Transcript Krawczeski-AKI after CPB - Pediatric Continuous Renal

Acute Kidney Injury
after Cardiopulmonary
Bypass
Catherine Krawczeski, MD
Associate Professor of Pediatrics
University of Cincinnati College of Medicine
Cardiac Intensive Care
Co-Director, Center for Acute Care Nephrology
The Heart Institute
Cincinnati Children’s Hospital Medical Center
Why Study AKI after Cardiac
Surgery?
• Over a million adults and 25,000 children undergo
cardiac surgery with CPB in the US each year
• Acute Kidney Injury (AKI) occurs in 30-40% of adult
and pediatric patients after CPB
• Pediatric patients- particularly infants- may be
especially vulnerable
• Planned period of renal ischemia
• Pediatric patients free of other “co-morbidities” that
may confound therapies
Impact of CS-AKI
• Independently associated with:
Increased mortality
Increased length of postoperative ventilation
Longer hospital and ICU lengths of stay
Increased hospital costs
Worse ventricular function on discharge echo
Lower long-term quality of life
430 infants <90d undergoing CPB-- 52% developed postoperative AKI
Long-term effects of CS-AKI in
pediatrics
• Growth (height) impairment
• Increased health care utilization
• Trend towards higher long-term mortality
• Unknown long-term risk of CKD
Morgan et al, J Pediatr, 2012 Aug 7 [Epub]
Brown et al, Ann Thorac Surg, 2010;90:1142-1149
Mechanisms of Injury during CPB
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Ischemia/reperfusion injury
Inflammation
Oxidative stress
RBC injury
Coagulopathy
Loss of pulsatile flow
Microembolism
Hypothermia
Altered hemodynamics
Mechanisms of AKI
Devarajan JASN 17:1503-20, 2006
Biochemistry of AKI
Devarajan JASN 17:1503-20, 2006
Risk Factors for CS-AKI
Adult Studies
Pediatric Studies
All Ages
↓ Pre-op renal fxn
Longer CPB time
Blood transfusion
Risk Factors for CS-AKI
Adult Studies
Pediatric Studies
All Ages
Advanced Age
↓ Pre-op renal fxn
African-American
ethnicity
Longer CPB time
Increased BMI
Blood transfusion
Hypertension
PVD
Diabetes
↓ LV function
Intra-op hypotension
Re-operation
Risk Factors for CS-AKI
Adult Studies
Pediatric Studies
All Ages
Advanced Age
Younger Age
↓ Pre-op renal fxn
African-American
ethnicity
DHCA
Longer CPB time
Increased BMI
Lower Gestational Age Blood transfusion
Hypertension
Chromosomal
Anomaly
PVD
Pre-op Ventilation
Diabetes
Cardiac Anatomy
↓ LV function
Surgical Complexity
Intra-op hypotension
Re-operation
Defining the “At Risk
Population”
Several Scoring systems have been
developed/studied:
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CICSS (Continuing Improvement in Cardiac Surgery
Study)
Cleveland Clinic
STS Bedside Risk
MCSPI (Multicenter study of perioperative ischemia)
AKICS (AKI after Cardiac Surgery)
NNECDSG (Northern New England Cardiovascular
Disease Study Group)
Reported AUC’s 0.72-0.84
Huen and Parikh, Ann Thorac Surg 2012;93: 337-47
Genetics and AKI
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Search for genetic
polymorphisms the
predispose to AKI
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Majority are SNPs
associated with gene
products that contribute
to:
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Proinflammatory state
Increased response to
oxidative stress
Impaired renal vascular
responsiveness
Genetics and AKI
1671 patients
Aorto-coronary surgery
• Highest AKI risk (4X
greater) with
combination AGT
842G + IL-6 -572
Potential Areas for Intervention
Apoptosis
inhibitors
Potential Areas for Intervention
Vasodilators
ATP donors
Apoptosis
inhibitors
Ca channel
blockers
NOS inhibitors
Irochelators
Iron
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Anti-oxidants
Currently Available Therapies
Mariscalco et al. Ann Thorac Surg 2011; 92: 1539-47
What’s on the Horizon
• Modification of diagnostic criteria for AKI
• Development of reliable tools to predict who
will develop AKI and for early rapid diagnosis
• Therapeutic trials