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©2013 MFMER | slide-1 Biomarkers of AKI: Kidney Troponin Kianoush Kashani, MD Assistant Professor in Internal Medicine Consultant Division of Nephrology and Hypertension Consultant Division of Pulmonary and Critical Care Program Director – Critical Care Fellowship Mayo Clinic Multidisciplinary Simulation Center (MCMSC)
©2013 MFMER | slide-2 Therapeutic Window Himmelfarb et al: Clin J Am Soc Nephrol 3:962, 2008 High Risk Volume Responsive AKI Volume Unresponsive AKI Therapeutic Window Kidney Function Mortality Biomarkers SensitiveTraditional Hypervolemia Euvolemia Hypovolemia
©2013 MFMER | slide-3 Kidney Troponin PeriodACSAKI 1960s LDHSerum creatinine 1970sCPK, myoglobinSerum creatinine 1980sCK-MBSerum creatinine 1990sTroponin TSerum creatinine 2000sTroponin ISerum creatinine Developed multiple therapies Developed multiple therapies mortality mortality Supportive therapy Supportive therapy High mortality High mortality
©2013 MFMER | slide-4 Serum and urinary cystatin C 13KDa protein Synthesized and released into plasma by all nucleated cells Still dependent on lean body mass (MacDonald, AJKD, 48(5) , 2006) Serum cystatin C freely filtered (small and non-ionic) More sensitive than Scr as marker of GFR Cystatin C catabolized in PT Tubular damage appearance in urine Won K et al, Curr Opin Crit Care, 10: , 2004
©2013 MFMER | slide-5 Cystatin C Obesity and Waste circumference Hyperthyroid Glucocorticoid use Smoker Non-Hispanic White Male Increased CRP Madero, et al; CO Neph HTN. 18:258–
©2013 MFMER | slide-6 Cystatin C and mortality N = 845 ICU patients Based on RIFLE criteria 271 AKI; 562 non-AKI Cystatin C and mortality related in both cohorts Stronger in patients without AKI Bell et al. Nephrol Dial Transplant (2009) 1 of 7
©2013 MFMER | slide-7 Cystatin C and mortality Bell et al. Nephrol Dial Transplant (2009) 1 of 7
©2013 MFMER | slide-8 Neutrophil Gelatinase-Associated Lipocalin (NGAL) Won K: Curr Opin Crit Care 10:476, 2004 Mishra J et al: JASN 14:534, 2003 Lipocalin superfamily Markedly up-regulated in early post-ischemic kidney in proliferating PT cells NGAL in plasma and urine Marker of AKI Appears in urine within 3 hours of ischemic injury and cisplatin exposure
©2013 MFMER | slide-9 NGAL 2-3 Hours After CPB as the Predictor of AKI Haase-Fielitz et al: NDT, May 27, 2009 Timing of NGALAUC-ROC to PatientsCreatinineTiming of postopmeasurementpredict AKI Reference(no.)Settingincreasecreatinine increase(after end of CPB)(plasma/urine) Mishra et al 71Paediatric>50%Within 5 daysAt 2 h0.91/0.99 Dent et al120Paediatric>50%Within 5 daysAt 2 h0.96/– Bennett et al196Paediatric>50%Within 5 daysAt 2 h–/0.95 Wagener et al 81Adult>50%Within 5 daysAt 3 h–/0.74 Wagener et al426Adult>50% orWithin 2 daysAt 3 h–/0.60 >0.3 mg/dL Koyner et al 72Adult>25% or needWithin 3 daysAt ~2 h*0.53/0.70 for RRT Haase-Fielitz et al100Adult>50%Within 5 daysAt ~2 h*0.80/– AKI definition
©2013 MFMER | slide-10 NGAL and Cystatin C after CPB Haase et al; Ann Thorac Surg 2009;88:124 –
©2013 MFMER | slide-11 NGAL predictive value Nickolas et al; Ann Intern Med. 2008;148:
©2013 MFMER | slide-12 Angiopoietin 2: A prognostic marker? Angiopoietin-2 (Ang-2) Circulating antagonistic ligand of the endothelial-specific Tie2 receptor Increases capillary leak Is not removed during dialysis n= 117 AKI at the time of initiation of RRT Circulating Ang-2 correlated with: Impaired oxygenation low mean arterial pressure vasopressor dose SOFA score Ang-2 significantly higher in non-survivors at day 0 and day 14 after initiation of RRT Kumpers et al. Intensive Care Med (2010) 36:462–470
©2013 MFMER | slide-13 Angiopoietin 2: A prognostic marker?
