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AKI Conference Biomarkers of Acute Kidney Injury – Early diagnosis, prediction and staging.

AKI Conference Biomarkers of Acute Kidney Injury – Early diagnosis, prediction and staging. Presenter: R4 詹雅婷 Supervisor: VS 吳允升 Date: September 22, 2014. Definition of AKI-RIFLE criteria. Critical Care 2004. Definition of AKI-AKIN criteria. Critical Care 2007.

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AKI Conference Biomarkers of Acute Kidney Injury – Early diagnosis, prediction and staging.

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  1. AKI ConferenceBiomarkers of Acute Kidney Injury – Early diagnosis, prediction and staging. Presenter: R4 詹雅婷 Supervisor: VS 吳允升 Date: September 22, 2014

  2. Definition of AKI-RIFLE criteria Critical Care2004

  3. Definition of AKI-AKIN criteria Critical Care2007

  4. Definition of AKI-KDIGO Classification • Definition • Increase in SCrby ≥0.3mg/dl within 48 hours; or • Increase in SCrto ≥ 1.5 times baseline which is known or presumed to have occurred within prior 7 days; or • Urine volume <0.5ml/kg/hour for 6 hours • Staging Kidney Disease Improving Global Outcomes (KDIGO) Guideline 2012

  5. AKI incidence and mortality-USA AKI requiring dialysis AKI Kidney Int 2007

  6. AKI incidence in Taiwan • NTUH: 19.1% in SICU during 2002-2007 • 15.9%, 1.6%, and 1.6%for stage 1, 2, and 3 AKI • CGMH: 60.8% in ICU with septic shock, ARDS or hepatic cirrhosis during 2003-2006 • 19.6%, 16.8%, and 31.6% for stage 1, 2, and 3 AKI By NSARF Study Group Shock 2010

  7. Difficulties of creatinine for AKI • Affected by non-renal factors: BW, race, age, sex, muscle mass, protein intakes, drugs • Lag in response

  8. Proposed Framework for Evaluating AKI ex: ATN ex: pre-renal Acute Dialysis Quality Initiative(ADQI) X Consensus Conference 2012

  9. Conceptual Model of AKI Kidney International 2014

  10. Novel Biomarkers of AKI American J Kidney Disease, 2011 Jun;57(6):930-40

  11. Location of AKI Biomarkers Nature Biotechnology 2010; 28:436-440

  12. Potential Mechanisms of Urinary Biomarkers Nature Biotechnology 2010; 28:436-440

  13. Role of Novel Biomarkers • Risk assessment • Early diagnosis and staging of AKI • Differential diagnosis of AKI • Assess prognosis and guide management of AKI

  14. Neutrophil Gelatinase-Associated Lipocalin (NGAL)

  15. Nat. Rev. Nephrol.2013

  16. First discovered in 1989 • 178 amino acid residues, MW 25kDa • Normal condition: low levels in kidney, trachea, lungs, stomach and colon • Slightly increased in inflammation, infection and acertain cancer • Kidney damage: increased synthesis by renal tubular cells and released into blood and urine Haase M et al. Nephrol. Dial. Transplant. 2011;ndt.gfr248

  17. Intravenous administration of purified recombinant NGAL in mice Staining for apoptosis JASN 2004

  18. NGAL after Cardiac Surgery in Children Mishra J et al, Lancet 2005; 365:1231-1238

  19. NGAL after Cardiac Surgery in Children AUROC: 0.906 AUROC: 0.998 Best threshold=25mcg/L Best threshold=25mcg/L Mishra J et al, Lancet 2005; 365:1231-1238

  20. Urine NGAL after Cardiac Surgery in Adults Wagener G et al, Anesthesiology 2006; 105:485-491

  21. Urine NGAL after Cardiac Surgery in Adults • The cutoff value is the best threshold at 18h post-OP=213ng/ml Best threshold=213ng/ml AUC-ROC 0.80 Wagener G et al, Anesthesiology 2006; 105:485-491

