SPEC – Comprehensive Clinical Nephrology, 5e eBook (12-Month Access)

Richard J. Johnson; John Feehally; Jurgen Floege

BOOK

SPEC – Comprehensive Clinical Nephrology, 5e eBook (12-Month Access)

Richard J. Johnson | John Feehally | Jurgen Floege

(2014)

Additional Information

Book Details

ISBN: 978-0-323-24287-5
Edition: 5
Language: English
Pages: 1320
Subjects: Clinical & internal medicine
Diseases & disorders
Renal medicine & nephrology
Radiology

Abstract

Consult this title on your favorite e-reader, conduct rapid searches, and adjust font sizes for optimal readability.

The right amount of basic science and practical clinical guidance assists in making efficient and informed decisions.

Extensive updates on key topics keep you at the forefront of the field.

New chapters on glomerulonephritis associated with complement disorders, interventional treatments for hypertension, renal disease and cancer, and epidemiology and prognostic impact of acute kidney injury.

Over 1,500 color illustrations highlight key topics and detail pathogenesis for a full range of kidney conditions and clinical management.

Hundreds of color coded algorithms promote quick reference and to help you retain concepts.

Over 400 NEW self-assessment questions available at Expert Consult.

Section Title	Page	Action	Price
Front Cover	cover
Inside Front Cover	ifc1
Comprehensive Clinical Nephrology, 5/e	i
Copyright Page	iv
Dedication	v
Contributors	vi
Preface	xvi
Table Of Contents	xvii
I Essential Renal Anatomy and Physiology	1
1 Renal Anatomy	2
Structure of the Kidney	2
Nephrons	2
Collecting Ducts	2
Microvasculature	2
Nephron	3
Renal Glomerulus (Renal Corpuscle)	3
Glomerular Basement Membrane	4
Mesangium	6
Mesangial Cells	6
Mesangial Matrix	6
Endothelium	6
Visceral Epithelium (Podocytes)	6
Parietal Epithelium	7
Filtration Barrier	7
Stability of Glomerular Tuft	8
Renal Tubule	8
Proximal Tubule	8
Loop of Henle	9
Distal Convoluted Tubule	10
Collecting Duct System	10
Collecting Ducts	10
Juxtaglomerular Apparatus	10
Renal Interstitium	11
References	12
2 Renal Physiology	14
Glomerular Structure and Ultrastructure	14
Glomerular Filtration Rate	14
Measurement of Renal Plasma Flow	15
Autoregulation of Renal Blood Flow and Glomerular Filtration Rate	15
Tubular Transport	17
Passive Transport	17
Active Transport	17
Transport in Specific Nephron Segments	18
Proximal Tubule	19
Loop of Henle	19
Distal Nephron	19
Glomerulotubular Balance	21
Countercurrent System	21
Role of Urea	23
Vasa Recta	23
Renal Medullary Hypoxia	23
Vasopressin (Antidiuretic Hormone) and Water Reabsorption	23
Integrated Control of Renal Function	24
Renal Interstitial Hydrostatic Pressure and Nitric Oxide	24
Renal Sympathetic Nerves	25
Renin-Angiotensin-Aldosterone System	25
Eicosanoids	25
Atrial Natriuretic Peptide	25
Endothelins	25
Purines	26
References	26
II Investigation of Renal Disease	29
3 Assessment of Renal Function	30
Glomerular Filtration Rate	30
Measurement of the Glomerular Filtration Rate	30
Concept of Clearance	30
Urinary Clearance	30
Plasma Clearance	30
Exogenous Filtration Markers	30
Endogenous Filtration Markers	31
Estimated Glomerular Filtration Rate from Plasma Levels	31
Creatinine	31
Metabolism and Excretion	31
Creatinine Assay	32
Estimated Glomerular Filtration Rate from Serum Creatinine	33
Cockcroft-Gault Formula	33
Modification of Diet in Renal Disease Study	33
Chronic Kidney Disease Epidemiology Collaboration	35
Urea	35
Cystatin C	35
Metabolism and Excretion	35
Cystatin C Assay	36
Estimated Glomerular Filtration Rate from Serum Cystatin C	36
Other Filtration Markers	37
Clinical Application of Estimated Glomerular Filtration Rate	37
Chronic Kidney Disease	37
Acute Kidney Injury	37
Markers of Tubular Damage	38
References	38
4 Urinalysis	39
Definition	39
Urine Collection	39
Physical Characteristics	39
Color	39
Turbidity	39
Odor	40
Relative Density	40
Chemical Characteristics	40
pH	40
Hemoglobin	41
Glucose	41
Protein	41
Albumin Dipstick	41
24-Hour Protein Excretion	41
Protein-Creatinine Ratio on Random Urine Sample	41
Specific Proteins	42
Microalbuminuria	42
Tubular Proteins	42
Bence Jones Proteinuria	42
Selectivity of Proteinuria	42
Leukocyte Esterase	42
Nitrites	42
Bile Pigments	42
Ketones	42
Urine Microscopy	42
Methods	42
Cells	43
Erythrocytes	43
Leukocytes	43
Renal Tubular Epithelial Cells	43
Transitional Epithelial Cells	43
Squamous Epithelial Cells	43
Lipids	43
Casts	44
Crystals	47
Common Crystals	47
Uric Acid Crystals and Amorphous Urates	47
Calcium Oxalate Crystals	47
Brushite (Calcium Phosphate Crystals) and Amorphous Phosphates	47
Struvite (Triple Phosphate) Crystals	47
Pathologic Crystals	47
Cholesterol Crystals	47
Cystine Crystals	47
2,8-Dihydroxyadenine Crystals	47
Crystals Caused by Drugs	47
Other Crystals	47
Clinical Significance of Crystals	47
Organisms	49
Contaminants	49
Interpretation of Urine Sediment Findings	49
Nephrotic Syndrome	49
Nephritic Syndrome	49
Acute Tubular Necrosis	50
Urinary Tract Infection	50
BK Virus Infection	50
Urologic Diseases	50
Nonspecific Urinary Abnormalities	50
Automated Analysis of Urine Sediment	50
References	51
5 Imaging	53
Ultrasound	53
Kidney Size	53
Renal Echo Pattern	53
Renal Cysts	53
Simple Cysts	53
Complex Cysts	53
Bladder	54
Renal Vasculature	54
Renal Artery Duplex Scanning	54
Contrast-Enhanced and Three-Dimensional Ultrasound	57
Plain Radiography and Intravenous Urography	57
Renal Calcification	58
Intravenous Contrast Urography	58
Kidneys	59
Pelvicalyceal System	59
Ureters	59
Bladder	59
Retrograde Pyelography	59
Antegrade Pyelography	59
Ileal Conduits	59
Cystography	59
Computed Tomography	60
Tissue Density	60
Contrast-Enhanced and Noncontrast Computed Tomography	61
Computed Tomographic Angiography	62
Limitations of Computed Tomography	62
Magnetic Resonance Imaging	62
Contrast-Enhanced Magnetic Resonance Imaging	63
Magnetic Resonance Urography	63
Magnetic Resonance Angiography	63
Disadvantages of Magnetic Resonance Imaging	64
Incidental Findings	64
Measurement of Glomerular Filtration Rate	65
Angiography	65
Renal Venography	66
Nuclear Medicine	66
Glomerular Filtration Agents	66
Tubular Secretion Agents	67
Tubular Retention Agents	67
Renogram	67
Cortical Imaging	67
Vesicoureteral Reflux	68
Renal Transplant	68
Positron Emission Tomography	68
Molecular Imaging	68
Radiologic Contrast Agents	68
X-ray Contrast Agents	68
Contrast-Induced Nephropathy	69
Magnetic Resonance Contrast Agents	69
References	69
6 Renal Biopsy	71
Definition	71
Indications for Renal Biopsy	71
Nephrotic Syndrome	71
Acute Kidney Injury	71
Systemic Disease Associated with Renal Dysfunction	71
Renal Transplant Dysfunction	72
Non-nephrotic Proteinuria	72
Isolated Microhematuria	72
Unexplained Chronic Kidney Disease	72
Familial Renal Disease	72
Role of Repeat Renal Biopsy	72
Value of Renal Biopsy	73
Biopsy Adequacy	73
Is Renal Biopsy a Necessary Investigation?	73
Prebiopsy Evaluation	73
Contraindications to Renal Biopsy	74
Renal Biopsy Technique	74
Percutaneous Renal Biopsy	74
Native Renal Biopsy	74
Renal Transplant Biopsy	76
Postbiopsy Monitoring	76
Alternatives to the Percutaneous Approach	76
Transvenous (Transjugular or Transfemoral) Renal Biopsy	76
Open Renal Biopsy	77
Laparoscopic Renal Biopsy	77
Complications of Renal Biopsy	77
Pain	77
Hemorrhage	77
Arteriovenous Fistula	77
Other Complications	77
Death	77
References	78
III Fluid and Electrolyte Disorders	79
7 Disorders of Extracellular Volume	80
Extracellular Fluid Compartment	80
Regulation of Extracellular Fluid Homeostasis	80
Afferent (Sensor) Limb	80
Efferent (Effector) Limb	81
Sympathetic Nervous System	81
Renin-Angiotensin-Aldosterone System	81
Prostaglandins	81
Arginine Vasopressin	81
Natriuretic Peptides	82
Other Hormones	82
Extracellular Fluid Volume Contraction	82
Extrarenal Causes	82
Gastrointestinal Losses	82
Dermal Losses	82
Third-Space Sequestration	82
Hemorrhage	82
Renal Losses	82
Diuretic Use	83
Genetic and Acquired Tubular Disorders	83
Hormonal and Metabolic Disturbances	83
Renal Water Loss	83
Clinical Manifestations	83
Laboratory Tests	83
Therapy for Extracellular Volume Contraction	84
Extracellular Fluid Volume Expansion	84
Pathogenesis	84
Capillary Hemodynamic Disturbances	84
Renal Sodium Retention	85
Primary Renal Sodium Retention	85
Renal Sodium Retention as Compensatory Response to Effective Arterial Volume Depletion	85
Pathophysiology of Arterial Underfilling	85
Renal Response to Arterial Underfilling	85
Sodium and Water Retention in Cardiac Failure	86
Sodium and Water Retention in Cirrhosis	87
Sodium and Water Retention in Nephrotic Syndrome	87
Drug-Induced Edema	88
Idiopathic Edema	88
Sodium and Water Retention in Pregnancy	88
Clinical Manifestations	89
Diagnostic and Therapeutic Approach to Extracellular Volume Expansion	89
Diuretics	89
Principles of Action	89
Adverse Effects	89
Diuretic Tolerance and Resistance	90
Loop Diuretics	90
Distal Convoluted Tubule Diuretics	92
Collecting Duct Diuretics	92
Proximal Tubule Diuretics	92
Osmotic Diuretics	92
References	92
8 Disorders of Water Metabolism	94
Physiology of Water Balance	94
Vasopressin	94
Osmotic Stimuli for Vasopressin Release	94
Nonosmotic Stimuli for Vasopressin Release	94
Mechanism of Vasopressin Action	94
Thirst and Water Balance	94
Quantitation of Renal Water Excretion	95
Serum Sodium Concentration, Osmolality, and Tonicity	96
Estimation of Total Body Water	96
Hyponatremic Disorders	97
Etiology and Classification of Hyponatremia	97
Hypovolemia: Hyponatremia Associated with Decreased Total Body Sodium	97
Gastrointestinal and Third-Space Sequestered Losses	97
Diuretics	97
Salt-Losing Nephropathy	98
Mineralocorticoid Deficiency	98
Osmotic Diuresis	98
Cerebral Salt Wasting	98
Hypervolemia: Hyponatremia Associated with Increased Total Body Sodium	98
Congestive Heart Failure	98
Hepatic Failure	99
Nephrotic Syndrome	99
Advanced Chronic Renal Impairment	99
Euvolemia: Hyponatremia Associated with Normal Total Body Sodium	99
Glucocorticoid Deficiency	99
Hypothyroidism	99
Psychosis	99
Postoperative Hyponatremia	100
Exercise-Induced Hyponatremia	100
Drugs Causing Hyponatremia	100
Syndrome of Inappropriate Antidiuretic Hormone Secretion	100
Clinical Manifestations of Hyponatremia	101
Cerebral Edema	101
Osmotic Demyelination	102
Treatment of Hyponatremia	102
Acute Symptomatic Hyponatremia	102
Chronic Symptomatic Hyponatremia	102
Chronic “Asymptomatic” Hyponatremia	103
Fluid Restriction	103
Maneuvers that Increase Solute Excretion	103
Pharmacologic Inhibition of Vasopressin	104
Hypovolemic Hyponatremia	104
Hypervolemic Hyponatremia	104
Congestive Heart Failure	104
Cirrhosis	104
Hypernatremic Disorders	105
Etiology and Classification of Hypernatremia	105
Hypovolemia: Hypernatremia Associated with Low Total Body Sodium	105
Hypervolemia: Hypernatremia Associated with Increased Total Body Sodium	105
Euvolemia: Hypernatremia Associated with Normal Body Sodium	106
Diabetes Insipidus	106
Central Diabetes Insipidus	106
Clinical Features	106
Causes	107
Differential Diagnosis	107
Treatment	107
Congenital Nephrogenic Diabetes Insipidus	107
Acquired Nephrogenic Diabetes Insipidus	107
Chronic Kidney Disease	107
Electrolyte Disorders	107
Pharmacologic Agents	108
Sickle Cell Anemia	108
Dietary Abnormalities	108
Gestational Diabetes Insipidus	108
Clinical Manifestations of Hypernatremia	108
Treatment of Hypernatremia	108
References	109
9 Disorders of Potassium Metabolism	111
Normal Physiology of Potassium Metabolism	111
Potassium Intake	111
Potassium Distribution	111
Renal Potassium Handling with Normal Renal Function	112
Renal Potassium Handling in Chronic Kidney Disease	113
Hypokalemia	114
Epidemiology	114
Clinical Manifestations	114
Cardiovascular	115
