Critical Care Nephrology E-Book

Claudio Ronco; Rinaldo Bellomo; John A. Kellum; Zaccaria Ricci

BOOK

Critical Care Nephrology E-Book

Claudio Ronco | Rinaldo Bellomo | John A. Kellum | Zaccaria Ricci

(2017)

Additional Information

Book Details

ISBN: 978-0-323-51199-5
Edition: 3
Language: English
Pages: 1840
Subjects: Renal medicine & nephrology
Radiology
Critical care surgery

Abstract

Comprehensive and clinically relevant, the 3rd Edition of Critical Care Nephrology provides authoritative coverage of the latest advances in critical care procedures for patients with renal diseases or disorders. Using common guidelines and standardized approaches to critically ill patients, this multidisciplinary reference facilitates better communication among all physicians who care for critically ill patients suffering from kidney disease, electrolyte and metabolic imbalances, poisoning, severe sepsis, major organ dysfunction, and other pathological events.

Offers detailed discussions of different forms of organ support, artificial organs, infections, acute illness occurring in chronic hemodialysis patients, and much more.

Places a special emphasis on therapeutic interventions and treatment procedures for a hands on clinical reference tool.

Presents information clearly, in a format designed for easy reference – from basic sciences to clinical syndromes to diagnostic tools.

Covers special populations such as children, diabetic patients, and the elderly.
An exceptional resource for nephrologists, intensivists, surgeons, or critical care physicians – anyone who treats critically ill renal patients.

Shares a combined commitment to excellence lead by Drs. Claudio Ronco, Rinaldo Bellomo, John Kellum, and Zaccaria Ricci – unparalleled leaders in this field.

Addresses key topics with expanded coverage of acute kidney injury, stress biomarkers, and sepsis, including the latest developments on mechanisms and management.

Provides up-to-date information on extracorporeal therapies from new editor Dr. Zaccaria Ricci.

