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ACUTE KIDNEY INJURY IN CRITICALLY ILL
PATIENTS IN THE NEW MILLENIUM:
DEFINITION AND EPIDEMIOLOGY
JOSÉ ANTÓNIO LOPES, MD, PhD
Assistant Professor of Nephrology
Faculty of Medicine, University of Lisbon
Department of Nephrology and Renal Transplantation
Centro Hospitalar Lisboa Norte, EPE, Lisboa, Portugal
jalopes93@hotmail.com
Barcelona, 4th March 2014
DEFINITION AND CLASSIFICATION OF AKI
≠ DEFINITIONS
≠ INCIDENCE
≠ MORTALITY≠ MORTALITY
DEFINITION OF AKI
INCIDENCE AND MORTALITY
Chertow GM et al. J Am Soc Nephrol 2005
N=9.210
DEFINITION OF AKI
1. Easy to use
2. High sensitivity and specificity in ≠ settings
3. Consider variations in baseline SCr
4. Determine AKI severity
5. Identifiy early and late AKI
RIFLE Classification
Risk, Injury, Failure, Loss, End-stage kidney disease
Bellomo R et al. Crit Care 2004
Risk Injury Failure
Ricci Z et al. Kidney Int 2008
VALIDATION OF THE RIFLE IN THE ICU
RIFLE CLASSIFICATION
INCIDENCE AND STRATIFICATION OF AKI
Lopes JA et al. Clin Kidney J 2013




67%
36%
11%
36%
 18%
SAPS II RIFLE
AKI IN CRITICALLY ILL SEPTIC PATIENTS
Lopes JA et al. Crit Care 2007
0.778 0.750
Hoste E et al. Crit Care 2006
CRITICALLY ILL PATIENTS
Mehta RL et al. Crit Care 2007
AKIN CLASSIFICATION
Acute Kidney Injury Network
Chertow GM et al. J Am Soc Nephrol 2005
sCr ≥ 0.3 mg/dl -  IN-HOSPITAL MORTALITY
N=9.210
COMPARISON BETWEEN RIFLE
AND AKIN
INCIDENCE OF AKI AND PREDICTION OF
MORTALITY
Lopes JA et al. Crit Care 2008
P = 0.018
N=662
Lopes JA et al. Crit Care 2008
N=662
Acute kidney injury in critically ill patients classified by
AKIN versus RIFLE using the SAPS 3 database
Joannidis M et al. Intensive Care Med 2009
N=16.784
RIFLE
2004
AKIN
2009
LIMITATIONS STRENGTHS
KDIGO
2012
KDIGO Clinical Practice Guideline for AKI. Kidney Int 2012
KDIGO CLASSIFICATION
LIMITATIONS OF CLINICAL
CLASSIFICATIONS
URINE OUTPUT
Sensitivity and specificity
Hourly basis register (+++ ICU)
SCr
 variability in endogenous production and S release
Multiple factors can interfer with SCr determination
Hemodilution
Sepsis   production
CKD  late  in SCr
Marker of renal function and not of lesion
BIOMARKERS IN AKI
Murray PT et al. Kidney Int 2013
Coca SG et al. Kidney Int 2008
BIOMARKERS IN AKI
FRAMEWORK FOR EVALUATING AKI
BASED ON BIOMARKERS
Murray PT et al. Kidney Int 2013
BIOMARKERS IN AKI
FUTURE DIRECTIONS
 Confirm that the proposed expansion of the diagnostic criteria for AKI
to include the isolated presence of damage biomarkers, with
preserved function, is clinically relevant.
 Determine the mechanistic pathways that are involved in the
development of AKI and its natural course.
 Define the prognostic value of the combined use of functional and
damage markers in sequential measurements to confirm the
prognostic significance of these categories.
 Ascertain how well the combination of damage and functional markers
can improve recognition of AKI in the setting of CKD.
Murray PT et al. Kidney Int 2013
BIOMARKERS IN AKI
FUTURE DIRECTIONS
 Large population-based studies would be required across multiple
centers enrolling patients in the wide spectrum of AKI and different
disease states, to determine whether operationalizing the approach to
AKI with a simple 2x2 table to mechanistically define AKI cases and
their evolution usefully influences patient management and ultimately
improves outcomes.
 Discover and confirm the sensitivity and specificity of damage and
functional markers for specific situations.
 Establish standard techniques for collection, handling, and
presentation of biomarker data that permit appropriate interpretation
across settings.
