SPEC - Comprehensive Clinical Nephrology

Richard J. Johnson; John Feehally; Jurgen Floege; Marcello Tonelli

BOOK

SPEC - Comprehensive Clinical Nephrology

Richard J. Johnson | John Feehally | Jurgen Floege | Marcello Tonelli

(2018)

Additional Information

Book Details

ISBN: 978-0-323-54719-2
Edition: 6
Language: English
Pages: 1312
Subjects: Renal medicine & nephrology
Radiology

Abstract

Written and edited by world leaders in nephrology, Comprehensive Clinical Nephrology, 6th Edition, by Drs. John Feehally, Jurgen Floege, Richard J. Johnson, and Marcello Tonelli, provides current information on clinical procedures and conditions as well as the scientific facts and pathophysiology that are foundational to nephrology practice. Ideal for practicing nephrologists, fellows, residents, and internists, it thoroughly covers fluids and electrolytes, hypertension, diabetes, dialysis, and transplantation, and more – all in a single convenient volume.

A "just right" amount of basic science and practical clinical guidance helps you make efficient and informed decisions.

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

New quick-reference boxes with links to clinical guidelines in all relevant chapters.

New chapters on common issues regarding prescribing in kidney disease, palliative nephrology, endemic nephropathies, pathophysiology of chronic kidney disease, and outcomes of dialysis.