  22. Pooled Diagnostic & Prognostic Accuracy of NGAL Am J of Kidney Disease 2009

  23. Pooled Diagnostic & Prognostic Accuracy of NGAL Am J of Kidney Disease 2009

  24. NGAL can predict initiation of RRT RRT initiation AKI diagnosis AUC-ROC 0.782 NGAL can predict AKI across settings In-hospital mortality NGAL can predict mortality AUC-ROC 0.815 AUC-ROC 0.706 Am J of Kidney Disease 2009

  25. ClinicalUtility of NGAL

  26. Urinary Interleukin-18 (IL-18)

  27. Injurious Role of IL-18 in AKI • Proinflammatory cytokine of IL-1 superfamily • Produced by proximal tubules, activated by caspase 1, exceted into urine after ischeic injury Endothelial Injury Interstitial Inflammation Proximal Tubular Apoptosis & Necrosis Am J Kidney Disease 2011

  28. Urinary IL-18 in ICU Adults urine IL-18 measured 1 d before AKI. Urinary IL-18 is an early predictive biomarker of AKI in critically ill patients JASN 2005

  29. Urinary IL-18 after CPB in Children Urinary IL-18 is an early predictive biomarker of AKI after CPB in children Kidney International 2006

  30. Urinary IL-18 after CPB in Adults (uIL-18 at 24h after commencement of CPB) (Normalized by dividing to uCr) Urinary IL-18 does not predict AKI after CPB in adults AUROC 0.55 AUROC 0.59 Critical Care, 2008

  31. Meta-analysis for Urinary IL-18 sensitivity 0.58specificity 0.75 Am J Kidney Disease, 2013

  32. Meta-analysis for Urinary IL-18 AUC-ROC to predict AKI was 0.7 (95%CI 0.66-0.74) Am J Kidney Disease, 2013

  33. Sub-grouped Accuracy of IL-18 uIL-18 has moderate predictive value as a biomarker of AKI (did not perform very well) Am J Kidney Disease, 2013

  34. Diagnostic Accuracy of uIL-18 in Predicting AKI at Different Times No significant difference in the predictive performance of uIL-18 among various times Sensitivity and Specificity of Individual Studies for Urinary IL-18 to Predict Mortality Insufficient data for pooling studies for the prognosis of AKI Am J Kidney Disease, 2013

  35. ClinicalUtility of IL-18 ? ? ?

  36. Urinary Liver-Type Fatty Acid-Binding Protein(L-FABP)

  37. L-FABP • 14kDa protein • Location: hepatocytes and proximal tubular epithelial cells • Function: Response to hypoxic stress (ex. kidney ischemia-reperfusion injury) Kidney International, 2008

  38. URINE www.fabp.jp

  39. Am J Kidney Disease 2006

  40. L-FABP after CPB in Children Portilla D et al. Kidney International, 2008

  41. uL-FABP after CPB in Children AUROC 0.81 Portilla D et al. Kidney International, 2008

  42. Urinary L-FABP in ICU • uL-FABP can be a significant predictor for AKI diagnosis and mortality in critical care AUROC 0.748 14-day mortality AUROC 0.896 Critical Care Medicine 2011

  43. Meta-analysis for Urinary L-FABP Am J Kidney Dis 2013

  44. ClinicalUtility of L-FABP

  45. Kidney Injury Molecule-1

  46. KIM-1 (=TIM-1) Binding of KIM1 and KIM4 T-cell activation and expansion Clearance of apoptotic cells or bodiesUndetectable in normal kidney Nature reviews Immunology 2008

  47. KIM-1 • Expressed by proximal tubule cells in response to injury • Upregulatedin ischemia, nephrotoxic drug injury, CKD, and acute/chronic decreased kidney function after transplantation • Its ectodomainshed into the tubule lumen • Function: Involved in dedifferentiation, reduction of cast formation and subsequent tubular obstruction, and phagocytosis of pro-inflammatory necrotic and apoptotic cellular debris in AKI

  48. Normal Human Kidney Acute Tubular Necrosis Kidney International, Vol. 62 (2002), pp. 237–244

  49. Urinary KIM-1 for AKI Kidney International, 2002

  50. Meta-analysis for urinary KIM-1 • Pooled Sensitivity:0.74 [0.61-0.84] • Pooled Specificity: 0.86 [0.74-0.93] AUC=0.86 [0.83-0.89] • Pooled OR:17.43 [6.23-48.74] PLOS ONE 2014

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