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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) email@example.com
©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) 712-719, 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, 10:476-482, 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. 18:258–263. 2009
©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 –30. 2009
©2013 MFMER | slide-11 NGAL predictive value Nickolas et al; Ann Intern Med. 2008;148:810-819
©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: 237-244, 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=728 5 16 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) 0.40.90.80.70.60.5
©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=728 16 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=0.00008 P<0.00003 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
©2013 Astute Medical, Inc. PN 0138 Rev B 2013/03/19.
Biomarkers in the Cardiorenal Syndromes Catherine Krawczeski, MD Associate Professor of Pediatrics University of Cincinnati College of Medicine Cardiac.
Role of diuresis in AKI management W. Van Biesen, Renal Division, Ghent University Hospital.
Interobserver Reliability of Acute Kidney Injury Network (AKIN) criteria A single center cohort study Figure 2 The acute kidney injury network (AKIN) criteria.
PREDICTING AKI IS MORE CHALLENGING AS AGE PROGRESSES Sandra Kane-Gill, PharmD, MSc Associate Professor, School of Pharmacy.
Date of download: 11/12/2016 Copyright © The American College of Cardiology. All rights reserved. From: Diagnostic and Prognostic Stratification in the.
Risk prediction models of AKI DR.F.Haghverdi MD Outline AKI epidemiology and definition(brenner2016) Biomarkers Risk prediction models of AKI (post CABG,
Optimum Re 2015 Charlotte A. Lee, M.D., FLIM, DBIM EVALUATING RENAL FUNCTION.
IMPROVING OUR UNDERSTANDING OF DRUG ASSOCIATED AKI Sandra Kane-Gill, PharmD, MS, FCCM, FCCP Associate Professor of Pharmacy, Critical Care Medicine, and.
AKI Definitions Stuart L. Goldstein, MD Professor of Pediatrics University of Cincinnati College of Medicine Director, Center for Acute Care Nephrology.
The New Paradigm: Biomarkers to Define AKI Prasad Devarajan, MD Professor of Pediatrics and Developmental Biology University of Cincinnati College of Medicine.
Retrospective Monocentric 10-Year Analysis Of Sepsis-Associated Acute Kidney Injury: Impact On Outcome, Dialysis Dose And Residual Renal Function 1 Vincenzo.
URINARY NETRIN-1 PREDICT EARLY ISCHEMIC ACUTE KIDNEY INJURY AFTER CARDIOPULMONARY BYPASS Mohammad Hasan Aly¹,Alsayed Alnahal¹,Goerge Emad¹, Abdel Azim.
Novel Biomarkers of Kidney Disease NGAL and Cystatin C COL SOHAIL SABIR HOD NEPHROLOGY MILITARY HOSPITAL HOD MEDICAL EDUCATION ARMED FORCES POSTGRADUATE.
The long-term outcome after acute renal failure Presented by Ri 顏玎安.
Sean M Bagshaw, MD, MSc Division of Critical Care Medicine Faculty of Medicine and Dentistry, University of Alberta 1 st International Symposium on AKI.
Biomarkers of Acute Kidney Injury Dr Sameena Ghayur Shifa College of Medicine /Shifa International Hospital
Biomarkers to define AKI Michael Zappitelli, MD, MSc.
Excessive fluid is not needed: So why is Dr. Durward so wasteful? Timothy E Bunchman MD Professor & Director Pediatric Nephrology
Date of download: 6/28/2016 Copyright © The American College of Cardiology. All rights reserved. From: Combining Functional and Tubular Damage Biomarkers.
John A. Kellum, MD, MCCM Professor of Critical Care Medicine, Medicine, Bioengineering and Clinical & Translational Science Vice Chair for Research Director,
Dr. Waleed Khairy, MD Ain Shams University. There are more than 35 definitions of AKI (formerly acute renal failure) in literature!
Proteinuria as a Surrogate Outcome in IgA Nephropathy Ron Hogg MD Scott & White Medical Center Temple, Texas.
Raghavan Murugan, MD, MS, FRCP Associate Professor of Critical Care Medicine, and Clinical & Translational Science Core Faculty, Center for Critical Care.