Hormonal	115
Muscular	115
Renal	115
Etiology	115
Pseudohypokalemia	115
Redistribution	115
Nonrenal Potassium Loss	115
Renal Potassium Loss	115
Medications	115
Endogenous Hormones	116
Genetic Causes	116
Magnesium Depletion	116
Intrinsic Renal Defect	116
Bicarbonaturia	116
Diagnostic Evaluation	116
Treatment	116
Hyperkalemia	118
Epidemiology	118
Clinical Manifestations	118
Etiology	118
Pseudohyperkalemia	119
Redistribution	119
Excess Intake	119
Impaired Renal Potassium Secretion	120
Specific Medicine	120
Intrinsic Renal Defect	120
Distinguishing Between Renal and Nonrenal Mechanisms of Hyperkalemia	120
Treatment	120
Acute Therapy	120
Blocking Cardiac Effects	121
Cellular Potassium Uptake	121
Potassium Removal	122
Chronic Treatment	122
References	123
10 Disorders of Calcium, Phosphate, and Magnesium Metabolism	124
Calcium Homeostasis and Disorders of Calcium Metabolism	124
Distribution of Calcium in the Organism	124
Intestinal, Skeletal, and Renal Handling of Calcium	124
Hypercalcemia	128
Causes of Hypercalcemia	128
Malignant Neoplasias	128
Primary Hyperparathyroidism	129
Jansen Disease	129
Familial Hypocalciuric Hypercalcemia	129
Other Endocrine Causes	129
Other Causes	129
Clinical Manifestations	129
Diagnosis	129
Treatment	130
Hypocalcemia	130
Hypocalcemia Associated with Hyperphosphatemia	130
Hypocalcemia Associated with Hypophosphatemia	131
Clinical Manifestations	131
Laboratory and Radiographic Signs	131
Treatment	131
Phosphate Homeostasis	132
Distribution of Phosphate in the Organism	132
Hyperphosphatemia	133
Causes of Hyperphosphatemia	133
Acute Kidney Injury	133
Chronic Kidney Disease	134
Lytic States	134
Treatment-Induced Hyperphosphatemia	134
Hypoparathyroidism	134
Chronic Hypocalcemia	134
Acromegaly	134
Familial Tumoral Calcinosis	135
Respiratory Alkalosis with Prolonged Hyperventilation	135
Clinical Manifestations	135
Treatment	135
Hypophosphatemia	135
Causes of Hypophosphatemia	136
Inherited Forms of Hypophosphatemia	136
Autosomal Dominant Hypophosphatemic Rickets	136
X-Linked Hypophosphatemic Rickets	136
Autosomal Recessive Hypophosphatemic Rickets	136
Fanconi Syndrome and Proximal Renal Tubular Acidosis	136
Vitamin D–Dependent Rickets	136
Distal Renal Tubular Acidosis (Type 1)	136
Acquired Forms of Hypophosphatemia	136
Alcoholism	137
Hyperparathyroidism	137
Post-Transplant Hypophosphatemia	137
Acute Respiratory Alkalosis	137
Diabetic Ketoacidosis	137
Total Parenteral Nutrition	137
Oncogenic Hypophosphatemic Osteomalacia	137
Drug-Induced Hypophosphatemia	137
Clinical Manifestations	137
Treatment	137
Magnesium Homeostasis and Disorders of Magnesium Metabolism	137
Distribution of Magnesium in the Organism	137
Intestinal and Renal Handling of Magnesium	138
Hypermagnesemia	138
Clinical Manifestations	138
Treatment	138
Hypomagnesemia and Magnesium Deficiency	139
Clinical Manifestations	140
Treatment	140
References	140
11 Normal Acid-Base Balance	142
Definition	142
Net Acid Production	142
Buffer Systems in Regulation of pH	142
Respiratory System in Regulation of pH	142
Renal Regulation of pH	142
Renal Transport Mechanisms of Hydrogen and Bicarbonate Ions	143
Glomerulus	143
Proximal Tubule	143
Thick Ascending Limb of Henle Loop	144
Thick Distal Nephron	144
Net Acid Excretion	145
Ammonia Metabolism	146
Regulation of Renal Acidification	147
Blood pH	147
Mineralocorticoids, Distal Sodium Delivery, and Extracellular Fluid Volume	147
Plasma Volume	148
Potassium	148
References	148
12 Metabolic Acidosis	149
Definition	149
Non–Anion Gap (Normal Anion Gap) Metabolic Acidosis	149
Metabolic Acidosis of Renal Origin	150
Proximal Renal Tubular Acidosis (Type 2)	150
Hypokalemic Distal Renal Tubular Acidosis (Type 1)	152
Hyperkalemic Distal Renal Tubular Acidosis (Type 4)	153
Renal Tubular Acidosis in Chronic Kidney Disease	154
Metabolic Acidosis of Extrarenal Origin	154
Diarrhea	154
Ileal Conduits	155
Anion Gap Metabolic Acidosis	155
Lactic Acidosis	155
Diabetic Ketoacidosis	156
d-Lactic Acidosis	156
Starvation Ketosis	156
Alcoholic Ketoacidosis	156
Ethylene Glycol and Methanol Intoxications	157
Salicylate	157
Pyroglutamic Acidosis	158
Alkali Treatment of Metabolic Acidosis	158
References	159
13 Metabolic Alkalosis	160
Definition	160
Bicarbonate Transport in the Kidney	160
Pathophysiology of Metabolic Alkalosis	160
Secondary Stimulation of Collecting Duct Ion Transport	160
Chloride Depletion	160
Potassium Depletion	162
Primary Stimulation of Collecting Duct Ion Transport	162
Exogenous Alkali	162
Secondary Response to Alkalemia Induced by Bicarbonate Retention	162
Etiology	163
Secondary Stimulation of Collecting Duct Ion Transport	164
Vomiting or Nasogastric Drainage	164
Diuretic Administration	164
Genetic Impairment of Cl−-Linked Na+ Transport	164
Recovery from Chronic Hypercapnia	164
Congenital Chloridorrhea	164
Other Causes of Excessive Chloride Losses	164
Severe Potassium Deficiency	164
Primary Stimulation of Collecting Duct Ion Transport	164
Mineralocorticoid Excess	165
Apparent Mineralocorticoid Excess Syndromes	165
Alkali Administration	165
Other Causes	166
Clinical Manifestations	166
Diagnosis	166
Treatment	167
Chloride Depletion Alkalosis	167
Corticosteroid and Apparent Corticosteroid-Induced Metabolic Alkalosis	167
Alkali Ingestion	167
Special Problems in Management	167
References	168
14 Respiratory Acidosis, Respiratory Alkalosis, and Mixed Disorders	169
Respiratory Acidosis (Primary Hypercapnia)	169
Definition	169
Etiology and Pathogenesis	169
Secondary Physiologic Response	169
Clinical Manifestations	169
Neurologic Symptoms	170
Cardiovascular Symptoms	170
Renal Symptoms	170
Diagnosis	170
Treatment	170
Respiratory Alkalosis (Primary Hypocapnia)	172
Definition	172
Etiology and Pathogenesis	172
Secondary Physiologic Response	173
Clinical Manifestations	174
Diagnosis	175
Treatment	175
Mixed Acid-Base Disturbances	176
Definition	176
Etiology and Pathogenesis	176
Metabolic Acidosis and Respiratory Acidosis	176
Metabolic Alkalosis and Respiratory Alkalosis	176
Metabolic Alkalosis and Respiratory Acidosis	176
Metabolic Acidosis and Respiratory Alkalosis	176
Metabolic Acidosis and Metabolic Alkalosis	178
Mixed Metabolic Acidosis	178
Mixed Metabolic Alkalosis	178
Triple Disorders	178
Clinical Manifestations	179
Diagnosis	179
Treatment	181
References	181
IV Glomerular Disease	183
15 Introduction to Glomerular Disease:	184
Definition	184
Clinical Evaluation of Glomerular Disease	184
History	184
Physical Examination	184
Laboratory Studies	184
Imaging	185
Renal Biopsy	186
Asymptomatic Urine Abnormalities	186
Asymptomatic Microhematuria	186
Pathogenesis	186
Evaluation	186
Asymptomatic Non-nephrotic Proteinuria	187
Overflow Proteinuria	187
Tubular Proteinuria	187
Glomerular Proteinuria	188
Functional Proteinuria	188
Orthostatic Proteinuria	188
Fixed Non-nephrotic Proteinuria	188
Asymptomatic Proteinuria with Hematuria	188
Macrohematuria	188
Nephrotic Syndrome	188
Definition	188
Etiology	189
Hypoalbuminemia	189
Edema	190
Metabolic Consequences of Nephrotic Syndrome	190
Negative Nitrogen Balance	190
Hypercoagulability	190
Hyperlipidemia and Lipiduria	191
Other Metabolic Effects of Nephrotic Syndrome	191
Infection	192
Acute and Chronic Changes in Renal Function	192
Acute Kidney Injury	192
Chronic Kidney Disease	192
Nephritic Syndrome	193
V Diabetic Nephropathy	353
30 Pathogenesis, Clinical Manifestations, and Natural History of Diabetic Nephropathy	354
Definitions	354
Pathogenesis of Diabetic Nephropathy	354
Genetic and Environmental Factors	354
Hemodynamic Changes	354
Renal Hypertrophy	355
Mesangial Expansion and Nodule Formation	356
Inflammation and Diabetic Nephropathy	356
Mechanisms Underlying Proteinuria	356
Tubulointerstitial Fibrosis and Tubular Atrophy	357
Hyperglycemia and Diabetic Nephropathy	358
Role of Glucose Control	358
Protein Kinase C Pathway	358
Advanced Glycation End Products Pathway	358
Polyol Pathway	360
Hexosamine Pathway	360
Adenosine Monophosphate–Activated Protein Kinase Pathway	360
Renin-Angiotensin-Aldosterone System and Diabetic Nephropathy	360
Uric Acid and Fructose	360
Epidemiology	360
Clinical Manifestations and Natural History	361
Obesity, Metabolic Syndrome, and Renal Disease	361
Evolution of Diabetic Nephropathy	362
Hypertension and Diabetic Nephropathy	362
Associated Extrarenal Microvascular and Macrovascular Complications	362
Survival in Patients with Diabetic Nephropathy	363
Renal Pathology	363
Diagnosis and Differential Diagnosis	365
Measurement of Albuminuria or Proteinuria	366
Measurement of Blood Pressure	368
Measurement of Serum Creatinine and Estimation of Glomerular Filtration Rate	369
Differential Diagnosis	369
Indications for Renal Biopsy	369
Approach to the Diabetic Patient with Impaired Renal Function	369
References	370
31 Prevention and Treatment of Diabetic Nephropathy	372
Prevention of Diabetic Nephropathy	372
Glycemic Control	372
Blood Pressure Control	373
Renin-Angiotensin System Blockade in Prevention	374
Treatment of Dyslipidemia	374
Nonpharmacologic Interventions	374
Treatment of Diabetic Patients with Microalbuminuria or Overt Nephropathy	374
Antihypertensive Treatment	375
Renin-Angiotensin System Blockade in Treatment	375
Type 1 Diabetic Patients	375
Type 2 Diabetic Patients	376
Combination Therapy with Renin-Angiotensin System Antagonists	376
Dosing and Adverse Effects Associated with ACE Inhibitors and ARBs	376
Other Antihypertensive and Antiproteinuric Agents	376
Diuretics and Low Sodium Intake	376
Calcium Channel Blockers	377
β-Blockers	377
Glycemic Control	377
Treatment of Dyslipidemia	377
Nonpharmacologic Interventions	377
Emerging Treatments for Diabetic Nephropathy	378
References	379
32 Management of the Diabetic Patient with Chronic Kidney Disease	381
Hyperglycemia	381
Assessment	381
Treatment	381
Biguanides	381
Sulfonylureas	383
Thiazolidinediones	383
Meglinitides	383
Glucagon-like Peptide-1 Analogues	383
Gliptins	383
Insulin	384
Hypertension	384
Hyperlipidemia	385
Anemia	385
Antiplatelet Agents	385
Bone Disease	386
Extrarenal Complications of Diabetes Mellitus	386
Diet and Malnutrition	386
Prevention and Treatment of Cardiac Disease	386
Dialysis and Transplantation	387
Hemodialysis	387
Peritoneal Dialysis	388
References	388
VI Hypertension	391
33 Normal Blood Pressure Control and the Evaluation of Hypertension	392
Normal Blood Pressure Control	392
Definition of Hypertension	395
Blood Pressure in Relation to Morbidity and Mortality	395
Elevation of Blood Pressure by Arbitrary Cutoff Points	395
Threshold of Therapeutic Benefit	396
Operational Definitions	396
Special Definitions	396
Prehypertension (High-normal or Borderline Hypertension)	396
White Coat Hypertension	399
Masked Hypertension	399
Sustained Hypertension	399
Pseudohypertension	399
Isolated Systolic Hypertension	399
Resistant Hypertension	399
Hypertensive Urgencies and Emergencies	399
Hypertension in Children and Adolescents	400
Hypertension in Pregnancy	400
Classification by Cause of Hypertension	400
Evaluation of Hypertension	400
Blood Pressure Measurement	400
Variability of Blood Pressure	402
Wake-Sleep Cycle and Office Versus Home Blood Pressure	402
Home and Ambulatory Blood Pressure	403
Risk Factors for Hypertension	403
Evaluation for Primary Versus Secondary Hypertension	403
References	406
34 Primary Hypertension	407
Definition	407
Etiology and Pathogenesis	407
Genetic (Polygene) Hypothesis	407
Congenital (Low Nephron Number) Hypothesis	408
Acquired Renal Injury Hypothesis	409
Role of Renal Injury in Sodium Retention	409
How Does Salt Retention Lead to Hypertension?	409
Pathogenic Mechanisms Driving the Current Epidemic of Hypertension	410
Epidemiology	410
Clinical Manifestations	411
Pathology	412
Diagnosis	412
