title: Neutrophil Gelatinase-Associated Lipocalin for Acute Kidney Injury During Acute Heart Failure Hospitalizations: The AKINESIS Study.
abstract: Worsening renal function (WRF) often occurs during acute heart failure (AHF) and can portend adverse outcomes; therefore, early identification may help mitigate risk. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel renal biomarker that may predict WRF in certain disorders, but its value in AHF is unknown.
  
  
  
  This study sought to determine whether NGAL is superior to creatinine for prediction and/or prognosis of WRF in hospitalized patients with AHF treated with intravenous diuretic agents.
  
  
  
  This was a multicenter, prospective cohort study enrolling patients presenting with AHF requiring intravenous diuretic agents. The primary outcome was whether plasma NGAL could predict the development of WRF, defined as a sustained increase in plasma creatinine of 0.5 mg/dl or ≥50% above first value or initiation of acute renal-replacement therapy, within the first 5 days of hospitalization. The main secondary outcome was in-hospital adverse events.
  
  
  
  We enrolled 927 subjects (mean age, 68.5 years; 62% men). The primary outcome occurred in 72 subjects (7.8%). Peak NGAL was more predictive than the first NGAL, but neither added significant diagnostic utility over the first creatinine (areas under the curve: 0.656, 0.647, and 0.652, respectively). There were 235 adverse events in 144 subjects. The first NGAL was a better predictor than peak NGAL, but similar to the first creatinine (areas under the curve: 0.691, 0.653, and 0.686, respectively). In a post hoc analysis of subjects with an estimated glomerular filtration rate <60 ml/min/1.73 m(2), a first NGAL <150 ng/ml indicated a low likelihood of adverse events.
  
  
  
  Plasma NGAL was not superior to creatinine for the prediction of WRF or adverse in-hospital outcomes. The use of plasma NGAL to diagnose acute kidney injury in AHF cannot be recommended at this time. (Acute Kidney Injury Neutrophil Gelatinase-Associated Lipocalin [N-GAL] Evaluation of Symptomatic Heart Failure Study [AKINESIS]; NCT01291836).
authors.affiliation: Division of Cardiovascular Medicine, Veterans Affairs Medical Center, San Diego, La Jolla, California; Division of Cardiovascular Medicine, University of California, San Diego, La Jolla, California. Electronic address: amaisel@ucsd.edu.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Maisel
authors.affiliation: Division of Cardiovascular Medicine, University of California, San Diego, La Jolla, California.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wettersten
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.affiliation: Department of Cardiology, University Hospital Basel, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Mueller
authors.affiliation: Department of Cardiology, Athens University Hospital Attikon, University of Athens, Athens, Greece.
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Filippatos
authors.affiliation: Department of Emergency Medicine, Henry Ford Hospital System, Detroit, Michigan.
authors.forename: Richard
authors.initials: R
authors.lastname: Nowak
authors.affiliation: Division of Emergency Medicine and Acute Care Surgical Services, VCU Medical Center, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Hogan
authors.affiliation: Division of Cardiology, VCU Medical Center, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Kontos
authors.affiliation: Department of Emergency Medicine, University of Kansas Hospital, Kansas City, Kansas.
authors.forename: Chad M
authors.initials: CM
authors.lastname: Cannon
authors.affiliation: Department of Nephrology and Rheumatology, University Medical Center Göttingen, University of Göttingen, Göttingen, Germany.
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Müller
authors.affiliation: Department of Emergency Medicine, New York Methodist, Brooklyn, New York.
authors.forename: Robert
authors.initials: R
authors.lastname: Birkhahn
authors.affiliation: Division of Cardiovascular Medicine, Veterans Affairs Medical Center, San Diego, La Jolla, California.
authors.forename: Paul
authors.initials: P
authors.lastname: Clopton
authors.affiliation: Division of Cardiovascular Medicine, University of California, San Diego, La Jolla, California.
authors.forename: Pam
authors.initials: P
authors.lastname: Taub
authors.affiliation: Departement of Emergency Medicine, University of California, San Diego, La Jolla, California.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Vilke
authors.affiliation: Department of Cardiology, St. Vincent's University Hospital, Dublin, Ireland; Department of Nephrology, Mater Misericordaie University Hospital, University College Dublin, Dublin, Ireland.
authors.forename: Kenneth
authors.initials: K
authors.lastname: McDonald
authors.affiliation: Department of Nephrology, Mater Misericordaie University Hospital, University College Dublin, Dublin, Ireland; Department of Cardiology, Mater Misericordaie University Hospital, Dublin, Ireland.
authors.forename: Niall
authors.initials: N
authors.lastname: Mahon
authors.affiliation: Department of Cardiology, Hospital Clínico Universitario Valencia, University of Valencia, Valencia, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Nuñez
authors.affiliation: Department of Cardiology, Clinica Mediterranea, Naples, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Briguori
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, Fondazione Gabriele Monasterio, Pisa, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Passino
authors.affiliation: Department of Nephrology, Mater Misericordaie University Hospital, University College Dublin, Dublin, Ireland.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Murray
mesh_terms: D000208:Acute Disease; D058186:Acute Kidney Injury / Q000097:blood* / Q000175:diagnosis* / Q000209:etiology; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood*; D004232:Diuretics / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D006760:Hospitalization; D006801:Humans; D000071068:Lipocalin-2 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D004232:Diuretics; D000071068:Lipocalin-2; D003404:Creatinine
keywords: biomarkers; cardiorenal syndrome; diuretics; worsening renal function