Critical care conference

1. Critical care conference Acute Kidney Injury: A Relevant Complication After Cardiac Surgery 2011 society of thoracic surgeons 主講人: R2 顏介立

2. Introduction • Acute kidney injury (AKI) occurs in 40% patients after cardiac surgery, 1% requires dialysis - Poor outcome and high cost in AKI patient • AKI: consequence of interplay of different pathophysiologic mechanism • Several biomarkers for acute kidney injury • Protective therapy for AKI

3. Acute kidney injury after cardiac surgery • Incidence of post-op AKI: 1%-30% of patient after cardiac surgery • Incidence of hemodialysis: 1%-6% of patient • Different type of cardiac operation: @ CABG: lowest incidence 2%-5% @ valvular disease or combied disease: 30% • Different AKI definition =>new classification critieria

4. Classification of AKI criteria

5. Pathology @ Post-op AKI: progressive course with different phase • Vasomotor change : alteration in vaso-reactivity and renal perfusion • Prerenal azotemia, ATP depletion, oxidative injury => bone marrow/ endothelium: proinflammatory state • Inflammatory cells adhere peritubular capillaries=> proximal tubule • Proliferation of tubule cells=> function reconstitution  post-operative AKI is acute tubular necrosis

6. Pathogenesis • AKI is the consequence of different mechanisms inerplay • Major cause: • 1. CPB (cardiopulmonary bypass) 2. patient-related factor( risk factor)

7. Pathogenesis • Cardiopulmonary bypass (CPB) • Kidney blood circulation • ischemia-reperfusion injury, low cardiac ouput hemodilution, loss of pulsatile flow • Hypothermia • CPB induced systemic inflammation • CPB related emoblization

8. Risk Factor -many factor associated with AKI • pre-op renal function: baseline creatinine 2-4 =>10-20% hemodialysis baseline creatinine > 4 =>30% hemodialysis • pre-op anemia • DM • Intravenous contrast and ACEi Identified risk factor associated with AKI is important

9. Pathogenesis

10. Biomarkers for AKI • Problem of conventional renal biomarker 1. become abnormal too late (urea, creatinine) 2. lack specificity (urine ouput) • New biomarker of AKI ex. cystatin C, NGAL(neutrophil gelatinase associated lipocalin), IL-6, IL-18, KIM-1( kidney injury molecule-1) , L-FABP, NAG…….

11. Biomarkers for AKI • Neutrophil gelatinase-associated lipocalin(NGAL) @Measure tubular stress, increase after tubular injury @precedes creatinine more than 24hrs!! • Liver type FABP @ cell uptake fatty acid and promote metabolism @ increase within 4hr after surgery, accuracy of 81% of AKI development - KIM-1(kidney injury molecular-1) @ predict AKI immediately after surgery=>than NGAL @ more specific to ischemic injury than NGAL

12. Strategies to prevent AKI • Difficulty of AKI prevention: complex AKI pathophysiology • Intravenous contrast - vasoconstriction-mediated medullary ischemia and direct cytotoxicity on glomerular cells - delay cardiac surgery beyond 24hrs of exposure to contrast

13. Strategies to prevent AKI 2. Drugs increasing blood flow a. dopamine: no protective effect and even exacerbate renal tubular injury b. Fenoldopam: increase renal blood flow in dose-dependent manner

14. Strategies to prevent AKI c. Atrial and brain natriuretic peptide increase GFR and inhibit sodium reabsorption => decrease renal dysfunction d. Agent attenuating systemic inflammaatory -Statins attenuate inflammation and oxidative stress - N-acetylcysteine, dexamethasone,….. etc. (anti-inflammation agent)

15. Strategies to prevent AKI

16. Strategies to prevent AKI e. CPB use • The most relevant pathophysiologic mechanism • nonpulsatile flow @ pulsatile perfusion =>improved renal protection -Presta and colleagues research (2009) • Poor oxygen availability to renal medulla when CPB @ Hct<26% , oxygen delivery less than 272ml/kg/min (Ranucci and collegue, 2005) @pump flow > 3.0L /min/m2(von Heymann, 2006)

17. Strategies to prevent AKI e. CPB use • off-pump coronary bypass graft technique @ controversial renal effect

18. Cost and Outcomes • post-op AKI has shown to be related to poor prognosis • Relationship between In-hospital mortality and post-op GFR (Thakear and colleagues, 2005) • Less than 30% decline GFR • Mortality 0.4% • More than 30% decline • Mortality 5.9% • Hemodialysis => Mortality 54%

19. Cost and Outcomes - AKI contributes to long- term mortality @10years survival rate with RIFLE criteria (Hobson and colleague 2009) Risk: 51% Injury: 42% failure: 26%

20. Cost and Outcomes • Duration of AKI with long-term survival @long term mortality is proportional to AKI duration @importance of continuous monitoring of renal function

21. Cost and Outcomes post-op AKI mortality • Plausible mechanism : . Fluid overloading, dialysis catheter insertion, impaired host immunity and infection @ post-op infection: (Thaker and colleague 2003) 1.6% without AKI, 23.7% with AKI, 58.5 % with hemodialysis

22. Cost and Outcomes • Hospital cost and length of stay increase as AKI severity worsen @ post- op AKI: higher intensive care unit cost(1.7-fold) pharmacy cost(2.3-fold) laboratory cost (1.6-fold)

23. Conclusion • Acute kidney injury after cardiac surgery -increase mortality and morbidity. Longer hospitalization and increase cost -consequence of interplay of different mechanism - patients who are at high risk - novel renal biomarker - protective strategies

24. Thank you for your attention !! Any question????