Natural History	412
Kidney Disease	413
Effect of Antihypertensive Therapy on Natural History of Hypertensive Cardiovascular Disease and Kidney Disease Progression	414
Can Primary Hypertension Spontaneously Remit?	415
References	415
35 Nonpharmacologic Prevention and Treatment of Hypertension	417
Prevention	417
Weight Loss	417
Physical Activity	417
Exercise Training Dose Response	418
Mechanisms	418
Antihypertensive Medication and Guidelines for Exercise	418
Diet	418
Salt Intake	418
Potassium Intake	421
Calcium and Dairy Food Intake	421
Magnesium Intake, Other Micronutrients and Bioactive Food Components	421
Dietary Fats and Sugars	422
Dietary Approaches to Stop Hypertension (DASH) Diet	422
Smoking	423
Alcohol	423
Caffeine	423
Psychological Stress	423
Adopting Lifestyle Modifications	423
References	423
36 Pharmacologic Treatment of Hypertension	425
Defining Who Should Receive Pharmacologic Treatment	425
Blood Pressure Thresholds for Intervention (Office Blood Pressure)	425
Clinical Dilemma of End-Organ Damage and “Normal” Blood Pressure	425
Blood Pressure Thresholds for Intervention (Ambulatory and Home Blood Pressure Monitoring)	425
What are the Blood Pressure Treatment Goals?	425
Guide to Selection of Antihypertensive Agents	428
Key Principles from Clinical Trials	428
Selection of Drug Therapy	428
Thiazide and Thiazide-like Diuretics	429
Potassium-Retaining Diuretics (e.g., Spironolactone, Amiloride, Eplerenone)	430
β-Adrenoceptor Blocking Drugs	431
Calcium Channel Blockers	431
Blockade of Renin-Angiotensin System	431
Angiotensin-Converting Enzyme Inhibitors	431
Angiotensin Receptor Blockers	432
Direct Renin Inhibitor	432
α-Adrenergic Blocking Drugs	432
Centrally Acting Sympatholytic Drugs	432
Direct Vasodilators	433
Treatment Strategies	433
Initial Drug Therapy	433
Choice of Initial Therapy	433
Combination Therapy for Controlling Blood Pressure	434
Initial Therapy with a Two-Drug Combination	434
Combining Renin-Angiotensin-Aldosterone System Blockade?	435
Resistant Hypertension	436
Medication to Reduce Cardiovascular Risk	436
Follow-up	436
Withdrawal of Therapy	436
Indications for Specialist Referral	436
Hypertension in People of Black African Origin	436
Hypertension in Older People	437
References	437
37 Evaluation and Treatment of Hypertensive Urgencies and Emergencies	439
Etiology and Pathogenesis	439
Epidemiology	440
Diagnostic Evaluation	441
Treatment	441
General Principles for Managing Hypertensive Emergencies	441
Specific Aspects of Antihypertensive Drug Use for Hypertensive Emergencies	444
Treatment of Hypertensive Urgencies	445
References	445
38 Interventional Treatments for Resistant Hypertension	447
Pathogenesis	447
Sympathetic Nervous System in Hypertension and Cardiovascular Disease	447
Renal Efferent Sympathetic Activity	447
Renal Afferent Sympathetic Activity	447
Carotid Baroreflex Sensitivity	447
Surgical Sympathetic Denervation	447
Percutaneous and Minimally Invasive Approaches to Renal Sympathetic Denervation	447
Published Experience with Percutaneous Renal Sympathetic Denervation	448
Symplicity Hypertension 1 Study	448
Symplicity Hypertension 2 Study	449
Impact on Renal Function: Studies in Patients with Hypertension and Renal Failure	449
Safety with Percutaneous Renal Sympathetic Denervation	450
Ongoing Percutaneous Renal Denervation Studies: Symplicity Hypertension 3 Study	450
Novel Approaches to Percutaneous Renal Denervation	450
Radiofrequency Ablation	450
Ultrasound	450
Baroreflex Activation Therapy	450
DEBUT Study	451
Rheos Pivotal Trial	452
Ongoing Studies	452
References	452
39 Renovascular Hypertension and Ischemic Nephropathy	453
Definition and Etiology	453
Pathophysiology of Renovascular Hypertension	453
Atherosclerotic Renovascular Disease	455
Epidemiology	455
Relationship to “Ischemic” Renal Disease	456
Clinical Manifestations	457
Renovascular Hypertension	457
Ischemic Renal Disease	458
Renal Impairment in Patients with Renovascular Hypertension or in Atherosclerotic Age Range	458
Acute Kidney Injury After Starting Antihypertensives/RAAS Blockade	458
“Flash” Pulmonary Edema	458
Oligoanuric Acute Superimposed on Chronic Kidney Disease	458
Incidental Renal Artery Stenosis	459
Natural History	459
Risk of Mortality	459
Fibromuscular Dysplasia	459
Epidemiology	459
Pathophysiology	459
Clinical Manifestations	461
Natural History	461
Diagnosis of Renovascular Hypertension	461
Treatment of Renovascular Disease	463
Medical Therapy	463
Renal Revascularization	464
Percutaneous Transluminal Renal Angioplasty for Fibromuscular Dysplasia	464
Atherosclerotic Disease: Endovascular Stents	465
Surgical Revascularization	466
Realistic Outcomes and Controversies with Renal Revascularization	466
Integrated Approach to Treating Renovascular Disease	467
References	468
40 Endocrine Causes of Hypertension:	470
Etiology and Pathogenesis	470
Epidemiology	470
Clinical Manifestations	471
Pathology	472
Diagnosis and Differential Diagnosis	473
Natural History	475
Treatment	475
References	476
41 Endocrine Causes of Hypertension	478
Cushing Syndrome	478
Definition	478
Etiology, Pathogenesis, and Epidemiology	478
Clinical Manifestations	479
Differential Diagnosis	479
Diagnosis	479
Treatment and Prognosis	480
Pheochromocytoma	480
Definition	480
Etiology, Pathogenesis, and Epidemiology	480
Clinical Manifestations	480
Diagnosis	481
Treatment	481
Adrenal Incidentaloma	482
Definition and Epidemiology	482
Management	482
Renin-Secreting Tumor	483
Definition	483
Etiology and Pathogenesis	483
Clinical Manifestations	483
Pathology	483
Diagnosis and Differential Diagnosis	483
Treatment	484
Acromegaly	484
Definition and Epidemiology	484
Clinical Manifestations	484
Diagnosis	484
Treatment	485
Management of Hypertension in Acromegaly	485
Hypothyroidism	485
Definition and Epidemiology	485
Clinical Features	485
Diagnosis	485
Hyperthyroidism	486
Definition and Epidemiology	486
Clinical Features	486
Diagnosis and Treatment	486
References	486
42 Neurogenic Hypertension, Including Hypertension Associated with Stroke or Spinal Cord Injury	488
Physiology and Pathophysiology	488
Neural Control of Blood Pressure	488
Cerebrovascular Autoregulation	488
Hypertension After Stroke	489
Epidemiology	489
Pathophysiology	489
Diagnosis and Treatment	490
Acute Ischemic Stroke	490
Intracerebral Hemorrhage	491
Subarachnoid Hemorrhage	492
Hypertension After Carotid Endarterectomy and Endovascular Procedures	492
Definition, Incidence, and Clinical Features	492
Pathophysiology	492
Diagnosis and Treatment	492
Hypertension After Spinal Cord Injury	493
Definition and Epidemiology	493
Pathophysiology and Diagnosis	493
Treatment	493
Cerebrovascular Effects of Antihypertensive Agents	493
References	494
VII Pregnancy and Renal Disease	497
43 Renal Physiology in Normal Pregnancy	498
Anatomy	498
Systemic Hemodynamics	498
Renal Hemodynamics	498
Abnormal Renal Hemodynamics	501
Renal Tubular Function in Pregnancy	501
Uric Acid	501
Glucose	501
Water-Soluble Vitamins and Amino Acids	501
Acid-Base Balance	501
Potassium	501
Calcium	501
Protein	501
Sodium	502
Osmoregulation	502
Volume Regulation	502
Impact of Maternal Hemodynamic Changes on Fetal Programming	503
References	504
44 Renal Complications in Normal Pregnancy	506
Urinalysis and Microscopy	506
Hematuria	506
Definition and Epidemiology	506
Etiology and Outcome	506
Differential Diagnosis	506
Treatment	506
Proteinuria	506
Definition	506
Differential Diagnosis	507
Natural History	507
Treatment	507
Pyuria	507
Urinary Tract Infection	507
Definitions	507
Epidemiology	507
Pathogenesis	508
Clinical Manifestations	508
VIII Hereditary and Congenital Diseases of the Kidney	535
46 Autosomal Dominant Polycystic Kidney Disease	536
Definition	536
Etiology and Pathogenesis	536
Genetic Mechanisms	536
Polycystic Kidney Disease Proteins	536
Mechanisms of Cyst Formation	536
Liver Cyst Development	538
Hypertension	538
Epidemiology	538
Phenotypic Variability	538
Diagnosis	539
Renal Ultrasound	539
Genetic Testing	539
Differential Diagnosis	539
Clinical Manifestations	539
Renal Manifestations	539
Renal Size	539
Pain	540
Hematuria and Cyst Hemorrhage	540
Urinary Tract Infection and Cyst Infection	540
Nephrolithiasis	540
Hypertension	540
End-Stage Renal Disease	541
Extrarenal Manifestations	541
Polycystic Liver Disease	541
Intracranial Aneurysms	542
Other Vascular Abnormalities	542
Valvular Heart Disease and Other Cardiac Manifestations	542
Other Associated Conditions	543
Pathology	543
Treatment	544
Flank Pain	544
Cyst Hemorrhage	544
Urinary Tract and Cyst Infection	545
Nephrolithiasis	545
Hypertension	545
Progressive Renal Failure	545
Polycystic Liver Disease	545
Intracranial Aneurysm	546
Novel Therapies	546
Vasopressin Antagonists	546
Somatostatin Analogues	546
mTOR Inhibitors	547
Other Investigational Therapies	547
Transplantation	547
References	547
47 Other Cystic Kidney Diseases	549
Autosomal Recessive Polycystic Kidney Disease	549
Definition	549
Etiology and Pathogenesis	549
Genetic Basis of ARPKD	549
Pathogenetic Mechanisms	549
Epidemiology	549
Clinical Manifestations	549
Pathology	550
Kidney	550
Liver	551
Diagnosis	551
Imaging	551
Genetic Testing	552
Treatment	552
Transplantation	553
Juvenile Nephronophthisis–Medullary Cystic Disease Complex	553
Definitions	553
Autosomal Recessive Juvenile Nephronophthisis	553
Genetic Basis of NPHP	553
Clinical Manifestations	553
Renal Disease	553
Associated Extrarenal Abnormalities	554
Pathology	554
Diagnosis	554
Treatment	554
Autosomal Dominant Medullary Cystic Kidney Disease	554
Medullary Sponge Kidney	555
Definition	555
Etiology and Pathogenesis	555
Epidemiology	555
Clinical Manifestations	555
Pathology	555
Diagnosis	555
Treatment	556
Tuberous Sclerosis Complex	556
Definition	556
Etiology and Pathogenesis	556
Epidemiology	556
Clinicopathologic Manifestations	557
Renal Angiomyolipomas	557
Renal Cysts	557
Renal Neoplasms	557
Diagnosis	558
Treatment	558
Renal Angiomyolipomas	558
Renal Cysts	559
Renal Carcinoma	559
Transplantation	559
Von Hippel–Lindau Disease	559
Definition	559
Etiology and Pathogenesis	559
Clinical Manifestations	559
Pathology	559
Diagnosis	560
Differential Diagnosis	560
Treatment	560
Simple Cysts	561
Definition	561
Etiology and Pathogenesis	561
Clinical Manifestations	561
Pathology	561
Diagnosis	561
Treatment	562
Solitary Multilocular Cysts	562
Renal Lymphangiomatosis	562
Glomerulocystic Kidney Disease	562
Acquired Cystic Disease	563
Hypokalemic Cystic Disease	563
Hilar Cysts	563
Perinephric Pseudocysts	563
Acquired Cystic Disease in Renal Failure	563
References	563
48 Alport and Other Familial Glomerular Syndromes	565
Alport Syndrome	565
Definition	565
Etiology and Pathogenesis	565
Type IV Collagen	565
Genetics	565
X-Linked Alport Syndrome	565
Autosomal Recessive Alport Syndrome	565
Autosomal Dominant Alport Syndrome	565
Type IV Collagen in Alport Basement Membranes	566
Clinical Manifestations	566
Renal Defects	566
Cochlear Defects	567
Ocular Defects	567
Leiomyomatosis	567
Hematologic Defects	568
Arterial Abnormalities	568
Pathology	568
Diagnosis and Differential Diagnosis	568
Natural History	569
Treatment	571
Transplantation	572
Thin Basement Membrane Nephropathy: Familial and Sporadic	572
Definition	572
Etiology and Pathogenesis	573
Clinical Manifestations	573
Pathology	573
Diagnosis and Differential Diagnosis	573
Treatment	574
Fabry Disease (Anderson- Fabry Disease)	574
Definition	574
Etiology and Pathogenesis	574
Clinical Manifestations and Pathology	574
Renal Defects	574
Heart Defects	575
Nervous System	575
Skin	575
Eyes	575
Lungs	576
Diagnosis	576
Treatment	576
Fabry Disease in Childhood	576
Nail-Patella Syndrome	576
Definition	576
Etiology and Pathogenesis	576
Clinical Manifestations	576
