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

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

4. Urinary Biomarkers for Kidney Injury in Humans

5. Promising biomarkers for AKI in humans

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

20. AKIN staging criteria for AKI

21. Results

22. S T U D Y R E S U L T S

23. Biomarker Values & Outcome

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)

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)

29. AKIN staging criteria for AKI

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

37. Future Directions

40. THANK YOU

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