The Efficacy of Remote Ischemic Preconditioning in ... The Efficacy of Remote Ischemic Preconditioning

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  • The Efficacy of Remote Ischemic

    Preconditioning in Prevention of Acute

    Kidney Injury Post Cardiac Surgery on

    Cardiopulmonary Bypass.

    Thesis Submitted for fulfillment of M.D degree in anesthesiology and intensive

    care

    Presented By

    Nabil Abd Elazim Mohamed M.B.B.ch,MSc

    Faculty of Medicine, Benha University

    Under Supervision of

    Prof. Saad Ibrahim Saad Professor of anesthesia and ICU

    Faculty of medicine - Benha University

    DR. Ahmed Mostafa Abd El-Hamid Assist. Professor of anesthesia and ICU

    Faculty of medicine - Benha University

    DR. Mohamed Hamed Abd El-Fattah Lecturer of anesthesia and ICU

    Faculty of medicine - Benha University

    Faculty of Medicine Benha University

    2016

  • DEDICATION

    To all my family especially my parents for always

    believe in me, for their continuous love and their

    support in my decisions. Without whom I could not

    have made it here, to my wife, Raghdaa Ahmed .

    She was always there cheering me up and stood by

    me through the good times and bad, my lovely

    children Mena and Mohamed and to the souls of

    my beloved ones.

  • List of contents

    chapter Title page

    List of abbreviations II

    List of Tables III

    List of Figures IV

    1 Introduction V

    2 Review of literature:

     Acute kidney injury post CPB.

     Assessment of acute kidney injury.

     Neutrophil gelatinase-associated lipocalin

     Remote Ischemic preconditioning effect

    1

    24

    34

    47

    3

     Aim of the work

    59

    4  Patients and methods

    60

    5

     Results

    66

    6

     Discussion

    78

    7

     Conclusion

    85

    8

     Summary 86

    9

     References 89

    10

     Arabic Summary

  • List of Abbreviations

    Acute kidney injury AKI

    Acute kidney injury network AKIN

    Risk injury failure end stage renal disease RIFLE

    Remote ischemic preconditioning RIPC

    Neutrophil gelatinase-associated lipocalin NGAL

    Cardiopulmonary bypass CPB

    Coronary artery bypass graft CABG

    Urine osmolality Uosm

    Urinary Na Una

    Glomerulonephritis GN

    Acute tubular necrosis ATN

    Glomerular filtration rate GFR

    Cystain C Cys C

    kidney injury molecule 1 Kim1

    Interleukin 6 IL6

    C Reactive protein CRP

    liver fatty-acid-binding protein l-FABP

    Glutathione-S-transferase GST

  • Interleukin 18 IL-18

    Intra-aortic balloon pump IABP

    Left ventricle LV

    Systemic inflammatory response syndrome SIRS

    Acute renal failure ARF

    Thick ascending limbs of loop of Helen mTAL

    Kilo pascal KPa

    Antidiuretic hormone ADH

    Chronic renal failure CRF

    Adenosine tri phosphate ATP

    Neutrophils PMN

    Macrophages M0

    Invariant natural killer t lymphocyte iNKT

    Adhesion molecules ICAM-1

    Toll like receptors TLRs

    Dendritic cells DCs

    Ischemia reperfusion injury IRI

    tubular epithelial cells TECs

    major histocompatibility complex MHC

  • Angiotensin converting enzyme inhibitors ACE

    Urine output UO

    Serum creatinine SCr

    Acute Dialysis Quality Initiative ADQI

    Modification of Diet in Renal Disease MDRD

    Renal replacement therapy RRT

    Creatinine Cr

    Chronic kidney disease CKD

    Dalton kDa

    Nuclear factor Κb (NF)-κB

    Simian vacuolating virus 40 SV40

    Mitochondrial reactive oxygen species ROS mitochondrial

    Manganese superoxide dismutase MnSOD

    Heat shock protein 32 HSP32

    Phosphorylated heat shock protein 27 pHSP27

    Heat shock protein 70 HSP70

    Phosphorylated protein kinase B on serine-473 PAkt

    Protein kinase B Akt

    Extracellular signal- regulated kinase ½ ERK1/2

    Kidney injury molecule-1 KIM-1

    Interleukin-1β IL-1β

  • Tumor necrosis factor-α TNF-α

    Intercellular adhesion molecule-1 ICAM-1

    Activator protein-1 AP-1

    Cyclic guanosine mono- phosphate Cgmp

    Calcitonin gene-related peptide CGRP

    Cyclooxygenase 2 COX2

    Janus kinase JAK

    Hypoxia-inducible factor 1a HIF-1a

    Heat shock protein; HSP

    Inducible nitric oxide synthase Inos

    Mitochondrial permeability transition pore m PTP

    nuclear factor (erythroid-derived 2 Nrf2

    signal transducer and activator of transcription STAT1/3.