Renal Defects	576
Skeletal Defects	576
Nails	576
Pathology	576
Treatment	577
References	577
49 Inherited Disorders of Sodium and Water Handling	579
Physiology of Sodium and Water Reabsorption	579
Sodium Reabsorption	579
Water Reabsorption	579
Disorders of Sodium Handling	579
Conditions with Hypokalemia, Metabolic Alkalosis, and Normal Blood Pressure	579
Bartter Syndrome	579
Pathogenesis	580
Clinical Manifestations	582
Diagnosis	582
Differential Diagnosis	582
Treatment	582
Outcome	583
Gitelman Syndrome	583
IX Infectious Diseases and the Kidney	631
53 Bacterial Urinary Tract Infections	632
Definition	632
Epidemiology	632
Pathogenesis	632
Uncomplicated Infection	632
Complicated Infection	633
Etiologic Agents	633
Clinical Syndromes	634
Acute Uncomplicated Cystitis in Young Women	634
Recurrent Acute Uncomplicated Cystitis in Women	635
Acute Uncomplicated Pyelonephritis in Women	636
Acute Cystitis in Healthy Adults with Possible Occult Renal or Prostatic Involvement	638
Complicated Infections	639
Chronic Kidney Disease	639
Catheter-Associated Infections	639
Spinal Cord Injury	640
Prostatitis	640
Renal Abscess	640
Papillary Necrosis	641
Emphysematous Pyelonephritis	641
Renal Malacoplakia	641
Xanthogranulomatous Pyelonephritis	641
Asymptomatic Bacteriuria	642
Imaging of the Urinary Tract	642
References	643
54 Tuberculosis of the Urinary Tract	644
Definition	644
Etiology	644
Pathogenesis	644
Clinical Manifestations	646
Pathology	647
Diagnosis and Differential Diagnosis	647
Natural History	649
Treatment	649
Surgical Treatment	650
Treatment Regimens in Special Situations	650
Women During Pregnancy and Lactation	650
Patients with Liver Disease	650
Patients with Chronic Kidney Disease	651
Renal Allograft Recipients	651
Acquired Immunodeficiency Syndrome	651
Patients Who Fail Treatment	651
Monitoring of Patients	651
References	651
55 Fungal Infections of the Urinary Tract	652
Candida	652
Epidemiology	652
Pathogenesis	652
Microbiology	652
Clinical Manifestations	652
Diagnosis	653
Treatment with Systemic Antifungal Agents	654
Local Antifungal Administration	655
Localized Candida Infections	655
Other Yeasts	655
Aspergillus and Other Molds	656
Endemic Fungi	656
References	656
56 The Kidney in Schistosomiasis	657
Pathogenesis	657
Clinical Manifestations	658
Lower Urinary Tract Schistosomiasis	658
Bladder Cancer	658
Human Immunodeficiency Virus Infection	659
Upstream Consequences	659
Interstitial Nephritis	659
Glomerulonephritis	661
Diagnosis	663
Schistosoma haematobium Urinary Tract Disease	663
Schistosoma mansoni Glomerulonephritis	663
Treatment	664
Schistosoma haematobium Urinary Tract Disease	664
Schistosoma mansoni Glomerulonephritis	664
References	664
57 Glomerular Diseases Associated with Infection	665
General Characteristics of Glomerular Diseases Associated with Infection	665
Histologic Patterns and Pathogenesis	665
Bacterial Infections	665
Poststreptococcal Glomerulonephritis	665
Epidemiology	665
Pathogenesis	666
Pathology	667
Clinical Manifestations	667
Management	668
Prognosis	668
Endocarditis-associated Glomerulonephritis	668
Clinical Manifestations and Diagnosis	668
Staphylococcal Infections with Glomerular IgA Deposition	669
Clinical and Pathologic Characteristics	669
Pathogenesis	669
Differential Diagnosis and Treatment	669
Shunt Nephritis	669
Glomerulonephritis Associated with Other Bacterial Infections	670
Viral Infections	671
Hepatitis A Virus–Associated Renal Disease	671
Hepatitis B Virus–Associated Renal Disease	671
Hepatitis B Virus–Associated Membranous Nephropathy	671
Hepatitis B Virus–Associated Membranoproliferative Glomerulonephritis	671
Mesangial Proliferative Glomerulonephritis with IgA Deposits	671
Treatment of Hepatitis B Virus– Associated Glomerulonephritis	671
Polyarteritis Nodosa	672
Hepatitis C Virus–Associated Renal Disease	672
Human Immunodeficiency Virus–Associated Renal Disease	672
Other Virus-Associated Renal Disease	672
Parasitic Infections	673
Malaria	673
Filariasis	675
Leishmaniasis	676
References	676
58 Human Immunodeficiency Virus Infection and the Kidney	678
Human Immunodeficiency Virus–Associated Kidney Disease	678
Glomerular Disorders	678
Human Immunodeficiency Virus–Associated Collapsing Glomerulopathy	678
Etiology and Pathogenesis	678
Clinical Manifestations	679
Pathology	679
Diagnosis and Differential Diagnosis	679
Treatment	679
Natural History	680
Human Immunodeficiency Virus–associated Immune Complex Glomerulonephritis	680
Other Glomerular Disorders	680
Arterionephrosclerosis	681
Tubular Disorders	681
Chronic Kidney Disease and End-Stage Renal Disease in Human Immunodeficiency Virus–Infected Patients	682
Epidemiology	682
The Developed World	682
The Developing World	682
Dosage of Antiretroviral Therapy in Chronic Kidney Disease	683
Renal Replacement Therapy in the Patient with Human Immunodeficiency Virus Infection	684
Hemodialysis	684
Peritoneal Dialysis	684
Kidney Transplantation	684
Screening for Chronic Kidney Disease	684
References	686
X Urologic Disorders	687
59 Nephrolithiasis and Nephrocalcinosis	688
Nephrolithiasis	688
Epidemiology	688
Pathogenesis	688
Clinical Manifestations	689
Pain	689
Hematuria	689
Loin Pain–Hematuria Syndrome	689
Asymptomatic Stone Disease	690
Clinical Evaluation of Stone Formers	690
Basic Evaluation	690
History	690
Physical Examination	691
Laboratory Findings	691
Stone Analysis	692
Imaging	692
Complete Evaluation	693
General Treatment	694
Medical Management	694
Fluid Intake	694
Salt Intake	694
Dietary Protein	694
Dietary Calcium	694
Vitamin D	695
Specific Types of Stones	695
Calcium Stones	695
Hypercalciuria	695
Etiology	695
Treatment	695
Dietary Recommendations	696
Hyperoxaluria	696
Etiology	696
Treatment of Dietary and Enteric Hyperoxaluria	696
Treatment of Primary Hyperoxaluria	697
Hypocitraturia	697
Distal Renal Tubular Acidosis	697
Hyperuricosuria	697
Uric Acid Stones	697
Epidemiology	697
XI Tubulointerstitial and Vascular Diseases	727
62 Acute Interstitial Nephritis	728
Definition	728
Pathogenesis	728
Epidemiology	728
Drug-Induced Acute Interstitial Nephritis	728
Clinical Manifestations	728
Renal Manifestations	729
Extrarenal Manifestations	729
Other Specific Drug Associations	729
Pathology	731
Diagnosis	732
Identification of the Causative Drug	733
Natural History	733
Treatment	733
Acute Interstitial Nephritis Secondary to Infectious Diseases	733
Acute Interstitial Nephritis Associated with Systemic Diseases	734
Sarcoidosis	734
Sjögren Syndrome	735
Systemic Lupus Erythematosus	735
Other Systemic Diseases	735
Acute Interstitial Nephritis Associated with Malignant Neoplasms	735
Idiopathic Acute Interstitial Nephritis	735
Acute Interstitial Nephritis in Renal Transplants	735
References	735
63 Primary Vesicoureteral Reflux and Reflux Nephropathy	737
Definition	737
Classification	737
Epidemiology	737
Etiology and Pathogenesis	737
Reflux Nephropathy	738
Pathology	739
Clinical Manifestations	739
Presentation with Vesicoureteral Reflux	739
Reflux Identified Secondary to Antenatal Hydronephrosis	740
Reflux Identified After a Urinary Tract Infection	740
Sibling Vesicoureteral Reflux	740
Reflux Nephropathy	740
Hypertension	741
Proteinuria	741
End-Stage Renal Disease	741
Presentation of Vesicoureteral Reflux in the Mother During Pregnancy	741
Other Presentations	741
Diagnosis of Vesicoureteral Reflux and Reflux Nephropathy	741
Renal Ultrasound	741
Voiding Cystourethrography	741
DMSA Renal Scintigraphy	742
Magnetic Resonance Imaging	742
Proteinuria as a Marker for Reflux Nephropathy	742
Natural History of Vesicoureteral Reflux and Reflux Nephropathy	742
Treatment	743
Medical Management	743
Antibiotic Prophylaxis Versus Surveillance Only	743
Hypertension and Proteinuria	744
Surgical Management	744
References	744
64 Chronic Interstitial Nephritis	746
Definition	746
Pathogenesis	746
Epidemiology	746
Pathology	746
Clinical Manifestations	746
Treatment	747
Drug-Induced Chronic Interstitial Nephritis	747
Lithium Nephropathy	748
Definition and Epidemiology	748
Pathogenesis	748
Pathology	748
Clinical Manifestations	748
Lithium-associated Diabetes Insipidus	748
Chronic Lithium Nephropathy	748
Treatment	748
Analgesic Nephropathy	749
Definition and Epidemiology	749
Pathogenesis and Pathology	749
Clinical Manifestations	749
Diagnosis	749
Treatment	749
Chronic Interstitial Nephritis Caused by Metabolic Disorders	750
Chronic Uric Acid Nephropathy	750
Definition and Epidemiology	750
Pathogenesis	750
Pathology	750
Clinical Manifestations	750
XII Geriatric Nephrology	779
67 Geriatric Nephrology	780
Aging-Associated Structural Changes	780
Anatomic Changes	780
Glomerular Changes	780
Tubular and Interstitial Changes	780
Vascular Changes	780
Aging-Associated Changes in Renal Function	780
Glomerular Filtration Rate	780
Renal Plasma Flow	780
Proteinuria	780
Assessment of Renal Function in the Elderly	780
Prevalence of Chronic Kidney Disease in the Elderly	781
Risk Factors for Chronic Kidney Disease in the Elderly	782
Pathogenesis of Age-Related Chronic Kidney Disease	783
Fluid and Electrolytes in Aging	784
Sodium Balance and Hypertension	784
Osmoregulation and Water Handling	785
Other Tubular Defects and Electrolyte Problems	785
Endocrine Function and Renal Hormones	785
Clinical Manifestations	785
General Considerations	785
Glomerular Diseases	785
Renovascular and Atheroembolic Disease	786
Acute Kidney Injury	786
Urinary Tract Infections	786
Obstructive Uropathy	786
Urinary Incontinence	786
Hematuria	787
Nephrotoxicity and Drug Dosage	787
End-Stage Renal Disease and Renal Replacement Therapy	787
References	788
XIII Renal Disease and Cancer	791
68 Onconephrology:	792
Acute Kidney Injury	792
Pre-renal Acute Kidney Injury	792
Intrarenal Acute Kidney Injury	792
Post-renal Acute Kidney Injury	792
Myeloma and Amyloidosis	792
Anti–Vascular Endothelial Growth Factor Therapy	794
Tumor Lysis Syndrome	794
Cancer-Related Glomerulonephritis	795
Hematopoietic Stem Cell Transplantation	795
Electrolyte Abnormalities	796
Cancer Therapy in Chronic Kidney Disease and End-Stage Renal Disease Patients	798
References	798
XIV Acute Kidney Injury	801
69 Pathophysiology and Etiology of Acute Kidney Injury	802
Definition	802
Etiologic Overview	802
Pathophysiology and Etiology of Pre-Renal Acute Kidney Injury	802
Pathophysiology and Etiology of Post-Renal Acute Kidney Injury	803
Pathophysiology of Acute Tubular Necrosis	803
Histology	804
Tubular Injury in Acute Tubular Necrosis	804
Blood Supply	804
High Tubular Energy Requirements	805
Glycolytic Ability of Tubular Cells	805
Hemodynamic Factors in the Development of Acute Tubular Necrosis	805
Impaired Renal Autoregulation	805
Intrarenal Vasoconstriction	805
Tubuloglomerular Feedback	805
Endothelial Cell Injury and the Development of Acute Tubular Necrosis	806
Tubular Epithelial Cell Injury and the Development of Acute Tubular Necrosis	806
Inflammatory Factors in the Development of Acute Tubular Necrosis	807
Recovery Phase	808
Nephrotoxic Agents and Mechanisms of Toxicity	809
Nonsteroidal Anti-inflammatory Drugs	809
Angiotensin-converting Enzyme Inhibitors and Angiotensin Receptor Blockers	809
Aminoglycosides	809
Amphotericin	809
Antiviral Therapy	810
Acyclovir	810
Foscarnet	811
Cidofovir and Adefovir	811
Other Antiviral Agents	811
Immunosuppressive Agents	811
Calcineurin Inhibitors	811
Other Immunosuppressive Agents	811
Acetaminophen (Paracetamol)	811
Ethylene Glycol	811
Warfarin Nephropathy	811
Illicit Drug Use	811
Bisphosphonates	811
Acute Phosphate Nephropathy	812
Occupational Toxins	812
Heavy Metals	812
Organic Solvents	812
Herbal Remedies	812
Radiocontrast-induced Nephropathy	812
Pathogenesis	812
Other Specific Causes of Acute Kidney Injury	812
Heme Pigment Nephropathy	812