Section Title	Page	Action	Price
Front Cover	cover
Inside Front Cover	ifc1
Comprehensive Clinical Nephrology	i
Copyright Page	iv
Table Of Contents	v
Preface	viii
List of Contributors	ix
Dedication	xix
I Essential Renal Anatomy and Physiology	1
1 Renal Anatomy	1
Structure of the Kidney	1
Nephrons	1
Collecting Ducts	1
Microvasculature	1
Glomerulus (Renal Corpuscle)	2
Glomerular Basement Membrane	3
Mesangium	4
Mesangial cells.	4
Mesangial matrix.	4
Endothelium	4
Visceral Epithelium (Podocytes)	5
Function and Maintenance of the Filtration Barrier	6
Filtration pressure and expansion.	6
Filtrate flow and shear stress.	6
Barrier function.	7
Pathology.	8
Parietal Epithelium	8
Renal Tubule	8
Proximal Tubule	8
Intermediate Tubule	9
Distal Straight Tubule (Thick Ascending Limb of the Loop of Henle)	9
Distal Convoluted Tubule	9
Collecting Duct System	9
Collecting Ducts	10
Juxtaglomerular Apparatus	10
Renal Interstitium	12
References	12
Self-assessment Questions	13.e1
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	16
Tubular Transport	17
Passive Transport	17
Active Transport	18
Transport in Specific Nephron Segments	18
Proximal Tubule	18
Loop of Henle	18
Distal Nephron	18
Glomerulotubular Balance	20
Countercurrent System	22
Role of Urea	23
Vasa Recta	24
Renal Medullary Hypoxia	24
Vasopressin (Antidiuretic Hormone) and Water Reabsorption	24
Integrated Control of Renal Function	25
Renal Interstitial Hydrostatic Pressure and Nitric Oxide	25
Renal Sympathetic Nerves	25
Renin-Angiotensin-Aldosterone System	25
Eicosanoids	26
Atrial Natriuretic Peptide	26
Endothelins	26
Purines	27
Exosomes, Other Extracellular Vesicles and Luminal Factors	27
References	27
Self-assessment Questions	28.e1
II Investigation of Renal Disease	29
3 Assessment of Glomerular Filtration Rate	29
Glomerular Filtration Rate	29
Measurement and Estimation of the Glomerular Filtration Rate	29
Clearance Measurements	29
Concept of Clearance	29
Urinary Clearance	30
Plasma Clearance	30
Estimation of the Glomerular Filtration Rate	30
Filtration Markers	31
Exogenous Filtration Markers	31
Endogenous Filtration Markers	31
Creatinine	31
Metabolism and Excretion	31
Creatinine Assay	32
Estimated Glomerular Filtration Rate From Serum Creatinine	33
Equation Currently Recommended for Use	33
Equations Previously Recommended for Use	33
Other Equations That Could Be Considered for Use in Selected Populations	33
Cystatin C	33
Metabolism and Excretion	33
Cystatin C Assay	33
Estimated Glomerular Filtration Rate From Serum Cystatin C	33
Urea and Other Metabolites	34
Other Low-Molecular-Weight Serum Proteins	34
Clinical Application of Estimated Glomerular Filtration Rate	34
Chronic Kidney Disease	34
Acute Kidney Disease	34
Living Kidney Donor Candidates	35
Drug Dosing	35
References	37
Self-Assessment Questions	38.e1
4 Urinalysis	39
Definition	39
The Urine Sample	39
Physical Characteristics	39
Color	39
Turbidity	40
Odor	40
Relative Density	40
Chemical Characteristics	40
pH	41
Hemoglobin	41
Glucose	41
Protein	41
Albumin Reagent Strip	41
24-Hour Protein Excretion	41
Protein-to-Creatinine Ratio and Albumin-to-Creatinine Ratio on Random Urine Sample	41
Specific Proteins	42
Albuminuria.	42
Tubular proteins.	42
Bence Jones proteinuria.	42
Leukocyte Esterase	42
Nitrites	42
Ketones	42
Urine Microscopy	42
Methods	42
Cells	43
Erythrocytes	43
Leukocytes	44
Renal Tubular Epithelial Cells	44
Transitional Epithelial Cells	44
Squamous Epithelial Cells	44
Lipids	44
Casts	44
Crystals	47
Common Crystals	47
Uric acid crystals and amorphous urates.	47
Calcium oxalate crystals.	47
Calcium phosphate crystals (brushite) and amorphous phosphates.	47
Triple phosphate (struvite) crystals.	47
Pathologic Crystals	47
Cholesterol crystals.	47
Cystine crystals.	47
2,8-dihydroxyadenine(2,8-DHA) 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 Kidney Injury	49
Urinary Tract Infection	50
BK Virus Infection	50
Urologic Diseases	51
Nonspecific Urinary Abnormalities	51
Automated Analysis of Urine Sediment	51
References	51
Self-Assessment Questions	52.e1
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	57
Intravenous Contrast Urography	58
Kidneys	58
Pelvicalyceal System	59
Ureters	59
Bladder	59
Retrograde Pyelography	59
Antegrade Pyelography	59
Imaging Ileal Conduits	59
Cystography	59
Computed Tomography	60
Tissue Density	60
Contrast-Enhanced and Noncontrast Computed Tomography	60
Computed Tomographic Angiography	61
Dual-Energy Computed Tomography	62
Limitations of Computed Tomography	62
Magnetic Resonance Imaging	62
Contrast-Enhanced Magnetic Resonance Imaging	63
Magnetic Resonance Urography	64
Magnetic Resonance Angiography	65
Disadvantages of Magnetic Resonance Imaging	65
Incidental Findings	66
Measurement of Glomerular Filtration Rate	66
Angiography	66
Renal Venography	66
Nuclear Scintigraphy	66
Glomerular Filtration Agents	67
Tubular Secretion Agents	67
Tubular Retention Agents	67
Renogram	67
Cortical Imaging	68
Vesicoureteral Reflux	68
Renal Transplant	68
Positron Emission Tomography	68
Molecular Imaging	69
Radiologic Contrast Agents	69
X-ray Contrast Agents	69
Contrast-Induced Nephropathy	69
Magnetic Resonance Contrast Agents	69
References	70
Self-Assessment Questions	71.e1
6 Renal Biopsy	72
Indications for Renal Biopsy	72
Nephrotic Syndrome	72
Acute Kidney Injury	72
Systemic Disease Associated With Renal Dysfunction	72
Renal Transplant Dysfunction	73
Non-Nephrotic Proteinuria	73
Isolated Microhematuria	73
Unexplained Chronic Kidney Disease	73
Familial Renal Disease	73
Role of Repeat Renal Biopsy	73
Value of Renal Biopsy	73
Biopsy Adequacy	73
Is Renal Biopsy a Necessary Investigation?	74
Prebiopsy Evaluation	74
Contraindications to Renal Biopsy	75
Renal Biopsy Technique	75
Percutaneous Renal Biopsy	75
Native Renal Biopsy	75
Renal Transplant Biopsy	77
Postbiopsy Monitoring	77
Alternatives to the Percutaneous Approach	78
Transvenous (Transjugular or Transfemoral) Renal Biopsy	78
Open Renal Biopsy	78
Laparoscopic Renal Biopsy	78
Complications of Renal Biopsy	78
Pain	78
Hemorrhage	78
Arteriovenous Fistula	78
Other Complications	78
Death	79
References	79
Self-assessment Questions	79.e1
III Fluid and Electrolyte Disorders	80
7 Disorders of Extracellular Volume	80
Extracellular Fluid Compartment	80
Regulation of Extracellular Fluid Homeostasis	80
Afferent (Sensor) Limb	80
Glomerulotubular Balance	81
Pressure Natriuresis	82
Efferent (Effector) Limb	82
Renin-Angiotensin-Aldosterone System	82
Sympathetic Nervous System	83
Natriuretic Peptides	83
Prostaglandins	83
Arginine Vasopressin	83
Other Hormones	83
Terms Useful for Disorders of Extracellular Fluid Volume	83
Extracellular Fluid Volume Contraction	83
Extrarenal Causes	83
Gastrointestinal Losses	83
Dermal Losses	84
Third-Space Sequestration	84
Hemorrhage	84
Renal Losses	84
Diuretic Use	84
Genetic and Acquired Tubular Disorders	84
Hormonal and Metabolic Disturbances	84
Renal Water Loss	84
Clinical Manifestations of Extracellular Fluid Volume Contraction	84
Laboratory Tests	84
Therapy of Extracellular Fluid Volume Contraction	85
Extracellular Fluid Volume Expansion	85
Pathogenesis	86
Capillary Hemodynamic Disturbances	86
Renal Sodium Retention	86
Primary renal sodium retention.	86
Secondary renal sodium retention.	86
Sodium and Water Retention in Heart Failure	86
Sodium and Water Retention in Cirrhosis	87
Sodium and Water Retention in Nephrotic Syndrome	87
Drug-Induced Edema	89
Idiopathic Edema	89
Sodium and Water Retention in Pregnancy	89
Clinical Manifestations of Extracellular Fluid Volume Expansion	89
Diagnostic and Therapeutic Approach to Extracellular Volume Expansion	89
Diuretics	90
Principles of Action	90
Classes of Diuretics	90
Loop diuretics.	90
Distal convoluted tubule diuretics.	91
Collecting duct diuretics.	91
Proximal tubule diuretics.	91
Osmotic diuretics.	91
Adverse Effects	91
