The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies.

The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies.

MedLine Citation:	PMID: 21511111 Owner: NLM Status: MEDLINE
Abstract/OtherAbstract:	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.

Authors:	Michael Haase; Prasad Devarajan; Anja Haase-Fielitz; Rinaldo Bellomo; Dinna N Cruz; Gebhard Wagener; Catherine D Krawczeski; Jay L Koyner; Patrick Murray; Michael Zappitelli; Stuart L Goldstein; Konstantinos Makris; Claudio Ronco; Johan Martensson; Claes-Roland Martling; Per Venge; Edward Siew; Lorraine B Ware; T Alp Ikizler; Peter R Mertens
Publication Detail:	Type: Comparative Study; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Journal Detail:	Title: Journal of the American College of Cardiology Volume: 57 ISSN: 1558-3597 ISO Abbreviation: J. Am. Coll. Cardiol. Publication Date: 2011 Apr
Date Detail:	Created Date: 2011-04-22 Completed Date: 2011-06-20 Revised Date: 2013-05-06
Medline Journal Info:	Nlm Unique ID: 8301365 Medline TA: J Am Coll Cardiol Country: United States
Other Details:	Languages: eng Pagination: 1752-61 Citation Subset: AIM; IM
Copyright Information:	Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Affiliation:	Department of Nephrology and Intensive Care, Charité-University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:	Acute Kidney Injury / blood, diagnosis, urine Acute-Phase Proteins / urine Adolescent Adult Aged Biological Markers / blood, urine Child Child, Preschool Cohort Studies Female Humans Lipocalins / blood, urine Male Middle Aged Prospective Studies Proto-Oncogene Proteins / blood, urine Retrospective Studies Treatment Outcome Young Adult
Grant Support
ID/Acronym/Agency:	K23DK081616/DK/NIDDK NIH HHS; K24 HL103836/HL/NHLBI NIH HHS; U01 HL081332/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:	0/Acute-Phase Proteins; 0/Biological Markers; 0/LCN2 protein, human; 0/Lipocalins; 0/Proto-Oncogene Proteins
Comments/Corrections
Comment In:	J Am Coll Cardiol. 2011 Apr 26;57(17):1762-4 [PMID: 21511112 ]

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