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Urine Neutrophil Gelatinase-Associated Lipocalin Moderately Predicts Acute Kidney Injury in Critically Ill Adults Edward D. Siew,* Lorraine B. Ware,† Tebeb Gebretsadik,‡ Ayumi Shintani,‡ Karel G. M. Moons,§ Nancy Wickersham,† Frederick Bossert,† and T. Alp Ikizler* *Vanderbilt University Medical Center, Department of Medicine, Division of Nephrology, Nashville, Tennessee; †Vanderbilt University Medical Center, Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Nashville, Tennessee;  ‡ Vanderbilt University Medical Center, Department of Biostatistics, Nashville, Tennessee;  §Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands Anand Reddy, MD   MSSM, Aug 26 th  2009 J Am Soc Nephrol 20: 1823-1832, 2009
Urgent need for early biomarkers in the management of AKI ,[object Object],[object Object],[object Object],[object Object],[object Object]
AKI Biomarkers ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Urinary Biomarkers for  Kidney Injury in Humans
Promising biomarkers for AKI in humans
Kidney Injury Molecule-1 (KIM-1) ,[object Object],[object Object],[object Object],[object Object]
Interleukin-18 (IL-18) ,[object Object],[object Object],[object Object],[object Object],[object Object]
Cystatin C (Cys-C) ,[object Object],[object Object],[object Object],[object Object],[object Object]
NGAL (Neutrophil Gelatinase–Associated Lipocalin) ,[object Object],[object Object],[object Object],[object Object],[object Object]
Physiology of NGAL ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
NGAL
NGAL after CABG Bennett et al,  Clin J Am Soc Nephrol  3: 665-673, 2008
Nickolas, T. L. et. al. Ann Intern Med 2008;148:810-819 Kidney injury biomarkers versus clinical outcome N-acetyl- ß -D-glucosominidase (NAG) 1-microglobulin (A1M)  1-acid glycoprotein (AAG)
NGAL as a biomarker
Urine Neutrophil Gelatinase-Associated Lipocalin Moderately Predicts Acute Kidney Injury in Critically Ill Adults Edward D. Siew,* Lorraine B. Ware,† Tebeb Gebretsadik,‡ Ayumi Shintani,‡ Karel G. M. Moons,§ Nancy Wickersham,† Frederick Bossert,† and T. Alp Ikizler* *Vanderbilt University Medical Center, Department of Medicine, Division of Nephrology, Nashville, Tennessee; †Vanderbilt University Medical Center, Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Nashville, Tennessee;  ‡ Vanderbilt University Medical Center, Department of Biostatistics, Nashville, Tennessee;  §Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands J Am Soc Nephrol 20: 1823-1832, 2009
Purpose of the study ,[object Object],[object Object]
Study Characteristics ,[object Object],[object Object],[object Object]
Patient Characteristics ,[object Object],[object Object],[object Object],APACHE II ("Acute Physiology and Chronic Health Evaluation II")  SAPS II ("Simplified Acute Physiology Score II")
 
AKIN staging criteria for AKI
Results
S T U D Y R E S U L T S
Biomarker Values & Outcome
Association between  uNGAL and AKI Development   Within 24 Hrs,  AKI 64 patients (median uNGAL 313 [interquartile range (IQR): 59 to 2355] ng/mg) No AKI 386 (median uNGAL 56 [interquartile range (IQR): 16 to 194] ng/mg) ( P < 0.001) Within 48 Hrs AKI 86 patients (median uNGAL 190 [interquartile range (IQR): 32 to 995] ng/mg) No AKI 305 (median uNGAL 57 [interquartile range (IQR): 17 to 203] ng/mg) ( P < 0.001)
Association between uNGAL and AKI Development ,[object Object],[object Object]
Sensitivity Analyses of Baseline Renal Function ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Sensitivity Analyses of Baseline Renal Function ,[object Object],[object Object],[object Object],[object Object],[object Object]
Association between uNGAL and Dialysis or Mortality Within 28 d of enrollment, Dead : 83 patients with uNGAL levels 223 [IQR:36 to 1074] ng/mg)  Survived : 407 Patients with uNGAL levels 56 [IQR:16 to 195] ng/mg)( P  0.001) Dialysis : 17 uNGAL Levels 548 [IQR:156 to 4665] ng/ mg)  No Dialysis : 473 with uNGAL levels 61 [IQR:17 to 232] ng/mg)( P  0.001)
AKIN staging criteria for AKI
uNGAL and AKIN Staging
uNGAL and AKIN Staging
Relative Contribution of uNGAL to a Clinical Prediction Model
Relative Contribution of uNGAL to a Clinical Prediction Model
Relative Contribution of uNGAL to a Clinical Prediction Model
Discussion ,[object Object],[object Object],[object Object]
Limitation of the Study ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Future Directions
References ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
References  …Contd ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
THANK YOU
Urine Neutrophil Gelatinase-Associated Lipocalin Moderately Predicts Acute Kidney Injury in Critically Ill Adults Edward D. Siew,* Lorraine B. Ware,† Tebeb Gebretsadik,‡ Ayumi Shintani,‡ Karel G. M. Moons,§ Nancy Wickersham,† Frederick Bossert,† and T. Alp Ikizler* *Vanderbilt University Medical Center, Department of Medicine, Division of Nephrology, Nashville, Tennessee; †Vanderbilt University Medical Center, Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Nashville, Tennessee;  ‡ Vanderbilt University Medical Center, Department of Biostatistics, Nashville, Tennessee;  §Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands Anand Reddy, MD   MSSM, Aug 26 th  2009