Section Title	Page	Action	Price
Front Cover	cover
Inside Front Cover	ifc1
Critical Care Nephrology	i
Copyright Page	iv
Dedication	v
Contributors	vii
Preface	xxiii
Table Of Contents	xxv
1 Principles of Critical Care	1
1 The Critically Ill Patient	1
Objectives	1
Organ Dysfunction	1
Cardiovascular	1
Respiratory	1
Renal	2
Hematologic	2
Neurologic	2
Hepatic	2
Gastrointestinal	2
Quantifying Organ Dysfunction	2
Principles of Management: The VIP Rule	3
Monitoring Systems	4
The ICU Stay as Part of a Trajectory	4
Conclusion	4
Key Points	4
References	4.e1
2 The Pathophysiologic Foundations of Critical Care	5
Objectives	5
Principles	5
Applied Physiology at the Bedside	5
Basics of Cardiovascular Physiology	6
Circulatory Shock: Resuscitation Guidelines and Protocols	8
Sepsis and Septic Shock	9
Summary	9
Key Points	9
References	9.e1
3 Mechanical Ventilation	10
Objectives	10
Physiology Relevant to Ventilatory Support	10
Indications for Mechanical Ventilation	11
Inadequate Alveolar Ventilation	11
Inadequate Oxygenation	11
Excessive Respiratory Workload	11
Types of Invasive Ventilation	12
Pressure-Preset (Pressure-Targeted) Ventilation	12
Flow-Controlled, Volume-Cycled Ventilation	12
Differences Between Pressure-Targeted and Volume-Targeted Ventilation	12
Modes and Settings	13
Assist-Control Ventilation	13
Synchronized Intermittent Mandatory Ventilation	13
Pressure-Support Ventilation	14
Routine Settings	14
Flow-Targeted, Volume-Controlled Ventilation	14
Other Settings	15
General Principles of Patient Management	15
Conceptual Advances	16
Driving Pressure	16
Dynamic Determinants of Risk of Ventilator-Induced Lung Injury	16
Prone Positioning	16
Timely Use of Muscle Relaxants	16
Ventilator-Induced Diaphragmatic Dysfunction	16
Importance and New Approaches to Patient-Ventilator Synchrony	16
Post-Intensive Care Syndrome	17
Strategies to Hasten Liberation From Invasive Ventilation	17
Tools for the Bedside	17
High-Frequency Oscillation	17
High-Flow Nasal Oxygen	17
Extracorporeal Gas Exchange	17
Specifics of Patient Management	18
Discontinuation of Ventilatory Support	19
Noninvasive Ventilation	19
Conclusion	20
Key Points	20
Key References	21
References	21.e1
4 Hemodynamic Support in the Critically Ill Patient	21
Objectives	21
Hemodynamic Monitoring	21
Pharmacologic Cardiovascular Support	22
Nonpharmacologic Cardiovascular Support	23
Temporary Mechanical Circulatory Support	23
Long-Term Mechanical Circulatory Support	24
Conclusion	24
Key Points	24
Key References	24
References	25.e1
5 Monitoring Organ Dysfunction in Critical Care	25
Objectives	25
Principles of Biomarker Analysis to Assess Organ Dysfunction	25
Cardiovascular Function and Hemodynamic Monitoring	25
Respiratory Functional Assessment	27
Neurologic Functional Assessment	28
Renal Functional Assessment	28
Conclusion	28
Key Points	29
Key References	29
References	29.e1
6 Kidney-Specific Severity Scores	29
Objectives	29
Kidney-Specific Severity Scores and Their External Validation	29
Bullock’s Score	29
Liaño’s Score	30
Mehta’s Score	31
SHARF-II Score	31
PICARD Score	31
Demirjian’s Score	31
Problems of Currently Available Kidney-Specific Severity Scores	32
Risk Factors for Hospital Death in Patients With Acute Renal Failure	32
Key Points	33
Key References	33
References	34.e1
2 Principles of Renal Physiology	35
7 The Physiology of the Glomerulus	35
Objectives	35
Basic Anatomy	35
Flow Regulation	36
Role of Flow Regulation	36
Myogenic Response	36
Tubuloglomerular Feedback	37
Angiotensin II	37
Endothelial Factors	38
Short- and Long-Term Regulation	38
Glomerular Capillaries	38
Vascular Endothelial Growth Factor	38
Glomerular Capillary Diseases	39
Mechanical Filtration	39
Filtered Molecules	39
Endothelium	40
Basement Membrane	40
Podocytes	40
Podocyte Structure and Function	41
Mesangium	41
Key Points	41
Key References	41
References	42.e1
8 The Physiology of the Loop of Henle	42
Objectives	42
Sodium Transport and the Countercurrent System	42
Acid-Base Transport	43
Basolateral Membrane	44
Cell pH and Bicarbonate Transport	44
Other Regulating Factors	45
Ammonia and Ammonium Ion Transport	45
The Function of the Macula Densa	46
Transport of Divalent Cations	46
Calcium Transport	46
Magnesium Reabsorption	46
The Calcium-Magnesium–Sensing Receptor	47
Conclusion	47
Key Points	47
Key References	47
References	48.e1
9 Glomerular Filtration Rate, Renal Functional Reserve, and Kidney Stress Testing	48
Objectives	48
Mechanism of Glomerular Filtration	48
Measurement of Glomerular Filtration Rate	51
GFR and Estimated GFR in Acute Kidney Injury	52
Regulation and Measurement of GFR in Acute Kidney Injury	53
Renal Functional Reserve and Renal Stress Testing	54
Renal Functional Reserve—Glomerular	55
Baseline (Unstressed) GFR	55
Renal Functional Reserve	55
Kidney Stress Test of Glomerular Function in Clinical Practice and Future Research	56
Tubular Function Assessment in Kidney Disease	57
Tubular Function Assessment in Chronic Kidney Disease	57
Tubular Assessment in Acute Kidney Injury	57
Key Points	58
Key References	59
References	59.e1
10 Renal Energy Consumption and Metabolism	59
Objectives	59
Normal Renal Bioenergetics	59
Renal Oxygenation and Energy Consumption	59
Renal Energy Production	60
Renal Bioenergetics in Acute Kidney Injury	61
Regional Oxygenation and Energy Metabolism During Experimental AKI	61
Renal Oxygenation and Energy Metabolism During Clinical AKI	62
Interventions Affecting Renal Bioenergetics	62
Loop Diuretic Agents	62
Vasopressors	63
Noradrenaline	63
Vasopressin	63
Angiotensin II	63
Atrial Natriuretic Peptide	63
Intravenous Fluid Therapy	64
Pyruvate	64
Conclusion	64
Key Points	64
Key References	64
References	64.e1
3 Epidemiology of Acute Kidney Injury in Critical Care	65
11 Acute Kidney Injury	65
Objectives	65
Normal Kidney	66
Increased Susceptibility	66
Acute Kidney Stress	66
Renal Angina	68
Concept of Subclinical Acute Kidney Injury	68
Molecular Diagnosis of Acute Kidney Injury	68
Cell Cycle Arrest Biomarkers	69
Constitution of Nephrocheck Rapid Response Team	72
Conclusion	73
Key Points	74
Key References	75
References	75.e1
12 Community- and Hospital-Acquired Acute Kidney Injury	75
Objectives	75
Community-Acquired Acute Kidney Injury	76
Hospital-Acquired Acute Kidney Injury	77
Cause of Acute Kidney Injury	78
Contrast-Induced Acute Kidney Injury	78
Community-Acquired Pneumonia and Acute Kidney Injury	78
Drugs and Acute Kidney Injury	78
Sepsis and Acute Kidney Injury	79
Human Immunodeficiency Virus Infection and Acute Kidney Injury	79
Malaria and Acute Kidney Injury	79
Gyneco-Obstetric and Acute Kidney Injury	79
Postoperative Acute Kidney Injury	80
Acute Kidney Injury in the Elderly Population	80
Conclusion	80
Key Points	80
Key References	80
References	80.e1
13 Epidemiology of Acute Kidney Injury in Critically Ill Patients	81
Objectives	81
Incidence of Acute Kidney Injury	81
Incidence of Acute Kidney Injury Treated With Renal Replacement Therapy	81
Incidence of Acute Kidney Injury	82
Etiology of Acute Kidney Injury and Risk Factors for Acute Kidney Injury	82
Outcomes of Acute Kidney Injury	82
Kidney Outcomes	82
Patient Outcomes	83
Length of Stay	83
Mortality	83
Long-Term Outcome	84
Key Points	84
Key References	85
References	85.e1
14 Acute Kidney Injury in Patients With Chronic Kidney Disease	85
Objectives	85
Chronic Kidney Disease and the Development of Acute Kidney Injury	85
Acute Kidney Injury and the Progression of Chronic Kidney Disease	87
Management End-Stage Renal Disease Patients in the Intensive Care Unit	88
Conclusion	88
Key Points	89
Key References	89
References	89.e1
4 Exposures and Patient Susceptibility	90
15 Genetic Predisposition for Acute Kidney Injury (AKI)	90
Objectives	90
Background	90
Genetic Approaches	90
Association With Candidate Genes	90
Genetic Variability and Acute Kidney Injury	91
Difficulties in Defining the Genes of Interest in Acute Kidney Injury	91
Genes Associated With Acute Kidney Injury	91
Mechanistic Approach to Select Gene Associations	91
Investigated Gene Associations With Acute Kidney Injury	91
Inflammatory Genes	91
Genes Regulating the Vasomotor Tone	92
Other Gene Polymorphisms	93
Future Directions: Genome-Wide Associations	93
Key Points	93
Key References	93
References	94.e1
16 Risk Factors and Risk Assessment in Acute Kidney Injury	94
Objectives	94
Risk Assessment and Preventative Strategies	95
Common Risk Factors for Acute Kidney Injury	95
Specific Risk Settings for Acute Kidney Injury	96
Risk Assessment Scoring Systems	97
Using Risk Factors in Clinical Decision Making When the Insult Is Not Predictable	97
Biomarkers to Enhance Risk Prediction Models	97
Genetic Polymorphisms and Their Association With Risk for Acute Kidney Injury	98
Using the Electronic Medical Record to Assess Risk for Acute Kidney Injury	98
Summary	98
Key Points	98
Key References	98
References	98.e1
17 Experimental Models of Acute Kidney Injury	99
Objectives	99
In vitro Models of Acute Kidney Injury	99
Cultured Renal Cells	99
Isolated Renal Proximal Convoluted Tubules	100
Isolated Glomeruli	100
Renal Tissue Slices	100
Isolated Perfused Kidney	100
In Vivo Models of Acute Kidney Injury	100
Renal Ischemia	100
Nephrotoxins	101
Sepsis	101
Endotoxin.	101
Bacteremia.	101
Peritonitis.	101
Translation to Human Disease	101
Supportive Therapies	102
Single Versus Multiple Insults	102
Chronic Renal Disease and Age	103
Genetic Diversity	103
Severity of Disease	103
Trajectory of Disease	103
Interspecies Differences	103
Experimental Design	103
Terminology	103
Emerging Research Techniques	103
Tissue Engineering	103
Molecular Studies of Cell Death	104
Genetic Studies	104
Zebrafish	104
Microcirculation	104
Magnetic Resonance Imaging	104
Summary	105
Key Points	105
Key References	105
References	105.e1
5 Humoral and Cellular Mechanisms of Kidney Damage	106
18 Renal Blood Flow and Perfusion Pressure	106
Objectives	106
Relationship Between Renal Blood Flow and Perfusion Pressure, or Renal Autoregulation	106
Definition of Autoregulation	106
Autoregulation Zone	106
Physiologic Conditions	106
Pathophysiologic Conditions	107
Mechanism of Autoregulation	107
Determinants of Perfusion Pressure	107
Mean Arterial Pressure	107
Renal Venous Pressure	108
Conclusion	109
Key Points	109
Key References	109
References	109.e1
19 Humoral Mediators in Sepsis	109
Objectives	109
Humoral Mediators in the Pathogenesis of Sepsis	109
Coagulation Cascade Activation in Sepsis: the Role of Platelet-Activating Factor	110
Proinflammatory and Antiinflammatory Cytokine Network During Sepsis	111
Key Points	113
Key References	113
References	113.e1
20 Cell Death Pathways	113
Objectives	113
Mechanisms of Cell Death	114
Regulated Cell Death	114
Apoptosis	114
Regulated Necrosis	116
Necroptosis	116
Other Forms of Regulated Necrosis	116
Cell Death in Acute Kidney Injury	116
Apoptosis During Acute Kidney Injury	118
Ischemia Reperfusion Injury	118
Nephrotoxic Injury	118
Cell Death Regulated by Necrosis During Acute Kidney Injury	118
Necroptosis	118
Cyclophilin D–Mediated Regulated Necrosis	119
Parthanatos	119
Pyroptosis	119
Ferroptosis	119
Potential Therapies	120
Key Points	121
Key References	121
References	121.e1
21 Pathogen-Associated Molecular Patterns, Damage-Associated Molecular Patterns, and Their Receptors in Acute Kidney Injury	121
Objectives	121
PAMPs and DAMPs	122
Pattern Recognition Receptors	122
Toll-Like Receptors	122
Nod-Like Receptors, Signalosomes, and Inflammasomes	124
PAMPs, DAMPs, and PRRs in Acute Kidney Injury	124
Conclusion	126
Key Points	126
Key References	127
References	127.e1
6 Clinical Course of Acute Kidney Injury and Biomarkers	128
22 Acute Kidney Disease	128
Objectives	128
Acute and Chronic Kidney Disease	128
Baseline Renal Function	129
Clinical Course After AKI	130
Novel Biomarkers	131
Key Points	131
Key References	131
References	132.e1
23 Acute Kidney Disease, Renal Recovery, and Post–Acute Kidney Injury Care	132
Objectives	132
Acute Kidney Injury and Associated Outcomes	132
Mortality	132
Cardiovascular Disease	132
Chronic Kidney Disease and End-Stage Renal Disease	133
Development of CKD After AKI (AKI Transition to CKD)	133
Recognition and Detection of Persistent Renal Injury and Renal Recovery	133
Care After Acute Kidney Injury	134
Need for Care After Acute Kidney Injury	134
Qualifying for Care After Acute Kidney Injury in a Specialized Clinic	135
Management of Acute Kidney Injury Survivors	135
Obstacles to Care After Acute Kidney Injury	136
Summary and Future Directions	137
Key Points	137
Key References	137
References	137.e1
24 The Role of Biomarkers in the Diagnosis and Management of Acute Kidney Injury	138
Objectives	138
Role of Biomarkers in Acute Kidney Injury Risk Stratification	138
Role of Biomarkers in Early Diagnosis of Acute Kidney Injury	139
Role of Biomarkers in Acute Kidney Injury Intervention	139
Role of Biomarkers in Acute Kidney Injury Prognosis	140
Biomarkers in Acute Kidney Injury: Pediatric Perspective	140
Key Points	140
Key References	141
References	141.e1
25 Functional Biomarkers	141
Objectives	141
Background	141
Creatinine and the Assessment of Renal Function	141
Mathematical Estimation of Glomerular Filtration Rate	142
Clearance Measurements	142
Alternative Glomerular Filtration Markers	143
Urine Output as a Renal Functional Biomarker	144
Key Points	144
Key References	145
References	145.e1
26 Damage Biomarkers	145
Objectives	145
Urinary Damage Biomarkers of Acute Kidney Injury: The Search for “Renal Troponin I”	145
Damage Biomarkers Studied in Hospitalized Patients	146
NGAL	146
KIM-1	146
IL-18	146
L-FABP	146
Cystatin C	146
AKI After Cardiopulmonary Bypass in Children: The Ideal Clinical Setting for Damage Biomarker Assessment	146
Damage Acute Kidney Injury Biomarkers in Other Settings	146
Early Single-Center Adult Studies	146
Single-Center Pediatric Intensive Care Unit Studies	146
Subsequent Adult Damage Biomarker Studies	147
Putting It All Together	147
Key Points	147
Key References	148
References	148.e1
27 Kidney Stress Biomarkers	148
Objectives	148
Stress Response	148
Systemic Stress Response	148
Cellular Stress Response	149
Kidney Stress Response	149
Cell Cycle Arrest	149
Cell Cycle Arrest and Acute Kidney Injury	150
Kidney Stress Biomarkers	150
IGFBP7	150
Tissue Inhibitor of Metalloproteinase-2	150
Kidney Stress Biomarkers: Clinical Studies	150
Discovery and Validation	150
Cutoff Levels	151
Subgroups Analyses of Validation Studies	151
Follow-Up Studies in Different Cohorts	151
Kidney Stress Biomarkers: Clinical Applications and Summary	151
Summary	152
Key Points	152
Key References	153
References	153.e1
7 Mechanisms of Repair or Progression	154
28 Renal Repair and Recovery	154
Objectives	154
Normal Renal Architecture	154
Acute Kidney Injury: Common Pathophysiologic Mechanisms of Injury	154
Recovery From Acute Kidney Injury: Mechanisms of Maladaptive Repair	155
Recovery From Acute Kidney Injury: the Progenitor Cell	156
Recovery From Acute Injury: the Cellular Stress Response	156
Recovery From Acute Injury: Role of Endothelium	156
Recovery From Acute Injury: Role of Growth Factors	157
Epidermal Growth Factor	157
Insulin-like Growth Factor-1	157
Alpha-Melanocyte Stimulating Hormone	157
Erythropoietin	158
Hepatocyte Growth Factor	158
Bone Morphogenetic Protein-7	158
Transforming Growth Factor-β	158
Emerging Research Areas: Role of Epigenetics in Acute Kidney Injury	158
Strategies to Accelerate Renal Recovery: Human Studies	158
Conclusion	159
Key Points	159
Acknowledgments	159
Key References	159
References	159.e1
29 Maladaptive Repair and Progression to CKD	159
Objectives	159
Resident Cells	160
Tubular Cells	160
Endothelial Cells	161
Pericytes	161
Innate Immune System	161
Macrophages	161
Complement	162
Adaptive Immune System	162
Senescence: the Bridge Between AKI and CKD	162
Maladaptive Repair as a Therapeutic Target	163
Key Points	163
Key References	163
References	163.e1
30 Biomarkers of Recovery and/or Repair Following Acute Kidney Injury	164
Objectives	164
Conventional Measures	164
Biomarkers Related to Inflammation	165
Biomarkers Reflecting Cellular Injury	165
Biomarkers Reflecting Cell Cycle Arrest	165
The Future	165
Conclusions	166
Key Points	166