Causes of Rhabdomyolysis	812
Causes of Hemoglobinuria	813
Pathogenesis of Heme Pigment Nephropathy	813
Atheroembolic Renal Disease	814
Renal Artery Occlusion	814
Acute Interstitial Nephritis	814
Thrombotic Microangiopathy	814
Glomerular Disease	814
Specific Clinical Situations	814
Acute Kidney Injury in the Patient with Multiorgan Failure	814
Acute Kidney Injury in the Postoperative Patient	814
After Vascular Surgery	815
After Cardiac Surgery	815
After Hepatobiliary Surgery	815
Abdominal Compartment Syndrome	815
Pulmonary-Renal Syndromes	815
Acute Kidney Injury and Liver Disease	815
Acute Kidney Injury in Heart Failure (Cardiorenal Syndrome)	816
Acute Kidney Injury in the Cancer Patient	816
Tumor Lysis Syndrome	816
Hypercalcemia	816
Chemotherapeutic Agents	817
References	817
70 Acute Kidney Injury in the Tropics	818
Snakebites	818
Clinical Features	818
Pathology	818
Pathogenesis	818
Management	819
Arthropods	819
Natural Medicines	820
Pathogenesis of Natural Medicine–Induced Acute Kidney Injury	822
Malaria	822
Pathophysiology	822
Clinical Manifestations	822
Leptospirosis	823
Hemorrhagic Fevers	824
Dengue Fever	824
Yellow Fever	824
References	825
71 Diagnosis and Clinical Evaluation of Acute Kidney Injury	827
Diagnosis and Clinical Evaluation of Acute Kidney Injury	827
Early Detection of Acute Kidney Injury	827
Diagnostic Approach to Acute Kidney Injury	828
Acute Kidney Injury Versus Chronic Kidney Disease	829
Clinical Assessment	829
Laboratory Tests	830
Ratio of Blood Urea Nitrogen to Creatinine	830
Urine Volume	831
Urinalysis and Urine Microscopy	831
Fractional Excretion of Sodium and Urea	831
Imaging Studies	832
Renal Biopsy	833
Acute Kidney Injury in Specific Settings	833
Acute Tubular Necrosis	833
Acute Interstitial Nephritis	833
Acute Kidney Injury from Intratubular Obstruction	834
Rhabdomyolysis	834
Acute Kidney Injury in Multiple Myeloma	834
Contrast-Induced Nephropathy	835
Acknowledgment	835
References	835
72 Epidemiology and Prognostic Impact of Acute Kidney Injury	836
Incidence of Acute Kidney Injury	836
Causes of Acute Kidney Injury	836
Risk Factors for Acute Kidney Injury	836
Age	836
Chronic Kidney Disease	837
Proteinuria	837
Associations Between Acute Kidney Injury and Adverse Outcomes	838
Mortality	838
Chronic Kidney Disease	839
Health Care Costs	840
Acute Kidney Injury as a Public Health Issue	840
References	840
73 Prevention and Nondialytic Management of Acute Kidney Injury	842
Risk Assessment	842
Primary Preventive Measures	842
Optimizing Volume Status and Hemodynamic Status	842
Prevention of Contrast-Induced Acute Kidney Injury	845
Prevention of Drug- and Nephrotoxin-Induced Acute Kidney Injury	846
Amphotericin	846
Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Blockers, and Nonsteroidal Anti-Inflammatory Drugs	846
Aminoglycosides	846
Tumor Lysis Syndrome	846
Secondary Prevention	846
Traumatic and Nontraumatic Rhabdomyolysis	846
Hyperglycemia	847
Pharmacologic Approaches	847
N-Acetylcysteine	847
Loop Diuretics and Natriuretics	847
Vasoactive Agents	847
Statins	848
Calcium Channel Blockers	848
Adenosine Antagonists	849
Emerging Agents	849
Treatment of Acute Kidney Injury	849
General Management	849
Fluid and Electrolyte Management	849
Drugs to Promote Recovery from Acute Kidney Injury	850
Loop Diuretic Therapy	850
Natriuretics	850
Vasoactive Agents	851
Other Agents	851
Treatment of Acute Kidney Injury Complications	851
Fluid Overload	851
Potassium Disorders	851
Sodium Disorders	852
Calcium, Phosphorus, and Magnesium Disorders	852
Acid-Base Disorders	852
Nutrition	852
References	853
74 Dialytic Management of Acute Kidney Injury and Intensive Care Unit Nephrology	855
Organizational Aspects of Acute Renal Replacement Therapy Programs	855
Overview of Acute Renal Replacement Therapies	855
Intermittent Acute Renal Replacement Therapy	857
Techniques for Acute Intermittent Hemodialysis	857
Strategies to Reduce Intradialytic Hemodynamic Instability During Intermittent Hemodialysis	857
Prolonged Intermittent Renal Replacement Therapy	857
Dosage of Acute Intermittent Renal Replacement Therapy	858
Continuous Renal Replacement Therapy	858
Techniques for Continuous Renal Replacement Therapy	859
Mechanisms of Solute Removal	859
Hemodialysis	859
Hemofiltration	860
Hemodiafiltration	860
Specific Techniques	860
Dosage of Continuous Renal Replacement Therapy	861
Technical Aspects of Continuous Renal Replacement Therapy	861
Equipment	861
Hemofilters	861
Replacement Fluids and Dialysate	861
Vascular Access	861
Anticoagulation in Acute Renal Replacement Therapy	862
Modality Choice and Outcomes in Acute Renal Replacement Therapy	863
Acute Renal Replacement Therapy During Mechanical Circulatory Support	864
Technical Aspects of Acute Renal Replacement Therapy During Mechanical Circulatory Support	865
Drug Dosage in Acute Renal Replacement Therapy	865
References	865
75 Management of Refractory Heart Failure	867
Definition and Scope of the Problem	867
Pathogenesis	867
Venous Congestion	867
Adenosine Mediators	867
Inflammatory Cytokines	868
Anemia	868
Diuretic Tolerance and Adverse Effects	868
Treatment	868
General Approach and Limitations	868
Pharmacologic Therapeutic Strategies	868
Diuretics	869
Renin-Angiotensin-Aldosterone System Antagonists	869
Adenosine Receptor Antagonists	869
Erythropoiesis-Stimulating Agents	869
Antidiuretic Hormone Antagonists	869
Natriuretic Peptides	869
Nonrenal Salt and Water Removal	869
Paracentesis	869
Ultrafiltration: Peritoneal Dialysis	870
Extracorporeal Ultrafiltration: Conventional Hemodialysis or Hemofiltration	870
Ultrafiltration: Setting the Rate of Fluid Removal	871
Effect of Extracorporeal Ultrafiltration on the Pathophysiology of Heart Failure	871
Effect of Extracorporeal Ultrafiltration on Renal Function	871
Ultrafiltration: Recent Advances in Extracorporeal Techniques	871
Safety and Risks to Extracorporeal Therapies	872
Summary	872
References	872
76 Hepatorenal Syndrome	873
Definition	873
Pseudohepatorenal Syndrome	873
Pathophysiology and Pathogenesis	873
Circulatory Dysfunction: Renal and Systemic Hemodynamic Changes	873
Neurohumoral Abnormalities	873
Summary of Pathogenetic Events	874
Epidemiology	874
Clinical Manifestations	876
Pathology	876
Diagnosis and Differential Diagnosis	876
Natural History	877
Prevention and Treatment	877
General Principles in the Prevention of Renal Failure	877
Preventive Measures	877
General Approach to Treatment	877
Pharmacotherapy	877
Transjugular Intrahepatic Portosystemic Shunt	879
Extracorporeal Liver Support Therapy	879
Renal Replacement Therapy	880
Liver Transplantation	880
Therapeutic Algorithm	880
References	881
XV Drug Therapy in Kidney Disease	883
77 Principles of Drug Therapy, Dosing, and Prescribing in Chronic Kidney Disease and Renal Replacement Therapy	884
Pharmacokinetic Principles	884
Absorption: Bioavailability	884
Distribution	884
Volume of Distribution	884
Plasma Protein Binding	884
Metabolism	885
Elimination	885
Prescribing Principles for Chronic Kidney Disease and Renal Replacement Therapy	886
Initial Assessment and Laboratory Data	886
Estimating Renal Function for Drug Dosage	886
Activity and Toxicity of Metabolites	886
Fraction of Active Drug (and Active or Toxic Metabolite) Excreted Unchanged in Urine	886
Therapeutic Index of the Drug or Metabolites	887
Avoid Nephrotoxic Drugs	887
Drugs That Aggravate the Metabolic Effects of Renal Impairment	887
Effect of Renal Impairment on Pharmacodynamic or Physiologic Mechanisms	888
Effect of Renal Impairment on the Concentration of Drug at the Site of Action	888
Location of Drug Action	889
Method of Administration	889
Drug Interactions	889
Clinical Condition of the Patient	889
Methods of Dose Reduction	889
Loading Doses	889
Maintenance Doses	890
Interval Method	890
Dose Method	890
Combination Method	890
Ongoing Assessment	890
Therapeutic Drug Monitoring	891
Clinical Response	891
Extracorporeal Drug Losses	891
Hemodialysis	891
Peritoneal Dialysis	891
Continuous Renal Replacement Therapy	891
Common Prescribing Issues in Chronic Kidney Disease and Renal Replacement Therapy	891
Anemia	891
Erythropoiesis-Stimulating Proteins	891
Iron Therapy	892
Analgesics	892
Acetaminophen (Paracetamol)	892
Opioid Analgesics	892
Nonsteroidal Anti-inflammatory Drugs	893
Drugs for Neuropathic Pain	893
Antihistamines	893
Anti-infective Agents	893
Antibacterials	893
Aminoglycosides	893
Aminoglycoside Dosage Schedules	893
Aminoglycoside Concentration Monitoring	893
Carbapenems	894
Cephalosporins	894
Fluoroquinolones	894
Glycopeptides	894
Lincosamides	894
Macrolides	894
Penicillins	894
Rifamycins	894
Tetracyclines	894
Sulfonamides and Trimethoprim	895
Other Antibiotics	895
Antimycobacterials	895
Antifungals	895
Amphotericin	895
Azole Antifungals	895
Other Antifungals	895
Antivirals	895
Guanine Analogues	895
Hepatitis B and C	895
Neuraminidase Inhibitors	895
Other Antivirals	896
Anticoagulants, Antiplatelet Agents, Thrombolytics, and Hemostatics	896
Unfractionated Heparin	896
Low-Molecular-Weight Heparins	896
Other Parenteral Anticoagulants	896
Oral Anticoagulants	896
Antiplatelet Drugs	896
Thrombolytics	896
Hemostatics	896
Diuretics	896
Thiazide Diuretics	896
Loop Diuretics	896
Potassium-Sparing Diuretics	896
Antihypertensives	896
Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers	896
β-Blockers	897
Calcium Channel Blockers	897
Other Antihypertensives	897
Antianginal Agents	897
Antiarrhythmics	897
Lipid-Lowering Agents	897
Bile Acid–Binding Resins	897
Statins	897
Fibrates	897
Diabetes	897
Diabetes Management in Peritoneal Dialysis	897
Biguanides	897
Insulin	898
Meglitinides	898
Sulfonylureas	898
Thiazolidinediones	898
Drugs for Thyroid Disorders	898
Mineral and Bone Disorders	898
Phosphate Binders	898
Vitamin D	898
Calcimimetics	898
Dyspepsia, Gastroesophageal Reflux Disease, and Peptic Ulcers	898
Antacids	898
H2 Antagonists	898
Proton Pump Inhibitors	898
Antiemetics	899
Dopamine Antagonists	899
5-HT3 Antagonists	899
Aperients and Laxatives	899
Antidiarrheals	899
Drugs for Erectile Dysfunction	899
Phosphodiesterase-5 Inhibitors	899
Intracavernosal Therapy	899
Immunosuppressants	899
Calcineurin Inhibitors	899
Corticosteroids	899
Antiproliferative and Cytotoxic Agents	899
mTOR Inhibitors	900
Immunosuppressant Antibodies	900
Musculoskeletal Drugs	900
Nonsteroidal Anti-inflammatory Drugs	900
Miscellaneous Arthritis Drugs	900
Gout and Hyperuricemia	900
Bisphosphonates	900
Antiepileptics	900
Benzodiazepines	900
Carbamazepine	900
Phenytoin	901
Other Antiepileptics	901
Antiparkinsonian Drugs	901
Antimigraine Drugs	901
Psychotropic Drugs	901
Monoamine Oxidase Inhibitors	901
Selective Serotonin Reuptake Inhibitors	901
Tricyclic Antidepressants	901
Other Antidepressants	901
Antipsychotics	901
Benzodiazepines	902
Vaccines	902
Vitamin Supplementation	902
References	902
78 Herbal and Over-the-Counter Medicines and the Kidney	905
Herbal Medications and the Kidney	905
Aristolochic Acid Nephropathy or Balkan Nephropathy	905
Aristolochic Acids	905
Aristolochic Acid Nephropathy	906
Epidemiology	907
Clinical Manifestations	907
Pathology	907
Pathogenesis	908
XVI Chronic Kidney Disease and the Uremic Syndrome	915
79 Epidemiology, Natural History, and Pathophysiology of Chronic Kidney Disease	916
Definition and Classification of Chronic Kidney Disease	916
Limitations of Chronic Kidney Disease Classification	916
Estimating Glomerular Filtration Rate	916
Microalbuminuria (Moderately Increased Albuminuria) as a Definition for Chronic Kidney Disease	916
Age-Related Decline in Kidney Function	916
Further Considerations	916
Epidemiology of Chronic Kidney Disease	917
Chronic Kidney Disease Detection Recommendations	917
Epidemiology of End-Stage Renal Disease	919
