71) and 0.10 (CI, 0.03 to 0.29); these values were superior to those for NAG, ₁-microglobulin, ₁-acid glycoprotein, fractional excretion of sodium, and serum creatinine. In multiple logistic regression, urinary NGAL level was highly predictive of clinical outcomes, including nephrology consultation, dialysis, and admission to the intensive care unit (odds ratio, 24.71 [CI, 7.69 to 79.42]).

Limitations: All patients came from a single center. Few kidney biopsies were performed.

Conclusion: A single measurement of urinary NGAL helps to distinguish acute injury from normal function, prerenal azotemia, and chronic kidney disease and predicts poor inpatient outcomes.

Editors' Notes Context Studies in surgical patients suggest that urinary neutrophil gelatinase–associated lipocalin (NGAL) may be an effective test for diagnosing acute kidney injury. Contribution The authors measured markers of renal function in 635 consecutive adults who were admitted to the emergency department of 1 urban hospital; of these patients, 30 had a final clinical diagnosis of acute kidney injury. When urinary NGAL was at least 130 µg/g creatinine, the test was highly discriminatory for acute kidney injury (sensitivity, 0.90; specificity, 0.995; positive likelihood ratio, 181.5; and negative likelihood ratio, 0.10). Caution Patients were from 1 setting in 1 hospital. Kidney diagnoses were clinical, not biopsy-proven. Implication Urinary NGAL is a promising test because of its large effect on the probability of acute kidney injury. —The Editors

 

Author and Article Information

From Columbia University, New York, New York; Kyoto University Graduate School of Medicine, Kyoto, Japan; and Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, Ohio.

Note: Drs. Nickolas and Yang and Mr. O'Rourke contributed equally to this work.

Disclaimer: The contents of this article are solely the responsibility of the authors and do not necessarily represent the official view of the National Center for Research Resources or the NIH.

Acknowledgment: The authors thank Dean Lee Goldman, Columbia University, for critical review. This work would not have been possible without the generous support of the Emerald Foundation.

Grant Support: From the Emerald Foundation; the National Institutes of Health (grants DK55388, DK58872, and DK73462); the March of Dimes; the Doris Duke Foundation; the National Center for Research Resources, a component of the NIH (grant UL1 RR024156); and NIH Roadmap for Medical Research.

Potential Financial Conflicts of Interest: Honoraria: P. Devarajan (Biosite, Abbott). Grants pending: P. Devarajan (Abbott, Biosite). Patents pending: T.L. Nickolas (NGAL for diagnosis of chronic renal failure), K. Mori (NGAL for diagnosis of chronic renal failure), P. Devarajan (NGAL for diagnosis of acute renal failure and NGAL for diagnosis of chronic renal failure), J. Barasch (NGAL for diagnosis of acute renal failure and NGAL for diagnosis of chronic renal failure). Cincinnati Children's Hospital Medical Center and Columbia University have received licensing fees from Biosite and Abbott Diagnostics for technology to use NGAL as a biomarker of acute renal failure.

Reproducible Research Statement: Study protocol, statistical code, and data set: Available by written agreement from Dr. Nickolas (e-mail, tln2001{at}columbia.edu).

Requests for Single Reprints: Thomas L. Nickolas, MD, MS, Columbia University, PH 4 Stem, Room 124, 622 West 168th Street, New York, NY 10032; e-mail, tln2001{at}columbia.edu.

Current Author Addresses: Drs. Nickolas, Canetta, Khan, and J. Barasch; Ms. Sise; Mr. Buchen; and Mr. N. Barasch: Department of Medicine, Columbia University, 630 West 168th Street, New York, NY 10032.

Mr. O'Rourke: College of Physicians and Surgeons, Columbia University Medical School, 630 West 168th Street, New York, NY 10032.

Dr. Yang: Saint Luke's Roosevelt Hospital, Columbia University, 1000 Tenth Avenue, New York, NY 10019.

Dr. Mori: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku hio 45229-3039, Kyoto 606-8507, Japan.

Dr. Giglio: Department of Emergency Medicine, Columbia University, 630 West 168th Street, New York, NY 10032.

Dr. Devarajan: Section of Nephrology, Cincinnati Children's Hospital, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229-3039.

Author Contributions: Conception and design: T.L. Nickolas, M.J. O'Rourke, J. Yang, N. Barasch, K. Mori, J. Giglio, P. Devarajan, J. Barasch.

Analysis and interpretation of the data: T.L. Nickolas, M.J. O'Rourke, M.E. Sise, P.A. Canetta, N. Barasch, C. Buchen, F. Khan, K. Mori, J. Giglio, P. Devarajan, J. Barasch.

Drafting of the article: T.L. Nickolas, M.J. O'Rourke, M.E. Sise, P.A. Canetta, N. Barasch, C. Buchen, K. Mori, J. Giglio, P. Devarajan, J. Barasch.

Critical revision of the article for important intellectual content: T.L. Nickolas, M.J. O'Rourke, M.E. Sise, P.A. Canetta, K. Mori, J. Giglio, P. Devarajan, J. Barasch.

Final approval of the article: T.L. Nickolas, M.J. O'Rourke, J. Yang, M.E. Sise, P.A. Canetta, N. Barasch, C. Buchen, F. Khan, K. Mori, J. Giglio, P. Devarajan, J. Barasch.

Provision of study materials or patients: T.L. Nickolas, M.J. O'Rourke, M.E. Sise, N. Barasch.

Statistical expertise: T.L. Nickolas, K. Mori.

Obtaining of funding: T.L. Nickolas, J. Barasch.

Administrative, technical, or logistic support: T.L. Nickolas, M.J. O'Rourke, M.E. Sise, N. Barasch, C. Buchen, F. Khan, K. Mori, J. Giglio, J. Barasch.

Collection and assembly of data: T.L. Nickolas, M.J. O'Rourke, M.E. Sise, N. Barasch, C. Buchen, F. Khan.