Key References	166
References	166.e1
8 Renal Histopathology in Acute Kidney Injury	167
31 Practical Considerations of Renal Biopsies in Critical Care Patients	167
Objectives	167
Indications and Contraindications for Renal Biopsy	167
Special Considerations in the Elderly and During Pregnancy	168
Elderly	168
Pregnancy	168
Biopsy Technique and Modalities	168
Bleeding Complications in Percutaneous Kidney Biopsies	169
Imaging	169
Peribiopsy Anticoagulation	170
Antiplatelet Agents	170
Desmopressin	171
Additional Complications of Percutaneous Renal Biopsies	171
Arteriovenous Fistula	171
Infection	171
Page Kidney	171
Pre- and Postbiopsy Management	171
Diagnosis and Therapy	171
Conclusion	172
Key Points	173
Key References	173
References	173.e1
32 Localization of Injury and Repair Pathways	173
Objectives	173
Localization of Injury	173
Adaptive Repair After Acute Kidney Injury: the Renal Stress Response	174
Heme Oxygenase and Antioxidant Genes	174
Heat Shock Proteins	174
Stress-Activated Protein Kinases	175
Other Adaptive and Reparative Mechanisms	176
Hypoxia and Oxidative Stress Mediators	176
Wnt/β-Catenin Pathway	176
Selective Autophagy	177
Renal Repair After Acute Kidney Injury: Evidence for the Existence of a Tubular Progenitor Response	177
Conclusion	178
Key Points	178
Key References	178
References	178.e1
9 Imaging Techniques in Critical Care Nephrology	179
33 Ultrasonography and Doppler Techniques	179
Objectives	179
Definition of Acute Kidney Injury	179
Pathogenesis of Acute Damage and Role of Microcirculation	179
Role of Ultrasound in Clinical WorkUp	180
PreRenal Acute Kidney Injury	180
Acute Kidney Injury Due to Acute Heart Failure	180
Lung Comet Tails	181
Acute Kidney Injury Due to Chronic Heart Failure	181
Liver Stasis	181
Pleural Effusion, Ascites, and Peripheral Oedema	182
Central Venous Pressure and Hepatic Veins Spectral Tracing	182
Hepato-Renal Syndrome	182
Parenchymal Acute Kidney Injury	183
Parenchymal Diseases	183
Vascular Diseases	183
Postrenal AKI	183
Key Points	185
Key References	185
References	185.e1
34 Contrast-Enhanced Renal Ultrasound	186
Objectives	186
Background	186
Contrast-Enhanced Ultrasonography	186
Ultrasound Contrast Agents	186
Ultrasound Equipment and Settings	186
Safety	186
Clinical Applications for Renal Contrast-Enhanced Ultrasonography	186
Vascular Imaging With Contrast-Enhanced Ultrasonography	187
Renal Infarction	187
Acute Cortical Necrosis	188
Cholesterol Emboli Syndrome	188
Renal Transplant	189
Blood Flow Quantification With Contrast-Enhanced Ultrasonogaphy	189
Overview	189
Clinical Use of Contrast-Enhanced Ultrasonography to Quantify Renal Perfusion	189
Limits and Pitfalls	190
Future Research	190
Conclusion	191
Key Points	191
Key References	191
References	191.e1
35 Traditional Radiology, Computed Tomography, and Magnetic Resonance Imaging in Critical Care Nephrology	191
Objectives	191
Computed Tomography	191
Magnetic Resonance Imaging	193
Functional Magnetic Resonance Imaging	195
Dynamic Contrast-Enhanced Magnetic Resonance Imaging	195
Blood Oxygen Level–Dependent Magnetic Resonance Imaging	195
Arterial Spin Labeling	196
Diffusion-Weighted Imaging	196
Key Points	196
Key References	197
References	197.e1
36 Radionuclides Diagnostic Techniques	197
Objectives	197
Principles of Nuclear Medicine	197
Radionuclides Techniques in Renal Evaluation	198
Static Renal Scintigraphy	198
Dynamic Radionuclide Renography	199
Dynamic Radionuclide Renography in Acute Renal Failure	200
Transplanted Kidney Evaluation	200
Role of Nuclear Medicine in Cardiac Diseases	201
Role of Nuclear Medicine in Inflammation, Infection, and Cancer Diseases	202
Key Points	203
Key References	203
References	204.e1
10 Clinical Syndromes and Acute Kidney Injury	205
37 Multiple Organ Dysfunction	205
Objectives	205
Mechanisms	205
Cellular Hypoxia	205
Mitochondrial Dysfunction and Cellular Dysoxia	206
Inflammation	206
An Adaptive State?	207
Reversal of Multiorgan Dysfunction Syndrome and Recovery	207
Future Therapies	207
Summary	208
Key Points	208
Key References	208
References	208.e1
38 Acute Kidney Injury in Burns and Trauma	209
Objectives	209
Traumatic Acute Kidney Injury	209
Epidemiology of Acute Kidney Injury in Major Trauma	209
Cause of Acute Kidney Injury After Major Trauma	209
Rhabdomyolysis	210
Burn Injuries and Acute Kidney Injury	212
Pathophysiology of Acute Kidney Injury in Burns	212
Management of the Burns Patient With Acute Kidney Injury	213
Outcomes and Follow-Up After Acute Kidney Injury in Trauma or Burns	213
Key Points	214
Key References	214
References	214.e1
39 Drug-Induced Acute Kidney Injury	214
Objectives	214
Antiinfective Agents	215
Aminoglycosides	215
Vancomycin	216
Amphotericin B	217
Polymyxins	218
Highly Active Antiretroviral Therapy	219
Nonsteroidal Antiinflammatory Drugs	219
Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Blockers, and Renin Inhibitors	219
Chemotherapeutic Agents	220
Key Points	221
Key References	221
References	221.e1
40 Acute Kidney Injury in Pregnancy	222
Objectives	222
Epidemiology of Acute Kidney Injury in Pregnancy	222
Renal Physiology: Alterations in Pregnancy	223
Anatomic Changes of the Upper Urinary Tract	223
Systemic Cardiovascular Changes	223
Renal Hemodynamic Alterations During Pregnancy	223
Mechanisms Underlying Renal Hemodynamic Alterations During Pregnancy	224
Renal Handling of Substrates During Pregnancy	225
Protein	225
Glucose	225
Uric Acid	225
Acid-Base Homeostasis	225
Fetal Considerations	225
Uteroplacental Hemodynamics and Fetal Oxygen Delivery	225
Fetal Surveillance and Monitoring	226
Fetal Interventions and the Maternal-Fetal Balance	226
Causes of Pregnancy-Related Acute Kidney Injury	226
Pregnancy-Specific Acute Kidney Injury Diagnoses	227
Hypertension and Thrombotic Microangiopathy	227
Preeclampsia and HELLP Syndrome.	227
Acute Fatty Liver of Pregnancy.	227
Amniotic Fluid Embolism.	228
Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome.	229
Postpartum Idiopathic Acute Renal Failure.	229
Infection and Sepsis	229
Volume Depletion	230
Obstruction	231
Other Intrinsic Renal Dysfunction in Pregnancy	231
Evidence-Based Approach to Evaluation and Management of Pregnancy-Related Acute Kidney Injury	232
Management of Acute Kidney Injury in Pregnancy	232
Conclusion	233
Key Points	234
Key References	234
References	234.e1
41 Acute Kidney Injury in Oncology and Tumor Lysis Syndrome	234
Objectives	234
Epidemiology and Risk Factors	235
Acute Kidney Injury in Solid Tumors	236
Acute Nephrotoxicity From Cytotoxic Chemotherapy	236
Cisplatin	236
Mitomycin-C	236
Gemcitabine	236
Methotrexate	237
Ifosfamide	237
Pemetrexed	238
Acute Nephrotoxicity From Targeted Therapies	238
Acute Kidney Injury in Hematologic Malignancies	238
Acute Nephrotoxicity in Leukemia and Lymphoma	238
Lysozymuria	239
Leukostasis	239
Acute Nephrotoxicity in Multiple Myeloma	239
Kidney Involvement and Pathology	239
Cast Nephropathy	239
Therapeutic Plasma Exchange	240
High Cutoff Hemodialysis	240
Amyloid light chain (AL) Amyloidosis	241
Acute Kidney Injury in Hematopoietic Stem Cell Transplantation	241
Causes of Acute Kidney Injury in the Hematopoietic Stem Cell Transplantation Setting: Conditioning Regimen	241
Causes of Acute Kidney Injury in the Hematopoietic Stem Cell Transplantation Setting: Prophylaxis for Complications	241
Causes of Acute Kidney Injury in the Hematopoietic Stem Cell Transplantation Setting: Other Causes	241
Acute Kidney Injury and Viral Infections in the Setting of Hematopoietic Stem Cell Transplantation	242
Managing Acute Kidney Injury in the Setting of Hematopoietic Stem Cell Transplantation	243
Hepatic Sinusoidal Obstruction Syndrome	243
Tumor Lysis Syndrome	243
Risk Factors for Tumor Lysis Syndrome	244
Pathophysiology of Tumor Lysis Syndrome	244
Prevention and Treatment of Tumor Lysis Syndrome	245
Volume Expansion	246
Allopurinol	246
Febuxostat	246
Rasburicase	246
Renal Replacement Therapy	246
Thrombotic Microangiopathies	246
Cancer-Related Thrombotic Microangiopathies	247
Cancer Drugs–Induced Thrombotic Microangiopathies	247
Type I Cancer Drugs–Induced Thrombotic Microangiopathies	247
Type II Cancer Drugs–Induced Thrombotic Microangiopathies	247
Management of Thrombotic Microangiopathies in Cancer Patients	248
General Supportive Care	248
Specific Treatments	248
Thrombotic Microangiopathy After Hematopoietic Stem Cell Transplantation	248
Acute Kidney Injury in Renal Cell Carcinoma and Urothelial Cancers	249
Renal Cell Carcinoma	249
Urothelial Cancers	249
Acute Kidney Injury in Abdominal Compartment Syndrome	249
Contrast-Induced Nephropathy in Cancer Patients	249
Conclusion	250
Key Points	250
Key References	250
References	250.e1
42 Acute Kidney Injury in Cardiac Surgery	250
Objectives	250
Definition of Cardiac Surgery–Associated Acute Kidney Injury	251
Pathophysiology of Cardiac Surgery–Associated Acute Kidney Injury	251
Cardiopulmonary Bypass	251
Blood Pressure During Cardiopulmonary Bypass	252
Contrast-Induced Nephropathy	252
Assessing Renal Function and Acute Kidney Injury	252
Neutrophil Gelatinase-Associated Lipocalin	252
Cystatin C	252
TIMP-2 and IGFBP7	253
Interventions to Prevent Acute Kidney Injury	253
Statin Therapy	253
Early Initiation of Renal Replacement Therapy	253
Sodium Bicarbonate	253
Remote Ischemic Preconditioning	253
Key Points	254
Key References	254
References	254.e1
43 Acute Kidney Injury in Major Surgery	254
Objectives	254
Epidemiology and Outcomes in Surgical Patients	254
Definition of Acute Kidney Injury	254
Acute Kidney Injury in Adult Noncardiac Surgery	255
Acute Kidney Injury in Pediatric Surgery	255
Acute Kidney Injury in Relation to Other Complications	255
Clinical Outcomes	255
Costs	255
Diagnosis and Risk Stratification	256
Use of Imaging Techniques in Risk Stratification	256
Use of Urine and Plasma Biomarkers	256
Use of Clinical Prediction Scores	256
Prevention and Treatment	256
Summary	257
Key Points	257
Key References	257
References	257.e1
44 Acute Kidney Injury in Heart Failure	257
Objectives	257
Pathophysiology	257
Clinical Management	258
Hemodynamics, Renal Blood Flow, Glomerular Filtration	258
Neurohormonal Activation	260
Cell Signaling in Cardiorenal Failure	261
Renal Response to Diuretics	261
Prognosis	262
Conclusion	262
Key Points	262
Key References	263
References	263.e1
45 Acute Kidney Injury in Cirrhosis	263
Objectives	263
Pathophysiology of Acute Kidney Injury in Cirrhosis	263
Assessment of Kidney Function	265
Definition of Acute Kidney Injury	265
Cause of Acute Kidney Injury	265
Prevention of Acute Kidney Injury	266
Evaluation and Management of Acute Kidney Injury	267
Acute Kidney Injury in Candidates for Liver Transplantation	268
Biomarkers	269
Key Points	270
Key References	270
References	271.e1
46 Acute Renal Failure in Kidney Transplant Recipients	271
Objectives	271
Epidemiology of Acute Kidney Injury in the Early Postrenal Transplantation Period	271
Pathophysiology of Posttransplant Acute Kidney Injury	272
Pathophysiology of Ischemia/Reperfusion Injury	272
Ischemia/Reperfusion Injury Enhances Allograft Immunogenicity	272
Long-Term Graft Dysfunction Outcomes	272
Clinical Evaluation	274
Management of Risk Factors for Acute Kidney Injury and Delayed Graft Function	274
Future Diagnostics in Acute Kidney Injury	274
Management of Acute Kidney Injury Posttransplant and With Delayed Graft Function	275
Conclusion	275
Key Points	275
Key References	275
References	275.e1
47 Acute Glomerulonephritis	275
Objectives	275
Approach to Management of Rapidly Progressive Glomerulonephritis	276
Diagnosis	276
Specific Treatment	276
Complications of Treatment	277
Management in the Intensive Care Unit	278
Prognosis	279
Clinical Presentation and Management of Rapidly Progressive Glomerulonephritis	279
Small-Vessel Vasculitis	279
Microscopic Polyangiitis	279
Antineutrophil Cytoplasmic Antibodies in Small-Vessel Vasculitis	279
Antineutrophil Cytoplasmic Antibodies and Disease Pathogenesis	279
Treatment	280
Response to Treatment	280
Clinical Course	280
Disease-Associated Morbidity and Mortality	280
Anti–Glomerular Basement Membrane Disease	280
Clinical Features	280
Diagnosis	281
Disease Pathogenesis	281
Treatment and Outcome	281
Other Types of Glomerulonephritis That Cause Acute Renal Failure	281
Systemic Lupus Erythematosus	281
Immunoglobulin A Glomerulonephritis	282
Poststreptococcal Glomerulonephritis	282
Key Points	282
Acknowledgments	282
Key References	282
References	282.e1
48 Contrast-Induced Acute Kidney Injury	282
Objectives	282
Registry Data on Contrast-Induced Acute Kidney Injury	283
Renal Injury Resulting From Iodinated Contrast	283
Clinical Outcomes	285
Principles of Prevention and Management	285
Future Developments	287
Conclusion	288
Key Points	288
Key References	288
References	288.e1
49 Abdominal Compartment Syndrome	288
Objectives	288
Intraabdominal Hypertension	289
Abdominal Compartment Syndrome	289
At-Risk Patient Populations	290
Monitoring Techniques	290
Biomarkers	292
Therapeutic Interventions	292
Nonsurgical Interventions	292
Surgical Interventions	292
Mitigation Strategies	293
Future Directions	293
Key Points	294
Key References	294
References	294.e1
50 Hemolytic Uremic Syndrome	294
Objectives	294
Definition	294
Laboratory Exams	296
STEC-HUS	296
Pathogenesis	296
Clinical Manifestations	296
Treatment	297
Supportive Care	297
Plasma Therapy	297
Eculizumab	297
Kidney Transplantation	297
Atypical HUS	297
Pathogenesis	297
Complement Factor H Mutations, Complement Factor H–Hybrid Genes and Anti-FH Autoantibodies	297
Membrane Cofactor Protein Mutations	297
Complement Factor I Mutations	299
Mutations in the AP C3 Convertase Components	299
Thrombomodulin Mutations	299
Combined Complement Abnormalities	299
Diacylglycerol Kinase Epsilon Mutations	299
Incomplete Penetrance and Triggering Factors	299
Clinical Manifestations	300
Treatment	300
Plasma Therapy	300
Eculizumab	300
Organ Transplantation	300
Acknowledgments	301
Key Points	301
Key References	301
References	301.e1
11 Prevention and Treatment: General Treatment Concepts	302
51 Nonpharmacologic Management of Acute Renal Injury	302
Objectives	302
Risk Assessment and Early Diagnosis of Acute Kidney Injury	302
Adequate Volume and Hemodynamic Status	303
Choice of Fluids for Prevention of Acute Kidney Injury	303
Maintenance of Adequate Mean Arterial Pressure	304
Minimizing Nephrotoxin Exposure	305
Prevention of Contrast-Induced Acute Kidney Injury	305
Aminoglycosides	305
Amphotericin B	306
Conclusion	306
Key Points	307
Key References	307
References	307.e1
52 Novel Drugs for Acute Kidney Injury	307
Objectives	307
Novel Therapies for Prerenal Disease	308
Fluid Restriction	308
Type of Fluid	308
Novel Therapies for Intrinsic Disease	308
Alpha Lipoic Acid	309
I5NP	309
Alkaline Phosphatase	310
Selenium	310
Sodium-2-Mercaptoethane Sulphonate	310
Propofol	311
Angiotensin	311
Curcumin	311
Dipeptidylpeptidase-4 Inhibitors	312
Sphingosine 1 Phosphate Analogues	313
Adenosine Analogues	313
Conclusion	313
Key Points	313
Key References	313
References	314.e1
53 Remote Ischemic Preconditioning	314
Objectives	314
Potential Mechanisms of Protection	314
Clinical Trials	316
Acute Kidney Injury	316
Contrast-Induced Acute Kidney Injury	317
Transplantation Medicine	317
Future of Remote Ischemic Preconditioning	318
Conclusion	318
Key Points	318
Key References	319
References	319.e1
12 Fluid and Electrolytes	320
54 Blood Biochemistry:	320
Objectives	320
Key Points	322
Key References	322
References	322.e1
55 Assessment of Urine Biochemistry	323
Objectives	323
Urine Sodium	323
Context in the Literature	323
Spot Urine Sodium and Fractional Excretion of Sodium	324
Fractional Excretion of Urea	324
Context in the Literature	324
13 Acid-Base	374
64 Laboratory Tests	374
Objectives	374
Blood Gas Variables: Measured and Calculated	374
Oxygen Tension and Hemoglobin Saturation	374
Carbon Dioxide Tension	374
pH, Bicarbonate, and Base Excess	374
Ion Gaps Can Be Used to Estimate the Quantity of Unmeasured Ions	375
The Anion Gap	375
Anion Gap Corrections for Albumin, Phosphate, and Lactate.	375
The Strong Ion Gap	375
Interpretation of the Gaps	376
General Considerations	376