©2013 MFMER | slide-14 Kidney injury molecule-1 (KIM-1) Transmembrane protein Not detectable in normal kidney tissue Very high in dedifferentiated PT cells after ischemic or toxic injury Protein and mRNA up-regulated in 48-hr post ischemic Won et al, KI, 62: , 2002
©2013 MFMER | slide-15 Rena-Stick Human Rena-Stick Vaidya et al, Kidney International (2009) 76, 108–114
©2013 MFMER | slide-16 Multi-bead assay Vaidya et al, 2008 Clin. Trans Sci.
©2013 MFMER | slide-17 Urinary and Serum Biomarkers for the Diagnosis Of AKI: An In-depth Review of the Literature Vanmassenhove et al. Nephrol Dial Transplant (2012) 0: 1–20
©2013 MFMER | slide-18 Discovery Cohort in Search for New Kidney Troponins
©2013 MFMER | slide-19 Vienna Cohort Age 18 ICU + sepsis n=134 Vienna Cohort Age 18 ICU + sepsis n=134 Duke Cohort Age 18 At least 1 risk factor n=123 Duke Cohort Age 18 At least 1 risk factor n=123 Mayo Cohort Age 18 At least 1 risk factor n=265 Mayo Cohort Age 18 At least 1 risk factor n=265 Sapphire Study 35 sites (20 North American, 15 Europe) Age >21, critically ill 3, no AKI (stage 2 or 3) 4 n=744 Sapphire Study 35 sites (20 North American, 15 Europe) Age >21, critically ill 3, no AKI (stage 2 or 3) 4 n=744 No stage 1 n=211 No stage 1 n=211 No stage 2 n=83 No stage 2 n=83 AKI stage 3 n=18 AKI stage 3 n=18 No AKI n=416 No AKI n=416 n= patients excluded (2 withdrew consent, 7 lost to follow-up, 7 with invalid or missing test results) Within 12 hr Validation Discovery Best 2 markers Pilot studies
©2013 MFMER | slide-20 ROC-AUC – Comparison of Novel Markers [TIMP-2] [IGFBP7] Urine TIMP-2 Urine IGFBP7 Urine NGAL Serum creatinine Plasma NGAL Plasma cystatin C AUC (with 95% CI)
©2013 MFMER | slide-21 Sapphire Trial
©2013 MFMER | slide-22 Vienna Cohort Age 18 ICU + sepsis n=134 Vienna Cohort Age 18 ICU + sepsis n=134 Duke Cohort Age 18 At least 1 risk factor 1 n=123 Duke Cohort Age 18 At least 1 risk factor 1 n=123 Mayo Cohort Age 18 At least 1 risk factor 2 n=265 Mayo Cohort Age 18 At least 1 risk factor 2 n=265 Sapphire Study 35 sites (20 North American, 15 Europe) Age >21, critically ill, no AKI (stage 2 or 3) n=744 Sapphire Study 35 sites (20 North American, 15 Europe) Age >21, critically ill, no AKI (stage 2 or 3) n=744 AKI stage 1 n=211 AKI stage 1 n=211 AKI stage 2 n=83 AKI stage 2 n=83 AKI stage 3 n=18 AKI stage 3 n=18 No AKI n=416 No AKI n=416 n= patients excluded (2 withdrew consent, 7 lost to follow-up, 7 with invalid or missing test results) Within 12 hr Validation Discovery Best 2 markers Sapphire Trial
©2013 MFMER | slide-23 Urine KIM-1 Sapphire Study Concentration (ng/mL) ICU admission Cardiovascular Cerebrovascular Sepsis Respiratory Surgery Diabetes CHF CADCKD COPD Emphysema Chronic bronchitis Respiratory other No RIFLE RIFLE R RIFLE I RIFLE F Subjects without AKIAKI subjects stratified by RIFLE
©2013 MFMER | slide-24 Urine NGAL Sapphire Study Concentration (ng/mL) ICU admission Cardiovascular Cerebrovascular Sepsis Respiratory Surgery Diabetes CHF CADCKD COPD Emphysema Chronic bronchitis Respiratory other No RIFLE RIFLE R RIFLE I RIFLE F Subjects without AKIAKI subjects stratified by RIFLE
©2013 MFMER | slide-25 Sapphire Study ICU admission Cardiovascular Cerebrovascular Sepsis Respiratory Surgery Diabetes CHF CADCKD COPD Emphysema Chronic bronchitis Respiratory other No RIFLE RIFLE R RIFLE I RIFLE F Subjects without AKIAKI subjects stratified by RIFLE [TIMP2] [IGFBP7]
©2013 MFMER | slide-26 Sapphire Study P= P< Relative risk of RIFLE-I/F
©2013 MFMER | slide-27 MAKE 30 Composite score Major adverse kidney events truncated in 30 days 1.Death 2.Need for RRT 3.Double Scr at 30 day or d/c [TIMP2] [IGFBP7] ((ng/mL) 2 /1000) Risk of MAKE 30 Risk for AKI (KDIGO stage 2-3) Sensitivity threshold 0.3 Specificity threshold 2
©2013 MFMER | slide-28 Kidney Troponin: where are we? PeriodACSAKI 1960s LDHSerum creatinine 1970sCPK, myoglobinSerum creatinine 1980sCK-MBSerum creatinine 1990sTroponin TSerum creatinine 2000sTroponin ISerum creatinine
©2013 MFMER | slide-29 شكراً “The best interest of the patient is the only interest to be considered”
©2013 MFMER | slide-30 Questions & Discussion
Dr. Waleed Khairy, MD Ain Shams University. There are more than 35 definitions of AKI (formerly acute renal failure) in literature!