Approach to Diuretic Treatment of Extracellular Fluid Volume Expansion	92
Diuretic Resistance	92
References	92
Self-Assessment Questions	93.e1
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	96
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 kidney disease.	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	100
Cerebral Edema	101
Osmotic Demyelination	101
Treatment of Hyponatremia	102
Acute Symptomatic Hyponatremia	102
Chronic Symptomatic Hyponatremia	102
Chronic “Asymptomatic” Hyponatremia	103
Fluid restriction.	103
Increase solute excretion.	104
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	105
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
Self-assessment Questions	110.e1
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	114
Hypokalemia	115
Epidemiology	115
Clinical Manifestations	115
Cardiovascular	115
Hormonal	115
Muscular	115
Renal	115
Etiology	116
Pseudohypokalemia	116
Redistribution	116
Nonrenal Potassium Loss	116
Renal Potassium Loss	116
Drugs.	116
Endogenous hormones.	116
Genetic causes.	116
Magnesium depletion.	116
Primary renal defect.	116
Bicarbonaturia.	116
Diagnostic Evaluation	116
Treatment	117
Hyperkalemia	118
Epidemiology	118
Clinical Manifestations	118
Etiology	118
Pseudohyperkalemia	119
Redistribution	119
Excess Intake	120
Impaired Renal Potassium Excretion	120
Determining the Role of Excessive Potassium Intake in Chronic Hyperkalemia	120
Treatment	120
Acute Therapy	120
Blocking cardiac effects.	121
Cellular potassium uptake.	121
Potassium removal.	121
Chronic Treatment	122
References	122
Self-Assessment Questions	123.e1
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	130
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	133
Lytic States	134
Treatment-Induced Hyperphosphatemia	134
Hypoparathyroidism	134
Chronic Hypocalcemia	134
Acromegaly	134
Familial Tumoral Calcinosis	134
Respiratory Alkalosis With Prolonged Hyperventilation	134
Clinical Manifestations	135
Treatment	135
Hypophosphatemia	135
Causes of Hypophosphatemia	135
Inherited Forms of Hypophosphatemia	135
Autosomal dominant hypophosphatemic rickets.	135
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.	136
Hyperparathyroidism.	136
Post-transplant hypophosphatemia.	136
Acute respiratory alkalosis.	136
Diabetic ketoacidosis.	136
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	137
Hypermagnesemia	139
Clinical Manifestations	139
Treatment	139
Hypomagnesemia and Magnesium Deficiency	139
Clinical Manifestations	140
Treatment	140
References	140
Self-Assessment Questions	141.e1
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 the Loop of Henle	144
Distal Nephron	144
Net Acid Excretion	145
Ammonia Metabolism	146
Regulation of Renal Acidification	146
Blood pH	146
Mineralocorticoids, Distal Sodium Delivery, and Extracellular Fluid Volume	147
Plasma Volume	148
Potassium	148
References	148
Self-Assessment Questions	148.e1
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
Self-Assessment Questions	159.e1
13 Metabolic Alkalosis	160
Definition	160
Bicarbonate Transport Along the Nephron	160
Factors Affecting Bicarbonate Reabsorption and Secretion	160
Angiotensin II	160
Aldosterone	160
Pendrin	160
Hypokalemia	160
Pathophysiology of Metabolic Alkalosis	160
Secondary Stimulation of Collecting Duct Ion Transport	161
Chloride Depletion	161
Potassium Depletion	162
Primary Stimulation of Collecting Duct Ion Transport	162
Exogenous Alkali	162
Secondary Response to the Alkalemia Induced by HCO3− Retention	163
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	165
Congenital Chloridorrhea	165
Other Causes of Excessive Chloride Losses	165
Severe K+ Deficiency	165
Primary Stimulation of Collecting Duct Ion Transport	165
Mineralocorticoid Excess	165
Apparent Mineralocorticoid Excess Syndromes	166
Alkali Administration	166
Other Causes	166
Clinical Manifestations	167
Diagnosis	167
Treatment	167
Chloride Depletion Metabolic Alkalosis	167
Mineralocorticoid and Apparent Mineralocorticoid-Induced Metabolic Alkalosis	167
Alkali Ingestion	168
Special Problems in Management	168
References	169
Self-assessment Questions	169.e1
14 Respiratory Acidosis, Respiratory Alkalosis, and Mixed Disorders	170
Respiratory Acidosis (Primary Hypercapnia)	170
Definition	170
Etiology and Pathogenesis	170
Secondary Physiologic Response	170
Clinical Manifestations	171
Neurologic	171
Cardiovascular	171
Renal	171
Diagnosis	171
Treatment	171
Respiratory Alkalosis (Primary Hypocapnia)	174
Definition	174
Etiology and Pathogenesis	174
Secondary Physiologic Response	175
Clinical Manifestations	175
Diagnosis	176
Treatment	176
Mixed Acid-Base Disturbances	176
Definition	176
Etiology and Pathogenesis	176
Metabolic Acidosis and Respiratory Acidosis	176
Metabolic Alkalosis and Respiratory Alkalosis	177
Metabolic Alkalosis and Respiratory Acidosis	177
Metabolic Acidosis and Respiratory Alkalosis	177
Metabolic Acidosis and Metabolic Alkalosis	178
Mixed Metabolic Acidosis	178
Mixed Metabolic Alkalosis	179
Triple Disorders	179
Clinical Manifestations	179
Diagnosis	180
Treatment	181
References	182
Self-assessments Questions	183.e1
IV Glomerular Disease	184
15 Introduction to Glomerular Disease	184
Definition	184
Clinical Evaluation of Glomerular Disease	184
History	184
Physical Examination	184
Laboratory Studies	185
Imaging	186
Renal Biopsy	186
Asymptomatic Urine Abnormalities	186
Asymptomatic Microhematuria	186
Pathogenesis	187
Evaluation	187
Asymptomatic Non-Nephrotic Proteinuria	187
Overflow Proteinuria	188
Tubular Proteinuria	188
Glomerular Proteinuria	188
Functional proteinuria.	188
Orthostatic proteinuria.	188
Fixed non-nephrotic proteinuria.	188
Asymptomatic Proteinuria With Hematuria	188
Macrohematuria	188
Nephrotic Syndrome	189
Definition	189
Etiology	189
Hypoalbuminemia	190
Edema	190
Metabolic Consequences of Nephrotic Syndrome	190
Negative Nitrogen Balance	190
Hypercoagulability	191
Hyperlipidemia and Lipiduria	191
Other Metabolic Effects of Nephrotic Syndrome	192
Infection	192
Acute and Chronic Changes in Renal Function	192
Acute Kidney Injury	192
Chronic Kidney Disease	192
Nephritic Syndrome	192
V Diabetic Kidney Disease	357
30 Pathogenesis, Clinical Manifestations, and Natural History of Diabetic Kidney Disease	357
Definitions	357
Pathogenesis of Diabetic Kidney Disease	357
Genetic and Environmental Factors	357
Hemodynamic Changes	357
Renal Hypertrophy and Mesangial Matrix Expansion	358
Inflammation and Diabetic Kidney Disease	359
Mechanisms Underlying Proteinuria	360
Tubular Changes	361
Hyperglycemia and Diabetic Kidney Disease	361
Role of Glucose Control	361
Protein kinase C pathway.	362
Advanced glycation end products pathway.	362
Polyol pathway.	362
Hexosamine pathway.	362
Adenosine monophosphate kinase.	362
Kallikrein-kinin pathway.	362
Activation of innate immunity.	363
Renin-Angiotensin-Aldosterone System and Diabetic Kidney Disease	363
Uric Acid and Fructose	364
Epidemiology	364
Clinical Manifestations and Natural History	365
Obesity, Metabolic Syndrome, and Renal Disease	365
Evolution of Diabetic Kidney Disease	365
Hypertension and Diabetic Kidney Disease	366
Associated Extrarenal Microvascular and Macrovascular Complications	366
Survival in Patients With Diabetic Kidney Disease	367
Renal Pathology	367
Diagnosis and Differential Diagnosis	369
Measurement of Albuminuria or Proteinuria	369
Measurement of Blood Pressure	369
Measurement of Serum Creatinine and Estimation of Glomerular Filtration Rate	371
Differential Diagnosis	371
Indications for Renal Biopsy	372
Approach to the Diabetic Patient With Impaired Renal Function	373
References	373
Self-Assessment Questions	375.e1
31 Prevention and Treatment of Diabetic Kidney Disease	376
Glycemic Control	376
Glycemic Targets	377
Antihyperglycemic Therapeutic Options in Type 2 Diabetic Kidney Disease	378
SGLT2 Inhibitors	378