Impact of Chronic Kidney Disease on Morbidity and Mortality	919
Natural History of Chronic Kidney Disease	920
Causes and Natural History of Community Chronic Kidney Disease	920
Causes and Natural History of Referred Chronic Kidney Disease	920
Predictors of Progressive Chronic Kidney Disease	921
Chronic Kidney Disease Risk Factors	921
Nonmodifiable Chronic Kidney Disease Progression Risk Factors	921
Genetics	921
Modifiable Chronic Kidney Disease Progression Risk Factors	921
Hypertension	921
Proteinuria	922
Renin-Angiotensin-Aldosterone System	922
Additional Factors Implicated in Chronic Kidney Disease Progression	923
Mechanisms of Progression of Chronic Kidney Disease	923
Inflammatory Response to Tissue Injury	923
Lymphocytes	924
Monocytes	924
Dendritic Cells	925
Bone Marrow–Derived Cells	925
Intrinsic Renal Cell Activation, Proliferation, and Loss	926
Glomerular Cells	926
Endothelial Cells	926
Mesangial Cells	926
Podocytes	926
Tubular Cells and the Renal Interstitium	926
Vascular Cells	927
Extracellular Matrix Accumulation	927
References	929
80 Retarding Progression of Kidney Disease	931
Level of Glomerular Filtration Rate and the Risk of Natural Progression	931
Proteinuria Magnitude and the Risk of Natural Progression	931
Diagnosis of Natural Progression	931
Monitoring Kidney Disease Progression	931
Monitoring Proteinuria Trends	931
Monitoring Glomerular Filtration Rate Trends	933
Glomerular Filtration Rate Trajectories in Chronic Kidney Disease	934
Indexing Proteinuria and Albuminuria by Estimated Glomerular Filtration Rate to Predict Risk of Chronic Kidney Disease Progression	934
Therapy for Natural Progression	934
Level 1 Recommendations to Slow Natural Progression	934
Control Blood Pressure	934
Renin-Angiotensin System Blockers	935
Combination Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Therapy	935
Renin Inhibitor Therapy	935
Avoid Dihydropyridine Calcium Channel Blockers	935
Control Protein Intake	935
Level 2 Recommendations to Slow Natural Progression	938
Restrict Salt Intake and Diuretic Therapy	938
Nondihydropyridine Calcium Channel Blocker Therapy	938
Control Each Component of the Metabolic Syndrome	938
Aldosterone Antagonist Therapy	939
β-Blocker Therapy	939
Control Serum Phosphorous	939
Smoking Cessation	939
Allopurinol and Febuxostat Therapy	939
Avoid Overanticoagulation with Warfarin	940
Alkali Therapy	940
Correct Vitamin D Deficiency	940
References	940
81 Clinical Evaluation and Management of Chronic Kidney Disease	942
Definitions	942
Clinical Presentation	942
Evaluation of Chronic Kidney Disease	942
Establishing Chronicity	942
Assessment of Glomerular Filtration Rate	942
Assessment of Proteinuria	943
Kidney Imaging	943
Further Investigations	943
Predicting Prognosis	943
Monitoring and Defining Progression	943
When to Refer to the Nephrologist	944
Prevention of Chronic Kidney Disease Progression	944
Hypertension	944
Dietary Advice	945
Management of Complications of Chronic Kidney Disease	945
Anemia	945
Bone and Mineral Metabolism	945
Metabolic Acidosis	946
Cardiovascular Risk	946
Risk of Infections	946
Care of the Patient with Progressive Chronic Kidney Disease	946
Chronic Kidney Disease and Risk of Acute Kidney Injury	946
Timing the Initiation of Renal Replacement Therapy	947
Conservative Management	947
References	947
82 Cardiovascular Disease in Chronic Kidney Disease	949
Epidemiology	949
Prevalence of Cardiovascular Complications in Chronic Kidney Disease	949
Cardiovascular Disease Is Present Before the Start of Renal Replacement Therapy	949
Racial and International Differences in Cardiovascular Disease Prevalence	949
Reverse Epidemiology	950
Etiology and Risk Factors	950
Traditional Risk Factors	950
Age, Gender, and Smoking	950
Diabetes Mellitus	950
Hypertension	950
Dyslipidemia	953
Insulin Resistance and Atherosclerosis	953
Nontraditional and Uremia-Specific Risk Factors	954
Oxidative Stress	954
Inflammation	954
Endothelial Dysfunction	954
Anemia	954
Secondary Hyperparathyroidism and Mineral Metabolism	954
Cardiovascular Calcification	955
Advanced Glycation End Products	955
Dialysis Modality	955
Clinical Manifestations and Natural History	956
Chest Pain, Coronary Heart Disease, and Acute Myocardial Infarction	956
Peripheral Arterial Disease	957
Cerebrovascular Disease and Atrial Fibrillation	957
Left Ventricular Remodeling and Hypertrophy	957
Extracellular Volume Overload	958
Pericarditis	958
Autonomic Dysfunction	958
Valvular Disease	958
Infective Endocarditis	958
Sudden Cardiac Arrest	958
Diagnosis and Differential Diagnosis	959
Blood Pressure Measurements	959
Electrocardiography and Echocardiography	959
Stress Tests and Screening Renal Transplant Candidates	959
Coronary Angiography	960
Imaging of Vascular Calcification	960
Biomarkers	961
Treatment and Prevention of Cardiovascular Disease	961
Risk Factor Reduction	961
Lifestyle Factors and Smoking	961
Weight and Diet	961
Hypertension and Coronary Heart Disease	961
Diabetes Mellitus	962
Dyslipidemia	962
Volume	962
Anemia	962
Inflammation	962
Oxidative Stress	962
Chronic Kidney Disease–Mineral Bone Disorder	962
Revascularization	963
References	963
83 Anemia in Chronic Kidney Disease	967
Pathogenesis	967
Epidemiology and Natural History	968
Diagnosis and Differential Diagnosis	968
Clinical Manifestations	969
Treatment	970
Erythropoiesis-Stimulating Agents	970
Epoetin Therapy	970
Darbepoetin Alfa	971
C.E.R.A. (Methoxy Polyethylene Glycol–Epoetin Beta)	971
Adverse Effects of the Erythropoiesis-Stimulating Agents	971
Other Erythropoiesis-Stimulating Agents	971
Initiation of and Maintenance Therapy with Erythropoiesis-Stimulating Agents	971
Hyporesponsiveness to Erythropoiesis-Stimulating Agents	972
Iron Management	973
References	974
84 Other Blood and Immune Disorders in Chronic Kidney Disease	975
Platelet Dysfunction and Coagulation Defects	975
Bleeding Diathesis in Uremia	975
Platelet Dysfunction	975
Platelet Number in Uremia	976
Therapeutic Strategies	977
Dialysis	977
Correction of Anemia	977
Cryoprecipitate	977
Desmopressin	978
Conjugated Estrogens	978
Tranexamic Acid	978
Platelet Hyperaggregability In Uremia	978
Indications for Antiplatelet Agents in End-Stage Renal Disease	978
Anticoagulation and Associated Complications in Uremia	979
Heparin-Induced Thrombocytopenia	979
Danaparoid	980
Argatroban	980
Lepirudin	980
Fondaparinux	980
Regional Anticoagulation with Citrate	980
Thrombotic Events in Patients with End-Stage Renal Disease	980
Immune Dysfunction in Uremia	981
Vaccinations in Uremia	981
Hepatitis B Vaccination	981
Hepatitis A Vaccination	982
Vaccination Against Influenza and Pneumococcal Disease	982
Tetanus and Diphtheria	982
Varicella Zoster Virus Vaccination	982
References	983
85 Bone and Mineral Metabolism in Chronic Kidney Disease	984
Definition	984
Epidemiology	984
Pathogenesis	984
Osteitis Fibrosa: Hyperparathyroidism—High-Turnover Renal Bone Disease	984
Abnormalities of Calcium Metabolism	984
Abnormalities of Phosphate Metabolism	984
Abnormalities of Vitamin D Metabolism	985
Abnormalities of Parathyroid Gland Function	987
Abnormal Skeletal Response to Parathyroid Hormone	987
Clinical Manifestations of High-Turnover Renal Osteodystrophy	987
Diagnosis and Differential Diagnosis	987
Serum Biochemistry	987
Parathyroid Hormone	987
Vitamin D Metabolites	988
Markers of Bone Formation and Bone Resorption	988
Radiology of the Skeleton	988
Measurements of Bone Density	988
Bone Biopsy	989
Treatment of High-Turnover Bone Disease	989
Prevention of Hypocalcemia	989
Control of Phosphate	990
Dietary Phosphate Restriction	990
Phosphate Binders	990
Use of Vitamin D Metabolites	991
Role of Calcimimetics	992
Role of Parathyroidectomy	992
Synthesis of Therapeutic Strategies	992
Low-Turnover Renal BONE DISEASE	993
Pathogenesis of Adynamic Bone Disease	993
Diagnosis and Differential Diagnosis	994
Serum Biochemistry	994
Bone Biopsy	994
Radiology and Measurements of Bone Density	995
Treatment of Adynamic Bone Disease	995
Osteoporosis in Chronic Kidney Disease	995
Pathogenesis of Osteoporosis in Chronic Kidney Disease	995
Diagnosis and Differential Diagnosis	995
Treatment of Osteoporosis in Chronic Kidney Disease	996
β2-Microglobulin–Derived Amyloid	996
Pathogenesis	996
Epidemiology	996
Clinical Manifestations and Diagnosis	996
Diagnosis	997
Treatment and Prevention	997
References	998
86 Neurologic Complications of Chronic Kidney Disease	1000
Uremic Encephalopathy	1000
Pathogenesis	1000
Clinical Manifestations	1000
Diagnosis and Differential Diagnosis	1001
Treatment	1001
Peripheral Neuropathy	1001
Autonomic Neuropathy	1003
Cranial Neuropathies	1003
Sleep Disorders	1003
Restless Legs Syndrome (Ekbom Syndrome)	1003
Neurologic Syndromes Associated with Renal Replacement Therapy	1004
References	1004
87 Gastroenterology and Nutrition in Chronic Kidney Disease	1005
Gastrointestinal Problems in Chronic Kidney Disease	1005
Gastrointestinal Disease in Chronic Kidney Disease	1005
Oral Disease in Chronic Kidney Disease	1005
Gastroesophageal Reflux Disease and Esophagitis	1005
Peptic Ulcer Disease, Gastritis, and Duodenitis	1005
Delayed Gastric Emptying and Gastroparesis	1005
Large Bowel Disorders	1006
Gastrointestinal Pseudo-obstruction	1006
Vascular Disease of the Gastrointestinal Tract	1006
Gastrointestinal Hemorrhage	1007
Clostridium difficile Infection	1007
Acute Pancreatitis	1008
Acute Abdomen	1008
Gastrointestinal-Renal Syndromes	1008
Diabetes	1008
Systemic Vasculitis	1008
Systemic Amyloidosis	1008
Autosomal Dominant Polycystic Kidney Disease	1009
Inflammatory Bowel Disease	1009
Celiac Disease	1009
Drugs and Gastrointestinal Disease in Chronic Kidney Disease	1009
Specific Gastrointestinal Complications of Renal Replacement Therapy	1009
Idiopathic Dialysis-Related Ascites	1009
Peritoneal Dialysis–Related Gastrointestinal Conditions	1009
Dialysis-Related Amyloidosis	1009
Transplantation and Gastrointestinal Disturbance	1009
Nutrition in Chronic Kidney Disease	1010
Malnutrition: Protein-Energy Wasting	1010
Assessment of Nutritional Status	1010
Estimation of Intake	1011
Body Composition	1011
Visceral Protein	1012
Nutritional Guidelines	1012
Hyperlipidemia	1012
Hypertension	1013
Vitamins, Minerals, and Trace Elements	1013
Monitoring and Treatment	1013
Enteral Supplementation	1013
Supplementation of Dialysate Fluids	1013
Appetite Stimulants	1014
Metabolic Acidosis	1014
Exercise	1014
References	1014
88 Dermatologic Manifestations of Chronic Kidney Disease	1015
Uremic Pruritus	1015
Clinical Manifestations	1015
Pathogenesis	1015
Treatment	1015
Optimizing Dialysis and Mineral Metabolism Therapy	1015
Skin Emollients	1016
Antihistaminic Drugs	1016
Phototherapy	1017
5-Hydroxytryptamine Antagonist	1017
Opioid Receptor Agonists	1017
Gabapentin	1017
Immunomodulators and Immunosuppressive Agents	1017
Long-Chain Essential Fatty Acids	1018
Capsaicin	1018
Oral Activated Charcoal	1018
Miscellaneous	1018
Bullous Dermatoses	1018
Calcific Uremic Arteriolopathy (Calciphylaxis)	1018
Definition	1018
Pathogenesis	1018
Epidemiology and Risk Factors	1019
Clinical Manifestations	1019
Pathology	1019
Diagnosis and Differential Diagnosis	1019
Natural History	1019
Prevention and Treatment	1019
Nephrogenic Systemic Fibrosis	1020
Definition	1020
Pathogenesis	1020
Epidemiology	1020
Clinical Manifestations and Natural History	1021
Pathology	1022
Diagnosis and Differential Diagnosis	1022
Treatment and Prevention	1022
References	1022
89 Acquired Cystic Kidney Disease and Malignant Neoplasms	1024
Definition	1024
Pathogenesis	1024
Epidemiology	1024
Clinical Manifestations	1024
Acquired Cystic Kidney Disease–Associated Renal Cell Carcinoma	1024
Pathology	1025
Diagnosis and Differential Diagnosis	1026
