Neutrophil Gelatinase-Associated Lipocalin and Contrast-Induced Acute Kidney Injury.
BACKGROUND
Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of acute kidney injury (AKI).


RESULTS
Urine NGAL and serum NGAL (sNGAL) were assessed at 2, 6, 24, and 48 hours after contrast media (CM) exposure in 458 high-risk patients (development set). Optimal thresholds in predicting contrast-induced AKI (serum creatinine [sCr] increase ≥0.3 mg/dL at 48 hours after CM administration) were identified. Major adverse events (MAE; death, dialysis, nonfatal myocardial infarction, sustained kidney injury, and myocardial revascularization) at 1 year were assessed. In the development set, optimal thresholds for contrast-induced AKI occurred at 6 hours for both urine NGAL (≥20 ng/mL; 97% negative predictive value and 27% positive predictive value) and sNGAL (≥179 ng/mL; 93% negative predictive value and 20% positive predictive value). Furthermore, sNGAL ≥179 ng/mL at 6 hours was an independent predictor of 1-year MAE. 1-year MAE occurred in 27/198 patients (13.5%) with sNGAL <179 ng/mL and sCr <0.3 mg/dL, in 57/193 (29.5%) patients with only sNGAL ≥179 ng/mL, and in 37/67 (55%) patients with sCr ≥0.3 mg/dL. In additional 253 patients (validation set), no patient with urine NGAL <20 ng/mL or sNGAL <179 ng/mL at 6 hours developed contrast-induced AKI. Furthermore, 6/68 (9%) patients with sNGAL <179 ng/mL and sCr increase <0.3 mg/dL had 1-year MAE versus 17/57 (30%) patients with sNGAL ≥179 ng/mL and sCr increase <0.3 mg/dL and 8/16 (50%) patients with sCr increase ≥0.3 mg/dL.


CONCLUSIONS
Urine NGAL <20 ng/mL and sNGAL <179 ng/mL at 6 hours are reliable markers for ruling out contrast-induced AKI. sNGAL ≥179 ng/mL at 6 hours predicts 1-year MAE.


BACKGROUND
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01098032.
From the Department of Molecular Medicine and Medical Biotechnology, "Federico II" University, Naples, Italy (C.Q., E.P., G.C.); Institute of Genetics and Biomedical Research, Milan Unit, Milan, Italy (C.V.A., E.D.); Humanitas Research Hospital, Rozzano, Italy (C.V.A., E.D.); Laboratory of Interventional Cardiology and Department of Cardiology, Clinica Mediterranea, Naples, Italy (F.D.M., G.V., B.G., A.F., B.R., C.B.); Institute for Endocrinology and Experimental Oncology, National Research Council, Naples, Italy (G.R., L.P., G.C.); and SDN Foundation, Naples, Italy (E.D.).
Cristina
C
Quintavalle
From the Department of Molecular Medicine and Medical Biotechnology, "Federico II" University, Naples, Italy (C.Q., E.P., G.C.); Institute of Genetics and Biomedical Research, Milan Unit, Milan, Italy (C.V.A., E.D.); Humanitas Research Hospital, Rozzano, Italy (C.V.A., E.D.); Laboratory of Interventional Cardiology and Department of Cardiology, Clinica Mediterranea, Naples, Italy (F.D.M., G.V., B.G., A.F., B.R., C.B.); Institute for Endocrinology and Experimental Oncology, National Research Council, Naples, Italy (G.R., L.P., G.C.); and SDN Foundation, Naples, Italy (E.D.).
Chiara Viviani
CV
Anselmi
From the Department of Molecular Medicine and Medical Biotechnology, "Federico II" University, Naples, Italy (C.Q., E.P., G.C.); Institute of Genetics and Biomedical Research, Milan Unit, Milan, Italy (C.V.A., E.D.); Humanitas Research Hospital, Rozzano, Italy (C.V.A., E.D.); Laboratory of Interventional Cardiology and Department of Cardiology, Clinica Mediterranea, Naples, Italy (F.D.M., G.V., B.G., A.F., B.R., C.B.); Institute for Endocrinology and Experimental Oncology, National Research Council, Naples, Italy (G.R., L.P., G.C.); and SDN Foundation, Naples, Italy (E.D.).