Murray PT et al. Kidney Int 2013
EPIDEMIOLOGY OF AKI IN THE ICU
INCIDENCE
Bagshaw SM et al. Crit Care 2007
N=91.254
Lopes JA et al. Clin Kidney J 2013




67%
36%
11%
36%
INCIDENCE OF AKI IN THE ICU
Uchino S et al. JAMA 2005
EPIDEMIOLOGY OF AKI IN THE ICU
PATIENT CHARACTERISTICS AND RISK FACTORS
N=29.269
EPIDEMIOLOGY OF AKI IN THE ICU
SHORT- AND LONG-TERM OUTCOMES
Bagshaw SM et al. Nephrol Dial Transplant 2008
N=120.123
A multi-centre evaluation of the RIFLE criteria for
early acute kidney injury in critically ill patients
Long-term risk of mortality after acute kidney injury
in patients with sepsis: a contemporary analysis
Lopes JA et al. BMC Nephrol 2010
N=234
Bihorac A et al. Ann Surg 2009
N=10.518
Gammelager et al. Crit Care 2012
N=30.762
Bagshaw SM et al. Crit Care 2005
Prognosis for long-term survival and renal recovery in
critically ill patients with severe acute renal failure: a
population-based study
Hobson CE et al. Circulation 2009
N=2.973
Ishani A et al. J Am Soc Nephrol 2009
N= 233.803
Acute kidney injury increases risk of ESRD among elderly
Lai CF et al. Crit Care 2012
N=634
Ponte B et al. Nephrol Dial Transplant 2008
Hansen et al. Crit Care 2013
N=1.030
SEPSIS
HEMORRHAGE
FLUID OVERLOAD
ACUTE KIDNEY INJURY
• INFLAMMATION
• OXIDATIVE STRESS
• APOPTOSIS
Xiang Li et al. Curr Opin Crit Care 2010
SUMMARY
 The KDIGO work group has made the fusion of the RIFLE
and AKIN classifications in order to establish one
classification of AKI for practice, research, and public
health.
 The conceptual framework of functional and damage
biomarkers will need to be validated through future
studies, and additional evidence will be required to
establish their best combinations for utilization in clinical
practice.
SUMMARY
 AKI is an increasingly common complication in ICU
patients.
 Patients with AKI have higher ICU and in-hospital mortality
and longer lengths of stay, and AKI survivors are more
likely to be discharged to an extended care facility.
 Patients who survive AKI have a greater rate of long-term
mortality and other adverse outcomes (i.e. progression to
or acceleration of CKD and cardiovascular disease) than
patients who survive hospitalization without AKI.

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Acute kidney injury in critically ill patients in the new millenium: definition and epidemiology. Dr. José Antonio Lopes.

  • 1. ACUTE KIDNEY INJURY IN CRITICALLY ILL PATIENTS IN THE NEW MILLENIUM: DEFINITION AND EPIDEMIOLOGY JOSÉ ANTÓNIO LOPES, MD, PhD Assistant Professor of Nephrology Faculty of Medicine, University of Lisbon Department of Nephrology and Renal Transplantation Centro Hospitalar Lisboa Norte, EPE, Lisboa, Portugal jalopes93@hotmail.com Barcelona, 4th March 2014
  • 2. DEFINITION AND CLASSIFICATION OF AKI ≠ DEFINITIONS ≠ INCIDENCE ≠ MORTALITY≠ MORTALITY
  • 3. DEFINITION OF AKI INCIDENCE AND MORTALITY Chertow GM et al. J Am Soc Nephrol 2005 N=9.210
  • 4.
  • 5. DEFINITION OF AKI 1. Easy to use 2. High sensitivity and specificity in ≠ settings 3. Consider variations in baseline SCr 4. Determine AKI severity 5. Identifiy early and late AKI
  • 6. RIFLE Classification Risk, Injury, Failure, Loss, End-stage kidney disease Bellomo R et al. Crit Care 2004
  • 7. Risk Injury Failure Ricci Z et al. Kidney Int 2008 VALIDATION OF THE RIFLE IN THE ICU
  • 8. RIFLE CLASSIFICATION INCIDENCE AND STRATIFICATION OF AKI
  • 9. Lopes JA et al. Clin Kidney J 2013     67% 36% 11% 36%  18%
  • 10. SAPS II RIFLE AKI IN CRITICALLY ILL SEPTIC PATIENTS Lopes JA et al. Crit Care 2007 0.778 0.750
  • 11. Hoste E et al. Crit Care 2006 CRITICALLY ILL PATIENTS
  • 12. Mehta RL et al. Crit Care 2007 AKIN CLASSIFICATION Acute Kidney Injury Network
  • 13. Chertow GM et al. J Am Soc Nephrol 2005 sCr ≥ 0.3 mg/dl -  IN-HOSPITAL MORTALITY N=9.210
  • 14. COMPARISON BETWEEN RIFLE AND AKIN INCIDENCE OF AKI AND PREDICTION OF MORTALITY
  • 15. Lopes JA et al. Crit Care 2008 P = 0.018 N=662
  • 16. Lopes JA et al. Crit Care 2008 N=662
  • 17. Acute kidney injury in critically ill patients classified by AKIN versus RIFLE using the SAPS 3 database Joannidis M et al. Intensive Care Med 2009 N=16.784