Analogues of Human Glucagon-Like Peptide-1	378
Dipeptidyl Peptidase-4 Inhibitors	378
Blood Pressure Control	379
Renin-Angiotensin System Blockade in the Prevention of Diabetic Kidney Disease	379
Renin-Angiotensin System Blockade in the Treatment of Diabetic Kidney Disease	379
Type 1 Diabetic Patients	379
Type 2 Diabetic Patients	380
Aldosterone Blockade in Diabetic Kidney Disease	380
Combination Therapy With Renin-Angiotensin System Antagonists	380
Dosing and Adverse Effects Associated With Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers	380
Other Antihypertensive and Antiproteinuric Agents	381
Diuretics and Low Sodium Intake	381
Calcium Channel Blockers	381
β-Blockers	381
Treatment of Dyslipidemia	381
Nonpharmacologic Interventions	381
Emerging Treatments for Diabetic Kidney Disease	381
Mineralocorticoid Receptor Antagonists	382
Endothelin Receptor Antagonists	382
Vitamin D Receptor Activators	382
Xanthine Oxidase Inhibitors	383
Phosphodiesterase Inhibitors	383
Novel Therapeutic Approaches	383
References	383
32 Management of the Diabetic Patient With Chronic Kidney Disease	385
Diagnostic Considerations	385
General Management Considerations	385
Monitoring Diabetic Renal Disease (Stage CKD3b-5)	385
Hemoglobin A1c	385
Albuminuria	385
Management of Diabetes in Subjects With Stage 3B-5 CKD	387
Hypoglycemia and Hyperglycemia	388
Oral Hypoglycemic Agents	388
Biguanides	388
Sulfonylureas	388
Thiazolidinediones	388
Meglinitides	389
Incretin Mimetics: Glucagon-Like Peptide-1 Analogues	389
Gliptins: Dipeptidyl Peptidase-4 Inhibitors	389
α-Glucosidase Inhibitors	389
Amylin Analogues	389
SGLT-2 Inhibitors	389
Insulin	390
Types of insulin.	390
Future Therapeutics	390
Management of Hypertension in the Diabetic Subject With Chronic Kidney Disease	390
Blood Pressure Goals	390
What Agents Should Be Used?	392
Renin-Angiotensin-Aldosterone System Blockade	392
Cardiovascular Complications	392
Coronary Heart Disease	392
Peripheral Vascular Disease	392
Erectile Dysfunction	392
Antiplatelet Agents	392
Dyslipidemia	392
Microvascular Complications of Diabetes	393
Retinopathy	393
Neuropathy	393
Autonomic Neuropathy	393
Diabetic Foot Disease	393
Complications From Chronic Kidney Disease	393
Anemia	393
Mineral Bone Disease	393
Diet and Malnutrition	393
Electrolytes and Fluid Retention	394
End-Stage Renal Disease	394
Dialysis	394
Hemodialysis	394
Vascular Access	394
Peritoneal Dialysis	394
Transplantation	394
References	394
Self-assessment Questions	395.e1
VI Hypertension	396
33 Normal Blood Pressure Control and the Evaluation of Hypertension	396
Normal Blood Pressure Control	396
Definition and Classification of Hypertension	398
Blood Pressure in Relation to Morbidity and Mortality	399
Elevation of Blood Pressure by Arbitrary Cut-Off Points	400
Threshold of Therapeutic Benefit	401
Operational Definitions	401
Special Definitions	402
Prehypertension.	402
White coat hypertension.	403
Masked hypertension.	403
Sustained hypertension.	403
Pseudohypertension.	403
Isolated systolic hypertension.	405
Resistant hypertension.	405
Hypertensive emergencies and urgencies.	405
Hypertension in children and adolescents.	405
Hypertension in pregnancy.	406
Classification by Cause of Hypertension	406
Evaluation of Hypertension	406
Blood Pressure Measurement	406
Variability of Blood Pressure	406
Office Versus Home Blood Pressure and Circadian Variation	406
Home and Ambulatory Blood Pressure Monitoring	407
Risk Assessment in Hypertension	407
Consideration of Primary Versus Secondary Hypertension	408
References	410
Self-Assessment Questions	411.e1
34 Primary Hypertension	412
Definition	412
Etiology and Pathogenesis	412
Genetic (Polygene) Hypothesis	412
Congenital (Low Nephron Number) Hypothesis	412
The Role of the Immune System and Acquired Renal Injury	413
What Initiates the Renal Inflammatory Response?	414
How Does Sodium Retention Lead to Hypertension?	414
Pathogenic Mechanisms Driving the Current Epidemic of Hypertension	415
Epidemiology	415
Clinical Manifestations	416
Pathology	417
Diagnosis	417
Natural History	417
Kidney Disease	418
Effect of Antihypertensive Therapy on Natural History of Hypertensive Cardiovascular Disease and Kidney Disease Progression	419
Can Primary Hypertension Spontaneously Remit?	420
References	420
Self-Assessment Questions	421.e1
35 Nonpharmacologic Prevention and Treatment of Hypertension	422
Prevention	422
Weight Loss	422
Physical Activity	423
Exercise Training Dose Response	423
Mechanisms	423
Antihypertensive Medication and Guidelines for Exercise	423
Diet	423
Salt Intake	423
Potassium Intake	426
Calcium, Vitamin D, and Dairy Food Intake	427
Magnesium Intake, Other Micronutrients, and Bioactive Food Components	427
Dietary Sugars and Fats	427
Dietary Approaches to Lower Blood Pressure	427
Smoking	427
Alcohol	427
Caffeine	427
Psychological Stress	428
Adopting Lifestyle Modifications	428
References	428
Self-assessment Questions	429.e1
36 Pharmacologic Treatment of Hypertension	430
Defining Who Should Receive Pharmacologic Treatment	430
Blood Pressure Thresholds for Intervention (Office Blood Pressure)	430
Clinical Dilemma of End-Organ Damage and “Normal” Blood Pressure	430
Blood Pressure Thresholds for Intervention (Ambulatory and Home Blood Pressure Monitoring)	431
Blood Pressure Treatment Goals	431
Guide to Selection of Antihypertensive Agents	433
Key Principles From Clinical Trials	433
Selection of Drug Therapy	434
Thiazide and Thiazide-Like Diuretics	435
Potassium-Retaining Diuretics	436
β-Adrenoceptor Blockers	436
Calcium Channel Blockers	437
Blockade of Renin-Angiotensin System	437
Angiotensin-converting enzyme inhibitors.	437
Angiotensin receptor blockers.	437
Direct renin inhibitor.	438
α-Adrenergic Blockers	438
Combined α-Adrenergic and β-Adrenergic Blocker	438
Centrally Acting Sympatholytic Drugs	438
Direct Vasodilators	438
Treatment Strategies	438
Initial Drug Therapy	439
Choice of initial therapy.	439
Combination Therapy	440
Initial therapy with a two-drug combination.	441
Combining Renin-Angiotensin System Blockade	441
Resistant Hypertension	441
Medication to Reduce Cardiovascular Risk	442
Follow-Up	442
Withdrawal of Therapy	442
Indications for Specialist Referral	442
Hypertension in People of Black African Origin	442
Hypertension in Older People	442
References	443
Self-assessment Questions	443.e1
37 Evaluation and Treatment of Hypertensive Emergencies and Urgencies	444
Etiology and Pathogenesis	444
Epidemiology	446
Diagnostic Evaluation	446
Treatment	447
General Principles for Managing Hypertensive Emergencies	447
Specific Aspects of Antihypertensive Drug Use for Hypertensive Emergencies	447
Treatment of Hypertensive Urgencies	450
References	451
Self-assessment Questions	452.e1
38 Endocrine Causes of Hypertension	453
Etiology and Pathogenesis	453
Pathogenesis of Aldosterone-Dependent Hypertension	453
Other Hormones That Can Cause Hypertension Through Mineralocorticoid Receptor Activation	453
Types of Primary Aldosteronism	453
Familial Forms of Primary Aldosteronism	454
Familial Hypertension Type I	454
Familial Hyperaldosteronism Type II	454
Familial Hyperaldosteronism Type III	455
Familial Hyperaldosteronism Type IV	455
Sporadic Forms	456
Epidemiology	456
Clinical Manifestations	456
Diagnosis and Differential Diagnosis	457
Who to Screen for Primary Aldosteronism	457
Evaluation of Suspected Primary Aldosteronism	457
Use of the Aldosterone-Renin Ratio (ARR)	457
Effect of Drugs on Screening for Primary Aldosteronism	457
When to Withold Drugs That Affect the Renin-Angiotensin-Aldosterone System Before Screening	457
Confirmatory Testing	459
Differentiation of Etiology	459
Selection of Patients for Further Testing	459
Imaging Approaches	459
Adrenal Vein Sampling	460
Other Testing Options	460
Natural History	460
Treatment	460
Adrenalectomy	460