Strong Ions in Fluids Other Than Plasma	377
Key Points	377
Acknowledgement	378
Key References	378
References	378.e1
65 Acid-Base Physiology and Diagnosis of Disorders	378
Objectives	378
Conventional Comprehensive Acid-Base Model	378
Charge-Balance Based Modeling of Acid-Base	379
Water Dissociation	379
Charge Balance With SID	379
Supplementary Note 1	379
Monovalent Weak Acid	379
Charge Balance	380
Exploring the Utility of the Charge-Balance Model to Understand Acid-Base	381
Modeling Intracellular pH	382
Supplementary Notes 2a and 2b	382
Buffering Based on Charge-Balance Modeling	382
Supplementary Note 3	383
Supplementary Note 4	383
Modeling Renal Acid-Base Transports	384
Supplementary Note 5	385
Diagnosing Acid-Base Disorders	385
Supplementary Note 6	385
Practical Approach	386
Application of Strong Ion Analysis	387
Fundamental Critique of Charge-Balance Construct	387
Supplementary Note 7	387
Key Points	387
Key References	387
References	387.e1
66 Metabolic Acidosis	388
Objectives	388
Brief Review of the Quantitative Approach	388
Effects of Acidosis in Human Physiology	389
Sources of Acids in Health and Disease	389
Sepsis	390
Trauma and Hemorrhagic Shock	391
Excessive Low SID Solution and Albumin Infusion	391
Gastrointestinal Losses	391
Poisoning	391
Association Between Type of Acidosis and Outcome in Critically Ill Patients	392
Therapeutic Considerations	392
Conclusion	393
Key Points	393
Key References	393
References	393.e1
67 Hyperlactatemia and Lactic Acidosis	394
Objectives	394
Normal Metabolism of Lactate and Physiologic Hyperlactatemia During Exercise	394
Lactate Production	394
Lactate Utilization (Removal): Gluconeogenesis and Oxidation	394
Gluconeogenesis and the Cori Cycle	395
Oxidation of Lactate	396
Transport of Lactate Through Lipid Membranes and the Monocarboxylate Transporters	396
Mitochondrial L-Lactate Dehydrogenase and the Mitochondrial Lactate Oxidation Complex	396
Compartmentalization of Cellular Intermediary Metabolism and the Lactate Intracellular and Cell-Cell Shuttle Theories	396
Pathophysiology of Hyperlactatemia in Critical Illness	397
Source of Lactate During Critical Illness	397
Lactate Utilization During Critical Illness	398
Diagnostic Considerations	399
Anion Gap and Lactic Acidosis	399
Blood Lactate Level and Prognosis	400
Approach to Lactic Acidosis of Uncertain Cause	400
Conclusion	400
Key Points	404
Key References	404
References	404.e1
68 Renal Tubular Acidosis	405
Objectives	405
Definition	405
Types of Renal Tubular Acidosis	405
Pathophysiology of Renal Tubular Acidosis	405
Type 1: Distal Renal Tubular Acidosis (dRTA)	405
Type 2: Proximal Renal Tubular Acidosis (pRTA)	406
Type 3: Combined Renal Tubular Acidosis (cRTA)	407
Type 4: Hyperkalemic Renal Tubular Acidosis (hRTA)	407
Diagnosis of Renal Tubular Acidosis	407
Treatment	408
Key Points	408
Key References	408
References	408.e1
69 Metabolic Alkalosis	409
Objectives	409
Definition of Alkalinity and Alkalosis	409
Pathophysiology of Metabolic Alkalosis	409
Sodium-Retention Metabolic Alkalosis	409
Chloride-Depletion Metabolic Alkalosis	409
Algorithm of the Differential Diagnosis	410
Complications and Options for Medical Management	410
Key Points	411
Key References	411
References	411.e1
70 Respiratory Acid-Base Disorders	411
Objectives	411
Pathophysiology of the Control of Breathing	412
Compensatory Mechanisms	412
Buffering	412
Renal Electrolyte Handling	413
Causes of Respiratory Acid-Base Disorders	413
Signs and Symptoms of Respiratory Acid-Base Disorders	414
Therapeutic Options	415
Respiratory Acidosis	415
Increase Carbon Dioxide Elimination	415
Reduce Carbon Dioxide Production	415
Correct pH While Tolerating Hypercapnia	416
Respiratory Alkalosis	416
Key Points	416
Key References	416
References	416.e1
71 Iatrogenic and Poison-Derived Acid Base Disorders	417
Objectives	417
Specific Disturbances	417
High Anion Gap Metabolic Acidosis	417
Propofol	417
Metformin	418
Propylene Glycol	418
Acetaminophen	418
Isopropyl Alcohol	419
Ethylene Glycol	419
Methanol	419
Salicylates	420
β-Agonist	421
Non-Anion Gap Metabolic Acidosis	422
Hyperchloremia	422
Antiviral and Antimicrobial Agents	422
Lithium	422
Conclusion	423
Key Points	423
Key References	423
References	423.e1
14 Metabolism and Nutrition in Critical Illness and Acute Kidney Injury	424
72 Energy Requirement and Consumption in the Critically Ill Patient	424
Objectives	424
Metabolic Response to Critical Illness	424
Physiologic Aspects of Energy Metabolism	424
Components of Energy Expenditure	425
Measurement Methods	425
Estimation of Energy Expenditure	426
Energy Requirement Versus Energy Consumption	427
Key Points	428
Key References	429
References	429.e1
73 Impact of Renal Replacement Therapy on Metabolism and Nutrient Requirements in the Critically Ill Patient	429
Objectives	429
Intermittent Renal Replacement Therapy, Intermittent Hemodialysis, Hemodiafiltration, and Slow-Efficiency Extended Hemodialysis	429
Metabolic Effects of Hemodialysis Modalities	429
Therapeutic Implications	430
Metabolic Effects of Continuous Renal Replacement Therapy Modalities	430
Heat Loss	431
Glucose Balance	431
Lactate, Acetate, and Citrate Intake	431
Electrolyte Derangements	431
Loss of Nutrients	432
Elimination of Peptides and Short-Chain Proteins (“Mediators”)	432
Adsorption of Proteins (Mediators), Drugs, and Endotoxin	432
Activation of Protein Catabolism During Continuous Renal Replacement Therapy	433
15 Infectious Diseases and Sepsis	473
81 Microbiologic Considerations in the Intensive Care Patient	473
Objectives	473
Epidemiology of Infections in the Intensive Care Unit	473
Systemic Manifestation of Infection in the Intensive Care Unit	473
Multi-Drug–Resistant Organisms in the Intensive Care Unit	474
Antimicrobial Stewardship in the Intensive Care Unit	474
Strategies to Decrease Infections in the Intensive Care Unit	475
Central Line–Associated Bloodstream Infections	475
Ventilator-Associated Pneumonia	475
Immunosupression in the Intensive Care Unit	475
Key Points	476
Key References	476
References	476.e1
82 Innate Immunity and the Kidney	476
Objectives	476
A Brief History of Discoveries of the Innate and Adaptive Host Immune Responses	476
Introduction Into Innate Immunity	477
Cellular and Humoral Components of Host Innate Immune Defenses	477
Cells of the Innate Immune System	477
Major Distinguishing Features Between Innate Immunity and Adaptive Immunity	479
Soluble Pattern Recognition Receptors of the Innate Immune Response	480
Molecules of the Innate Immune Arsenal That Are Expressed in the Urinary Tract	480
Defensins	480
Tamm-Horsfall Protein	481
Other Proteins	481
Complement Activation	481
Resolution of Inflammation and Deactivation of Innate Immune Responses	482
Conclusion	482
Key Points	482
Key References	482
References	482.e1
83 Adaptive Immunity and Critical Illness	483
Objectives	483
Immune System: an Overview	483
Recognition of Foreign Molecules	483
Innate Immune Response	483
Activation of the Adaptive Immune Response	484
Adaptive Immune Response in Acute Kidney Injury	485
Septic Acute Kidney Injury	485
Ischemic Acute Kidney Injury	485
Nephrotoxic Acute Kidney Injury	486
Resolution of Inflammation	486
Chronic Kidney Disease	486
Key Points	487
Key References	487
84 Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome	487
Objectives	487
Pathogenesis of Spontaneous Bacterial Peritonitis	487
Clinical Manifestations and Diagnosis of Spontaneous Bacterial Peritonitis	488
Pathogenesis of Hepatorenal Syndrome in Patients With Spontaneous Bacterial Peritonitis	488
Treatment of Spontaneous Bacterial Peritonitis	489
Antibiotic Treatment	489
Prevention of Acute Kidney Injury	490
Management of Acute Kidney Injury and Hepatorenal Syndrome in Patients With Spontaneous Bacterial Peritonitis	490
Prophylaxis of Spontaneous Bacterial Peritonitis	491
Key Points	491
Key References	491
References	492.e1
85 Tropical Infections Causing Acute Kidney Injury	492
Objectives	492
Tropical Infections Associated With Acute Kidney Injury and “One Health” Perspective	492
Overview of Tropical Infections Causing Acute Kidney Injury	493
Clinical Features, Pathogenesis, and Management of Common Tropical Infections Causing Acute Kidney Injury	493
Leptospirosis and Acute Kidney Injury	493
Epidemiology.	493
Clinical Features.	493
Pathogenesis	493
Direct kidney damage: acute interstitial nephritis.	493
Indirect kidney damage: hemodynamic instability.	494
Hyperbilirubinemia.	494
Rhabdomyolysis.	494
Management.	494
Malaria and Acute Kidney Injury	495
Epidemiology.	495
Clinical Features.	495
16 Acute Intoxication and Poisoning	574
98 Drugs and Antidotes in Acute Intoxication	574
Objectives	574
Toxidromes	574
Anticholinergic Toxidrome	574
Antidote Considerations: Physostigmine	575
Cholinergic Toxidrome	575
Organophosphates	576
Antidote Considerations	577
Atropine.	577
Pralidoxime.	577
Adrenergic Toxidrome	577
Note About Recreational Drugs	578
GABAergic Toxidrome	578
Antidote Considerations: Flumazenil	578
Sodium and Potassium Channel—Blocking Agents	578
Sodium Channel	578
Potassium Channel	579
Treatment	579
Serotonin Syndrome	579
Opiate Toxidrome	580
Antidote Considerations: Naloxone	581
Specific Poisons and Antidotes	581
Acetaminophen	581
Treatment	582
Ethylene Glycol	582
Clinical Manifestations	583
Laboratory Findings	583
17 Acute Kidney Injury and Organ Crosstalk	630
102 Bleeding and Hemostasis in Acute Renal Failure	630
Objectives	630
Physiologic Hemostasis	630
Primary Hemostasis	630
Coagulation	630
Fibrinolysis	631
Pathophysiology	632
Bleeding	632
Thrombocytopenia	632
Platelet Abnormalities	632
Anemia	633
Anticoagulants	633
Thrombosis	634
Platelet Alterations	634
Inflammation and Endothelial Dysfunction	634
Effect of Uremic Toxins on Coagulation and Fibrinolysis	634
Conclusion	635
Key Points	635
Key References	635
References	635.e1
103 Gastrointestinal Problems in Acute Kidney Injury	635
Objectives	635
Pathogenesis of Uremic Lesions in the Gastrointestinal Tract	636
Gastrointestinal Problems Commonly Associated With Acute Renal Failure	636
Dysgeusia, Anorexia, Dyspepsia, Hiccups, Nausea, and Vomiting	636
Stomatitis, Uremic Fetor, and Inflammation of Salivary Glands	636
Gastrointestinal Hemorrhage	636
Gastritis, Duodenitis, and Peptic Ulcer Disease	638
Pancreatitis	638
Cholecystitis	638
Enterocolitis and Other Colonic Problems	638
Hepatic Disease	639
Gastrointestinal Tract–Related Acid-Base and Electrolyte Disturbances Associated With Acute Renal Failure	639
Drug-Prescribing Guidelines in Acute Renal Failure	640
Key Points	640
Key References	640
References	640.e1
104 Cardiovascular Problems in Acute Kidney Injury	641
Objectives	641
Cardiovascular Complications in Chronic Kidney Disease	641
Cardiovascular Complications in Acute Kidney Injury	641
Pathophysiology of Cardiopulmonary Dysfunction in Acute Kidney Injury	643
Renin-Angiotensin-Aldosterone System	643
Nitric Oxide/Reactive Oxygen Species System	643
Sympathetic Nervous System	643
Cytokine-Mediated Effects of Acute Renal Failure on Cardiac Function	644
Coronary Vasoregulation in Acute Renal Failure	644
Pulmonary Injury in Acute Renal Failure	644
Direct Effects of Renal Replacement Therapy on Cardiovascular Complications	644
Conclusion	645
Key Points	645
Key References	645
References	645.e1
105 Water and Electrolyte Disturbances in Acute Renal Failure	645
Objectives	645
Hyperkalemia	645
Treatment of Hyperkalemia in Acute Renal Failure	646
Hyponatremia	647
Correction and Therapy of Hyponatremia	648
Hypernatremia	648
Disorders of Calcium and Phosphate Balance	648
Acknowledgment	648
Key Points	649
Key References	649
References	649.e1
106 Neurologic Problems in Acute Renal Failure	649
Objectives	649
Basic Pathophysiology of the Brain in Acute Renal Failure	649
Infections Causing Acute Renal Failure and Cerebral Dysfunction	650
Vascular Diseases Causing Acute Renal Failure Causing Cerebral Dysfunction	650
Electrolyte Imbalance in Acute Renal Failure Causing Cerebral Dysfunction	651
Metabolic Disorders Causing Cerebral Dysfunction With Acute Renal Failure	652
Drugs Causing Acute Brain and Kidney Injury	652
Conclusion	653
Key Points	654
Key References	654
References	654.e1
107 Immunologic and Infectious Complications of Acute Kidney Injury	654
Objectives	654
Epidemiology of Infection in Patients With Acute Kidney Injury	654
Pathogenesis of Infection in Patients With Acute Kidney Injury	655
Increased Inflammation	655
Decreased Immunity	656
Loss of Protective Barriers Against Invading Microorganisms	656
Volume Overload and Altered Permeability of Tissue Membranes	657
Pulmonary Function	657
Cardiac Function	657
Hematologic: Spleen and Bone Marrow	657
Gastrointestinal and Liver Function	657
Neuromuscular Function	657
Malnutrition	657
Glucose Metabolism	658
Pharmacokinetics of Antimicrobial Agents	658
Conclusion	658
Key Points	658
Key References	658
References	658.e1
108 Cellular Response to Acute Kidney Injury	659
Objectives	659
Acute Kidney Injury as a Systemic Disease	659
Acute Kidney Injury and Cytokines	659
Acute Kidney Injury, Cytokines, and the Lungs	659
Acute Kidney Injury, Cytokines, and the Heart	660
Acute Kidney Injury, Cytokines, and the Brain	660
Acute Kidney Injury, Cytokines, and the Gastrointestinal Tract	660
Experimental Acute Kidney Injury and Cytokine Homeostasis	660
Acute Kidney Injury and Impaired Neutrophil Function	660
Experimental Findings	660
Acute Kidney Injury and Neutrophils: Cellular Changes in Patients	660
Acute Kidney Injury and Neutrophils: Intracellular Changes	661
Resistin: Linking Uremia and Inflammation During Acute Kidney Injury	661
Summary	663
Key Points	663
Key References	663
References	663.e1
18 Interaction of the Heart and the Kidney	664
109 Heart-Kidney Cross-Talk	664
Objectives	664
Predisposing Factors	664
Subclinical Acute Kidney Injury	665
Cardiac and Renal Fibrosis	665
Hemodynamics and Congestion	666
Neurohormonal Activation	666
Hypothalamic-Pituitary Stress Reaction	667
Inflammation and Immune Cell Signaling	667
Subclinical Endotoxemia	667
Concurrent Infection	668
Complications of Medical Therapy	668
Oxidative Stress as Result of Heart Kidney Cross-Talk	669
Counterregulatory Mechanisms	669
Conclusion	669
Key Points	670
Key References	670
References	670.e1
110 Classification of Cardiorenal Syndrome	670
Objectives	670
Definition of Cardiorenal Syndrome	670
Cardiorenal Syndrome Type – 1 (Acute Cardiorenal Syndrome)	671
Cardiorenal Syndrome Type – 2 (Chronic Cardiorenal Syndrome)	672
Cardiorenal Syndrome Type – 3 (Acute Renocardiac Syndrome)	672
Cardiorenal Syndrome Type – 4 (Chronic Renocardiac Syndrome)	673
Cardiorenal Syndrome Type – 5	675
Key Points	676
Key References	677
References	677.e1
111 Cardiorenal Syndrome Type 1	677
Objectives	677
Epidemiology	677
Risk Factors and Patient’s Susceptibility	678
Obesity and Metabolic Syndrome	678
Cachexia	679
Hypertension and Diabetes	680
Proteinuria	680
Uremic Solute Retention	680
Anemia	680
Repeated Episodes of Subclinical Acute Kidney Injury	680
Cardiac and Renal Fibrosis	681
Pathophysiology	681
Acute Pathways of Cardiorenal Syndrome Type 1	682
Hemodynamic Alterations and Venous Congestion	682
Neurohormonal Activation	683
Hypothalamic-Pituitary Stress Reaction	685
Inflammation and Immune Cell Signaling	685
Role of the Gut and Endotoxemia	685
Superimposed Infection	686
Iatrogenic Interventions	686
Oxidative Stress	687
Failure of Counterregulatory Mechanisms	687
Treatment	688
Conclusion	689
Key Points	689
Key References	689
References	689.e1
112 Cardiorenal Syndrome Type 2	690
Objectives	690
Epidemiology of Cardiorenal Syndrome Type 2	690
Pathogenesis	690
Neurohormonal Changes in Heart Failure	690
Role of Congestion and Cardiorenal Hemodynamics	691
Inflammation	691
Link Between Cardiorenal Syndrome Types 1 and 2	691
Diagnosis and Biomarkers	691
Biomarkers	692
Management	692
RAAS Blockers	693
Diuretics	694
Cardiorenal Anemia Syndrome	694
Over the Horizon	694
Cardiac Resynchronization Therapy	694
Implantable Pulmonary Artery Pressure Sensor	694
Conclusion	695
Key Points	695
Key References	695
References	695.e1
113 Cardiorenal Syndrome Type 3	695
Objectives	695
Animal Models	697