  • 19. KDIGO Clinical Practice Guideline for AKI. Kidney Int 2012 KDIGO CLASSIFICATION
  • 20. LIMITATIONS OF CLINICAL CLASSIFICATIONS URINE OUTPUT Sensitivity and specificity Hourly basis register (+++ ICU) SCr  variability in endogenous production and S release Multiple factors can interfer with SCr determination Hemodilution Sepsis   production CKD  late  in SCr Marker of renal function and not of lesion
  • 21. BIOMARKERS IN AKI Murray PT et al. Kidney Int 2013
  • 22. Coca SG et al. Kidney Int 2008 BIOMARKERS IN AKI
  • 23. FRAMEWORK FOR EVALUATING AKI BASED ON BIOMARKERS Murray PT et al. Kidney Int 2013
  • 24. BIOMARKERS IN AKI FUTURE DIRECTIONS  Confirm that the proposed expansion of the diagnostic criteria for AKI to include the isolated presence of damage biomarkers, with preserved function, is clinically relevant.  Determine the mechanistic pathways that are involved in the development of AKI and its natural course.  Define the prognostic value of the combined use of functional and damage markers in sequential measurements to confirm the prognostic significance of these categories.  Ascertain how well the combination of damage and functional markers can improve recognition of AKI in the setting of CKD. Murray PT et al. Kidney Int 2013
  • 25. BIOMARKERS IN AKI FUTURE DIRECTIONS  Large population-based studies would be required across multiple centers enrolling patients in the wide spectrum of AKI and different disease states, to determine whether operationalizing the approach to AKI with a simple 2x2 table to mechanistically define AKI cases and their evolution usefully influences patient management and ultimately improves outcomes.  Discover and confirm the sensitivity and specificity of damage and functional markers for specific situations.  Establish standard techniques for collection, handling, and presentation of biomarker data that permit appropriate interpretation across settings. Murray PT et al. Kidney Int 2013
  • 26. EPIDEMIOLOGY OF AKI IN THE ICU INCIDENCE Bagshaw SM et al. Crit Care 2007 N=91.254
  • 27. Lopes JA et al. Clin Kidney J 2013     67% 36% 11% 36% INCIDENCE OF AKI IN THE ICU
  • 28. Uchino S et al. JAMA 2005 EPIDEMIOLOGY OF AKI IN THE ICU PATIENT CHARACTERISTICS AND RISK FACTORS N=29.269
  • 29.
  • 30. EPIDEMIOLOGY OF AKI IN THE ICU SHORT- AND LONG-TERM OUTCOMES
  • 31. Bagshaw SM et al. Nephrol Dial Transplant 2008 N=120.123 A multi-centre evaluation of the RIFLE criteria for early acute kidney injury in critically ill patients
  • 32. Long-term risk of mortality after acute kidney injury in patients with sepsis: a contemporary analysis Lopes JA et al. BMC Nephrol 2010 N=234
  • 33. Bihorac A et al. Ann Surg 2009 N=10.518
  • 34. Gammelager et al. Crit Care 2012 N=30.762
  • 35. Bagshaw SM et al. Crit Care 2005 Prognosis for long-term survival and renal recovery in critically ill patients with severe acute renal failure: a population-based study
  • 36. Hobson CE et al. Circulation 2009 N=2.973
  • 37. Ishani A et al. J Am Soc Nephrol 2009 N= 233.803 Acute kidney injury increases risk of ESRD among elderly
  • 38. Lai CF et al. Crit Care 2012 N=634
  • 39. Ponte B et al. Nephrol Dial Transplant 2008
  • 40. Hansen et al. Crit Care 2013 N=1.030
  • 42. • INFLAMMATION • OXIDATIVE STRESS • APOPTOSIS Xiang Li et al. Curr Opin Crit Care 2010
  • 43. SUMMARY  The KDIGO work group has made the fusion of the RIFLE and AKIN classifications in order to establish one classification of AKI for practice, research, and public health.  The conceptual framework of functional and damage biomarkers will need to be validated through future studies, and additional evidence will be required to establish their best combinations for utilization in clinical practice.
  • 44. SUMMARY  AKI is an increasingly common complication in ICU patients.  Patients with AKI have higher ICU and in-hospital mortality and longer lengths of stay, and AKI survivors are more likely to be discharged to an extended care facility.  Patients who survive AKI have a greater rate of long-term mortality and other adverse outcomes (i.e. progression to or acceleration of CKD and cardiovascular disease) than patients who survive hospitalization without AKI.