1. ©2012 MFMER | slide-1 Acute Kidney Injury Post-op: Kidney attack Kianoush Kashani 5 th Anesthesia and Critical Care Conference Kuwait 2013

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4. ©2012 MFMER | slide-4 Outlines Definition Epidemiology/outcome Pathophysiology Diagnosis Management Vs treatment

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6. ©2012 MFMER | slide-6 RIFLE Criteria GFR criteriaUrine output criteria Risk Injury Failure Loss ESRD High sensitivity High specificity Persistent ARF = complete loss of renal function >4 weeks End-stage renal disease Increased creatinine x3 or GFR decrease >75% or creatinine  4 mg/ 100 mL (acute rise of  0.5 mg/100 mL dL) Increased creatinine x2 or GFR decrease >50% Increased creatinine x1.5 or GFR decrease >25% UO <0.5 mL kg -1 h -1 x6 hr UO <0.5 mL kg -1 h -1 x12 hr UO <0.3 mL kg -1 h -1 x24 hr or anuria x12 hr Oliguria

7. ©2012 MFMER | slide-7 AKIN Definition for AKI AKIN Conference, Vancouver 2006 Stage I Stage II Stage III Inc Scr  0.3 mg/dL or >150-200% from baseline Inc Scr >200-300% from baseline Inc Scr >300% Scr >4 with acute min rise of 0.5 mg/dL Need for RRT <0.3 mL/kg/hr for 24 hr Anuria for 12 hr 12 hr 6 hr

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9. ©2012 MFMER | slide-9 Reasons for  incidence Age Comorbid conditions CKD More sensitive criteria Hou et al: Am J Med 74:243, 1983 Nash et al: JASN 7:376, 1996 Nash et al: AJKD 39:930, 2002 Year % Incidence of AKI

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11. ©2012 MFMER | slide-11 AKI and Mortality Ricci Z: Kidney Int 73:538, 2008 0.010.1110100 Study or subcategory 01 General ICU (Cr and UO criteria) Abosaif Ahlstrom Cruz Hoste 02 General ICU (without UO criteria) Lopes (HIV) Lopes (sepsis) Ostermann 03 Cardiosurgery Kuitunen Lin 04 Other ICU Coca Lopes (bmt) Lopes (burns) 05 Not confined to ICU Uchino 0.010.11101000.010.1110100 Mortality Risk vs Non-AKI RR (random) 95% CI Mortality Injury vs Non-AKI RR (random) 95% CI Mortality Failure vs Non-AKI RR (random) 95% CI

12. ©2012 MFMER | slide-12 AKI and Long-Term Mortality Lafrance et al: JASN 21(2):345, 2010 Cumulative probability of survival (%) Follow-up (years) No AKI AKIN I AKIN II AKIN III Number at risk 782,222601,772443,730296,128138,820No AKI 52,33837,23425,79816,4417,758AKIN I 19,77113,6929,2105,7122,633AKIN II 10,6027,1734,6392,7231,200AKIN III

13. ©2012 MFMER | slide-13 ESRD After AKI Probability of ESRD Days from hospital discharge Probability of ESRD Days from hospital discharge No AKI AKI P<0.0001, DF=1 P<0.0001, DF=3 No AKI or CKD CKD only AKI only AKI and CKD

14. ©2012 MFMER | slide-14 RRT epidemiology (NEFROINT data) Piccinni et al. Minerva anestheiology 2011; 77:1-2 ICU admissions (ESRD excluded) 576 No AKI on admission 57.3% Never developed AKI 34.2% New AKI 23.1% AKI on admission 42.7% Ever AKI 65.8% Never recovered 27.2% Partial recovery 13.5% Complete recovery 59.4% Required RRT 8.3%

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16. ©2012 MFMER | slide-16 Etiology of Hospital-Acquired AKI % Comprehensive Clinical Nephrology, Johnson 3 rd edition

17. ©2012 MFMER | slide-17 Ischemia induced AKI Abuelo et al, NEJM 2007, 357 (8)

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19. ©2012 MFMER | slide-19 Symptoms Polyuria Oliguria/anuria Hematuria Dysuria Azotemia Mental status changes Acidosis (  respiratory rate) Hypervolemia/hypertension Hyperkalemia Pericarditis

20. ©2012 MFMER | slide-20 Urinary Index Schrier: J Clin Invest 114(1):5, 2004 Prerenal Laboratory testazotemiaATN Urine osmolality (mOsm/kg)>500<400 Urine sodium level (mEq/L) 40 Urine/plasma creatinine ratio >40 <20 Fractional excretion of sodium (%) 2 Fractional excretion of urea (%) 35 Urinary sedimentNormal;Renal tubular occasional hyalineepithelial cells; or fine granulargranular and castsmuddy brown casts