Francesca
F
De Micco
From the Department of Molecular Medicine and Medical Biotechnology, "Federico II" University, Naples, Italy (C.Q., E.P., G.C.); Institute of Genetics and Biomedical Research, Milan Unit, Milan, Italy (C.V.A., E.D.); Humanitas Research Hospital, Rozzano, Italy (C.V.A., E.D.); Laboratory of Interventional Cardiology and Department of Cardiology, Clinica Mediterranea, Naples, Italy (F.D.M., G.V., B.G., A.F., B.R., C.B.); Institute for Endocrinology and Experimental Oncology, National Research Council, Naples, Italy (G.R., L.P., G.C.); and SDN Foundation, Naples, Italy (E.D.).
Giuseppina
G
Roscigno
From the Department of Molecular Medicine and Medical Biotechnology, "Federico II" University, Naples, Italy (C.Q., E.P., G.C.); Institute of Genetics and Biomedical Research, Milan Unit, Milan, Italy (C.V.A., E.D.); Humanitas Research Hospital, Rozzano, Italy (C.V.A., E.D.); Laboratory of Interventional Cardiology and Department of Cardiology, Clinica Mediterranea, Naples, Italy (F.D.M., G.V., B.G., A.F., B.R., C.B.); Institute for Endocrinology and Experimental Oncology, National Research Council, Naples, Italy (G.R., L.P., G.C.); and SDN Foundation, Naples, Italy (E.D.).
Gabriella
G
Visconti
From the Department of Molecular Medicine and Medical Biotechnology, "Federico II" University, Naples, Italy (C.Q., E.P., G.C.); Institute of Genetics and Biomedical Research, Milan Unit, Milan, Italy (C.V.A., E.D.); Humanitas Research Hospital, Rozzano, Italy (C.V.A., E.D.); Laboratory of Interventional Cardiology and Department of Cardiology, Clinica Mediterranea, Naples, Italy (F.D.M., G.V., B.G., A.F., B.R., C.B.); Institute for Endocrinology and Experimental Oncology, National Research Council, Naples, Italy (G.R., L.P., G.C.); and SDN Foundation, Naples, Italy (E.D.).
Bruno
B
Golia
From the Department of Molecular Medicine and Medical Biotechnology, "Federico II" University, Naples, Italy (C.Q., E.P., G.C.); Institute of Genetics and Biomedical Research, Milan Unit, Milan, Italy (C.V.A., E.D.); Humanitas Research Hospital, Rozzano, Italy (C.V.A., E.D.); Laboratory of Interventional Cardiology and Department of Cardiology, Clinica Mediterranea, Naples, Italy (F.D.M., G.V., B.G., A.F., B.R., C.B.); Institute for Endocrinology and Experimental Oncology, National Research Council, Naples, Italy (G.R., L.P., G.C.); and SDN Foundation, Naples, Italy (E.D.).
Amelia
A
Focaccio
From the Department of Molecular Medicine and Medical Biotechnology, "Federico II" University, Naples, Italy (C.Q., E.P., G.C.); Institute of Genetics and Biomedical Research, Milan Unit, Milan, Italy (C.V.A., E.D.); Humanitas Research Hospital, Rozzano, Italy (C.V.A., E.D.); Laboratory of Interventional Cardiology and Department of Cardiology, Clinica Mediterranea, Naples, Italy (F.D.M., G.V., B.G., A.F., B.R., C.B.); Institute for Endocrinology and Experimental Oncology, National Research Council, Naples, Italy (G.R., L.P., G.C.); and SDN Foundation, Naples, Italy (E.D.).
Bruno
B
Ricciardelli
From the Department of Molecular Medicine and Medical Biotechnology, "Federico II" University, Naples, Italy (C.Q., E.P., G.C.); Institute of Genetics and Biomedical Research, Milan Unit, Milan, Italy (C.V.A., E.D.); Humanitas Research Hospital, Rozzano, Italy (C.V.A., E.D.); Laboratory of Interventional Cardiology and Department of Cardiology, Clinica Mediterranea, Naples, Italy (F.D.M., G.V., B.G., A.F., B.R., C.B.); Institute for Endocrinology and Experimental Oncology, National Research Council, Naples, Italy (G.R., L.P., G.C.); and SDN Foundation, Naples, Italy (E.D.).
