1. 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

2. HEART KIDNEY

3. 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

4. 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

5. 430 infants <90d undergoing CPB-- 52% developed postoperative AKI

6. 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

7. Mechanisms of Injury during CPB Ischemia/reperfusion injury Inflammation Oxidative stress RBC injury Coagulopathy Loss of pulsatile flow Microembolism Hypothermia Altered hemodynamics

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

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

10. Risk Factors for CS-AKI Adult StudiesPediatric StudiesAll Ages ↓ Pre-op renal fxn Longer CPB time Blood transfusion

11. Adult StudiesPediatric StudiesAll Ages Advanced Age↓ Pre-op renal fxn African-American ethnicity Longer CPB time Increased BMIBlood transfusion Hypertension PVD Diabetes ↓ LV function Intra-op hypotension Re-operation Risk Factors for CS-AKI

12. Adult StudiesPediatric StudiesAll Ages Advanced AgeYounger Age↓ Pre-op renal fxn African-American ethnicity DHCALonger CPB time Increased BMILower Gestational AgeBlood transfusion HypertensionChromosomal Anomaly PVDPre-op Ventilation DiabetesCardiac Anatomy ↓ LV functionSurgical Complexity Intra-op hypotension Re-operation Risk Factors for CS-AKI

14. 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

15. Huen and Parikh, Ann Thorac Surg 2012;93: 337-47

16. 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

17. Genetics and AKI 1671 patients Aorto-coronary surgery Highest AKI risk (4X greater) with combination AGT 842G + IL-6 -572

18. Potential Areas for Intervention Apoptosis inhibitors

19. Potential Areas for Intervention Iro n Vasodilators Apoptosis inhibitors Ca channel blockers Anti-oxidants Iron chelators ATP donorsNOS inhibitors

20. Currently Available Therapies Mariscalco et al. Ann Thorac Surg 2011; 92: 1539-47

21. 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