Author + information
- Received September 1, 2010
- Revision received November 1, 2010
- Accepted November 9, 2010
- Published online April 26, 2011.
- Michael Haase, MD⁎,†,
- Prasad Devarajan, MD‡,
- Anja Haase-Fielitz, PharmD⁎,†,
- Rinaldo Bellomo, MD§,⁎ (, )
- Dinna N. Cruz, MD, MPH∥,
- Gebhard Wagener, MD¶,
- Catherine D. Krawczeski, MD‡,
- Jay L. Koyner, MD#,
- Patrick Murray, MD⁎⁎,
- Michael Zappitelli, MD, MSc††,
- Stuart L. Goldstein, MD‡‡,
- Konstantinos Makris, PhD§§,
- Claudio Ronco, MD∥,
- Johan Martensson, MD∥∥,
- Claes-Roland Martling, MD∥∥,
- Per Venge, MD∥∥,
- Edward Siew, MD¶¶,
- Lorraine B. Ware, MD¶¶,
- T. Alp Ikizler, MD¶¶ and
- Peter R. Mertens, MD†
- ↵⁎Reprint requests and correspondence:
Dr. Rinaldo Bellomo, Department of Intensive Care, Austin Hospital, Studley Road, 3084 Victoria, Australia
Objectives The aim of this study was to test the hypothesis that, without diagnostic changes in serum creatinine, increased neutrophil gelatinase-associated lipocalin (NGAL) levels identify patients with subclinical acute kidney injury (AKI) and therefore worse prognosis.
Background Neutrophil gelatinase-associated lipocalin detects subclinical AKI hours to days before increases in serum creatinine indicate manifest loss of renal function.
Methods We analyzed pooled data from 2,322 critically ill patients with predominantly cardiorenal syndrome from 10 prospective observational studies of NGAL. We used the terms NGAL(−) or NGAL(+) according to study-specific NGAL cutoff for optimal AKI prediction and the terms sCREA(−) or sCREA(+) according to consensus diagnostic increases in serum creatinine defining AKI. A priori-defined outcomes included need for renal replacement therapy (primary endpoint), hospital mortality, their combination, and duration of stay in intensive care and in-hospital.
Results Of study patients, 1,296 (55.8%) were NGAL(−)/sCREA(−), 445 (19.2%) were NGAL(+)/sCREA(−), 107 (4.6%) were NGAL(−)/sCREA(+), and 474 (20.4%) were NGAL(+)/sCREA(+). According to the 4 study groups, there was a stepwise increase in subsequent renal replacement therapy initiation—NGAL(−)/sCREA(−): 0.0015% versus NGAL(+)/sCREA(−): 2.5% (odds ratio: 16.4, 95% confidence interval: 3.6 to 76.9, p < 0.001), NGAL(−)/sCREA(+): 7.5%, and NGAL(+)/sCREA(+): 8.0%, respectively, hospital mortality (4.8%, 12.4%, 8.4%, 14.7%, respectively) and their combination (4-group comparisons: all p < 0.001). There was a similar and consistent progressive increase in median number of intensive care and in-hospital days with increasing biomarker positivity: NGAL(−)/sCREA(−): 4.2 and 8.8 days; NGAL(+)/sCREA(−): 7.1 and 17.0 days; NGAL(−)/sCREA(+): 6.5 and 17.8 days; NGAL(+)/sCREA(+): 9.0 and 21.9 days; 4-group comparisons: p = 0.003 and p = 0.040, respectively. Urine and plasma NGAL indicated a similar outcome pattern.
Conclusions In the absence of diagnostic increases in serum creatinine, NGAL detects patients with likely subclinical AKI who have an increased risk of adverse outcomes. The concept and definition of AKI might need re-assessment.
- acute kidney injury (AKI)
- neutrophil gelatinase-associated lipocalin (NGAL)
- renal replacement therapy (RRT)
A full list of author disclosures can be found at the end of this paper. Drs. Haase, Devarajan, and Haase-Fielitz contributed equally to this work.
- Received September 1, 2010.
- Revision received November 1, 2010.
- Accepted November 9, 2010.
- American College of Cardiology Foundation