Natural History	1028
Treatment	1028
Malignant Neoplasms in Dialysis Patients	1028
References	1029
XVII Dialytic Therapies	1031
90 Approach to Renal Replacement Therapy	1032
Treatment Options for Renal Replacement Therapy	1032
Prediction of the Start of Dialysis	1032
Multidisciplinary Care in Advanced Chronic Kidney Disease	1032
Predialysis Education Programs	1032
Education About Transplantation	1034
When Should Dialysis Be Started?	1034
Limitations of a Purely Clinical Approach to the Initiation of Dialysis	1034
Limitations of a Purely “Lab Result–Based” Approach in the Initiation of Dialysis	1035
Choice Between Peritoneal Dialysis and Hemodialysis	1035
Contraindications to Peritoneal Dialysis	1035
Fresh Intra-abdominal Foreign Body	1035
Body Size Limitations and Intolerance of Intra-abdominal Fluid Volume	1036
Bowel Disease and Other Sources of Infection	1036
Severe Malnutrition or Morbid Obesity	1036
Contraindications to Hemodialysis	1036
Home Hemodialysis	1036
Patient Choice of Hemodialysis or Peritoneal Dialysis	1037
Reimbursement of Physicians and Funding of Dialysis Facilities	1037
Physician Preference	1037
Importance of Dialysis Access	1037
Decision Whether to Offer Renal Replacement Therapy	1037
Availability of Dialysis Facilities	1037
Selection of Patients by Physicians and Nephrologists	1039
Rationing Versus Rational Dialysis Treatment	1039
Predictive Factors	1040
Advising Patients About Prognosis on Dialysis	1040
Patient Who Does Not Want Dialysis	1041
Disagreement About a Decision to Dialyze	1041
Management of Disruptive Patients on Dialysis	1041
Resuscitation and Withdrawal of Dialysis	1042
Cardiopulmonary Resuscitation	1042
Withdrawal of Dialysis	1042
References	1042
91 Vascular Access for Dialytic Therapies	1045
Evaluation of the Patient for Vascular Access	1045
Primary Autologous Vascular Access	1045
Radiocephalic Arteriovenous Fistula	1045
Nonmaturation of Radiocephalic Arteriovenous Fistula	1046
Secondary Autologous Vascular Access	1046
Forearm Cephalic and Basilic Vein Transposition and Elevation	1046
Elbow and Upper Arm Cephalic Vein Arteriovenous Fistula	1046
Upper Arm Basilic Vein Arteriovenous Fistula	1046
Nonautogenous Prosthetic Vascular Access	1047
Measures to Improve Graft Patency	1048
Pharmacologic Approaches for Access Patency	1048
Lower Limb Vascular Access	1049
Vascular Access Complications	1049
Nonmaturation of Arteriovenous Fistulas	1049
Stenosis and Thrombosis	1050
Autogenous Fistula Stenosis or Thrombosis	1050
Arteriovenous Graft Stenosis or Thrombosis	1050
Central Venous Obstruction	1050
Endovascular Intervention	1050
Surgical Intervention	1051
Vascular Access–Induced Ischemia	1051
Diagnosis of Ischemia	1051
Endovascular and Surgical Management of Ischemia	1051
Central Venous Catheter Access	1052
Nontunneled Catheters	1052
Tunneled Catheters	1052
Catheter Infection	1053
Infections Involving Temporary Catheters	1053
Exit Site Versus Tunnel Track Infections	1053
Catheter-Associated Bacteremia	1053
Catheter Removal	1054
Prevention of Infection	1054
Catheter Obstruction	1054
References	1055
92 Diagnostic and Interventional Nephrology	1057
Ultrasound	1057
Applications and Limitations of Ultrasound	1057
Chronic Kidney Disease	1057
Acute Kidney Injury	1057
Renal Transplant	1057
Renal Biopsy	1057
Urinary Bladder	1057
Hemodialysis Access	1057
Renovascular Ultrasound	1057
Equipment	1058
Procedure	1058
Training and Certification	1058
Peritoneal Dialysis Catheters	1058
Catheter Insertion	1058
Burying the Peritoneal Dialysis Catheter	1061
Complications of Peritoneal Dialysis Catheter Insertion	1061
Catheter Repositioning	1061
Removal of Peritoneal Dialysis Catheters	1061
Training and Certification	1062
Tunneled Hemodialysis Catheters	1062
Catheter Insertion	1062
Catheter Dysfunction	1062
Catheter Exchange and Fibrin Sheath Removal	1063
Training and Certification	1063
Procedures on Arteriovenous Fistulas and Grafts	1063
Percutaneous Balloon Angioplasty	1063
Percutaneous Thrombectomy	1064
Stents	1064
Training and Certification	1065
References	1065
93 Hemodialysis:	1067
Dialysis System	1067
Dialyzer Designs	1067
Dialysis Membranes	1067
Materials	1067
Transport Properties	1067
Safety Monitors	1068
Anticoagulation	1068
Dialysate Fluid	1069
Water and Water Treatment	1069
Dialysis Solution	1070
Biocompatibility	1071
Hemofiltration	1071
Hemodiafiltration	1071
Dialysis Time and Frequency	1072
Additional Devices and Technologies	1073
Relative Blood Volume Monitoring	1073
Ultrafiltration Profiling	1073
Sodium Profiling	1073
Online Clearance Monitoring	1073
Blood Temperature Monitoring	1073
Bioimpedance	1073
Sorbents, Nanotechnology, Wearable Artificial Kidney	1073
References	1073
94 Hemodialysis:	1075
Adequacy of Dialysis Dose	1075
Uremic Toxins	1075
Urea as a Surrogate Marker of Uremic Toxicity	1075
Assessment of Dialysis Dose	1075
Intradialytic Urea Kinetics	1077
Urea Reduction Ratio	1077
Single-Pool Kt/V (spKt/V)	1078
Weekly Standard Kt/V (std-Kt/V)	1078
Prescription of Dialysis Dose	1079
Example	1079
Is V the Adequate Denominator for Kt/V?	1079
Factors Affecting Delivered Kt/V	1079
Recommendations for Dialysis Dose Adequacy	1080
Other Dialysis Factors Related to Outcomes	1080
Middle Molecule Removal	1080
Phosphate Removal	1080
Preservation of Residual Renal Function	1081
Dialysate Composition	1081
Sodium	1081
Potassium	1081
Calcium	1081
Bicarbonate	1081
Treatment Time	1081
Fluid Status	1082
Nutritional Status	1082
Vascular Access	1082
Quality of Life	1082
References	1082
95 Acute Complications During Hemodialysis	1084
Cardiovascular Complications	1084
Intradialytic Hypotension	1084
Intradialytic Hypertension	1084
Cardiac Arrhythmias	1085
Sudden Death	1086
Pericarditis	1086
Dialysis-Associated Steal Syndrome	1086
Neuromuscular Complications	1087
Muscle Cramps	1087
Restless Legs Syndrome	1087
Dialysis Disequilibrium Syndrome	1087
Seizures	1087
Headache	1087
Hematologic Complications	1088
Complement Activation and Dialysis-Associated Neutropenia	1088
Intradialytic Hemolysis	1088
Hemorrhage	1088
Thrombocytopenia	1089
Pulmonary Complications	1089
Dialysis-Associated Hypoxemia	1089
Technical Malfunctions	1089
Air Embolism	1089
Incorrect Dialysate Composition	1090
Hypernatremia	1090
Hyponatremia	1090
Metabolic Acidosis	1091
Metabolic Alkalosis	1091
Temperature Monitor Malfunction	1091
Blood Loss	1091
Clotting of Dialysis Circuit	1091
Dialysis Reactions	1091
Anaphylactic and Anaphylactoid Reactions	1091
Clinical Presentation	1091
First-Use Reactions	1092
Reuse Reactions	1092
Bradykinin-Mediated Reactions	1092
Drug-Induced Reactions	1093
Treatment and Prevention	1093
Mild Reactions	1093
Fever and Pyrogenic Reactions	1093
Investigation of a Dialysis Outbreak	1094
Miscellaneous Complications	1094
Postdialysis Fatigue	1094
Pruritus	1094
Genitourinary Problems	1094
Hearing and Visual Loss	1095
References	1095
96 Peritoneal Dialysis:	1097
Advantages and Limitations of Peritoneal Dialysis	1097
Principles of Peritoneal Dialysis	1097
Three-Pore Model	1097
Fluid Kinetics	1098
Effective Peritoneal (Vascular) Surface Area	1099
Peritoneal Access	1099
Techniques of Peritoneal Dialysis	1100
Peritoneal Dialysis Fluids	1101
Electrolyte Concentration	1101
Osmotic Agents	1101
Assessments of Peritoneal Solute Transport and Ultrafiltration	1102
Small-Solute Removal	1102
Large-Solute Removal	1102
Ultrafiltration	1102
Peritoneal Membrane Function	1102
Peritoneal Equilibration Test	1102
Mini–Peritoneal Equilibration Test	1103
Double–Mini–Peritoneal Equilibration Test	1103
Residual Renal Function	1103
Adequacy	1104
Small-Solute Clearance	1104
Fluid Balance	1104
Management of Fluid Overload	1104
Nutrition	1105
Outcome of Peritoneal Dialysis	1105
References	1105
97 Complications of Peritoneal Dialysis	1107
Catheter Malfunction	1107
Optimal Timing and Placement of the Peritoneal Dialysis Catheter	1107
Catheter Function: Inflow	1107
Catheter Function: Outflow	1107
Fibrin in the Dialysate	1107
Fluid Leaks	1108
External Leaks	1108
Internal Leaks	1108
Hydrothorax	1108
Pain Related To Peritoneal Dialysis	1109
Inflow Pain	1109
Outflow Pain	1109
Blood-Stained Dialysate	1109
Infectious Complications	1109
Peritonitis	1109
Diagnosis of Peritonitis	1109
Treatment of Peritonitis	1110
Fungal Peritonitis	1111
Relapsing Peritonitis	1111
Culture-Negative Peritonitis	1111
Exit Site Infection	1111
Reduced Ultrafiltration and Ultrafiltration Failure	1112
Definition and Significance of Ultrafiltration Failure	1112
Establishing the Causes of Ultrafiltration Failure	1112
Fast Peritoneal Solute Transport Rate–Related Ultrafiltration Failure: Diagnosis and Management	1112
Low Osmotic Conductance–Related Ultrafiltration Failure: Diagnosis and Management	1112
Changes in Peritoneal Structure and Function	1112
Preventing Membrane Injury	1113
Encapsulating Peritoneal Sclerosis	1114
Nutritional and Metabolic Complications	1114
Undernutrition	1114
Acid-Base Status	1115
Lipids and Obesity	1115
References	1115
98 Dialytic Therapies for Drug Overdose and Poisoning	1116
Treatment Modalities	1116
Intermittent Hemodialysis and Hemofiltration	1116
Peritoneal Dialysis	1117
Continuous Renal Replacement Therapy	1117
Hemoperfusion	1118
Other Modalities	1118
When Should Extracorporeal Removal Be Commenced?	1118
Extracorporeal Therapy for Specific Drugs and Poisons	1119
Alcohols	1119
β-Blockers	1119
Lithium	1120
Metformin	1120
Salicylates	1120
Theophylline	1120
Valproate	1120
References	1121
99 Plasma Exchange	1122
Techniques	1122
Complications	1125
Mechanisms of Action	1125
Indications for Plasma Exchange	1125
Anti–Glomerular Basement Membrane Antibody Disease (Goodpasture Disease)	1125
XVIII Transplantation	1131
100 Immunologic Principles in Kidney Transplantation	1132
Ischemia-Reperfusion Injury	1132
Antigen Presentation	1132
Antigen-Presenting Cells	1132
T Cell Ontogeny and Major Histocompatibility Complex Specificity	1133
Pathways of Allorecognition	1133
Major Histocompatibility Complex	1134
Human Leukocyte Antigen Typing and Transplantation	1135
Human Leukocyte Antigen Inheritance	1135
Non–Major Histocompatibility Complex Antigens	1135
T Cell Activation	1135
T Cell Receptor	1136
CD4 and CD8 Coreceptors	1136
T Cell Receptor Engagement of Antigen: Signal 1	1136
T Cell Costimulation: Signal 2	1136
T Cell Clonal Expansion and Differentiation	1136
Memory Cells	1137
Effector Functions	1138
Cytotoxic T Lymphocyte Differentiation and Function	1138
Macrophage Activation	1138
Humoral Immune Response	1139
Natural Killer Lymphocytes	1139
Termination of the Immune Response	1140
Allograft Rejection	1140
Recruitment of Cells into the Interstitium of Kidney Allografts	1140
Acute T Cell–Mediated Rejection	1141
Acute Antibody-Mediated Rejection	1142
Chronic Rejection	1142
Transplantation Tolerance	1142
References	1143
101 Immunosuppressive Medications in Kidney Transplantation	1144
Small-Molecule Drugs	1144
Corticosteroids	1144
Mechanism of Action	1144
Pharmacokinetics	1144
Side Effects	1144
Calcineurin Inhibitors	1144
Mechanism of Action	1146
Pharmacokinetics, Monitoring, and Drug Interactions	1146
Side Effects	1147
Mycophenolate	1147
Mechanism of Action	1147
Pharmacokinetics	1148
Side Effects	1148
Azathioprine	1148
Mammalian Target of Rapamycin Inhibitors	1148
Mechanism of Action	1148
Pharmacokinetics	1149
Side Effects	1149
Dihydroorotate Dehydrogenase Inhibitors	1149
Biologic Agents	1149
Polyclonal Antilymphocyte Sera	1149
Murine Monoclonal Anti-CD3 Antibody	1150
Humanized Monoclonal Anti-CD52 Antibody	1150
Monoclonal Anti-CD25 Antibody	1150
B Cell–Depleting Monoclonal Anti-CD20 Antibody	1150
Intravenous Immunoglobulin	1151
Belatacept	1151
Other Agents Used	1151
Bortezomib	1151
Eculizumab	1151