Mineralocorticoid Receptor Antagonists	460
Non–Mineralocorticoid Receptor Blocker Therapy	461
References	461
Self-Assessment Questions	462.e1
39 Other Endocrine Causes of Hypertension	463
Cushing Syndrome	463
Definition	463
Etiology, Pathogenesis, and Epidemiology	463
Clinical Manifestations	463
Differential Diagnosis	463
Diagnosis	464
Treatment and Prognosis	464
Pheochromocytoma	465
Definition	465
Etiology, Pathogenesis, and Epidemiology	465
Clinical Manifestations	465
Diagnosis	465
Treatment	466
Adrenal Incidentaloma	467
Definition and Epidemiology	467
Management	467
Renin-Secreting Tumor	467
Definition	467
Etiology and Pathogenesis	468
Clinical Manifestations	468
Pathology	468
Diagnosis and Differential Diagnosis	468
Treatment	468
Acromegaly	469
Definition and Epidemiology	469
Clinical Manifestations	469
Diagnosis	469
Treatment	469
Management of Hypertension in Acromegaly	470
Hypothyroidism	470
VII Renovascular Disease	482
41 Renovascular Hypertension and Ischemic Nephropathy	482
Normal Renovascular Anatomy	482
Clinical Syndromes Associated With Renal Vascular Disease	482
Renovascular Hypertension	482
Renal Artery Stenosis	485
Fibromuscular Dysplasia	485
Atherosclerotic Renal Artery Stenosis	485
Takayasu Arteritis	486
Coarctation and Middle Aortic Syndrome	487
Renal Artery Aneurysms	487
Ischemic Renal Disease	487
Heart Failure and Unstable Cardiac Conditions	488
Imaging Renovascular Hypertension and Renal Artery Stenosis	488
Treatment of Atherosclerotic Renal Artery Stenosis and Fibromuscular Dysplasia	490
Indications to Consider Renal Revascularization in Atherosclerotic Renal Artery Stenosis	491
Surgical Renal Revascularization	492
Transplant Renal Artery Stenosis	493
Renal Infarction	493
Treatment of Acute Renal Infarction	495
Atheroembolic Renal Disease	495
Clinical Presentation	495
Diagnosis	496
Differential Diagnosis	496
Pathology and Pathophysiology	496
Natural History	497
Treatment	497
Renal Vein Thrombosis	497
Acute Versus Chronic Renal Vein Thrombosis	497
Clinical Presentation	497
Etiology	497
Diagnosis	499
Treatment	499
References	499
Self-assessment Questions	501.e1
VIII Pregnancy and Renal Disease	502
42 Renal Physiology and Complications in Normal Pregnancy	502
Renal Physiology in Normal Pregnancy	502
Anatomy	502
Hemodynamic Changes	502
Systemic	502
Renal	502
Mechanisms of Increased Glomerular Filtration Rate	502
Measuring Glomerular Filtration Rate	502
Renin-Angiotensin-Aldosterone System	502
Renal Tubular Changes	503
Sodium Handling and Osmoregulation	503
Potassium	503
Calcium	503
Uric Acid	504
Acid-Base	504
Urine Protein	504
Glucose	504
Renal Complications in Normal Pregnancy	504
Urinalysis and Microscopy	504
Hematuria	504
Definition and Epidemiology	504
Etiology and Outcome	504
Differential Diagnosis	504
Treatment	504
Proteinuria	504
Definition	504
Differential Diagnosis	505
Natural History	505
Treatment	505
Pyuria	505
Urinary Tract Infection	505
Definitions	505
Epidemiology	505
Pathogenesis	506
Clinical Manifestations	506
IX Hereditary and Congenital Diseases of the Kidney	532
44 Autosomal Dominant Polycystic Kidney Disease	532
Definition	532
Etiology and Pathogenesis	532
Genetic Mechanisms	532
Polycystic Kidney Disease Proteins	532
Mechanisms of Cyst Formation	532
Liver Cyst Development	533
Hypertension	533
Epidemiology	534
Phenotypic Variability	534
Diagnosis	535
Renal Ultrasound	535
Genetic Testing	535
Differential Diagnosis	535
Clinical Manifestations	536
Renal Manifestations	536
Renal Size	536
Pain	536
Hematuria and Cyst Hemorrhage	536
Urinary Tract Infection and Cyst Infection	536
Nephrolithiasis	536
Hypertension	537
End-Stage Renal Disease	537
Extrarenal Manifestations	537
Polycystic Liver Disease	537
Intracranial Aneurysms	538
Other Vascular Abnormalities	538
Valvular Heart Disease and Other Cardiac Manifestations	538
Other Associated Conditions	538
Pathology	539
Treatment	540
Flank Pain	540
Cyst Hemorrhage	540
Urinary Tract and Cyst Infection	540
Nephrolithiasis	541
Hypertension	541
Progressive Renal Failure	541
Polycystic Liver Disease	542
Intracranial Aneurysm	542
Novel Therapies	542
Vasopressin Antagonists	542
Somatostatin Analogues	543
Mammalian Target of Rapamycin (mTOR) Inhibitors	543
Other Investigational Therapies	543
Transplantation	543
References	543
Self-assessment Questions	544.e1
45 Other Cystic Kidney Diseases	545
Autosomal Recessive Polycystic Kidney Disease	545
Definition	545
Etiology and Pathogenesis	545
Genetic Basis	545
Pathogenesis	545
Epidemiology	545
Clinical Manifestations	545
Pathology	546
Kidney	546
Liver	546
Diagnosis	546
Imaging	546
Genetic Testing	547
Treatment	547
Transplantation	548
Nephronophthisis: Autosomal Dominant Tubulointerstitial Kidney Disease	549
Definitions	549
Nephronophthisis	549
Genetic Basis	549
Clinical Manifestations	549
Renal Disease.	549
Associated Extrarenal Abnormalities.	549
Pathology	549
Diagnosis	550
Treatment	550
Autosomal Dominant Tubulointerstitial Kidney Disease	550
Medullary Sponge Kidney	550
Definition	550
Etiology and Pathogenesis	550
Epidemiology	550
Clinical Manifestations	550
Pathology	550
Diagnosis	551
Treatment	551
Tuberous Sclerosis Complex	551
Definition	551
Etiology and Pathogenesis	551
Epidemiology	552
Clinicopathologic Manifestations	552
Renal Angiomyolipomas	552
Renal Cystic Disease	553
Renal Neoplasms	553
Diagnosis	553
Treatment	554
Renal Angiomyolipomas	554
Renal Cystic Disease	554
Renal Carcinoma	554
Renal Replacement Therapy	554
Von Hippel–Lindau Disease	554
Definition	554
Etiology and Pathogenesis	554
Clinical Manifestations	555
Pathology	555
Diagnosis	555
Differential Diagnosis	555
Treatment	556
Simple Cysts	556
Introduction and Definition	556
Etiology and Pathogenesis	556
Clinical Manifestations	556
Pathology	557
Diagnosis	557
Treatment	557
Solitary Multilocular Cysts	557
Renal Lymphangiomatosis	558
Glomerulocystic Kidney Disease	558
Acquired Cystic Disease	558
Hypokalemic Cystic Disease	558
Hilar Cysts	558
Perinephric Pseudocysts	558
Acquired Cystic Disease in Renal Failure	558
References	558
Self-assessment Questions	559.e1
46 Alport Syndrome and Other Familial Glomerular Syndromes	560
Alport Syndrome	560
Definition	560
Etiology and Pathogenesis	560
Type IV Collagen	560
Genetics	560
X-Linked Alport syndrome.	560
Autosomal recessive Alport syndrome.	560
Autosomal dominant Alport syndrome.	561
Type IV Collagen in Alport Basement Membranes	561
Clinical Manifestations	561
Renal Defects	561
Cochlear Defects	562
Ocular Defects	562
Leiomyomatosis	563
Hematologic Defects	563
Arterial Abnormalities	563
Renal Pathology	563
Diagnosis and Differential Diagnosis	564
Natural History	566
Treatment	566
Transplantation	567
Hereditary Angiopathy with Nephropathy, Aneurysms, and Cramps (HANAC Syndrome)	568
Thin Basement Membrane Nephropathy	568
Definition	568
Etiology and Pathogenesis	568
Clinical Manifestations	568
Pathology	569
Diagnosis and Differential Diagnosis	569
Treatment	569
Fabry Disease (Anderson-Fabry Disease)	569
Definition	569
Etiology and Pathogenesis	569
Clinical Manifestations and Pathology	569
Renal Defects	570
Heart Defects	570
Nervous System	570
Skin	571
Eyes	571
Lungs	571
Diagnosis	571
Treatment	571
Fabry Disease in Childhood	571
Nail-Patella Syndrome	571
Definition	571
Etiology and Pathogenesis	571
Clinical Manifestations	571
Renal Defects	571
Skeletal Defects	572
Nails	572
Renal Pathology	572
Treatment	573
References	573
Self-assessment Questions	574.e1
47 Inherited Disorders of Sodium and Water Handling	575
Physiology of Sodium and Water Reabsorption	575
Sodium Transporters and the Corresponding Inherited Disorders	575
Water Reabsorption	575
Disorders of Sodium Handling	577
Conditions With Hypokalemia, Metabolic Alkalosis, and Low-Normal Blood Pressure	577
Bartter Syndrome	577
Pathogenesis	577
Clinical Manifestations	577
Diagnosis and Differential Diagnosis	578