BOOK02665/07 AKI in Pediatrics Patrick D. Brophy MD Associate Professor University of Iowa- Carver College of Medicine Dept. of Pediatrics Division of.
ACUTE KIDNEY INJURY Role of Novel Biomarkers R Bhimma Department of Paediatrics and Child Health Nelson R Mandela School of Medicine University of KwaZulu-Natal.
Irbesartan Diabetic Nephropathy Trial (IDNT) Collaborative Study Group N Eng J Med 345: , 2001 Edmund J. Lewis, M.D. Muehrcke Family Professor of.
Estimated GFR Based on Creatinine and Cystatin C Lesley A Stevens, MD, MS Tufts Medical Center, Tufts University School of Medicine Boston MA Chronic Kidney.
Exemplary Care Cutting-edge Research World-class Education Raghavan Murugan MD, MS, FRCP Associate Professor Dept. of Critical Care Medicine Clinical.
University of Minnesota – School of Nursing Spring Research Day Glycemic Control of Critically Ill Patients Lynn Jensen, RN; Jessica Swearingen, BCPS,
Section 2: Detection of CKD. What Tests Are Available? Direct GFR measurement –Inulin clearance –Radionuclides –Iohexol clearance 3 hr CrCl with Cimetidine.
Comparison of the New Mayo Clinic Risk Scores and Clinical SYNTAX Score in Predicting Adverse Cardiovascular Outcomes following Percutaneous Coronary Intervention.
Andrew Durward London 2015 Haemofiltration for sepsis: burial or resurrection?
High Cut-Off Hemodialyzers Efficiently Remove Immunoglobulin Free Light Chains And Reduce Tubular Injury Induced By Plasma Of Patients With Multiple Myeloma.
Did I do that? Drug-Induced Acute Kidney Injury Krista Rieger, PharmD, BCPS PGY2 Internal Medicine Resident.
ACUTE KIDNEY INJURY Martin Havrda. Acute kidney injury - RIFLE Risk –50% rise of s-creatinine –25% drop of GFR –Urine output < 0,5 ml/kg.h during 6 hours.
Acute Kidney Injury & Sepsis Patrick D Brophy, MD, MHCDS Director Pediatric Nephrology Professor The University of Iowa London 2015.
ECMO in CRRT – What are the Data? Jason S. Frischer, MD Director, ECMO Program Division of Pediatric General & Thoracic Surgery Cincinnati Children's Hospital.
Renal damage occurs in 1 out of 4 hypertensives Adapted from Leoncini et al. J Hypertens. 2008;26:
Stuart L. Goldstein, MD Professor of Pediatrics Baylor College of Medicine Pediatric Acute Kidney Injury and Biomarkers 6th PCRRT Conference, Rome 2010.
©2012 MFMER | slide-1 Acute Kidney Injury Post-op: Kidney attack Kianoush Kashani 5 th Anesthesia and Critical Care Conference Kuwait 2013.
Relationship of cystatin C with Cardiovascular risk factors and inflammatory markers in Hemodialysis Hyung-Jong Kim, Kyung Mi Park, Yeon Hee Lee, Dong.
Pro-Enkephalin (penKid): A novel plasma biomarker to assess renal impairment das Joachim Struck, PhD Chief Research Officer sphingotec GmbH (Hennigsdorf/Berlin,
Procalcitonin Over the past two decades, the body of literature on the clinical usefulness of procalcitonin (PCT) in adults has grown rapidly. Although.
Date of download: 6/28/2016 From: Sensitivity and Specificity of a Single Emergency Department Measurement of Urinary Neutrophil Gelatinase–Associated.
AKI to CKD: How Should We Look For It Prasad Devarajan, MD Professor of Pediatrics and Developmental Biology University of Cincinnati College of Medicine.
Acute Kidney Injury after Cardiopulmonary Bypass Catherine Krawczeski, MD Associate Professor of Pediatrics University of Cincinnati College of Medicine.
Early Detection and Prevention of Renal Failure Linda Fried, MD, MPH.
AKI ITSELF EPIDEMIOLOGY Michael Zappitelli, MD, MSc Montreal Children's Hospital McGill University Health Centre.
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