Cytokines and Cardiotoxicity	697
Neuroendocrine Activation	697
Mitochondrial Abnormalities	698
Metabolic Acidosis	698
FGF23, Klotho, and Phosphorus	698
Uremia Toxins	698
Renal Biomarkers and Cardiac Function	699
Human Studies	699
Short-Term Outcomes	700
Cardiovascular Events in Acute Kidney Injury (CHF, Infarction, Arrhythmia)	700
Long-Term Impact After AKI	700
Mortality After Acute Kidney Injury Event	700
Conclusion	701
Key Points	701
Key References	701
References	701.e1
114 Cardiorenal Syndrome Type 4	702
Objectives	702
Definition and Epidemiology	702
Cardiovascular Disease in Chronic Kidney Disease	702
Role of Posttranslational Modifications in Cardiorenal Syndrome Type 4	703
Carbamylation	703
Glycation	703
Oxidation/Carbonylation	703
Assessment and Management of Cardiovascular Risks in Chronic Kidney Disease	703
Hypertension	704
Anemia	704
Calcium/Phosphorus Abnormalities	704
Dyslipidemia	704
Conclusion	704
Key References	704
References	704.e1
115 Cardiorenal Syndrome Type 5	704
Objectives	704
Pathogenesis of Cardiorenal Syndrome Type 5	705
Cardiorenal Syndrome Type 5 and Sepsis	705
Cardiorenal Syndrome Type 5 and Amyloidosis	706
Cardiorenal Syndrome Type 5 and Systemic Lupus Erythematosus	707
CRS-5 and Fabry Disease	708
Pathology of Renal Involvement	708
Clinical Renal Involvement	709
Pathology of Cardiac Involvement	710
Clinical Cardiac Involvement	710
Diagnosis of Cardiorenal Syndrome Type 5	710
Management of Cardiorenal Syndrome Type 5	711
Key Points	711
Key References	711
References	711.e1
116 Renal Function During Cardiac Mechanical Support and Artificial Heart	712
Objectives	712
Indications and Types of Mechanical Cardiac Supports	712
Patterns of Use of Ventricular-Assist Device	713
Pathophysiologic Considerations	713
Preoperative Assessment	713
Preimplant Renal Function	714
Postimplant Renal and Patient Outcomes	715
Complications	716
Ventricular-Assist Device and Dialysis	716
Total Artificial Hearts	717
Key Points	717
Key References	718
References	718.e1
117 The Kidney in Diastolic Dysfunction	718
Objectives	718
Pathophysiology and Hemodynamics in Diastolic Dysfunction	718
From Heart to Kidney and the Cardiorenal Syndromes	719
Key Points	721
Key References	721
References	721.e1
118 Principles of Diuretic Management in Heart Failure	721
Objectives	721
Consequences of Extracellular Fluid Volume Expansion	722
Physiologic Response to Diuretics	722
Influence of Heart Failure on Diuretic Responsiveness	722
Influence of Chronic Kidney Disease on Diuretic Management	723
Benefits of Diuretics in Heart Failure	723
Negative Effects of Diuretics in Heart Failure	723
Diuretic Management	724
Beyond Diuretics	726
Tolvaptan	726
Hypertonic Saline and Furosemide	726
Rolofylline	726
Summary	726
Key Points	726
Key References	726
References	726.e1
119 Management of Overhydration in Heart Failure Patients	727
Objectives	727
Diuretics	727
Ultrafiltration	728
Pilot Studies	728
Ultrafiltration Versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Heart Failure Trial	729
Cardiorenal Rescue Study in Acute Decompensated Heart Failure Trial	730
Aquapheresis Versus Intravenous Diuretics and Hospitalizations for Heart Failure	731
Selection of Candidates for Ultrafiltration	732
Fluid Removal Targets	733
Blood Volume Estimation	734
Bioimpedance Vector Analysis	734
Biomarkers	735
Conclusion	735
Key Points	735
Key References	735
References	735.e1
120 Recent Advances for Stroke Prevention in Patients With Atrial Fibrillation and Advanced Kidney Disease	736
Objectives	736
Novel Oral Anticoagulants and Chronic Kidney Disease	736
Percutaneous Left Atrial Appendage Occlusion	737
Rationale and Clinical Evidence	737
Patient Selection and Preprocedural Screening	739
Procedure Overview	739
Conclusion	740
Key Points	740
Key References	740
References	740.e1
19 Interaction of the Lung and Kidney	741
121 Lung-Kidney Cross-Talk	741
Objectives	741
Alveolar-Capillary Barrier as a Functional Unit	741
Acute Lung Injury	741
Acute Lung Injury and the Kidney	743
Blood Gas Disturbances and Acid-Base Disorders	743
Pulmonary Hypertension, Venous Congestion, and Fluid Overload	743
Acute Kidney Injury and the Lung	745
Clinical Strategies in the Care of Patients With Combined Acute Lung Injury and Acute Kidney Injury	746
Chronic Kidney Disease and the Lung	746
Key Points	746
Key References	747
References	747.e1
122 The Kidney During Mechanical Ventilation	747
Objectives	747
Mechanical Ventilation Versus Spontaneous Breathing	747
Indications for Mechanical Ventilation	748
Ventilator-Induced Lung Injury	748
Mechanical Ventilation and the Kidney	748
Effects of Mechanical Ventilation on Renal Blood Flow	749
Pa2, PaO2, and the Kidney	749
Hypercapnia	749
Hypoxemia	749
Biotrauma and the Kidney	750
Conclusion	750
Key Points	750
Key References	751
References	751.e1
123 Extracorporeal Membrane Oxygenation and Renal Function	751
Objectives	751
Extracorporeal Membrane Oxygenation	751
Acute Kidney Injury in Extracorporeal Membrane Oxygenation Patients	751
Pathophysiology of Acute Kidney Injury in Extracorporeal Membrane Oxygenation Patients	752
Hemodynamics	752
Coagulation and Systemic Inflammation	753
Organs Cross-Talk	753
Renal Replacement Therapy During Extracorporeal Membrane Oxygenation	753
Conclusion	754
Key Points	754
Key References	754
References	754.e1
124 Extracorporeal Carbon Dioxide Removal	755
Objectives	755
From Renal to Respiratory Dialysis (Historical Perspective)	755
Carbon Dioxide Physiology	755
Technical Description of Extracorporeal Carbon Dioxide Removal Systems	756
Clinical Applications of Extracorporeal Carbon Dioxide Removal	757
Acute Respiratory Distress Syndrome	757
Chronic Obstructive Pulmonary Disease	758
Patients With Acute Kidney Injury Who Require Renal Replacement Therapy	758
Complications of Extracorporeal Carbon Dioxide Removal	758
Conclusion	759
Key Points	759
Key References	759
References	759.e1
125 Extracorporeal Membrane Oxygenation and Continuous Renal Replacement Therapy in Adults and Children	759
Objectives	759
Current Practice, Modality, and Indications	760
Impact of Renal Function and Renal Replacement Therapy on Outcome During Extracorporeal Membrane Oxygenation	761
Conclusion	763
Key Points	764
Key References	764
References	764.e1
126 Pulmonary-Renal Syndrome	764
Objectives	764
Immunopathogenesis of Immune-Mediated Pulmonary-Renal Syndromes	765
Antineutrophil Cytoplasmic Antibody–Associated Vasculitis	765
Anti–glomerular Basement Membrane Disease (Goodpasture Disease)	765
Immune Complex–Mediated Pulmonary-Renal Syndrome	765
Diagnostic Approach to Pulmonary-Renal Syndrome	766
Nonimmune Causes of Pulmonary Disease in Patients With Renal Disease	767
Principle Diseases Causing Pulmonary-Renal Syndrome: Clinical Features and Management	767
Anti–glomerular Basement Membrane Disease	767
20 The Liver and the Kidney	770
127 Liver-Kidney Interaction	770
Objectives	770
Role of Ammonia and Glutamine	770
Ureagenesis	770
Alternative Approach	772
Regulatory Role of Hepatocyte Heterogeneity	773
Acid-Base Balance in Hepatic Functional Impairment	773
Key Points	774
Key References	774
References	774.e1
128 Pathophysiology and Management of the Hepatorenal Syndrome	774
Objectives	774
Diagnostic Criteria of Hepatorenal Syndrome	775
Pathophysiology of Hepatorenal Syndrome	775
Peripheral Arterial Vasodilation Hypothesis	775
Cirrhotic Cardiomyopathy and the Systemic Inflammation Hypothesis	776
Hepatorenal Syndrome: Still Completely Functional?	777
Prophylaxis of Hepatorenal Syndrome	778
Management of Hepatorenal Syndrome	778
General Measures	778
Vasoconstrictors Plus Albumin	778
Transjugular Intrahepatic Portosystemic Shunt	779
Extracorporeal Liver Support Systems	780
Renal Replacement Therapy	780
Liver Transplantation	780
Key Points	780
Key References	781
References	781.e1
129 Kidney Dysfunction After Liver Transplantation	781
Objectives	781
Assessment of Renal Function Before and After Liver Transplantation	781
Risk Factors for Early Postoperative Acute Kidney Injury After Orthotopic Liver Transplantation	782
Pretransplantation Risk Factors	782
Hyponatremia	782
Hypoalbuminemia	783
Hyperbilirubinemia	783
Liver Disease Severity	783
Strategies to Reduce Pretransplantation Risk Factors	784
Studies Evaluating the Renoprotective Effect of Terlipressin (Not Available in the United States or Canada)	784
Intraoperative Risk Factors	784
Strategies to Reduce Intraoperative Risk Factors	785
Authors’ Perspective	785
Postoperative Risk Factors	785
Strategies to Reduce Postoperative Risk Factors	785
CNI-Sparing Protocols in the Immediate Postoperative Period	786
Polyclonal Induction Therapy.	786
Monoclonal Induction Therapy.	786
Mycophenolate Mofetil and Early CNI-Minimization Protocol	786
De Novo Use of Sirolimus (or mTOR Inhibitors) in CNI-Minimization Protocol	786
De Novo Use of Belatacept and CNI Avoidance	787
Authors’ Perspective on the Use of Immunosuppressive Strategies to Prevent Postoperative AKI	787
Factors Affecting Renal Dysfunction in Long-Term Survivors After Orthotopic Liver Transplantation	787
Strategies to Reduce Risk Factors in Long-Term Survivors	788
Mammalian Target of Rapamycin Inhibitors and CNI-Sparing Protocols Early After Liver Transplantation (1 to 3 Months Post-OLT)	788
Mammalian Target of Rapamycin Inhibitors and CNI Minimization or Withdrawal After the First 6 to 12 Posttransplant Months	788
CNI to Sirolimus Conversion.	788
CNI to Everolimus Conversion.	789
Mycophenolate Mofetil– and CNI-Sparing Protocols.	789
Authors’ Perspective on Various Immunosuppressive Strategies to Prevent, Halt, or Ameliorate CNI Nephrotoxicity in Long-Term Survivors	790
Conclusion	790
Key Points	792
Key References	793
References	793.e1
130 Extracorporeal Liver Support Devices	793
Objectives	793
Artificial Systems	794
Hemofiltration and Hemodiafiltration	794
Plasma Exchange	794
Albumin Dialysis-Based Approaches	795
Single-Pass Dialysis	795
Molecular Adsorbent Recirculating System	796
Fractionated Plasma Separation and Adsorption	796
Comparison of Extracorporeal Liver Support Devices	796
Extracorporeal Devices and Anticoagulation	797
Bioartificial Support Devices	797
Conclusion	798
Key Points	798
Key References	799
References	799.e1
21 Interaction of the Brain and the Kidney	800
131 Treatment of Combined Acute Renal Failure and Cerebral Edema	800
Objectives	800
Basic Pathophysiology of Cerebral Edema	800
Patients at Risk of Cerebral Edema	801
Supportive Management of Patients With Cerebral Edema	801
General Standard Care	801
Specific Medical Treatments for Intracranial Hypertension and Cerebral Edema	802
Choosing Renal Support for the Patient With Cerebral Edema	803
Prescribing Renal Support for Patients With Cerebral Edema	803
Modality	803
Anticoagulation	804
Conclusion	804
Key Points	804
Key References	804
References	804.e1
132 Renal Protection in the Organ Donor	805
Objectives	805
Medical Suitability	805
Brain Death and Physiologic Sequelae	805
Cardiovascular	806
Diabetes Insipidus	806
Hypothermia	806
Hyperglycemia	807
Anterior Pituitary Dysfunction	807
Inflammatory and Immunologic Changes	807
Respiratory Changes	807
Hematologic Changes	807
Management of the Brain-Dead Potential Organ Donor	807
Autonomic Storm	807
Arrhythmias	807
Hypovolemia	807
Hypotension and Low Cardiac Output	808
Diabetes Insipidus	808
Hormonal Supplementation	808
Vasopressin	808
Desmopressin	808
Combination Hormonal Therapy	808
Thyroid Hormone	808
Low-Dose (Replacement) Corticosteroids	809
High-Dose Corticosteroids	809
Metabolic Derangement	809
Hypothermia	809
Nutritional Considerations	809
Respiratory Changes	809
Anemia and Coagulopathy	809
Other Therapies	809
Donation After Circulatory Death	809
Controlled Donation After Circulatory Death	810
Uncontrolled Donation After Circulatory Death	810
Ex Vivo Organ Storage and Perfusion	810
Conclusion	810
Key Points	810
Key References	810
References	810.e1
133 Effect of Extracorporeal Therapies on the Brain	811
Objectives	811
Effect of Hemodialysis and Peritoneal Dialysis on the Brain (Chronic Setting)	811
Hemodialysis and Peritoneal Dialysis on Stroke	811
Hemodialysis and Peritoneal Dialysis on Cognitive Function	811
Dialysis Adequacy and Cognitive Function	812
Dialysis Disequilibrium Syndrome	812
Acute Defects in Cognition	812
Effect of Continuous Renal Replacement Therapy on the Brain (Acute Setting)	813
Effect of Extracorporeal Membrane Oxygenation on the Brain	813
Conclusion	814
Key Points	814
Key References	815
References	815.e1
22 Fluid Balance and Its Management in the Critically Ill	816
134 Components of Fluid Balance and Monitoring	816
Objectives	816
Normal Physiology	816
Macrocirculation	816
Microcirculation	817
Phases of Fluid Resuscitation	817
Assessment of Volume Status	818
Static Measures	819
Dynamic Measures	819
Assessment of the Microcirculation	819
Assessment of Fluid Overload	819
Pathogenesis of Fluid Overload	820
Association Between Fluid Overload and Adverse Outcomes	820
Role of Diuretics and Ultrafiltration in Acute Kidney Injury	820
Practical Issues and Conclusion	820
Key Points	821
Key References	821
References	821.e1
135 Noninvasive Methods of Fluid Status Assessment in Critically Ill Patients	821
Objectives	821
Physical Examination and Fluid Balance Recording	822
Physical Examination	822
Fluid Balance Recording	822
Body Weight Measurement	822
Chest Radiography	823
Bioelectrical Impedance Analysis	823
Bioelectrical Impedance Vector Analysis	823
Bioelectrical Impedance Spectroscopy	824
Ultrasonography Techniques	824
Lung Comet-Tails	824
Inferior Vena Cava Ultrasound	824
Conclusion	824
Key Points	825
Key References	825
References	825.e1
136 Management of Fluid Overload in Cardiorenal Patients	825
Objectives	825
Five Bs	827
Balance of Fluids	827
Blood Pressure	831
Biomarkers	831
Bioimpedance	832
Blood Volume	833
Conclusion	834
Key Points	834
Key References	835
References	835.e1
137 Mechanical Fluid Removal	835
Objectives	835
Rationale for Mechanical Fluid Removal	835
Options of Mechanical Fluid Removal	835
Indications for Mechanical Fluid Removal	835
Prescription of Mechanical Fluid Removal	836
Clinical Studies in Mechanical Fluid Removal	837
Conclusion	837
Key Points	837
Key References	837
References	837.e1
23 General Principles of Acute Renal Replacement Therapy	838
138 Indications for Renal Replacement Therapy in the Critically Ill	838
Objectives	838
Renal Indications	838
Uremia, Blood Urea Nitrogen, Creatinine	838
Volume Overload, Oliguria	839
Acute Kidney Injury Stage	839
Electrolyte Disturbances	839
Metabolic Acidosis	840
Nonrenal Indications	840
Sepsis	840
Thermoregulation (Hyperthermia, Therapeutic Hypothermia)	840
Drug Overdose, Intoxications	840
Rhabdomyolysis	840
Radiocontrast-Induced Acute Kidney Injury	840
Conclusion	840
Key Points	841
Key References	841
References	841.e1
139 Principles of Extracorporeal Circulation and Transport Phenomena	841
Objectives	841
Principles of Extracorporeal Circulation	841
Therapeutic Functions of Extracorporeal Circuit	842
Main Components of Extracorporeal Circuit	842
Blood Access	842
Blood Tubing	842
Blood Pump	842
Blood Purification Device	842
Anticoagulation System	842
Other Pumps	843
Main Safety Features of the Extracorporeal Circuit	843
System Integrity	843
Pressure Monitoring	843
Inflow Pressure.	843
PreFilter Pressure.	843
Outflow Pressure.	844
Effluent and Ultrafiltrate Pressure.	844
Filter Drop Pressure.	844
Transmembrane Pressure.	844
Air Embolism	844
Blood Loss	844
Fluid Imbalance	844
Transport Phenomena	845
Water Transport	845
Ultrafiltration	845
Osmosis	845
Solute Transport	845
Convection	845
Diffusion	845
Adsorption	846
Conclusion	847
Key Points	847
Key References	847
References	847.e1
140 Membranes and Filters for Use in Acute Renal Failure	847
Objectives	847
History and Evolution of Filters and Membranes	847
Overview on Devices and Membranes	848
Membrane Materials	849
Device Performance	850
Performance Parameters	850
Membrane Ultrafiltration Coefficient	850
Filter Ultrafiltration Coefficient	850
Sieving Coefficient	850
Cutoff and Retention Onset	850
Clearance	851
Clearance Determinations for Continuous Renal Replacement Therapy	851