Enzo
E
Perna
From the Department of Molecular Medicine and Medical Biotechnology, "Federico II" University, Naples, Italy (C.Q., E.P., G.C.); Institute of Genetics and Biomedical Research, Milan Unit, Milan, Italy (C.V.A., E.D.); Humanitas Research Hospital, Rozzano, Italy (C.V.A., E.D.); Laboratory of Interventional Cardiology and Department of Cardiology, Clinica Mediterranea, Naples, Italy (F.D.M., G.V., B.G., A.F., B.R., C.B.); Institute for Endocrinology and Experimental Oncology, National Research Council, Naples, Italy (G.R., L.P., G.C.); and SDN Foundation, Naples, Italy (E.D.).
Laura
L
Papa
From the Department of Molecular Medicine and Medical Biotechnology, "Federico II" University, Naples, Italy (C.Q., E.P., G.C.); Institute of Genetics and Biomedical Research, Milan Unit, Milan, Italy (C.V.A., E.D.); Humanitas Research Hospital, Rozzano, Italy (C.V.A., E.D.); Laboratory of Interventional Cardiology and Department of Cardiology, Clinica Mediterranea, Naples, Italy (F.D.M., G.V., B.G., A.F., B.R., C.B.); Institute for Endocrinology and Experimental Oncology, National Research Council, Naples, Italy (G.R., L.P., G.C.); and SDN Foundation, Naples, Italy (E.D.).
Elvira
E
Donnarumma
From the Department of Molecular Medicine and Medical Biotechnology, "Federico II" University, Naples, Italy (C.Q., E.P., G.C.); Institute of Genetics and Biomedical Research, Milan Unit, Milan, Italy (C.V.A., E.D.); Humanitas Research Hospital, Rozzano, Italy (C.V.A., E.D.); Laboratory of Interventional Cardiology and Department of Cardiology, Clinica Mediterranea, Naples, Italy (F.D.M., G.V., B.G., A.F., B.R., C.B.); Institute for Endocrinology and Experimental Oncology, National Research Council, Naples, Italy (G.R., L.P., G.C.); and SDN Foundation, Naples, Italy (E.D.). carlobriguori@clinicamediterranea.it gecondor@unina.it.
Gerolama
G
Condorelli
From the Department of Molecular Medicine and Medical Biotechnology, "Federico II" University, Naples, Italy (C.Q., E.P., G.C.); Institute of Genetics and Biomedical Research, Milan Unit, Milan, Italy (C.V.A., E.D.); Humanitas Research Hospital, Rozzano, Italy (C.V.A., E.D.); Laboratory of Interventional Cardiology and Department of Cardiology, Clinica Mediterranea, Naples, Italy (F.D.M., G.V., B.G., A.F., B.R., C.B.); Institute for Endocrinology and Experimental Oncology, National Research Council, Naples, Italy (G.R., L.P., G.C.); and SDN Foundation, Naples, Italy (E.D.). carlobriguori@clinicamediterranea.it gecondor@unina.it.
Carlo
C
Briguori
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000175:diagnosis* / Q000378:metabolism; D000209:Acute-Phase Proteins / Q000652:urine; D000368:Aged; D000369:Aged, 80 and over; D000792:Angiography; D017130:Angioplasty; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003287:Contrast Media / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood* / Q000652:urine; D008297:Male; D011518:Proto-Oncogene Proteins / Q000097:blood* / Q000652:urine; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D014283:Triiodobenzoic Acids / Q000009:adverse effects*
D000209:Acute-Phase Proteins; D015415:Biomarkers; D003287:Contrast Media; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D014283:Triiodobenzoic Acids; D003404:Creatinine; C044834:iodixanol
NGAL; contrast media; kidney; kidney disease; prognostic factor