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