Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy: A Systematic Review and Meta-analysis

Albert C 1 , Zapf A 2 , Haase M 3 , Röver C 4 , Pickering JW 5 , Albert A 6 Show all authors , Bellomo R 7 , Breidthardt T 8 , Camou F 9 , Chen Z 10 , Chocron S 11 , Cruz D 12 , de Geus HRH 13 , Devarajan P 14 , Di Somma S 15 , Doi K 16 , Endre ZH 17 , Garcia-Alvarez M 18 , Hjortrup PB 19 , Hur M 20 , Karaolanis G 21 , Kavalci C 22 , Kim H 20 , Lentini P 23 , Liebetrau C 24 , Lipcsey M 25 , Mårtensson J 26 , Müller C 8 , Nanas S 27 , Nickolas TL 28 , Pipili C 27 , Ronco C 29 , Rosa-Diez GJ 30 , Ralib A 31 , Soto K 32 , Braun-Dullaeus RC 33 , Heinz J 4 , Haase-Fielitz A 34

Affiliations 

  • 1 University Clinic for Cardiology and Angiology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany; Diaverum Renal Services Germany, Potsdam, Germany. Electronic address: christian.albert@diaverum.com
  • 2 Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg-Eppendorf, Germany
  • 3 Faculty of Medicine, Otto-von-Guericke University, Magdeburg, Germany; Diaverum Renal Services Germany, Potsdam, Germany
  • 4 Department of Medical Statistics, University Medical Center Göttingen, Göttingen, Germany
  • 5 Department of Medicine, University of Otago Christchurch; Emergency Department, Christchurch Hospital, Christchurch, New Zealand
  • 6 Diaverum Renal Services Germany, Potsdam, Germany; Department for Nephrology and Endocrinology, Klinikum Ernst von Bergmann, Potsdam, Germany
  • 7 Department of Intensive Care, The Austin Hospital, Melbourne, Australia; Centre for Integrated Critical Care, The University of Melbourne, Melbourne, Australia
  • 8 Department of Internal Medicine, University Hospital Basel, Basel, Switzerland; Department of Nephrology, University Hospital Basel, Basel, Switzerland; Department of Cardiology, University Hospital Basel, Basel, Switzerland
  • 9 Service de réanimation médicale, hôpital Saint-André, CHU de Bordeaux, France
  • 10 Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangdong, China
  • 11 Department of Thoracic and Cardio-Vascular Surgery, University Hospital Jean Minjoz, Besançon, France
  • 12 Division of Nephrology-Hypertension, University of California, San Diego, CA
  • 13 Department of Intensive Care, Erasmus University Medical Center, Rotterdam, the Netherlands
  • 14 Division of Nephrology and Hypertension, Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, OH
  • 15 Emergency Medicine, Department of Medical-Surgery Sciences and Translational Medicine, Sapienza' University of Rome S. Andrea Hospital, Rome, Italy
  • 16 Department of Emergency and Critical Care Medicine, The University of Tokyo, Tokyo, Japan
  • 17 Department of Nephrology, Prince of Wales Hospital and Clinical School, University of New South Wales, Sydney, Australia
  • 18 Department of Anesthesiology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
  • 19 Department of Intensive Care, Copenhagen University Hospital, Copenhagen, Denmark
  • 20 Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea
  • 21 Vascular Unit, First Department of Surgery, "Laiko" General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
  • 22 Emergency Department, Baskent University Faculty of Medicine, Ankara, Turkey
  • 23 Department of Nephrology and Dialysis, San Bassiano Hospital, Bassano del Grappa, Italy
  • 24 Department of Cardiology, Kerckhoff Clinic, Bad Nauheim, Germany
  • 25 CIRRUS, Hedenstierna laboratory, Anaesthesiology and Intensive care, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
  • 26 Section of Anaesthesia and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
  • 27 First Critical Care Department, 'Evangelismos' General Hospital, National and Kapodistrian University of Athens, Athens, Greece
  • 28 Columbia University Vagelos College of Physicians and Surgeons, New York, NY
  • 29 Department of Nephrology, Dialysis & Transplantation, University of Padova, Vicenza, Italy; International Renal Research Institute, San Bortolo Hospital, Vicenza, Italy
  • 30 Department of Nephrology, Dialysis and Transplantation, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
  • 31 Department of Anaesthesiology and Intensive Care, International Islamic University Malaysia, Pahang, Malaysia
  • 32 Department of Nephrology, Hospital Fernando Fonseca, Lisbon, Portugal; CEAUL, Centro de Estatística e Aplicações da Universidade de Lisboa, Lisbon, Portugal
  • 33 University Clinic for Cardiology and Angiology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany
  • 34 Department of Cardiology, Immanuel Diakonie Bernau, Heart Center Brandenburg, Brandenburg Medical School Theodor Fontane, Faculty of Health Sciences, University of Potsdam, Potsdam, Germany
Am J Kidney Dis, 2020 12;76(6):826-841.e1.
PMID: 32679151 DOI: 10.1053/j.ajkd.2020.05.015

Abstract

RATIONALE & OBJECTIVE: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction.

STUDY DESIGN: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines.

SETTING & STUDY POPULATIONS: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms.

SELECTION CRITERIA FOR STUDIES: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI.

DATA EXTRACTION: Individual-study-data meta-analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis.

ANALYTICAL APPROACH: Individual-study-data meta-analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses.

RESULTS: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.79-0.81) and 0.86 (95% CI, 0.84-0.86). Cutoff concentrations at 95% specificity for urinary NGAL were>580ng/mL with 27% sensitivity for severe AKI and>589ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were>364ng/mL with 44% sensitivity and>546ng/mL with 26% sensitivity, respectively.

LIMITATIONS: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies.

CONCLUSIONS: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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