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 Brown et al,

Ann Thorac Surg,

2010;90:1142-1149 Morgan et al,

J Pediatr,

2012 Aug 7 [Epub]

Mechanisms of Injury during CPB

• • • • • • • • • Ischemia/reperfusion injury Inflammation Oxidative stress RBC injury Coagulopathy Loss of pulsatile flow Microembolism Hypothermia Altered hemodynamics

Devarajan JASN 17:1503-20, 2006 Mechanisms of AKI

Devarajan JASN 17:1503-20, 2006 Biochemistry of AKI

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

Advanced Age African-American ethnicity Increased BMI Hypertension PVD Diabetes ↓ LV function Intra-op hypotension Re-operation

Pediatric Studies All Ages

↓ Pre-op renal fxn Longer CPB time Blood transfusion

Risk Factors for CS-AKI Adult Studies

Advanced Age African-American ethnicity Increased BMI Hypertension PVD Diabetes ↓ LV function Intra-op hypotension Re-operation

Pediatric Studies

Younger Age DHCA

All Ages

↓ Pre-op renal fxn Longer CPB time Lower Gestational Age Blood transfusion Chromosomal Anomaly Pre-op Ventilation Cardiac Anatomy Surgical Complexity

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

Apoptosis inhibitors

Potential Areas for Intervention

Potential Areas for Intervention

Vasodilators ATP donors NOS inhibitors Apoptosis inhibitors Ca channel blockers

n

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