Treatment	579
Outcome	579
Gitelman Syndrome	580
Pathogenesis	580
Clinical Manifestations and Diagnosis	580
X Infectious Diseases and the Kidney	626
51 Urinary Tract Infections in Adults	626
Definition	626
Epidemiology	626
Pathogenesis	626
Uncomplicated Infection	626
Complicated Infection	627
Etiologic Agents	627
Clinical Syndromes	628
Acute Uncomplicated Cystitis in Young Women	628
Recurrent Acute Uncomplicated Cystitis in Women	630
Acute Uncomplicated Pyelonephritis in Women	630
Complicated Infections	632
Chronic Kidney Disease.	633
Catheter-Associated Infections.	633
Spinal Cord Injury.	634
Prostatitis.	634
Renal Abscess.	634
Papillary Necrosis.	635
Emphysematous Pyelonephritis.	635
Renal Malacoplakia.	635
Xanthogranulomatous Pyelonephritis.	635
Asymptomatic Bacteriuria	636
Imaging of the Urinary Tract	636
References	637
Self-assessment Questions	638.e1
52 Tuberculosis of the Urinary Tract	639
Definition	639
Etiology	639
Pathogenesis	639
Clinical Manifestations	640
Asymptomatic Presentations	642
Lower Urinary Tract Symptoms	642
Proteinuria and Nephrotic Syndrome	642
Low Glomerular Filtration Rate	643
Pain	643
Stone Formation	643
Genital Involvement	643
Other Manifestations	643
Pathology	643
Diagnosis and Differential Diagnosis	643
Differential Diagnosis	644
Natural History	645
Treatment	645
Surgical Treatment	648
Treatment Regimens in Special Situations	648
Women During Pregnancy and Lactation	648
Patients With Liver Disease	648
Patients With Chronic Kidney Disease	648
Renal Allograft Recipients	648
Acquired Immunodeficiency Syndrome	648
Patients Who Fail Treatment	648
Patient Monitoring	648
References	649
Self-Assessment Questions	649.e1
53 Fungal Infections of the Urinary Tract	650
Candida	650
Epidemiology	650
Pathogenesis	650
Microbiology	650
Clinical Manifestations	650
Diagnosis	651
Treatment With Systemic Antifungal Agents	652
Local Antifungal Administration	653
Localized Candida Infections	653
Other Yeasts	653
Aspergillus and Other Molds	654
Endemic Fungi	654
References	654
Self-assessment Questions	654.e1
54 The Kidney in Schistosomiasis	655
Pathogenesis	655
Clinical Manifestations	656
Lower Urinary Tract Schistosomiasis	656
Bladder Cancer	657
Upstream Consequences	657
Interstitial Nephritis	657
Glomerulonephritis	658
Coinfection	660
Human Immunodeficiency Virus	660
Hepatitis B Virus	661
Diagnosis	661
Schistosoma haematobium Urinary Tract Disease	661
XI Urologic Disorders	689
57 Nephrolithiasis and Nephrocalcinosis	689
Nephrolithiasis	689
Epidemiology	689
Pathogenesis	689
Clinical Manifestations	690
Pain	690
Hematuria	690
Loin Pain–Hematuria Syndrome	690
Asymptomatic Stone Disease	691
Clinical Evaluation of Stone Formers	691
Basic Evaluation	691
History.	691
Physical examination.	693
Laboratory findings.	693
Stone analysis.	693
Imaging.	693
Complete Evaluation	695
General Treatment	695
Medical Management	695
Fluid intake.	695
Salt intake.	695
Dietary protein.	695
Dietary calcium.	696
Vitamin D.	696
Specific Types of Stones	696
Calcium Stones	696
Hypercalciuria	696
Etiology.	696
Treatment.	697
Dietary recommendations.	697
Hyperoxaluria	697
Etiology.	697
Treatment of dietary and enteric hyperoxaluria.	698
Treatment of primary hyperoxaluria.	698
Hypocitraturia	698
Distal Renal Tubular Acidosis	698
Hyperuricosuria	698
Uric Acid Stones	698
Epidemiology	698
Etiology and Pathogenesis	698
Treatment	698
Struvite Stones	699
Etiology and Pathogenesis	699
Treatment	700
Cystine Stones	700
Stones Associated With Melamine Exposure	700
Nephrocalcinosis	700
Etiology and Pathogenesis	700
Medullary Nephrocalcinosis	700
Cortical Nephrocalcinosis	702
Clinical Manifestations	702
Treatment	702
References	702
Self-assessment Questions	703.e1
58 Urinary Tract Obstruction	704
Definitions	704
Etiology and Pathogenesis	704
Congenital Urinary Tract Obstruction	704
Acquired Urinary Tract Obstruction	704
Intrinsic Obstruction	704
Intraluminal obstruction.	704
Intramural obstruction.	704
Extrinsic Obstruction	705
Pathophysiology	706
Changes in Glomerular Function	706
Changes in Tubular Function	706
Histopathologic Changes	707
Epidemiology	708
Clinical Manifestations	709
Pain	709
Lower Urinary Tract Symptoms	709
Urinary Tract Infections	709
Hematuria	709
Changes in Urine Output	709
Abnormal Physical Findings	709
Abnormal Laboratory Findings	709
Obstruction in Neonates or Infants	709
Diagnosis	710
Imaging	710
Ultrasound	711
Plain Abdominal Radiography	711
Intravenous Urography	711
Computed Tomography	711
Magnetic Resonance Urography	712
Retrograde Pyelography	712
Diuresis Renography	712
Pressure Flow Studies	713
Other Evaluations	713
Differential Diagnosis	713
Natural History	713
Treatment	713
General Considerations	713
Specific Therapies	714
Management of Postobstructive Diuresis	715
Future Prospects	716
References	716
Self-assessment Questions	716.e1
59 Urologic Issues for the Nephrologist	717
Advances in Management of Kidney Stones	717
Improvements in Imaging	717
Conservative (Nonsurgical) Management	717
Acute Surgical Intervention	717
Elective Surgical Intervention	717
Extracorporeal Shock Wave Lithotripsy	717
Percutaneous Nephrolithotomy	718
Open Stone Surgery	719
Ureteroscopy	719
Management of Staghorn Calculus	719
Stones in Transplanted Kidneys	720
Urinary Tract Obstruction	720
General Aspect	720
Acute Management	720
Specific Types of Obstruction	721
Pelviureteral Junction Obstruction	721
Retroperitoneal Fibrosis	721
Malignant Obstruction	721
Benign Ureteral Strictures	722
Bladder Outflow Obstruction	722
Neurologic Diseases of the Lower Urinary Tract	722
Investigation of Hematuria	722
Evaluation of Visible Hematuria	723
Evaluation of Microhematuria	723
Cyclophosphamide	723
Investigation and Management of a Renal Mass	723
Adjunctive Therapy for Renal Cancer	726
Natural History of Renal Impairment After Surgical Treatment of Renal Cancer	726
Renal Cell Carcinoma in von Hippel–Lindau Disease	726
References	727
Self-Assessment Questions	728.e1
XII Tubulointerstitial and Vascular Diseases	729
60 Acute Interstitial Nephritis	729
Definition	729
Pathogenesis	729
Epidemiology	729
Drug-Induced Acute Interstitial Nephritis	729
Clinical Manifestations	729
Renal Manifestations	730
Extrarenal Manifestations	730
Specific Drug Associations	730
Pathology	733
Diagnosis	734
Identification of the Causative Drug	734
Natural History	735
Treatment	735
Acute Interstitial Nephritis Secondary to Infectious Diseases	735
Acute Interstitial Nephritis Associated With Systemic Diseases	736
Sarcoidosis	736
Sjögren Syndrome	736
Systemic Lupus Erythematosus	736
Immunoglobulin G4–Related Disease	736
Other Systemic Diseases	736
Acute Interstitial Nephritis Associated With Malignant Neoplasms	736
Idiopathic Acute Interstitial Nephritis	736
Acute Interstitial Nephritis in Renal Transplants	736
Self-assessment Questions	737.e1
References	737
61 Primary Vesicoureteral Reflux and Reflux Nephropathy	738
Definition	738
Classification	738
Epidemiology	738
Etiology and Pathogenesis	738
Reflux Nephropathy	740
Pathology	740
Clinical Manifestations	740
Presentation of Vesicoureteral Reflux	740
Reflux Identified Secondary to Antenatal Hydronephrosis	740
Reflux Identified After a Urinary Tract Infection	741
Vesicoureteral Reflux in a Sibling	741
Presentation of Vesicoureteral Reflux in Women During Pregnancy	742
Other Presentations	742
Reflux Nephropathy	742
Hypertension	742
Proteinuria	742
End-Stage Renal Disease	742
Diagnosis of Vesicoureteral Reflux and Reflux Nephropathy	742
Renal Ultrasound	742
Voiding Cystourethrography	742
DMSA Renal Scintigraphy	743
Magnetic Resonance Imaging	743
Proteinuria as a Marker for Reflux Nephropathy	743
Natural History of Vesicoureteral Reflux and Reflux Nephropathy	743
Treatment	744
Medical Management	744
Antibiotic Prophylaxis Versus Surveillance Only	744
Hypertension and Proteinuria	745