BOOK02665/07 AKI in Pediatrics Patrick D. Brophy MD Associate Professor University of Iowa- Carver College of Medicine Dept. of Pediatrics Division of.
Nutrition in Acute Kidney Injury Antonio R. Paraiso, MD, FPCP, FPSN Medical Specialist IV, NKTI Asst. Professor, College of Medicine, UERMMMCI.
© 2010, American Heart Association. All rights reserved. A Validated Risk Score for In-hospital Mortality in Patients with Heart Failure from the American.
Journal Club Nir Hus MD., PhD. Ryder Trauma Center Jackson Memorial Hospital 9/12/2010 Nir Hus MD., PhD. Ryder Trauma Center Jackson Memorial Hospital.
Dyslipidemia in Hemodialysis Patients Turki Banamah Consultant Transplant nephrology King Abdulaziz medical city Jeddah.
“How Do You Solve A Problem like VIKI?” Rommel N. Tipones, MD, FPCP, FPCCP Section of Pulmonary Medicine, NKTI.
The valuable contribution of observational studies to nephrology Kitty J. Jager¹, Vianda S. Stel¹, Christoph Wanner², Carmine Zoccali³ and Friedo W. Dekker.
Prevention of Contrast-Induced Nephropathy (CIN) Sepehr Khashaei, MD Assistant professor Department of Internal Medicine.
Nephrology Grand Rounds March 16 th, 2010 Aditya Mattoo.
Renal disease Dr David MAKANJUOLA Renal unit St. Helier hospital.
Assesment of renal function in case of near normal creatinine (<1.5 ) Naseer Khan MD.
WHEN TO CONSIDER RRT Timothy E Bunchman Founder PCRRT
Program Chairman Joseph Varon, MD, FACP, FCCP, FCCM Clinical Professor of Medicine The University of Texas Health Science Center at Houston Professor,
MSC Confidential Take the Shock Out of Sepsis. MSC Confidential Program Overview: Simulation Workshop Didactic content review Documentation and policy.
ADRENAL INSUFFICIENCY IN CRITICALLY ILL PATIENTS Dalal Abdelgadir R2 pediatics.
Diabetes and Renal Disease. PACE guidelines for Diabetes 2002 Renal/Hypertension.
Cardiovascular Disease in Dialysis and Renal Transplantation Jeffrey Guardino, MD FACC Stanford Hospital Division of Cardiology.
Chronic kidney disease Implementing NICE guidance Second edition 2011 NICE clinical guideline 73.
Exercise Treadmill Testing Prognostication in Coronary Artery Disease Dr. Peter Krampl 11 October 2001.
Welcome to this Science-to-Strategy Summit. Critical Challenges and Landmark Advances in Thrombosis Management The Evolving and Foundation Role of LMWHs.
Perioperative Aspirin & POISE-2 Neal Gerstein, MD FASE Associate Professor, UNM Department of Anesthesiology Director, UNM Division of Cardiac Anesthesia.
Depression Care: Implementing Integrated Primary Care- Behavioral Health Solutions Mark Dreskin, MD Depression Care Program Southern California Kaiser.
Fever in the ICU Christopher Kia. Outline Definition of fever Why fever in the ICU is important Temperature measurement Etiology - infectious and noninfectious.
1 Anti-Infective Drugs Advisory Committee Meeting Xigris™ Drotrecogin Alfa (Activated) October 16, 2001 Eli Lilly and Company
(i) Clinically distinct forms of nephrotoxicity (nephritic syndrome, acute and chronic tubular necrosis, acute vs. chronic interstitial nephritis, forms.
Chronic Kidney Disease. Stage 5 0.2% Stage 4: 0.2% Stage 3: 4.3% Stage 2: 3.0% Stage 1: 3.3% Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence.
The Science and Medicine of Sepsis Management The Role of Inflammation, Signaling Cascades, and Immune Modulation on the Natural History and Treatment.
Dr: Wael H.Mansy, MD Assistant Professor College of Pharmacy King Saud University Diabetes Mellitus.
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