21. ©2012 MFMER | slide-21 FeNa Less than 1% Decreased renal perfusion Decreased intravascular volume NSAID ACE inhibitor/ARB Pigmenturia Hepatorenal syndrome Acute contrast nephropathy Acute (early) GN Early obstruction Acute embolic event

22. ©2012 MFMER | slide-22 FeNa More than 3% Tubular dysfunction ATN Chronic renal disease Diuretics/concentrating defects

23. ©2012 MFMER | slide-23 Urinary Sediments Brenner and Rector: The Kidney, 8 th edition SedimentDifferential diagnosis Normal or fewPrerenal azotemia Red blood cellsArterial thrombosis or embolism White blood cellsPreglomerular vasculitis HUS or TTP Scleroderma crisis Postrenal azotemia Granular castsATN (muddy brown) Glomerulonephritis or vasculitis Interstitial nephritis Red blood cell castsGlomerulonephritis or vasculitis Malignant hypertension Rarely interstitial nephritis White blood cell castsAcute interstitial nephritis or exudative glomerulonephritis Severe pyelonephritis Marked leukemic or lymphomatous infiltration Eosinophiluria (>5%)Allergic interstitial nephritis (antibiotics > NSAIDs) Atheroembolic disease CrystalluriaAcute urate nephropathy Calcium oxalate (ethylene glycol toxicity) Acyclovir Indinavir Sulfonamides Radiocontrast agents

24. ©2012 MFMER | slide-24 Ultrasonography in AKI Comprehensive Clinical Nephrology, Johnson 3 rd edition ObservationClue to diagnosis of Shrunken kidneysChronic kidney disease Normal size kidneysEchogenicAcute GN Normal EchoPrerenal Acute renal artery occlusion Enlarged kidneysMalignancy, renal vein thrombosis, diabetic nephropathy, HIV HydronephrosisObstructive nephropathy

25. ©2012 MFMER | slide-25 Pathology

26. ©2012 MFMER | slide-26 Pathology

27. ©2012 MFMER | slide-27 Hazard Tranche 1 Very high risk patients Increase in 0.1 mg/dL over baseline or 1 hour of oliguria in a appropriately resuscitated subject Hazard Tranche 2 High risk patients Increase in 0.3 mg/dL over baseline or 3 hours of oliguria in a appropriately resuscitated subject Hazard Tranche 3 Moderate risk patients Increase in 0.4 mg/dL over baseline or 5 hours of oliguria in a appropriately resuscitated subject Renal Angina Goldstein et al: cJASN 5:943, 2010 Renal Angina Threshold  serum creatinine (mg/dL) Oliguria (hr) Hazard Tranche #1 Hazard Tranche #2 Hazard Tranche #3 Hazard Tranche #1 Hazard Tranche #2 Hazard Tranche #3 Risk of developing acute kidney injury

28. ©2012 MFMER | slide-28 Biomarkers Cystatin C Functional marker in blood Tubular marker in urine NGAL In plasma less sensitive/specific than urine Others IL-18 Kim-1 L-FABP Netrin-1 Vimentin Stay tuned new markers are on the way

29. ©2012 MFMER | slide-29 Risk prediction

30. ©2012 MFMER | slide-30 Risk prediction

31. ©2012 MFMER | slide-31 Risk prediction

32. ©2012 MFMER | slide-32 Management

33. ©2012 MFMER | slide-33 KDIGO guidelines KI supplement, March 2012

34. ©2012 MFMER | slide-34 Mode of actionCompound Development stage Increase HIF signalling/proteins Prolyhydroxylase inhibitorsPre-clinical ErythropoietinClinical, phase 3 Protection against apoptosis Heat shock proteinsPre-clinical GeranylgeranylactonePre-clinical Adenosine receptor agonistsPre-clinical Ischaemic pre- conditioningClinical Reduce leucocyte adhesion in PTCs Anti-CTLA-4Pre-clinical Anti-ICAM-1Clinical, phase 1 GlitazonesPre-clinical Mesenchymal stem cellsPre-clinical Increase re-endothelialization PTCs ErythropoietinClinical Endothelial progenitor cellsPre-clinical Increase tubular regeneration Mesenchymal stem cellsPre-clinical Hepatocyte growth factorPre-clinical Insulin-like growth factorPre-clinical Epidermal growth factorPre-clinical Aydin, Z. et al. NDT. 2007 22:342-346

35. ©2012 MFMER | slide-35 شكراً “The best interest of the patient is the only interest to be considered”

36. ©2012 MFMER | slide-36 Questions & Discussion