Mass Transfer Area Coefficient K0A	851
Classification of Membranes and Filters	851
Factors Influencing Treatment Performance	851
Selection of Filters and Membranes	852
Future Developments	852
Conclusion	853
Key Points	853
Key References	853
References	853.e1
141 Continuous Renal Replacement Therapy Machine Technology	853
Objectives	853
Continuous Renal Replacement Therapy Machines: Historical Perspective	853
Continuous Renal Replacement Therapy Hardware	854
User Interface or Screen	854
Circuit Pumps and Pressure Monitoring	855
Fluid Mechanics of Blood Flow in the Extracorporeal Circuit	855
Pressure Measurements	855
Fluid Balance	857
Other Safety Features	857
Anticoagulation	857
Continuous Renal Replacement Therapy Disposables	858
Conclusion	859
Key Points	859
Key References	860
References	860.e1
142 Principles of Anticoagulation in Extracorporeal Circuits	860
Anticoagulation Intermittent Hemodialysis Heparin Clotting Membrane	860
Coagulation in Critically Ill Patients	860
Platelet Dysfunction	861
Fibrinolytic System	862
Extrinsic Pathway	862
Natural Anticoagulants	862
Hypercoagulable State	862
Contributions to Clotting	862
Catheter	862
Circuit, Tubing, and Membrane	862
Blood Flow	863
Effects of Ultrafiltration	864
Predilution Versus Postdilution	864
Use of Erythropoietin	864
Hematocrit	864
Anticoagulation Techniques for Intermittent Hemodialysis	864
Unfractionated Heparin	864
Regional Unfractionated Heparin	864
Low-Molecular-Weight Heparins	865
Heparinoids	865
Direct Thrombin Inhibitors	865
Prostanoids	865
Side Effects of Anticoagulants	865
Endothelium	865
Conclusion	866
Key Points	866
Key References	866
References	866.e1
143 Dialysis Solutions and Replacement Fluids	867
Objectives	867
Sodium and Potassium	867
Buffer	869
Citrate	869
Phosphorus	871
Magnesium	871
Continuous Renal Replacement Therapy Solutions and Energy Balance	872
Conclusion	872
Key Points	872
Key References	872
References	872.e1
144 Starting and Stopping Renal Replacement Therapy in the Critically Ill	873
Objectives	873
Predictors for Dialysis Requirement	873
Blood Urea Nitrogen	873
Creatinine and Creatinine Clearance	874
Urine Output	874
Fluid Balance	875
Hyperkalemia	875
Acidosis	875
Platelet Dysfunction	875
Uremic Encephalopathy and Neuropathy	876
Renal Replacement Therapy for Multisystem Organ Failure	876
Renal Support Versus Renal Replacement	876
Timing of Initiation	877
Scoring Systems to Guide Renal Replacement Therapy	877
Discontinuing Renal Replacement Therapy	877
Withholding and Withdrawing Therapy	878
Conclusion	878
Key Points	878
Key References	878
References	878.e1
145 The Concept of Renal Replacement Therapy Dose and Efficiency	879
Objectives	879
Efficiency, Intensity, Efficacy: Kt/V	879
History of Clinical Trials on Continuous RENAL Replacement Therapy Dose	880
From Bench to Bedside: The Clinical Meaning of Dose	881
From Bench to Bedside: The Prescription	881
Key Points	883
Key References	883
References	883.e1
146 Quantification of Acute Renal Replacement Therapy	883
Objectives	883
Clinical Dosing Targets for Acute Intermittent Hemodialysis	883
Clinical Dosing Targets for Continuous Renal Replacement Therapy	884
Calculation of Fractional Clearance for Intermittent Hemodialysis	884
Calculation of Indexed Solute Clearance for Continuous Renal Replacement Therapy	885
Unified Expressions of Dose for Acute Renal Replacement Therapy	887
Practical Quantification of Acute RENAL Replacement Dose Using Corrected Equivalent Renal Urea Clearance	889
Conclusion	891
Key Points	891
Key References	891
References	891.e1
147 Principles of Pharmacodynamics and Pharmacokinetics of Drugs Used in Extracorporeal Therapies	892
Objectives	892
Factors Affecting Drug Clearance During Renal Replacement Therapy	892
Principles of Drug Removal	892
Drug Properties	892
Molecular Weight	892
Plasma Protein Binding	893
Volume of Distribution	893
Proportion of Renal Clearance	893
Estimation of Drug Clearance During Hemofiltration	893
Device Properties	894
Operating Conditions	894
Patient’s Pathophysiology	894
Principles for Dosage Adjustments During Continuous Renal Replacement Therapy	894
Pharmacodynamics and Dosage Adjustments of Antimicrobial Agents During Renal Replacement Therapy	894
Conclusion	896
Key Points	896
Key References	896
References	896.e1
148 Ethical Considerations in Acute Renal Replacement Therapy	896
Objectives	896
Renal Replacement Therapy in the Care of the Critically Ill Patient	897
Morality of Renal Replacement	897
Information and Consent for Renal Replacement Therapy	897
Healthcare Workers and the Relatives of the Incompetent Patient	898
Guidelines and Moral Principles	898
Managing the Refusal of Renal Replacement Treatment	898
Right to Die Without Renal Replacement Therapy	900
Justifying Foregoing of Renal Replacement Therapy	900
Practice of Foregoing Renal Replacement Therapy	901
Limiting Treatments, Not Care	901
Clinical Research in Renal Replacement Therapy	901
Protecting Incompetent Patients Through Risk/Benefit Ratio Evaluation: The Role of Research Ethics Committees (RECs)	902
Promoting Better Research	902
Biosocial Aspects of Renal Replacement Therapy	903
Key Points	903
Key References	904
References	904.e1
24 Intermittent Renal Replacement Therapies	905
149 Intermittent Techniques for Acute Dialysis	905
Objectives	905
Physical Principles	905
Technical Aspects	905
Dialysis Machine	905
Pure Water	906
Dialysate	906
Vascular Access	906
Dialysis Membrane	906
Anticoagulation	906
Advantages and Limits in the Intensive Care Unit	906
Specificity of Intermittent Hemodialysis Use in Intensive Care Units	907
Metabolic Control and Dialysis Dose	907
Hemodynamic Tolerance	907
Different Modalities	907
Conventional Intermittent Hemodialysis	907
Sequential Intermittent Hemodialysis	908
Sustained Low-Efficiency Dialysis	908
Key Points	908
Key References	908
References	908.e1
150 Solute and Water Transport in Hemodialysis	909
Objectives	909
Diffusion and Convection	909
Membranes and Filters for Intermittent Hemodialysis	910
Cellulosic Membranes	910
Synthetic Membranes	911
Properties of Hemodialyzer Membranes That Influence Dialyzer Performance	911
Characterization of Dialyzer Performance: Clearance and Ultrafiltration Coefficient	912
Clearance	912
Whole Blood Clearance	912
Blood Water and Plasma Clearance	913
Dialysate-Side Clearance	913
Clearance Versus Mass Removal Rate	913
Concept of Kt/V	914
Determinants of Diffusive Solute Clearance	914
Blood Compartment	914
Dialysate Compartment	915
Diffusion and Convection as Competing Phenomena	915
Internal Filtration and Backfiltration	916
Conclusion	917
Key Points	917
Key References	918
References	918.e1
151 Biocompatibility of the Dialysis System	918
Objectives	918
Dialysis Membranes and Determinants of Biocompatibility	918
Protein Adsorption	919
Coagulation and Kallikrein-Kinin Systems	919
Complement Activation	919
Activation of Blood Cells, Inflammation and Oxidative Stress	920
Dialysate and Infusate	920
The Hemodialysis Circuit as a Possible Source of Toxins: Leachables and Sterilization Process	921
The Effect of Dialysis Membranes on Patients’ Outcomes in AKI	921
Conclusion	922
Key Points	922
Key References	922
References	922.e1
152 Composition of Hemodialysis Fluid	922
Objectives	922
Dialysate Components	923
Sodium	923
Potassium	924
Calcium	924
Magnesium	924
Buffer	925
Acetate	925
Bicarbonate	925
Chloride	925
Glucose	926
Dialysate Quality	926
Conclusion	927
Key Points	927
Key References	927
References	927.e1
153 Indications for and Contraindications to Intermittent Hemodialysis in Critically Ill Patients	928
Objectives	928
Operational Characteristics of Intermittent Hemodialysis and Hemofiltration	928
Intermittent Hemodialysis and Continuous Renal Replacement Therapy: Is One Better Than the Other?	929
Situations in Which Intermittent Hemodialysis Should Be Preferred	930
Complications of Acute Renal Failure	930
Hyperkalemia	930
Metabolic Acidosis	930
Azotemia	930
Poisoning	931
Risk of Hemorrhage and Contraindication to Anticoagulants	931
Other Indications	931
Situations in Which Intermittent Hemodialysis Should Be Avoided	931
Severe Hemodynamic Instability	931
Fluid Overload	932
Risk of Cerebral Edema	932
Conclusion	932
Key Points	932
Key References	932
References	932.e1
154 Technical and Clinical Complications of Intermittent Hemodialysis in the Intensive Care Unit	933
Objectives	933
Technical Complications	933
Vascular Access Problems	933
Infection	934
Access Recirculation	934
Air Embolism	934
Hemolysis	935
Electrolyte and Acid-Base Disorders	935
Clinical Complications	936
Bleeding and Thrombosis	936
Hypoxemia	936
Hypotension	936
Biocompatibility	938
Hypersensitivity Reactions	938
Cardiac Arrhythmias	939
Febrile Reactions	939
Dialysis Dysequilibrium Syndrome	939
Miscellaneous Complications	939
Nutritional and Metabolic Problems	939
Prolongation of Renal Recovery	939
Dialysis Dosing and Recovery of Renal Function in Acute Renal Failure	940
Issues With the Dose of Dialysis in the Intensive Care Unit	940
Key Points	941
Key References	941
References	941.e1
155 Correction of Water, Electrolyte, and Acid-Base Derangements by Hemodialysis and Derived Techniques	941
Objectives	941
Sodium Abnormalities	941
Potassium Abnormalities	943
Abnormalities of Divalent Ions	944
Acid-Base Abnormalities	946
Conclusion	946
Key Points	947
Key References	947
References	947.e1
156 Urea Kinetics, Efficiency, and Adequacy of Hemodialysis and Other Intermittent Treatments	947
Objectives	947
Goals of Dialysis	948
How to Measure the Dose	948
Urea Modeling	949
Modeling Protein Catabolism	949
Online Methods	950
Dialysis Efficiency	951
Timing of Dialysis Initiation	951
Discontinuation of Therapy	951
Solute Dysequilibrium: an Impediment to Delivering an Adequate Dose	951
Single-Pool Kt/V	952
Equilibrated Kt/V	952
Standard Kt/V	953
Urea Reduction Ratio	953
Limitations of Kt/V	953
Minimum Dose, Frequency, and Treatment Time	953
Patient Size and Urea Volume: Impediments to Dialysis?	953
Hemodialysis Versus Hemofiltration	954
Accounting for Residual Clearance	954
Drug Dosing During and Between Treatments	954
Simplified Methods	954
Other Benchmarks of Adequacy	955
Conclusion	955
Key Points	955
Key References	955
References	955.e1
157 Assessment of Fluid Status and Body Composition and Control of Fluid Balance With Intermittent Hemodialysis in the Critically Ill Patient	956
Objectives	956
Body Composition in Health and Disease	956
Evaluation of Fluid Status and Body Composition	956
Intermittent Hemodialysis in the Critically Ill Patient: Control of Fluid Balance and Prevention of Intradialytic Hypotension	958
Key Points	959
Key References	960
References	960.e1
158 Outcomes of Intermittent Hemodialysis in Critically Ill Patients With Acute Kidney Injury	960
Objectives	960
Vascular Access	961
Anticoagulation	961
Selection of the Membrane	962
Dose of Dialysis in Intermittent Hemodialysis	962
Comparison of Outcomes Between Intermittent Versus Continuous Dialysis Modalities	963
Hemodynamic Stability	963
Impact of Intermittent Hemodialysis Versus Continuous Renal Replacement Therapy on De Novo Chronic Kidney Disease and Progression to End-Stage Renal Disease	964
Contraindications to Intermittent Hemodialysis	965
Summary and Conclusions	965
Key Points	965
Key References	966
References	966.e1
159 Hybrid Dialysis Techniques in the Intensive Care Unit	966
Objectives	966
Technical Issues	967
Machinery	967
Water Quality	969
Hemodialyzers	969
Clinical Outcomes	970
Solute Control	970
Comparative Clinical Outcomes	970
ICU Length of Stay	970
Hemodynamics	970
Renal Recovery	972
Mortality	972
Introducing Hybrid Therapies (HTs)	972
Conclusion	973
Key Points	973
Key References	973
References	973.e1
160 The Role of Plasmapheresis in Critical Illness	973
Objectives	973
Techniques of Plasmapheresis	973
Replacement Fluid	974
Indications and Evidence of Plasmapheresis and Therapeutic Plasma Exchange in Critical Illness	974
Thrombotic Microangiopathies	974
Thrombotic Thrombocytopenic Purpura	974
Complement-Mediated Thrombotic Microangiopathies and Atypical Hemolytic Uremic Syndrome	974
Drug-Associated Thrombotic Microangiopathies	975
Liver Failure	975
Acute Liver Failure	975
Fulminant Wilson Disease With Acute Liver Failure	975
Neurologic Disorders	975
Renal Disorders	975
ABO-Incompatible Renal Transplantation	976
Sepsis With Multi-Organ Failure	976
Conclusion	976
Key Points	976
Key References	977
References	977.e1
161 Cascade Filtration for ABO Incompatible Transplant	977
Objectives	977
Barrier of ABO	977
Techniques for Antibody Removal	978
Cascade Filtration	978
Conclusion	979
Key Points	979
Key References	980
References	980.e1
162 Nursing Issues and Procedures in Continuous Renal Replacement Therapy	980
Objectives	980
Nursing Knowledge and Acute Kidney Injury	980
Group One Lectures	981
Group Two Tutorials and Practical One	981
Group Three Tutorials and Practical Two	981
Certification and Continuous Renal Replacement Therapy	982
Continuous Renal Replacement Therapy Machines	982
Protocols and Documents for Continuous Renal Replacement Therapy	984
Anticoagulation	984
Quality	985
Multidisciplinary Team	985
Extracorporeal Membrane Oxygenation and Continuous Renal Replacement Therapy	985
Continuous Renal Replacement Therapy in the Operating Room	986
Advanced Therapy	986
Conclusion	986
Key Points	986
Key References	986
References	986.e1
25 Continuous Renal Replacement Therapies (CRRT)	987
163 Indications for Continuous Renal Replacement Therapy	987
Objectives	987
Traditional Indications for Continuous Renal Replacement Therapy: Renal Indications	988
Fluid Overload	988
Cardiovascular Instability	989
Solute Removal: Uremic Symptoms and Signs	989
Metabolic Acidosis	990
Control of Electrolyte Derangements	990
Hyperkalemia	990
Hyponatremia and Hypernatremia	990
Renal Replacement Versus Renal Support	990
Nonrenal Indications for Continuous Renal Replacement Therapy	990
Severe Sepsis and Septic Shock	990
Continuous Renal Replacement Therapy in Sepsis and Multisystem Organ Failure	991
Severe Acute Pancreatitis	991
Fulminant Hepatic Failure	991
Treatment of Acute Distress Respiratory Syndrome	991
Continuous Renal Replacement Therapy in Heart Failure	992
Continuous Renal Replacement Therapy in Acute Brain Injury	992
Conclusion	992
Key Points	992
Key References	993
References	993.e1
164 Beginning and Ending Continuous Renal Replacement Therapy in the Intensive Care Unit	993
Objectives	993
Defining the Timing of Initiation of Continuous Renal Replacement Therapy	993
Rationale for When to Start Continuous Renal Replacement Therapy	994
Recent Clinical Studies of Timing of Continuous Renal Replacement Therapy	995
Rationale for When to Stop Continuous Renal Replacement Therapy	998
Conclusion	999
Key Points	999
Key References	999
References	999.e1
165 Solute and Water Kinetics in Continuous Therapies	1000
Objectives	1000
Transport Mechanism	1000
Fluid Removal	1000
Ultrafiltration	1000
Solute Removal	1000
Diffusion	1000
Convection	1000
Adsorption	1001
Continuous Renal Replacement Therapy Techniques	1001
Slow Continuous Ultrafiltration	1001
Continuous Venovenous Hemofiltration	1002
Continuous Venovenous Hemodialysis	1002
Continuous Venovenous High-Flux Hemodialysis	1003
Continuous Venovenous Hemodiafiltration	1003
Additional Considerations in the Delivery of Continuous Renal Replacement Therapy	1004
Anticoagulation	1004
Drug Removal During Continuous Renal Replacement Therapy	1004
Efficiency, Intensity, and Efficacy	1004
Conclusion	1005
Key Points	1005
Key References	1005
References	1005.e1
166 Continuous Renal Replacement Therapy	1005
Objectives	1005
Principles of Solute Removal	1006
Water Removal	1006
Solute Removal	1006
Continuous Renal Replacement Therapy	1006
Hemofiltration, Hemodialysis, and Hemodiafiltration	1007
Impact on Outcomes	1009
Conclusion	1009
Key Points	1009
Key References	1010
References	1010.e1
167 Vascular Access for Acute Renal Replacement Therapy	1010
Objectives	1010
Catheter Characteristics: Material, Geometry, and Design	1010
Methods of Central Venous Catheters Insertion	1011