Surgical Management	745
References	745
Self-assessment Questions	747.e1
62 Chronic Interstitial Nephritis	748
Definition	748
Pathogenesis	748
Epidemiology	748
Pathology	748
Clinical Manifestations	748
Treatment	749
Drug-Induced Chronic Interstitial Nephritis	749
Lithium Nephropathy	750
Definition and Epidemiology	750
Pathogenesis	750
Pathology	750
Clinical Manifestations	750
Lithium-associated diabetes insipidus.	750
Chronic lithium nephropathy.	750
XIII Renal Disease and Cancer	776
65 Onconephrology	776
Cancer and Kidney Disease	776
Acute Kidney Injury	776
Prerenal Acute Kidney Injury	776
Intrarenal Acute Kidney Injury	776
Postrenal Acute Kidney Injury	777
Chronic Kidney Disease	777
Mortality in Cancer Patients With Kidney Disease	777
Important Malignancies Associated With Kidney Disease	777
Multiple Myeloma and Amyloidosis	777
Leukemia and Lymphoma	778
Anticancer Drugs and Kidney Disease	778
Chemotherapeutic Agents	778
Immunotherapies	778
Immune Checkpoint Inhibitors	778
Interferon Therapy	778
Targeted Therapies	779
Antiangiogenesis Therapy	779
B-RAF Inhibitors	779
Anaplastic Lymphoma Kinase Inhibitors	779
Metabolic Complications	781
Tumor Lysis Syndrome	781
Common Electrolyte Disorders	781
Cancer-Related Glomerulonephritis	782
Hematopoietic Stem Cell Transplantation	783
Cancer Therapy in Chronic Kidney Disease and End-Stage Renal Disease	783
References	784
Self-assessment Questions	785.e1
XIV Acute Kidney Injury	786
66 Pathophysiology and Etiology of Acute Kidney Injury	786
Definition	786
Etiology Overview	786
Pathophysiology and Etiology of Prerenal Acute Kidney Injury	786
Pathophysiology and Etiology of Postrenal Acute Kidney Injury	787
Pathophysiology of Acute Tubular Necrosis	787
Histology	787
Site of Tubular Injury in Acute Tubular Necrosis	788
Hemodynamic Factors in the Development of Acute Tubular Necrosis	788
Impaired Renal Autoregulation	788
Intrarenal Vasoconstriction	789
Tubuloglomerular Feedback	789
Endothelial Cell Injury and the Development of Acute Tubular Necrosis	789
Tubular Epithelial Cell Injury and the Development of Acute Tubular Necrosis	789
Inflammatory Factors in the Development of Acute Tubular Necrosis	791
Recovery Phase	791
Nephrotoxic Agents and Mechanisms of Toxicity	792
Nonsteroidal Antiinflammatory Drugs	792
Acetaminophen (Paracetamol)	793
Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers	794
Aminoglycosides	794
Vancomycin	794
Amphotericin B	794
Antiviral Therapy	794
Acyclovir	794
Tenofovir	794
Atazanivir	795
Other Antiviral Agents	795
Hypoglycemic Therapy: SGLT2 Inhibitors	795
Immunosuppressive Agents	795
Calcineurin Inhibitors	795
Other Immunosuppressive Agents	795
Ethylene Glycol	795
Anticoagulation-Related Nephropathy	795
Acute Phosphate Nephropathy	795
Drugs of Abuse	795
Occupational Toxins	796
Heavy Metals	796
Organic Solvents	796
Herbal Remedies	796
Radiocontrast-Induced Nephropathy	796
Other Specific Etiologies of Acute Kidney Injury	796
Heme Pigment Nephropathy	796
Causes of Rhabdomyolysis	796
Causes of Hemoglobinuria	797
Pathogenesis of Heme Pigment Nephropathy	797
Atheroembolic Renal Disease	798
Renal Artery or Vein Occlusion	798
Acute Interstitial Nephritis	798
Thrombotic Microangiopathy	798
Glomerular Disease	798
Specific Clinical Situations	798
Acute Kidney Injury in the Patient With Sepsis	798
Acute Kidney Injury in the Trauma Patient	798
Acute Kidney Injury in the Postoperative Patient	798
After Cardiac Surgery	798
After Vascular Surgery	799
Abdominal Compartment Syndrome	799
Pulmonary-Renal Syndrome	799
Acute Kidney Injury and Liver Disease	799
Acute Kidney Injury in Heart Failure (Cardiorenal Syndrome)	799
Acute Kidney Injury in the Cancer Patient	800
Tumor Lysis Syndrome	800
Hypercalcemia	800
Chemotherapeutic Agents	800
References	800
Self-Assessment Questions	801.e1
67 Acute Kidney Injury in the Tropics	802
Snakebite	802
Clinical and Laboratory Features	802
Pathology	802
Pathogenesis	803
Management	803
Arthropods	803
Bees	803
Caterpillars	803
Loxosceles	804
Scorpions	804
Natural Medicine	804
Malaria	804
Pathophysiology	804
Clinical Manifestations	805
Leptospirosis	806
Hemorrhagic Fevers	807
Dengue Fever	807
Yellow Fever	807
Ebola Virus Disease	807
References	808
68 Diagnosis and Clinical Evaluation of Acute Kidney Injury	810
Early Detection of Acute Kidney Injury	810
Diagnostic Approach to Acute Kidney Injury	811
Acute Kidney Injury Versus Chronic Kidney Disease	811
Clinical Assessment	811
Electronic Health Record to Predict Acute Kidney Injury	812
Diagnostic Evaluation	813
Ratio of Blood Urea Nitrogen to Creatinine	814
Urine Volume	814
Urinalysis and Urine Microscopy	814
Fractional Excretion of Sodium and Urea	815
Laboratory Evaluation of Acute Kidney Injury in Systemic Illnesses	815
Imaging Studies	815
Kidney Biopsy	816
Acute Kidney Injury in Specific Settings	816
Acute Tubular Necrosis	816
Acute Interstitial Nephritis	817
Acute Kidney Injury from Intratubular Obstruction	817
Rhabdomyolysis	818
Acute Kidney Injury in Myeloma	818
Contrast-Induced Nephropathy	818
References	818
Self-Assessment Questions	819.e1
69 Epidemiology and Prognostic Impact of Acute Kidney Injury	820
Incidence of Acute Kidney Injury	820
Risk Factors for Acute Kidney Injury	820
Age	820
Reduced Estimated Glomerular Filtration Rate	820
Proteinuria	820
Hyperuricemia	820
Association Between Acute Kidney Injury and Adverse Outcomes	821
Mortality	821
Chronic Kidney Disease	823
Cardiovascular Risk	823
Health Care Costs	823
Acute Kidney Injury as a Public Health Issue	823
References	823
Self-assessment Questions	824.e1
70 Prevention and Nondialytic Management of Acute Kidney Injury	825
Risk Assessment	825
Primary Preventive Measures	825
Optimizing Volume and Hemodynamic Status	825
Prevention of Contrast-Induced Acute Kidney Injury	828
Prevention of Drug-Induced and Nephrotoxin-Induced Acute Kidney Injury	829
Amphotericin	829
Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Blockers	829
Nonsteroidal Antiinflammatory Drugs	829
Aminoglycosides	829
Tumor Lysis Syndrome	829
Traumatic and Nontraumatic Rhabdomyolysis	830
Hyperglycemia	830
Remote Ischemic Preconditioning	830
Pharmacologic Approaches	830
N-Acetylcysteine	830
Loop Diuretics and Natriuretics	830
Vasoactive Agents	831
Statins	831
Calcium Channel Blockers	832
Adenosine Antagonists	832
Emerging Agents	832
Summary	832
Treatment of Acute Kidney Injury	832
General Management	832
Fluid and Electrolyte Management	833
Drugs to Promote Recovery From Acute Kidney Injury	833
Loop Diuretics	833
Natriuretics	833
Vasoactive Agents	834
Other Agents	834
Summary	834
Treatment of Acute Kidney Injury Complications	834
Fluid Overload	834
Potassium Disorders	834
Sodium Disorders	835
Calcium, Phosphorus, and Magnesium Disorders	835
Acid-Base Disorders	835
Nutrition	835
References	835
Self-Assessment Questions	837.e1
71 Dialytic Management of Acute Kidney Injury and Intensive Care Unit Nephrology	838
Organizational Aspects of Acute Renal Replacement Therapy Programs	838
Overview of Acute Renal Replacement Therapies	838
Intermittent Acute Renal Replacement Therapy	840
Techniques for Acute Intermittent Hemodialysis	840
Strategies to Reduce Intradialytic Hemodynamic Instability During Intermittent Hemodialysis	841
Prolonged Intermittent Renal Replacement Therapy	841
Dosage of Intermittent Acute Renal Replacement Therapy	841
Continuous Renal Replacement Therapy	842
Techniques for Continuous Renal Replacement Therapy	842
Mechanisms of Solute Removal	843
Hemodialysis	843
Hemofiltration	843
Hemodiafiltration	843
Specific Techniques	843
Dosage of Continuous Renal Replacement Therapy	843
Technical Aspects of Continuous Renal Replacement Therapy	843
Equipment	843
Hemofilters	844
Replacement Fluids and Dialysate	844
Vascular Access	845
Anticoagulation in Acute Renal Replacement Therapy	845
