Neutrophil Gelatinase-Associated Lipocalin for Acute Kidney Injury During Acute Heart Failure Hospitalizations: The AKINESIS Study

Alan S. Maisel, Nicholas Wettersten, Dirk J. van Veldhuisen, Christian Mueller, Gerasimos Filippatos, Richard Nowak, Christopher Hogan, Michael C. Kontos, Chad M. Cannon, Gerhard A. Müller, Robert Birkhahn, Paul Clopton, Pam Taub, Gary M. Vilke, Kenneth McDonald, Niall Mahon, Julio Nuñez, Carlo Briguori, Claudio Passino, Patrick T. Murray

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Background 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. Objectives 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. Methods 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. Results 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 m2, a first NGAL <150 ng/ml indicated a low likelihood of adverse events. Conclusions 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)

Original languageEnglish (US)
Pages (from-to)1420-1431
Number of pages12
JournalJournal of the American College of Cardiology
Volume68
Issue number13
DOIs
StatePublished - Sep 27 2016

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Acute Kidney Injury
Hospitalization
Heart Failure
Kidney
Creatinine
Diuretics
Area Under Curve
Lipocalin-2
Lipocalins
Gelatinases
Renal Replacement Therapy
Glomerular Filtration Rate
Cohort Studies
Biomarkers
Prospective Studies

Keywords

  • biomarkers
  • cardiorenal syndrome
  • diuretics
  • worsening renal function

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Neutrophil Gelatinase-Associated Lipocalin for Acute Kidney Injury During Acute Heart Failure Hospitalizations : The AKINESIS Study. / Maisel, Alan S.; Wettersten, Nicholas; van Veldhuisen, Dirk J.; Mueller, Christian; Filippatos, Gerasimos; Nowak, Richard; Hogan, Christopher; Kontos, Michael C.; Cannon, Chad M.; Müller, Gerhard A.; Birkhahn, Robert; Clopton, Paul; Taub, Pam; Vilke, Gary M.; McDonald, Kenneth; Mahon, Niall; Nuñez, Julio; Briguori, Carlo; Passino, Claudio; Murray, Patrick T.

In: Journal of the American College of Cardiology, Vol. 68, No. 13, 27.09.2016, p. 1420-1431.

Research output: Contribution to journalArticle

Maisel, AS, Wettersten, N, van Veldhuisen, DJ, Mueller, C, Filippatos, G, Nowak, R, Hogan, C, Kontos, MC, Cannon, CM, Müller, GA, Birkhahn, R, Clopton, P, Taub, P, Vilke, GM, McDonald, K, Mahon, N, Nuñez, J, Briguori, C, Passino, C & Murray, PT 2016, 'Neutrophil Gelatinase-Associated Lipocalin for Acute Kidney Injury During Acute Heart Failure Hospitalizations: The AKINESIS Study', Journal of the American College of Cardiology, vol. 68, no. 13, pp. 1420-1431. https://doi.org/10.1016/j.jacc.2016.06.055
Maisel, Alan S. ; Wettersten, Nicholas ; van Veldhuisen, Dirk J. ; Mueller, Christian ; Filippatos, Gerasimos ; Nowak, Richard ; Hogan, Christopher ; Kontos, Michael C. ; Cannon, Chad M. ; Müller, Gerhard A. ; Birkhahn, Robert ; Clopton, Paul ; Taub, Pam ; Vilke, Gary M. ; McDonald, Kenneth ; Mahon, Niall ; Nuñez, Julio ; Briguori, Carlo ; Passino, Claudio ; Murray, Patrick T. / Neutrophil Gelatinase-Associated Lipocalin for Acute Kidney Injury During Acute Heart Failure Hospitalizations : The AKINESIS Study. In: Journal of the American College of Cardiology. 2016 ; Vol. 68, No. 13. pp. 1420-1431.
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abstract = "Background 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. Objectives 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. Methods 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. Results 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 m2, a first NGAL <150 ng/ml indicated a low likelihood of adverse events. Conclusions 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)",
keywords = "biomarkers, cardiorenal syndrome, diuretics, worsening renal function",
author = "Maisel, {Alan S.} and Nicholas Wettersten and {van Veldhuisen}, {Dirk J.} and Christian Mueller and Gerasimos Filippatos and Richard Nowak and Christopher Hogan and Kontos, {Michael C.} and Cannon, {Chad M.} and M{\"u}ller, {Gerhard A.} and Robert Birkhahn and Paul Clopton and Pam Taub and Vilke, {Gary M.} and Kenneth McDonald and Niall Mahon and Julio Nu{\~n}ez and Carlo Briguori and Claudio Passino and Murray, {Patrick T.}",
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TY - JOUR

T1 - Neutrophil Gelatinase-Associated Lipocalin for Acute Kidney Injury During Acute Heart Failure Hospitalizations

T2 - The AKINESIS Study

AU - Maisel, Alan S.

AU - Wettersten, Nicholas

AU - van Veldhuisen, Dirk J.

AU - Mueller, Christian

AU - Filippatos, Gerasimos

AU - Nowak, Richard

AU - Hogan, Christopher

AU - Kontos, Michael C.

AU - Cannon, Chad M.

AU - Müller, Gerhard A.

AU - Birkhahn, Robert

AU - Clopton, Paul

AU - Taub, Pam

AU - Vilke, Gary M.

AU - McDonald, Kenneth

AU - Mahon, Niall

AU - Nuñez, Julio

AU - Briguori, Carlo

AU - Passino, Claudio

AU - Murray, Patrick T.

PY - 2016/9/27

Y1 - 2016/9/27

N2 - Background 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. Objectives 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. Methods 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. Results 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 m2, a first NGAL <150 ng/ml indicated a low likelihood of adverse events. Conclusions 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)

AB - Background 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. Objectives 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. Methods 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. Results 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 m2, a first NGAL <150 ng/ml indicated a low likelihood of adverse events. Conclusions 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)

KW - biomarkers

KW - cardiorenal syndrome

KW - diuretics

KW - worsening renal function

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