Indications and Venous Site Choice Preferences for Central Venous Catheters	1012
Maintenance and Care of Catheters	1014
Catheter Performance	1015
Outcomes and Complications	1016
Perspectives	1017
Conclusion	1018
Key Points	1018
Key References	1018
References	1018.e1
168 Anticoagulation Strategies for Continuous Renal Replacement Therapy	1018
Objectives	1018
Nonanticoagulant Measures to Reduce Filter Clotting	1019
Venous Access and Circuit	1019
Hemodialysis Versus Hemofiltration	1019
Predilution Versus Postdilution	1020
Systemic Anticoagulation	1020
Unfractionated Heparin	1020
Low-Molecular-Weight Heparin	1020
Heparin-Induced Thrombocytopenia	1020
Argatroban	1021
Fondaparinux	1021
Nafamostat	1021
Prostacyclin	1021
No Anticoagulation	1021
Regional Anticoagulation	1021
Citrate	1021
Citrate: Regional Anticoagulation.	1021
Citrate: Buffer.	1021
Principles of the Citrate Circuit.	1022
Modalities.	1022
Monitoring of Citrate Anticoagulation.	1022
Citrate Accumulation.	1022
Benefits of Citrate Anticoagulation.	1022
Unfractionated Heparin: Protamine	1023
Recommendations	1023
Key Points	1023
Key References	1023
References	1023.e1
169 Nursing Strategies to Prevent Coagulation of the Extracorporeal Circuit	1024
Objectives	1024
Clotting: Where and How?	1024
Anticoagulants	1024
Access Catheter and Site	1025
Blood Pump–Flow Speed	1025
Membranes: Type, Size, Heparin Coating	1026
Fluid Administration—Predilution	1027
Venous Chamber	1027
Training, Education, and the Multidisciplinary Team	1027
Conclusion	1028
Key Points	1028
Key References	1028
References	1028.e1
170 Adequacy of Continuous Renal Replacement Therapy	1029
Objectives	1029
Use of Clearance to Quantify Dose in Renal Replacement Therapy	1029
Overview of Clearance	1029
Quantification of Renal Replacement Therapy Dose in Acute Kidney Injury Versus End-Stage Renal Disease: Important Distinctions	1030
Use of Urea Kinetics to Estimate Continuous Renal Replacement Therapy Dose	1030
Continuous Renal Replacement Therapy Dose and Outcome Studies	1031
Prescribed Versus Delivered Continuous Renal Replacement Therapy Dose	1032
Modality Considerations for Continuous Renal Replacement Therapy Dose	1032
Reconciling Effluent-Based and Clearance-Based Dose	1032
Summary	1034
Key Points	1034
Key References	1034
References	1034.e1
171 High-Volume Hemofiltration in the Intensive Care Unit	1034
Objectives	1034
Definition of High Volume	1034
Rationale	1035
Practical Aspects	1035
Clinical Results	1036
End of the Story?	1037
Conclusion	1037
Key Points	1037
Key References	1037
References	1037.e1
172 Pulse High-Volume Hemofiltration in Management of Critically Ill Patients With Severe Sepsis or Septic Shock	1038
Objectives	1038
Definition and Rationale	1038
Technical Considerations	1040
Clinical Experience	1040
Conclusion	1041
Key Points	1041
Key References	1041
References	1041.e1
173 High Cutoff Membranes for Mediators Removal	1042
Objectives	1042
Engineering Characteristics of High Cut-off Membrane	1042
Clinical Evidence	1043
Effects of High Cutoff Treatment on Cytokines	1043
Effects of High Cutoff Treatment on Albumin	1044
Effects on Organ Function	1044
Effects on Antibiotics	1045
Conclusion	1045
Key Points	1046
Key References	1046
References	1046.e1
174 Clinical Effects of Continuous Renal Replacement Therapies	1046
Objectives	1046
Fluid Removal	1046
Solute Removal, Acid-Base Control, and Electrolyte Balance	1047
Side Effects of Continuous Renal Replacement Therapy	1048
Trials on the Final Clinical Effect: Mortality	1049
Potential Compromise: Hybrid Techniques	1049
Conclusion	1050
Key Points	1050
Key References	1050
References	1050.e1
175 Antibiotic Adjustment in Continuous Renal Replacement Therapy	1051
Objectives	1051
Basic Pharmacologic Parameters of Antimicrobial Agents	1051
Pharmacokinetic Parameters	1051
Bioavailability	1051
Plasma Protein Binding	1051
Plasma Drug Concentration (Cmax, Cmin, AUC)	1051
Volume of Distribution	1052
Clearance	1052
Half-Life	1052
Antibiotics Classification Based on Physicochemical Properties	1052
Pharmacokinetic/Pharmacodynamic Relationship	1054
Pharmacokinetic/Pharmacodynamic Classification of Antibiotics	1054
Antibiotics in Critical Illness	1054
Rationale for Personalized Dosage Adjustment in Critically Ill Patients	1054
Impact of Critical Illness on the Pharmacology of Antimicrobial Agents	1054
Impact of Acute Kidney Injury on Pharmacologic Characteristics of Antimicrobial Agents	1057
Acute Kidney Injury Without Continuous Renal Replacement Therapy: Drug Dosing Adjustment	1057
Acute Kidney Injury Needing Continuous Renal Replacement Therapy	1058
Principles of Drug Removal During Renal Replacement Therapies: Technical Factors Specific to Extracorporeal Blood Purification Therapy	1063
Membrane	1063
Diffusion (Hemodialysis)	1063
Convection (Hemofiltration)	1064
Combination With Diffusion and Convection (Hemodiafiltration)	1064
Adsorption to Membrane	1065
High Volume-High Filtration	1065
Rationale for Appropriate Dosage Adjustment of Antibiotics During Continuous Renal Replacement Therapy	1065
Key Points	1067
Key References	1067
References	1067.e1
176 Nomenclature	1068
Objectives	1068
Characteristics of the Membrane and Filter	1068
Geometric Characteristics	1068
Performance Characteristics	1068
Membrane Ultrafiltration Coefficient and Filter Ultrafiltration Coefficient	1068
Mass Transfer Area Coefficient	1068
Membrane Sieving Coefficient/Rejection Coefficient	1069
Cutoff	1069
Mechanisms of Solute and Fluid Transport	1069
Ultrafiltration and Convection	1070
Transmembrane Pressure	1070
Diffusion	1071
Adsorption	1071
Modalities of Extracorporeal Renal Replacement Therapy	1071
Hemodialysis	1071
Hemofiltration	1071
Hemodiafiltration	1071
Isolated Ultrafiltration	1071
Plasmapheresis	1072
Hemoperfusion or Plasmaperfusion	1072
Fluids, Volumes, and Flows	1072
Filtration Fraction and Concentration Ratio	1072
Treatment Evaluation Methods: The “Dose” of Renal Replacement Therapy	1072
Target Dose (Prescribed)	1072
Target Machine Dose (Set)	1072
Current Dose (Estimated From Treatment Parameters)	1073
Average Dose (Measured/Calculated)	1073
Projected Dose (Calculated/Estimated)	1073
Current Effective Delivered Dose (Measured)	1073
Average Effective Delivered Dose (Measured)	1073
Efficiency, Intensity, and Efficacy	1073
Conclusion	1073
List of Abbreviations	1074
Key Points	1076
Key References	1076
References	1076.e1
177 Nomenclature	1077
Objectives	1077
Hardware and Devices	1077
Continuous Renal Replacement Machine: Procedures and Phases of Treatment	1078
Continuous Renal Replacement Thrapy Disposables	1078
Volume Management and Fluid Balance	1078
Extracorporeal Therapies and Treatments	1080
Continuous Therapies	1080
Slow Continuous Ultrafiltration	1080
Continuous Venovenous Hemofiltration	1080
Continuous Venovenous Hemodialysis	1080
Continuous Venovenous Hemodiafiltration	1080
Continuous Venovenous High-Flux Hemodialysis	1081
Intermittent Therapies	1081
Hybrid Therapies	1081
Other Extracorporeal Therapies	1081
Therapeutic Plasma Exchange	1081
Multiple Organ Support Therapy	1081
Heart Support.	1081
Liver Support.	1081
Lung Support.	1082
Blood Purification in Sepsis.	1082
Conclusion	1082
List of Abbreviations	1083
Key Points	1083
Key References	1083
References	1083.e1
26 Peritoneal Dialysis in the Intensive Care Unit	1084
178 Peritoneal Dialysis System	1084
Objectives	1084
Peritoneal Dialysis System	1084
Dialysate Compartment	1084
Peritoneal Dialysis Membrane	1085
Peritoneal Microcirculation	1086
Conclusion	1088
Key Points	1088
Key References	1088
References	1088.e1
179 Indications, Contraindications, and Complications of Peritoneal Dialysis in Acute Renal Failure	1088
Objectives	1088
Outcomes	1089
Renal Recovery	1089
Complications	1090
Clearance of Uremic Toxins	1090
Standard Single-Access Peritoneal Dialysis	1090
Continuous-Flow Peritoneal Dialysis	1092
Importance and Practicality of Tunneled Catheters	1093
Comparison of Risks	1094
Advantages and Disadvantages	1094
Conclusion	1095
Key Points	1095
Key References	1095
References	1095.e1
180 Solute and Water Transport Across the Peritoneal Barrier	1096
Objectives	1096
Structure of the Peritoneal Barrier and Transport Principles	1096
Distributed Nature of the Barrier	1096
Effects of the Interstitial Matrix on Transport	1097
Nature of the Endothelial Barrier	1098
Physiology of Transport: Normal Conditions	1098
Importance of the Surface Contact Area	1099
Solute Transfer Across the Peritoneal Barrier	1099
Water Flow and Calculation of Net Ultrafiltration	1100
Lymphatic Drainage From the Peritoneal Cavity	1100
Clinical Effects of Intraperitoneal Pressure	1101
Alteration of the Transport Barrier: Normal Physiology	1101
Acute Peritoneal Dialysis in the Intensive Care Unit: Special Conditions	1101
Hypotension and Peritoneal Blood Supply	1101
Dehydration and Hypotension	1101
Practical Limits of Solute Transfer	1101
Key Points	1102
Key References	1102
References	1102.e1
181 Choice of Peritoneal Dialysis Technique	1102
Objectives	1102
Continuous Versus Intermittent Techniques	1102
Advantages of Short Dwells	1103
Disadvantages of Short Dwells	1103
Continuous Ambulatory Peritoneal Dialysis Schedule	1104
Continuous-Flow Peritoneal Dialysis	1104
Conclusion	1104
Key Points	1104
Key References	1104
References	1104.e1
182 Correction of Fluid, Electrolyte, and Acid-Base Derangements by Peritoneal Dialysis in Acute Kidney Injury	1105
Objectives	1105
Prescription for Acute Peritoneal Dialysis	1105
Physical Aspects	1105
Prescription for Acute Peritoneal Dialysis	1106
Dialysis Solution	1106
Fluid Removal	1106
Electrolyte Abnormalities	1107
Acid-Base Derangements	1107
Conclusion	1108
Key Points	1108
Key References	1108
References	1108.e1
183 Feasibility, Efficiency, and Adequacy of Peritoneal Dialysis in Acute Kidney Injury	1108
Objectives	1108
Feasibility of Peritoneal Dialysis in Acute Kidney Injury	1109
Efficiency and Adequacy of Peritoneal Dialysis in Acute Kidney Injury	1109
Adequacy and Outcomes of Peritoneal Dialysis in Acute Kidney Injury	1110
Overall Role of Peritoneal Dialysis in Acute Kidney Injury	1111
Conclusion	1112
Key Points	1112
Key References	1112
References	1112.e1
184 Clinical Results and Complications of Peritoneal Dialysis in Acute Kidney Injury	1113
Objectives	1113
Historical Perspective	1113
Effect on Mortality	1113
Dialysis Adequacy	1114
Dialysis Dose	1116
Renal Recovery	1116
Lactate Versus Bicarbonate-Buffered Solutions	1117
Future Trends	1117
Complications of Acute Peritoneal Dialysis	1117
Infectious Complications	1117
Peritoneal Catheter–Related Infections	1117
Noninfectious Complications	1117
Surgical Complications	1117
Mechanical Complications	1117
Inflow and Outflow Difficulty	1118
Complications Related to Increased Intraabdominal Pressure	1118
Hydrothorax.	1118
Altered Mechanics of Breathing.	1118
Metabolic Complications	1118
Acid-Base Balance.	1118
Culture-Negative Cloudy Peritoneal Dialysate.	1118
Conclusion	1120
Key Points	1120
Key References	1120
References	1120.e1
185 Treatment of Peritonitis and Other Clinical Complications of Peritoneal Dialysis in the Critically Ill Patient	1120
Objectives	1120
Infectious Complications of Peritoneal Dialysis	1120
Peritonitis	1120
Pathophysiology and Microbiology of Peritonitis	1121
Clinical Features, Evaluation of Suspected Peritonitis, and Diagnosis	1121
Antibiotic Therapy	1121
Other Considerations	1122
Prevention	1122
Exit Site and Tunnel Infections	1123
Indications for Catheter Removal or Exchange	1123
Pressure Considerations	1123
Metabolic Complications of Peritoneal Dialysis	1123
Catheter-Related Complications	1123
Other Considerations	1124
Peritoneal Dialysis in the Surgical Patient	1124
Preserving Residual Renal Function	1124
Peritoneal Rest	1124
Key Points	1124
Key References	1125
References	1125.e1
186 Comparison of Peritoneal Dialysis With Other Treatments for Acute Kidney Injury	1125
Objectives	1125
Solute and Volume Control and Overall Outcomes	1125
Cost	1126
Dialysis Access	1127
Potential Benefits Favoring Peritoneal Dialysis	1127
Potential Limitations Favoring Other Modalities	1127
Conclusion	1127
Acknowledgments	1128
Key Points	1128
Key References	1128
References	1128.e1
187 Continuous-Flow Peritoneal Dialysis as Acute Therapy	1128
Objectives	1128
Rationale and Physiology	1128
Historical Perspective	1129
Technique	1129
Continuous-Flow Peritoneal Dialysis in Pediatric Acute Renal Failure	1131
Clinical Experience With Continuous-Flow Peritoneal Dialysis in Acute Renal Failure	1132
Advantages and Indications for Continuous-Flow Peritoneal Dialysis in Acute Renal Failure	1133
Conclusion and Future Directions	1133
Key Points	1134
Key References	1134
References	1134.e1
188 Nursing and Procedure Issues in Peritoneal Dialysis	1134
Objectives	1134
Procedure	1134
Step 1: Preparation of the Abdomen	1134
Step 2: Creating Ascitis	1134
Step 3: Peritoneal Dialysis Catheter Placement	1135
Step 4: Peritoneal Dialysis Exchanges	1135
Nursing Issues in Peritoneal Dialysis	1135
Review of Literature	1135
Conclusion	1135
Key Points	1135
Key References	1136
References	1136.e1
27 Extracorporeal Blood Purification Techniques Beyond Dialysis	1137
189 Sorbents	1137
Objectives	1137
Basic Principles	1137
Sorbent Materials and Structure	1138
Requirements for a Sorbent	1140
Mechanism of Solute Adsorption in Porous Media	1140
Flow Distribution in Packed Beds	1140
Efficiency of Adsorption	1142
Biocompatibility of Sorbents	1143
Rationale for the Use of Adsorption in Clinical Settings	1145
Typical Modalities of Utilization of Sorbents	1145
Hemoperfusion	1145
Hemoperfusion Coupled with Hemodialysis	1146
Double-Chamber Hemodiafiltration	1146
Coupled Plasma Filtration-Adsorption	1146
Derivative Techniques	1146
Sorbent-Based Adjunctive Therapies for Sepsis	1147
Coupled Plasma Filtration-Adsorption	1148
CytoSorb	1149
Polymyxin-B Hemoperfusion	1150
Novel Applications of Sorbents	1151
Lixelle β-2 Microglobulin Apheresis Column	1151
Virus Removal by Lectin Affinity Plasmapheresis	1152
Hemoperfusion for Sepsis-Induced Acute Lung Injury	1152
Sorbent Technology in Wearable Artificial Kidney Devices	1152
Conclusion	1153
Key Points	1154
Key References	1154
References	1154.e1
190 Therapeutic Apheresis in Critically Ill Patients	1154
Objectives	1154
Pathophysiologic Aspects of Apheresis in Critical Care Medicine	1155
General Aspects	1155
Modulation of the Immune Response by Apheresis	1155
Procedure-Related Considerations	1155
Modalities and Techniques	1156
Therapeutic Plasma Exchange	1156
Immunoadsorption	1156
Lipoprotein Apheresis	1156
Available Lipoprotein Apheresis Systems	1157
Indications	1157
Clinical Results	1158
Clinical Results in Established Nephrologic Indications (Category A)	1159
Granulomatosis With Polyangiitis and Microscopic Polyangiitis	1159
Antiglomerular Basement Membrane Disease	1159
Cryoglobulinemia and Cryoglobulinemic Vasculitis	1159
Thrombotic Microangiopathies	1159
Apheresis in Kidney Transplantation	1160
ABO-Incompatible Kidney Transplantation	1160
Humoral Kidney Transplantation Rejection	1160
Apheresis in Sepsis and Multi-Organ Failure	1160
Key Points	1160
Key References	1160
References	1160.e1
191 Extracorporeal Blood Purification Techniques Beyond Dialysis	1161
Objectives	1161
Regional Citrate Anticoagulation in Coupled Plasmafiltration-Adsorption	1163
Conclusion	1166
Key Points	1166
Key References	1166
References	1166.e1
192 Prometheus System	1167
Objectives	1167
Prometheus System	1167
Removal Efficiency and Selectivity	1167
Safety	1167
Clinical Data	1168
Conclusion	1168
Key Points	1168
Key References	1169
References	1169.e1
193 Toraymyxin and Other Endotoxin Adsorption Systems	1169
Objectives	1169
Role and Measurement of Endotoxin in Septic Patients	1169
Therapies Against Endotoxins: From Drugs to Medical Devices	1170
Toraymyxin System: Concept and Manufacturing Process	1170
Clinical Experience With Endotoxin Adsorption	1171
Measurement and Removal of Endotoxin: EUPHRATES a Theranostic Trial of PMX-DHP for Endotoxemic Septic Shock	1173
Key Points	1173
Key References	1173
References	1173.e1
194 Plasmafiltration-Adsorption-Dialysis System	1174
Objectives	1174
