The Outcome of Neutrophil Gelatinase-Associated Lipocalin-Positive Subclinical Acute Kidney Injury A Multicenter Pooled Analysis of Prospective Studies

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:57

Article

Haase, Michael^1,2,3  Devarajan, Prasad⁴  Haase-Fielitz, Anja^1,2,3  Bellomo, Rinaldo⁵  Cruz, Dinna N.⁶  Wagener, Gebhard⁷  Krawczeski, Catherine D.⁴  Koyner, Jay L.⁸  Murray, Patrick^9,10  Zappitelli, Michael¹¹  Goldstein, Stuart L.¹²  Makris, Konstantinos¹³  Ronco, Claudio⁶  Martensson, Johan¹⁴  Martling, Claes-Roland^14,15  Venge, Per^14,15  Siew, Edward^15,16  Ware, Lorraine B.¹⁶  Ikizler, T. Alp¹⁶  Mertens, Peter R.³ 

[1] Charite, Dept Nephrol & Intens Care, D-13353 Berlin, Germany

[2] Campus Virchow Klinikum, Berlin, Germany

[3] Otto VonGuericke Univ Magdegurg, Dept Nephrol & Hypertens & Endocrinol & Metab Dis, D-39016 Magdeburg, Germany

[4] Cincinnati Childrens Hosp, Med Ctr, Dept Pediat, Cincinnati, OH USA

[5] Austin Hlth, Dept Intens Care, Melbourne, Vic, Australia

[6] San Bortolo Hosp, Dept Nephrol Dialysis & Transplantat, IRRIV, Vicenza, Italy

[7] Columbia Univ, Dept Anesthesiol, Coll Phys & Surg, New York, NY USA

[8] Univ Chicago, Dept Med, Nephrol Sect, Chicago, IL 60637 USA

[9] Mater Misericordiae Univ Hosp, Dept Nephrol, Dublin, Ireland

[10] Mater Misericordiae Univ Hosp, Dept Clin Pharmacol, Dublin, Ireland

[11] McGill Univ, Dept Pediat, Div Nephrol, Montreal, PQ H3A 2T5, Canada

[12] Cincinnati Childrens Hosp, Div Nephrol & Hypertens, Cincinnati, OH USA

[13] KAT Gen Hosp, Dept Clin Biochem, Athens, Greece

[14] Uppsala Univ, Dept Physiol & Pharmacol, Karolinska Inst, Stockholm, Sweden

[15] Uppsala Univ, Dept Med Sci, Clin Chem, Stockholm, Sweden

[16] Vanderbilt Univ, Med Ctr, Dept Med, Div Nephrol,Allergy Pulm & Crit Care Med, Nashville, TN USA

关键词: acute kidney injury (AKI);    biomarker;    creatinine;    mortality;    neutrophil gelatinase-associated lipocalin (NGAL);    renal replacement therapy (RRT);   

DOI  :  10.1016/j.jacc.2010.11.051

来源: Elsevier

【 摘 要 】

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. (J Am Coll Cardiol 2011;57:1752-61) (C) 2011 by the American College of Cardiology Foundation

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