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Final ngal

  • 1. Urine Neutrophil Gelatinase-Associated Lipocalin Moderately Predicts Acute Kidney Injury in Critically Ill Adults Edward D. Siew,* Lorraine B. Ware,† Tebeb Gebretsadik,‡ Ayumi Shintani,‡ Karel G. M. Moons,§ Nancy Wickersham,† Frederick Bossert,† and T. Alp Ikizler* *Vanderbilt University Medical Center, Department of Medicine, Division of Nephrology, Nashville, Tennessee; †Vanderbilt University Medical Center, Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Nashville, Tennessee; ‡ Vanderbilt University Medical Center, Department of Biostatistics, Nashville, Tennessee; §Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands Anand Reddy, MD MSSM, Aug 26 th 2009 J Am Soc Nephrol 20: 1823-1832, 2009
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  • 4. Urinary Biomarkers for Kidney Injury in Humans
  • 5. Promising biomarkers for AKI in humans
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  • 11. NGAL
  • 12. NGAL after CABG Bennett et al, Clin J Am Soc Nephrol 3: 665-673, 2008
  • 13. Nickolas, T. L. et. al. Ann Intern Med 2008;148:810-819 Kidney injury biomarkers versus clinical outcome N-acetyl- ß -D-glucosominidase (NAG) 1-microglobulin (A1M) 1-acid glycoprotein (AAG)
  • 14. NGAL as a biomarker
  • 15. Urine Neutrophil Gelatinase-Associated Lipocalin Moderately Predicts Acute Kidney Injury in Critically Ill Adults Edward D. Siew,* Lorraine B. Ware,† Tebeb Gebretsadik,‡ Ayumi Shintani,‡ Karel G. M. Moons,§ Nancy Wickersham,† Frederick Bossert,† and T. Alp Ikizler* *Vanderbilt University Medical Center, Department of Medicine, Division of Nephrology, Nashville, Tennessee; †Vanderbilt University Medical Center, Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Nashville, Tennessee; ‡ Vanderbilt University Medical Center, Department of Biostatistics, Nashville, Tennessee; §Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands J Am Soc Nephrol 20: 1823-1832, 2009
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  • 22. S T U D Y R E S U L T S
  • 24. Association between uNGAL and AKI Development Within 24 Hrs, AKI 64 patients (median uNGAL 313 [interquartile range (IQR): 59 to 2355] ng/mg) No AKI 386 (median uNGAL 56 [interquartile range (IQR): 16 to 194] ng/mg) ( P < 0.001) Within 48 Hrs AKI 86 patients (median uNGAL 190 [interquartile range (IQR): 32 to 995] ng/mg) No AKI 305 (median uNGAL 57 [interquartile range (IQR): 17 to 203] ng/mg) ( P < 0.001)
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  • 28. Association between uNGAL and Dialysis or Mortality Within 28 d of enrollment, Dead : 83 patients with uNGAL levels 223 [IQR:36 to 1074] ng/mg) Survived : 407 Patients with uNGAL levels 56 [IQR:16 to 195] ng/mg)( P 0.001) Dialysis : 17 uNGAL Levels 548 [IQR:156 to 4665] ng/ mg) No Dialysis : 473 with uNGAL levels 61 [IQR:17 to 232] ng/mg)( P 0.001)
  • 30. uNGAL and AKIN Staging
  • 31. uNGAL and AKIN Staging
  • 32. Relative Contribution of uNGAL to a Clinical Prediction Model
  • 33. Relative Contribution of uNGAL to a Clinical Prediction Model
  • 34. Relative Contribution of uNGAL to a Clinical Prediction Model
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  • 41. Urine Neutrophil Gelatinase-Associated Lipocalin Moderately Predicts Acute Kidney Injury in Critically Ill Adults Edward D. Siew,* Lorraine B. Ware,† Tebeb Gebretsadik,‡ Ayumi Shintani,‡ Karel G. M. Moons,§ Nancy Wickersham,† Frederick Bossert,† and T. Alp Ikizler* *Vanderbilt University Medical Center, Department of Medicine, Division of Nephrology, Nashville, Tennessee; †Vanderbilt University Medical Center, Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Nashville, Tennessee; ‡ Vanderbilt University Medical Center, Department of Biostatistics, Nashville, Tennessee; §Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands Anand Reddy, MD MSSM, Aug 26 th 2009