Process of Plasmafiltration-Adsorption-Dialysis	1174
Preliminary Data From in vitro Studies	1177
Potential Clinical Effects of Plasmafiltration-Adsorption-Dialysis	1178
Key Points	1178
Key References	1178
References	1178.e1
195 Extracorporeal Membrane Oxygenation for Cardiac Support	1179
Objectives	1179
Technical Aspects	1179
Circuit Components	1180
Indications for Starting and Stopping VA-ECMO	1181
Extracorporeal Membrane Oxygenation for Cardiogenic Shock	1181
Extracorporeal Membrane Oxygenation and Cardiac Transplantation	1181
Extracorporeal Membrane Oxygenation for Cardiopulmonary Resuscitation	1181
Weaning	1182
Side Effects	1182
Conclusion	1182
Key Points	1182
Key References	1182
References	1182.e1
196 Extracorporeal Membrane Oxygenation for Pulmonary Support	1183
Objectives	1183
Background	1183
Origin and Technical Evolution of Membrane Oxygenators	1183
Clinical Pioneering of Extracorporeal Respiratory Support	1183
Cesar Trial and H1N1 Flu Pandemics	1184
Indications	1184
Physiology	1185
Artificial Lung	1185
Oxygenation	1185
Carbon Dioxide Removal	1186
Circuit	1186
Pumps	1186
Membrane Lung	1186
Cannulas for Adult Patients	1186
Monitoring and Management of Artificial Lung	1187
Ventilatory Management of the Native Lung	1188
Anticoagulation and Hematologic Monitoring	1188
Extracorporeal Membrane Oxygenation Complications	1189
Weaning From Venovenous Extracorporeal Membrane Oxygenation	1189
Key Points	1189
Key References	1190
References	1190.e1
197 Cell-Based Therapies	1190
Objectives	1190
Renal Tubule Assist Device	1191
Bioartificial Kidney in Series With Renal Replacement Therapy	1191
Leukocyte Cell Processing in situ	1191
Clinical Assessment of the Selective Cytopheretic Device	1192
RCA for Continuous Renal Replacement Therapy With the Selective Cytopheretic Device	1192
Conclusion	1193
Key Points	1193
Key References	1193
References	1193.e1
28 Critical Care Nephrology in Pediatrics	1194
198 Cellular and Molecular Mechanisms of Acute Kidney Injury	1194
Objectives	1194
Histologic Alterations	1194
Hemodynamic Alterations	1194
Alterations in Tubule Dynamics	1195
Alterations in Tubule Cell Metabolism	1195
Alterations in Tubule, Endothelial, and Glomerular Cell Cytoskeleton	1196
Alterations in Cell Viability	1197
Alterations in the Microvasculature	1199
Alterations in the Inflammatory Response	1200
Alterations in Gene Expression	1202
Nephrotoxic Acute Kidney Injury	1203
Acute Kidney Injury in Sepsis	1203
Clinicopathologic Correlations	1203
Systemic Injury and Organ Cross-Talk	1203
Key Points	1204
Key References	1204
References	1204.e1
199 Epidemiology of Pediatric Acute Kidney Injury	1205
Objectives	1205
Pediatric Acute Kidney Injury Epidemiology: Current State of Knowledge	1205
Acute Kidney Injury Epidemiology	1206
Standardized Definitions Improve the Assessment of Pediatric Acute Kidney Injury	1206
Conclusion and Future Directions	1206
Key Points	1206
Key References	1207
References	1207.e1
200 Treatment of Acute Kidney Injury in Children	1207
Objectives	1207
Cause	1207
General Approach to Conservative Management	1208
Removal or Correction of the Offending Cause	1208
Attention to Nutrition	1208
Volume Status	1208
Diuretics	1209
Dialytic Therapies	1209
Conclusion	1209
Key Points	1210
Key References	1210
References	1210.e1
201 Technical Aspects of Pediatric Continuous Renal Replacement Therapy	1210
Objectives	1210
Prescription	1211
Blood Priming	1211
Temperature Control	1212
Blood Flow	1212
Access	1212
Solutions	1212
Anticoagulation	1213
Membranes	1214
Conclusion	1214
key points	1214
Key References	1214
References	1214.e1
202 Multiple Organ Dysfunction in the Pediatric Intensive Care Unit	1215
Objectives	1215
Epidemiology and Scoring Systems for Pediatric Multiple-Organ Dysfunction Syndrome	1215
Pathophysiology	1215
Management of Multiple Organ Dysfunction Syndrome in the Pediatric Intensive Care Unit	1216
Diagnosis	1216
Treatment	1217
Key Points	1217
Key References	1217
References	1218.e1
203 Drug Dosing in Pediatric Acute Kidney Insufficiency and Renal Replacement Therapy	1218
Objectives	1218
Estimation of Creatinine Clearance	1218
Pharmacokinetic Alterations With Acute Kidney Insufficiency	1220
Dosing Considerations With Renal Failure	1221
Dosing Considerations With Renal Replacement Therapy	1222
Continuous Renal Replacement Therapy	1222
Intermittent Hemodialysis	1223
Therapeutic Drug Monitoring	1223
Conclusion	1223
Key Points	1224
Key References	1224
References	1224.e1
204 Nutrition of Critically Ill Children With Acute Renal Failure	1224
Objectives	1224
Assessment and Monitoring of Nutritional Status	1225
Nutrition Timing, Approach, and Modality in Acute Kidney Injury	1225
Energy Provision	1225
Protein Intake	1225
Electrolytes, Trace Elements, and Vitamins	1226
Conclusion	1227
Key Points	1227
Key References	1227
References	1227.e1
205 Outcome of Pediatric Acute Kidney Injury	1228
Objectives	1228
Hospitalized Children	1228
Critically Ill Pediatric Patients	1228
Critically Ill Children Who Require Renal Replacement Therapy	1229
Neonates and Infants	1229
Congenital Heart Disease	1229
Long-Term Outcome With Pediatric Acute Kidney Injury	1230
Key Points	1230
Key References	1230
References	1230.e1
206 Renal Replacement Therapy for the Critically Ill Infant	1230
Objectives	1230
Renal Failure and Other Indications for Renal Replacement Therapy	1231
Peritoneal Dialysis	1231
Indications	1231
Technique	1231
Disadvantages and Complications in the Infant	1232
Intermittent Hemodialysis	1232
Indications	1232
Technique	1232
Disadvantages and Complications	1233
Continuous Renal Replacement Therapy	1233
Indications	1233
Technique	1233
Disadvantages and Complications	1234
Conclusion	1234
Key Points	1234
Key References	1235
References	1235.e1
207 Neonatal Hyperammonemia and Continuous Renal Replacement Therapy	1235
Objectives	1235
Practical Use of Renal Replacement Therapy in Neonatal Hyperammonemia	1235
Technical Challenges and Considerations	1236
Clearance of Pharmacologic and Nutritional Substrates by Continuous Renal Replacement Therapy in Neonatal Hypoammonemia	1238
Key Points	1238
Key References	1238
References	1238.e1
208 Modified Ultrafiltration in Pediatric Heart Surgery	1238
Objectives	1238
Historical Background	1239
Inflammatory Response to Cardiopulmonary Bypass	1239
Modified Ultrafiltration	1240
Key Points	1244
Acknowledgments	1244
Key References	1244
References	1244.e1
209 Techniques and Machines for Pediatric Renal Replacement Therapy	1244
Objectives	1244
Modalities	1245
Prescription	1245
Studies on the Dose of Pediatric Continuous Renal Replacement Therapy	1246
Technical Aspects of Pediactric Continuous Renal Replacement Therapy	1246
Conclusion	1247
Key Points	1247
Key References	1247
References	1247.e1
210 Antibiotics in Critically Ill Newborns and Children	1247
Objectives	1247
Antibiotic Use in Critically Ill Newborns	1248
Epidemiology of Bacterial Infections in Newborns	1248
Empiric Therapy in the Newborn: Risks and Adverse Effects	1248
Drug Handling in the Neonatal Age: Theoretical Considerations	1248
Drug Absorption	1248
Volume of Distribution	1248
Clearance of Drugs	1248
Plasma Protein Binding	1249
Developmental Changes of Drug Metabolism	1249
Impact of Drugs in the Premature Kidney: A Complex Interplay and Risks for Renal Damage	1249
Premature Kidney: Complex Interplay	1249
Making the Right Choice: Help From Guidelines, Expert Opinion, and Practice	1250
Aminoglycosides	1250
Vancomycin	1250
Other Antibiotic Associations	1251
Resistant Bacteria	1251
Choosing the Right Dose: Not an Easy Task	1251
Adapting the Antibiotic Dose to Renal Function	1252
In Case of Renal Replacement Therapy: Modulation of Antibiotics	1252
Antibiotics in Dialysis: When to Decrease and When to Increase	1262
Intermittent Dialysis	1263
Peritoneal Dialysis	1263
Continuous Renal Replacement Therapy	1263
Key Points	1263
Key References	1263
References	1263.e1
29 Kidney Transplantation and Critical Care	1264
211 Patient Selection and Pretransplantation Care for Kidney Transplant Recipients	1264
Objectives	1264
Referring Patients for Kidney Transplantation	1264
Recipient Evaluation Process	1264
Evaluating Risks to Successful Transplantation	1266
Elderly Recipients	1266
Race and Ethnicity	1266
Obesity	1266
Recurrence of Primary Renal Disease After Transplantation	1266
Gastrointestinal Evaluation	1268
Cardiac Evaluation	1269
Malignancies	1269
Organ Allocation Systems	1269
Conclusion	1269
Key Points	1270
Key References	1270
References	1270.e1
212 Kidney Support and Perioperative Care in Kidney Transplantation	1270
Objectives	1270
Pretransplant Evaluation	1270
Immediate Postoperative Assessment	1271
Hemodynamic Status	1271
Respiratory Status	1272
Volume Status	1272
Cardiac Assessment	1273
Pain Control	1273
Electrolytes and Minerals	1273
Renal Function	1274
Calcium Phosphorus and Magnesium	1274
Dialysis Access	1274
Patient With Early Graft Dysfunction and Delayed Graft Function	1274
Indications for Dialysis in Patients with Delayed Graft Function	1276
Early Surgical Complications	1277
Renal Artery Thrombosis	1277
Renal Vein Thrombosis	1277
Other Surgical Complications	1278
Wound Infections	1278
Key Points	1278
Key References	1278
References	1278.e1
213 Acute Renal Failure in Kidney Transplant Recipients	1279
Objectives	1279
Causes and Risk Factors of Delayed Graft Function	1279
Risk Factors Related to the Donor	1280
Risk Factors Related to the Recipient	1281
Pathophysiology of Renal Ischemia-Reperfusion Injury	1281
Ischemia/Reperfusion Injury Enhances Allograft Immunogenicity	1281
Risk of Acute Rejection	1281
Risk of Long-Term Graft Dysfunction	1282
Strategies to Prevent Ischemia-Reperfusion Injury and Delayed Graft Function	1283
Preservation Solutions	1283
Recipient Fluid Management	1283
Immunosuppressive Management of Delayed Graft Function	1283
Allograft Acute Kidney Injury as a Template for Genomic Studies on Acute Kidney Injury	1284
Future Therapeutic Perspectives	1285
Key Points	1285
Key References	1285
References	1285.e1
30 Special Kidney Problems in the Intensive Care Unit	1286
214 Management of Chronic Kidney Disease and End-Stage Kidney Disease Patients in the Intensive Care Unit	1286
Objectives	1286
Pathophysiologic Relationship Between Chronic Kidney Diseases and Acute Kidney Injury	1286
Patients with Chronic Kidney Disease Who Develop Acute Kidney Injury	1287
Acute Kidney Injury Patients Toward Chronic Kidney Disease	1288
Chronic Kidney Disease and End-Stage Kidney Disease Patients Admitted in the Intensive Care Unit	1288
Clinical Pictures	1288
Cardiovascular Disease	1288
Infectious Processes	1288
Major Surgical Procedures	1289
Management	1289
Volume Status Control	1290
Electrolyte Control	1290
Dialysis Access and Vein Preservation	1290
Peritoneal Dialysis Catheters.	1290
Arteriovenous Fistulae and Grafts.	1290
Hemodialysis Catheters.	1290
Vein Preservation.	1290
Hemostasis	1290
Imaging	1290
Drug Use and Adjustment	1290
Anesthesia and Sedation.	1290
Diuretics.	1291
Antibiotics.	1291
Transition From Intermittent Hemodialysis or Peritoneal Dialysis to Continuous Renal Replacement Therapy	1291
Transition From Continuous Renal Replacement Therapy to Intermittent Hemodialysis or Peritoneal Dialysis	1291
Recovery From Acute Kidney Injury and Risk to Develop Chronic Kidney Disease	1292
Conclusion	1292
Key Points	1292
Key References	1292
References	1292.e1
215 Management of Patients with Diabetes in the Intensive Care Unit	1293
Objectives	1293
What Is Known and What Is Not Known	1293
Epidemiology and Burden of Illness	1293
Diabetic Kidney Disease: Kidneys at Risk	1293
Hyperfiltration: Missing Those at Risk	1293
Acute Kidney Injury	1294
Urinary Tract Infections	1294
Progressive Diabetic Renal Disease	1294
Metabolic Acidosis	1294
Drug-Induced Acidosis (Biguanides)	1294
Unique Problems: Type 4 Renal Tubular Acidosis	1295
Mixed Disorders	1295
Treatment	1295
General Principles	1295
Glycemic Control in Acute Care Settings	1295
Conclusion	1296
Key Points	1296
Key References	1296
References	1296.e1
216 Diagnosis and Management of Acute Kidney Injury in the Emergency Department	1296
Objectives	1296
Diagnostic Utility of Biomarkers	1298
Cystatin C	1298
Neutrophil Gelatinase-Associated Lipocalin	1298
Proenkephalin	1299
Tissue Inhibitor of Metalloproteinase-2 and Insulin-Like Growth Factor Binding Protein-7	1299
Management of Acute Kidney Injury in the Emergency Department	1299
Risk Assessment	1299
General Management of Acute Kidney Injury in the Emergency Department	1300
Prognostic Evaluation of Acute Kidney Injury in the Emergency Department	1300
Treatment of Acute Kidney Injury in the Emergency Department General Considerations	1300
Other Emergency Department Acute Kidney Injury Presentations	1301
Key Points	1301
Key References	1301
References	1301.e1
217 Anticancer Drugs and the Kidney	1302
Objectives	1302
Conventional Chemotherapy	1302
Cisplatin	1302
Carboplatin	1302
Methotrexate	1302
Pemetrexed	1303
Gemcitabine	1303
Mitomycin	1303
Ifosfamide	1303
Bisphosphonates	1303
Targeted and Biologic Therapy	1303
Antiangiogenic Therapy	1304
Immunotherapy	1304
Others	1304
Cancer Chemotherapy in Kidney Disease	1304
Conclusion	1304
Key Points	1305
Key References	1305
References	1305.e1
218 Antiinflammatory Drugs and the Kidney	1306
Objectives	1306
Mechanisms of Renal Damage Induced by Nonsteroidal Antiinflammatory Drugs	1306
Hemodynamically Mediated Acute Kidney Injury	1306
Nephrotoxic Acute Kidney Injury	1307
Clinical Disorders Associated With the Use of Nonsteroidal Antiinflammatory Drugs	1307
Acute Kidney Injury	1307
Acute Interstitial Nephritis	1308
Glomerular Disease	1308
Worsening of Chronic Kidney Disease (Acute-on-Chronic Renal Failure)	1308
Salt and Water Retention	1308
Hypertension	1308
Hyperkalemia	1308
Nonsteroidal Antiinflammatory Drug Overdose	1308
Conclusion	1309
Key Points	1309
Key References	1309
References	1309.e1
219 Calcineurin Inhibitors and Other Immunosuppressive Drugs and the Kidney	1309
Objectives	1309
Glucocorticoids	1309
Azathioprine	1310
Mycophenolic Acid	1310
Methotrexate	1310
Calcineurin Inhibitors	1310
Monoclonal Antibodies	1312
Belatacept	1312
Intravenous Immune Globulin	1313
Conclusion	1313
Key Points	1313
Key References	1313
References	1313.e1
220 Alternative Medicine and Chinese Herbs and the Kidney	1313
Objectives	1313
Definitions	1314
General Treatment Principles of Traditional Chinese Medicine	1314
Mechanisms of Nephrotoxicity of Herbal Medicine	1315
Herbs With Known Toxicity	1315
Herbs Containing Aristolochic Acid	1315
Licorice (Glycyrrhiza glabra)	1315
Ma Huang	1316
Flavonoid Drugs	1316
Use of Wrong Preparation or Substitute	1317
Contaminants and Adulterants	1317
Heavy Metals	1317
Drug Interactions	1317
Other Alternative Therapies	1317
Body Massage	1317
Mesotherapy	1317
Chelation Therapy	1318
Therapeutic Roles of Alternative Therapies in Kidney Disease	1318
Cordyceps sinensis	1318
Astragalus	1319
Tripterygium	1319
Rhubarb	1319
Radix bupleuri	1319
Others	1319
Key Points	1319
Key References	1319
References	1319.e1
221 Environment, Smoking, Obesity, and the Kidney	1320
Objectives	1320
Environment	1320
Environmental Nephrotoxins	1320
Conclusion	1320
Smoking	1320
Smoking Habit and the Intensive Care Unit Patient	1320
Smoking as a Renal Risk Factor	1321
Potential Mechanisms of Smoking-Related Nephrotoxicity	1321
Conclusion	1322
Obesity	1322
Obesity and the Intensive Care Unit Patient	1322
Obesity: An Independent Risk Factor for Renal Damage	1322
Pathophysiologic Mechanisms of Obesity-Related Renal Damage	1322
Management of Kidney Disease in the Obese Patient in the Intensive Care Unit	1323
Conclusion	1324
Key Points	1324
Key References	1324
References	1324.e1
222 Lead and Heavy Metals and the Kidney	1324
Objectives	1324
Mechanism of Heavy Metals Toxicity	1324
Therapeutic Approach	1325
Lead	1325
Source of Exposure	1325
Index	1362
A	1362
B	1368
C	1370
D	1377
E	1379
F	1381
G	1383
H	1384
I	1388
J	1390
K	1390
L	1391
M	1393
N	1395
O	1397
P	1397
Q	1401
R	1401
S	1404
T	1407
U	1409
V	1410
W	1411
Y	1411
Z	1411
Inside Back Cover	ibc1
Color plate	S30-1

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