References	1151
102 Evaluation and Preoperative Management of Kidney Transplant Recipient and Donor	1152
Recipient Evaluation	1152
Cardiovascular Disease	1152
Coronary Heart Disease and Left Ventricular Dysfunction	1152
Cerebrovascular Disease	1152
Peripheral Vascular Disease	1153
Cancer	1153
Infectious Complications	1154
Obesity	1155
Recurrent Disease	1155
Gastrointestinal Disease	1155
Genitourinary Disorders	1155
Pulmonary Disease	1155
Psychosocial Issues	1155
Presence of Multiple Comorbidities	1155
Reevaluation of Patients on the Waiting List	1156
Donor Evaluation	1156
Deceased Donors	1156
Classification of the Deceased Donor	1156
Evaluation of the Deceased Donor	1156
Deceased Donor Management Before Transplantation	1157
Living Donors	1157
Mortality and Morbidity	1158
Evaluation of the Living Donor	1158
Assessment of Renal Function	1159
Hypertension and Proteinuria in the Living Donor	1159
Obesity and Abnormal Glucose Tolerance in the Living Donor	1159
Renal Abnormalities in the Living Donor	1160
Malignant Disease	1160
Cardiovascular and Pulmonary Disease	1160
Compatibility and Immunologic Considerations	1160
Blood Group Compatibility	1160
Human Leukocyte Antigen Compatibility	1161
Assessing Human Leukocyte Antigen Sensitization	1161
References	1162
103 Kidney Transplantation Surgery	1164
Sources of Kidneys for Transplantation	1164
Donation Before Cardiac Death Donors	1164
Donation After Cardiac Death Donors	1164
Donation After Cardiac Death Protocol	1164
Uncontrolled DCD Donors	1164
Controlled DCD Donors	1165
Living Kidney Donors	1165
Preoperative Imaging	1165
Minimal Access (Laparoscopic) Donor Nephrectomy	1165
Transperitoneal Laparoscopic Donor Nephrectomy	1166
Hand-Assisted Laparoscopic Donor Nephrectomy	1167
Retroperitoneoscopic Operative Technique	1167
Contraindications to Minimal Access Donor Nephrectomy	1167
Effect of Pneumoperitoneum	1167
Graft Function and Acute Rejection	1167
Technical Issues	1167
Postoperative Recovery	1167
Choice of Donor Operative Technique	1167
Renal Preservation	1167
Renal Transplantation Procedure	1168
Vascular Anastomosis	1168
Urinary Drainage	1168
Alternative Techniques of Urinary Reconstruction	1169
Drainage and Wound Closure	1169
Postoperative Course	1169
Surgical Complications of Renal Transplantation	1169
Wound Infection	1170
Wound Dehiscence	1170
Vascular Complications	1170
Bleeding from Vessels in the Renal Hilum	1170
Anastomotic Hemorrhage	1170
Renal Artery Thrombosis	1171
Renal Vein Thrombosis	1171
Transplant Renal Artery Stenosis	1171
Lymphocele	1171
Urologic Complications	1172
Urinary Leaks	1172
Ureteral Obstruction	1172
Complications in the Transplant Bed	1174
Transplant Nephrectomy	1174
References	1174
104 Prophylaxis and Treatment of Kidney Transplant Rejection	1176
Definition	1176
Antibody-Mediated Rejection	1176
T Cell–Mediated Rejection	1178
Borderline Rejection	1179
Clinical Manifestations	1180
Prophylaxis and Prevention	1180
Prophylaxis	1180
Prevention of Acute T Cell–Mediated Rejection: Induction Therapy	1180
Prevention of Acute Antibody-Mediated Rejection: Desensitization	1181
Maintenance Therapy for the Prevention of Acute Rejection	1182
Calcineurin Inhibitors in the Prevention of Acute Rejection	1182
Antiproliferative Agents in the Prevention of Acute Rejection	1183
Acute Rejection Rates in Calcineurin Inhibitor– and Corticosteroid-Sparing Immunosuppression Regimens	1183
Treatment	1184
Acute T Cell–Mediated Rejection	1184
Acute Antibody-Mediated Rejection	1185
Chronic Rejection (T Cell and/or Antibody Mediated)	1185
Prognosis	1185
Summary	1185
References	1185
105 Medical Management of the Kidney Transplant Recipient:	1188
Infectious Diseases	1188
Immunizations Before and After Transplantation	1188
Infectious Causes	1188
Donor-Derived Infections	1188
Month 1 After Transplantation	1189
Months 1 to 6	1189
After 6 Months	1190
Management and Prophylactic Therapy for Selected Infections	1190
Cytomegalovirus Infection	1190
Clinical Manifestations	1190
Immunomodulating Effects of Cytomegalovirus Infection	1191
Risk Factors for Cytomegalovirus Infection	1191
Prevention	1191
Treatment	1191
Candida Infections	1192
BK Virus Infection	1192
Other Infections	1194
Gastrointestinal Disease	1195
Drug-Related Gastrointestinal Complications	1195
Infections	1195
Cytomegalovirus Infection	1195
Herpes Simplex Virus Infection	1195
Fungal Infections	1195
Helicobacter Infection	1195
Colon Disorders	1196
Transplant-Associated Malignant Neoplasms	1196
Post-transplant Lymphoproliferative Disorder	1197
Risk Factors	1198
Type of Organ Transplant	1198
Age	1198
Type of Immunosuppression	1198
Calcineurin Inhibitors	1198
mTOR Inhibitors	1198
Antimetabolites	1198
Induction Agents	1198
Belatacept	1198
Viral Infection	1198
Epstein-Barr Virus	1198
Cytomegalovirus	1198
Hepatitis C Virus	1198
Miscellaneous	1198
Clinical Manifestations	1198
Treatment	1199
Skin Cancers	1199
Management of Immunosuppressive Therapy in Post-transplantation Malignant Neoplasms	1199
References	1200
106 Medical Management of the Kidney Transplant Recipient:	1202
Cardiovascular Disease	1202
Conventional Cardiovascular Disease Risk Factors	1202
Post-transplantation Hypertension	1202
Post-transplantation Dyslipidemia	1203
New-Onset Diabetes After Transplantation	1204
Management of New-Onset Diabetes After Transplantation	1205
Patient-Centered Approach	1205
Target Hemoglobin A1c Levels	1205
Therapeutic Interventions	1206
Nonpharmacologic Management	1206
Pharmacologic Treatment	1206
Cigarette Smoking	1206
Obesity	1206
Aspirin and Antiplatelet Therapies	1207
Unconventional Cardiovascular Disease Risk Factors	1207
Proteinuria	1207
Cardiac Troponin T	1207
Common Laboratory Abnormalities	1207
Anemia	1207
Leukopenia and Thrombocytopenia	1208
Erythrocytosis	1208
Hyperkalemia	1208
Hypokalemia	1208
Hypophosphatemia	1209
Hypercalcemia	1209
Hypomagnesemia	1209
Abnormal Liver Function Tests	1209
Bone and Mineral Metabolism After Transplantation	1210
Post-transplantation Bone Disease	1210
Osteoporosis	1211
Avascular Necrosis	1211
Prevention and Management of Post-transplantation Bone Diseases	1211
Gout	1212
Outpatient Care	1213
References	1213
107 Chronic Allograft Injury	1214
Definitions and Epidemiology	1214
Pathogenesis: Nonimmunologic Factors	1214
Donor Age, Donor Gender, and Donor-Recipient Size Mismatching	1214
Ischemia-Reperfusion Injury and Delayed Graft Function	1214
BK Virus Nephropathy	1214
Calcineurin Inhibitor Toxicity	1216
Recurrent and De Novo Glomerular Diseases	1216
Cardiovascular Risk Factors	1216
Pathogenesis: Immunologic Factors	1216
Acute Rejection	1216
Chronic Antibody-Mediated Rejection	1217
Insufficient Immunosuppression and Nonadherence to Medication	1218
Clinical Manifestations	1219
Pathology	1219
Diagnosis and Differential Diagnosis	1219
Management	1219
Prevention of Antibody-Mediated Allograft Injury	1219
Treatment of Chronic Allograft Injury	1220
References	1220
108 Recurrent Disease in Kidney Transplantation	1222
Definitions	1222
Recurrent Glomerulonephritis	1222
Recurrence of Specific Glomerular Diseases	1224
IgA Nephropathy and Henoch-Schönlein Purpura	1224
Membranous Nephropathy	1225
Focal Segmental Glomerulosclerosis	1226
Membranoproliferative Glomerulonephritis	1227
Membranoproliferative Glomerulonephritis Type I	1227
Dense Deposit Disease	1228
Membranoproliferative Glomerulonephritis Type III	1228
Congenital Nephrotic Syndrome	1228
Antineutrophil Cytoplasmic Antibody–Associated Pauci-immune Vasculitis	1228
Goodpasture Disease	1228
Lupus Nephritis	1228
Thrombotic Microangiopathy and Hemolytic Uremic Syndrome	1229
Scleroderma	1229
Amyloid, Light-Chain Disease, and Fibrillary and Immunotactoid Glomerulopathies	1229
Amyloidosis	1229
Light-Chain Nephropathy	1230
Fibrillary and Immunotactoid Glomerulopathies	1230
Recurrence of Metabolic Diseases Affecting the Kidney Transplant	1230
Diabetes Mellitus	1230
Primary Hyperoxaluria	1230
Fabry Disease	1230
Recurrence of Virus-Associated Nephropathies and Tumors in the Transplanted Kidney	1230
References	1231
109 Outcomes of Renal Transplantation	1233
Methods of Measurement and Analysis	1233
Types of Outcome Analyses	1233
Half-Life Analysis	1233
Graft Survival	1233
Randomized Controlled Trials	1234
Cohort Studies	1235
Meta-Analyses	1235
Case Reports	1236
Expert Opinion Guidelines	1236
Qualitative Studies	1236
Types of Data Collection	1236
Registries	1236
International Statistical Collections	1236
Randomized Controlled Trials	1236
Structured Reviews	1237
Variables Affecting the Outcomes of Transplantation	1237
Deceased Donor Variables	1237
Living Donor Variables	1238
Other Donor Variables	1238
Recipient Variables	1239
Effects of Immunosuppression on Transplant Outcome	1239
Transplant Center Variables	1240
Transplantation Matching Variables	1240
Outcomes Inform the Recipient Decision	1241
References	1241
110 Pancreas and Islet Transplantation	1243
Patient Selection Criteria for Pancreas or Islet Transplantation	1243
Indications for Transplantation	1243
Medical Evaluation	1244
Pancreas Transplantation	1245
Patient and Graft Survival	1245
Enteric Drainage of the Pancreas Transplant	1245
Immunosuppression	1246
Graft Monitoring	1246
Antimicrobial Prophylaxis	1248
Metabolic Monitoring	1248
Surgical Complications	1248
Nonsurgical Complications	1249
Bladder Drainage of the Pancreas Transplant	1249
Current Indications	1249
Metabolic Complications	1249
Urologic Complications	1249
Urinary Tract Infections	1249
Enteric Conversion	1250
Late Complications	1250
Impact of Pancreas Transplantation on Diabetic Complications	1251
Hypoglycemia	1251
Hyperglycemia	1251
Microvascular Complications	1251
Retinopathy	1251
Neuropathy	1251
Nephropathy	1251
Vascular Disease	1251
Quality of Life and Social Issues	1252
Pregnancy After Pancreas Transplantation	1252
Islet Transplantation	1252
Islet After Kidney Transplantation	1252
Technique of Islet Transplantation	1253
Medical Complications	1253
Glycemic Control and Insulin Independence	1253
Immunosuppressive Regimens	1254
References	1255
111 Kidney Disease in Liver, Cardiac, Lung, and Hematopoietic Cell Transplantation	1257
Generic Issues of Kidney Disease in Nonrenal Solid Organ Transplantation	1257
Use of Serum Creatinine and Derived Equations to Measure Glomerular Filtration Rate	1257
Nephrotoxicity of Calcineurin Inhibitors	1257
Acute Kidney Injury in the Immediate Pretransplantation Period	1258
Acute Kidney Injury in the Early Post-transplantation Period	1258
Chronic Kidney Disease	1259
Management of Chronic Kidney Disease	1260
Prevention of Chronic Kidney Disease	1260
BK Virus Nephropathy	1260
Acute Kidney Injury in the Late Post-transplantation Period	1260
Kidney Disease in Liver Transplantation	1260
Kidney Disease in Cardiac Transplantation	1261
Kidney Disease in Lung Transplantation	1261
Kidney Disease in Hematopoietic Cell Transplantation	1262
Acute Kidney Injury After Hematopoietic Cell Transplantation	1262
Hepatic Sinusoidal Obstructive Syndrome	1263
Management of Acute Kidney Injury After Hematopoietic Cell Transplantation	1263
Chronic Kidney Disease After Hematopoietic Cell Transplantation	1263
Thrombotic Microangiopathy	1263
Calcineurin Inhibitor and Sirolimus Nephrotoxicity	1264
Glomerular Disease	1264
Management of Hematopoietic Cell Transplantation–Related Chronic Kidney Disease	1264
References	1265
Index	1267
A	1267
B	1270
C	1271
D	1275
E	1276
F	1278
G	1278
H	1280
I	1282
J	1284
K	1284
L	1285
M	1286
N	1288
O	1289
P	1289
Q	1292
R	1292
S	1295
T	1296
U	1297
V	1298
W	1299
X	1299
Y	1299
Z	1299
Inside Back Cover	ibc1

SPEC – Comprehensive Clinical Nephrology, 5e eBook (12-Month Access)

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