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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. - PowerPoint PPT Presentation
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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
HEART
KIDNE
Y
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 ventilationLonger hospital and ICU lengths of stayIncreased hospital costsWorse ventricular function on discharge echoLower 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
• 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
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
Risk Factors for CS-AKI
Defining the “At Risk Population”
Several Scoring systems have been developed/studied:
•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
• Search for genetic polymorphisms the predispose to AKI
• Majority are SNPs associated with gene products that contribute to:
• 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
Apoptosisinhibitors
Potential Areas for Intervention
Iron
Vasodilators
Apoptosisinhibitors
Ca channelblockers
Anti-oxidants
Iron chelators
ATP donors NOS inhibitors
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