    Mitocondrial activated protein kinase MAPK

    Manganese superoxide dismutase MnSOD

    Nitric oxide NO

    NG-nitro-L-arginine methyl ester hydrochloride L-NAME

    Protein kinases PKC

    ATP-dependent mitochondrial potassium channel KATP

    Catalase CAT

    Manganese superoxide dismutase MnSOD

    Heat shock protein 32 HSP32

  • Phosphorylated heat shock protein 27 pHSP27

    α-smooth muscle actin1/2 α-SMA

    Fibronectin-1 FN-1

  • List of Table

    Chapter Table Title Page

    1 1 Risk factors associated with AKI 7

    2 2 RIFLE criteria of AKI 27

    2 3 Three stages of AKI according AKIN 32

    5 4 The demographic characteristics of patients 66

    5 5 Changes in the intraoperative measurement

    of times

    68

    5 6 Serum Neutrophil Gelatinase Associated

    Lipocalin levels

    69

    5 7 Serum creatinine levels 70

    5 8 Regarding urine out value 71

    5 9 Estimated glomerular filtration rate 73

    5 10 Fluid management 74

    5 11 Mean arterial blood pressure measurement 74

    5 12 Central venous pressure measurement 76

    5 13 Inotropic support 77

  • List of Figures

    chapter Figure Title Page

    1 1 Characteristic of different type of renal injury 2

    1 2 Nephron structure 3

    1 3 Different phases of AKI 6

    1 4 Systemic inflammatory response syndrome with

    CPB

    16

    1 5 Inflammatory role of bone marrow-derived and

    kidney cells in AKI

    17

    1 6 Innate immune system response in AKI 18

    3 7 Iron thievery in NGAL expression 40

    3 8 Roles of NGAL in human biology 42

    4 9 Mechanisms of IPC in cardiac cells 49

    4 10 Mechanisms of RIPC in distant organs 50

    2 11 Comparison between both groups as regard age 66

    4 12 Comparison between both groups as regard sex 67

    4 13 Comparison between both groups as ASA

    classification

    67

    5 14 Comparison between both groups as regard

    groups as regards cross clamping time

    68

    5 15 Comparison between both groups as regard

    serum NGAL level

    69

    5 16 Comparison between both groups as regard as

    regard creatinine level

    70

    5 17 Comparison between both groups as regard

    UOP intraoperative

    72

  • 5 18 Comparison between both groups as regard

    UOP intraoperative in the first 6 hours

    72

    5 19 Comparison between both groups as regard

    UOP in the next 3 days

    72

    5 20 Comparison between both groups as regard

    EGFR

    73

    5 21 Comparison between both groups as regard

    MAPB

    75

    5 22 Comparison between both groups as regard

    CVP

    76

  • Introduction

    i

    Introduction

    Acute kidney injury (AKI) post cardiac surgical incidence varies

    between 5% and 30%. Acute kidney injury is associated with an increased

    risk of mortality and morbidity, predisposes patients to a longer

    hospitalization, requires additional treatments, and increases the hospital

    costs, acute kidney injury is characterized by a progressive worsening

    course, being the consequence of an interplay of different path

    physiological mechanisms, with patient-related factors and as major causes

    by cardiopulmonary bypass.1

    Such that even after adjustment for patient comorbid conditions and

    surgical complications, the presence of AKI requiring dialysis therapy

    increases the risk of death by 8 times in this patient group. Furthermore,

    changes 0.5 mg/dL in serum creatinine level after cardiac surgery also

    contribute to a significant increase in mortality at 30 days post-surgery .2

    Several different injury pathways including exogenous and

    endogenous toxins, metabolic and neurohormonal factors, renal ischemia

    and inflammatory surgical response contribute to the development of AKI

    during cardiac and vascular interventions.3

    New classification criteria have been recently proposed because of

    the wide variation in AKI definitions with a difficult result comparison

    across studies and populations. The RIFLE (an acronym for risk, injury,

    failure, loss, end-stage kidney disease) criteria and the Acute Kidney

    Injury Network (AKIN) criteria have emerged as diagnostic tools for

    monitoring the severity and progres

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