Modality Choice and Outcomes in Acute Renal Replacement Therapy	847
Acute Renal Replacement Therapy During Mechanical Circulatory Support	847
Technical Aspects of Acute Renal Replacement Therapy During Mechanical Circulatory Support	848
Access Options and Techniques	848
Monitoring and Management of Key Acute Renal Replacement Therapy–Related Issues	849
Drug Dosage in Acute Renal Replacement Therapy	849
References	849
Self-assessment Questions	851.e1
72 Dialytic Management of Refractory Heart Failure	852
Definition and Scope of the Problem	852
Pathogenesis	852
Venous Congestion	852
Adenosine	852
Anemia	853
Diuretic Resistance and Adverse Effects	853
Treatment	853
General Approach and Limitations	853
Pharmacologic Therapeutic Strategies	854
Diuretics	854
Renin-Angiotensin-Aldosterone System Antagonists	854
Neprilysin Inhibitors	854
Miscellaneous Therapies	854
Medications Under Development	855
Nonrenal Salt and Water Removal	855
Paracentesis	855
Peritoneal Dialysis	855
Conventional Hemodialysis or Hemofiltration	856
Setting the Rate of Fluid Removal	856
Effect of Extracorporeal Ultrafiltration on the Pathophysiology of Heart Failure	856
Effect of Extracorporeal Ultrafiltration on Renal Function	856
Recent Advances in Extracorporeal Techniques	856
Safety and Risks of Extracorporeal Therapies	857
Summary	857
References	857
Self-Assessment Questions	858.e1
73 Hepatorenal Syndrome	859
Definition	859
Pseudohepatorenal Syndrome	859
Pathophysiology and Pathogenesis	859
Circulatory Dysfunction: Renal and Systemic Hemodynamic Changes	859
Neurohumoral Abnormalities	859
Systemic Inflammation	860
Summary of Pathogenetic Events	860
Epidemiology	862
Clinical Manifestations	862
Pathology	863
Diagnosis and Differential Diagnosis	863
Natural History	863
Prevention and Treatment	863
General Principles in the Prevention of AKI	863
Preventive Measures	864
General Approach to Treatment	864
Pharmacotherapy	864
Transjugular Intrahepatic Portosystemic Shunt	865
Extracorporeal Liver Support Therapy	866
Renal Replacement Therapy	866
Liver Transplantation	867
Therapeutic Algorithm	867
References	868
Self-assessment Questions	869.e1
XV Drug Therapy in Kidney Disease	870
74 Principles of Drug Therapy, Dosing, and Prescribing in Chronic Kidney Disease and Renal Replacement Therapy	870
Pharmacokinetic Principles	870
Absorption: Bioavailability	870
Distribution	870
Volume of Distribution	870
Plasma Protein Binding	870
Metabolism	871
Elimination	872
Prescribing Principles for Chronic Kidney Disease and Renal Replacement Therapy	872
Initial Assessment and Laboratory Data	872
Estimating Renal Function for Drug Dosage	872
Activity and Toxicity of Metabolites	872
Fraction of Active Drug (and Active or Toxic Metabolite) Excreted Unchanged in Urine	872
Therapeutic Index of the Drug or Metabolites	873
Avoiding Nephrotoxic Drugs	873
Drugs That Aggravate the Metabolic Effects of Renal Impairment	873
Effect of Renal Impairment on Pharmacodynamic or Physiologic Mechanisms	875
Effect of Renal Impairment on the Concentration of Drug at the Site of Action	875
Location of Drug Action	875
Method of Administration	875
Drug Interactions	875
Clinical Condition of the Patient	875
Methods of Dose Reduction	875
Loading Doses	875
Maintenance Doses	876
Interval Method	876
Dose Method	876
Combination Method	876
Ongoing Assessment	877
Therapeutic Drug Monitoring	877
Clinical Response	877
Extracorporeal Drug Losses	877
Hemodialysis	877
Peritoneal Dialysis	877
Continuous Renal Replacement Therapy	877
References	878
Self-Assessment Questions	879.e1
75 Common Issues in Prescribing in Kidney Disease and Renal Replacement Therapy	880
Analgesics	880
Acetaminophen (Paracetamol)	880
Opioid Analgesics	880
Nonsteroidal Antiinflammatory Drugs	880
Drugs for Neuropathic Pain	880
Antimicrobial Agents	880
Antibacterials	881
Aminoglycosides	881
Aminoglycoside dosage schedules.	881
Aminoglycoside concentration monitoring.	881
Carbapenems.	881
Cephalosporins.	881
Fluoroquinolones.	881
Glycopeptides.	881
Lincosamides.	881
Macrolides.	881
Penicillins.	882
Rifamycins.	882
Tetracyclines.	882
Sulfonamides and trimethoprim.	882
Other antibiotics.	882
Antimycobacterials	882
Antifungals	882
Amphotericin.	882
Azole antifungals.	882
Other antifungals.	882
Antivirals	882
Guanine Analogues	882
Hepatitis B and C	882
Neuraminidase Inhibitors	882
Other Antivirals	883
Immunosuppressants	883
Calcineurin Inhibitors	883
Corticosteroids	883
Antiproliferative and Cytotoxic Agents	883
mTOR Inhibitors	883
Immunosuppressant Antibodies	883
Anticoagulants, Antiplatelet Agents, Thrombolytics, and Hemostatics	883
Unfractionated Heparin	883
Low Molecular Weight Heparins	887
Other Parenteral Anticoagulants	887
Oral Anticoagulants	887
Antiplatelet Drugs	887
Thrombolytics	887
Hemostatics	887
Diuretics	887
Thiazide Diuretics	888
Loop Diuretics	888
Potassium-Sparing Diuretics	888
Antihypertensives	888
Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers	888
β-Blockers	888
Calcium Channel Blockers	888
Other Antihypertensives	888
Antianginal Agents	888
Antiarrhythmics	888
Lipid-Lowering Agents	889
Bile Acid–Binding Resins	889
Statins	889
Fibrates	889
Diabetes	889
Diabetes Management in Peritoneal Dialysis	889
Biguanides	889
Insulins	889
Meglitinides	889
Sulfonylureas	889
SGLT2 Inhibitors	889
DPP-4 Inhibitors	889
Thiazolidinediones	889
Drugs for Thyroid Disorders	889
Mineral and Bone Disorders	890
Phosphate Binders	890
Vitamin D	890
Calcimimetics	890
Dyspepsia, Gastroesophageal Reflux Disease, and Peptic Ulcers	890
Antacids	890
Histamine-2 Antagonists	890
Proton Pump Inhibitors	890
Antiemetics	890
Dopamine Antagonists	890
5-HT3 Antagonists	890
Aperients and Laxatives	890
Antidiarrheals	890
Drugs for Erectile Dysfunction	890
Phosphodiesterase-5 Inhibitors	890
Intracavernosal Therapy	890
Musculoskeletal Drugs	890
Nonsteroidal Antiinflammatory Drugs	890
Miscellaneous Arthritis Drugs	890
Gout and Hyperuricemia	891
Bisphosphonates	891
Antiepileptics	891
Benzodiazepines	891
Carbamazepine	891
Phenytoin	891
Other Antiepileptics	891
Antiparkinsonian Drugs	891
Antimigraine Drugs	891
Psychotropic Drugs	891
Selective Serotonin Reuptake Inhibitors	891
Tricyclic Antidepressants	892
Monoamine Oxidase Inhibitors	892
Other Antidepressants	892
Antipsychotics	892
Benzodiazepines	892
Anemia Drugs	892
Erythropoiesis-Stimulating Proteins	892
Iron Therapy	892
Antihistamines	892
Vaccines	892
Vitamin Supplementation	892
References	892
Self-assessment Questions	893.e1
76 Herbal and Over-the-Counter Medicines and the Kidney	894
Herbal Medications and the Kidney	894
Aristolochic Acid Nephropathy	894
Aristolochic Acids	894
Aristolochic Acid Nephropathy	895
Definition	895
Epidemiology	895
Clinical Manifestations	895
Pathology	896
Pathogenesis	896
Diagnosis	897
Treatment	897
Kidney Injury Caused by Other Medicinals	898
Acute Kidney Injury	898
Mushrooms	899
Diagnosis of Acute Kidney Injury Induced by Folk Remedies	899
Treatment	899
Other Renal Complications of Herbal Remedies	899
Hypertension	899
Crystalluria and Nephrocalcinosis	899
Hyperkalemia	899
Urinary Obstruction	899
Renal Toxicity From Contaminants Within Herbal Medicines	900
Herb-Drug Interactions Resulting in Adverse Renal Effects	900
Over-the-Counter Medicines and the Kidney	900
Analgesics	901
Analgesic Nephropathy	901
Proton Pump Inhibitors	901
References	901
Self-assessment Questions	902.e1
XVI Chronic Kidney Disease and the Uremic Syndrome	903
77 Epidemiology of Chronic Kidney Disease and Dialysis	903
Defining Chronic Kidney Disease	903
Chronic Kidney Disease Staging	903
Classification Based on Estimated Glomerular Filtration Rate	903
Classification Based on Albuminuria	903
Classification Based on Chronic Kidney Disease Cause	903
Rationale for the Chronic Kidney Disease Definition	904
Associations With Adverse Outcomes	904
Persistent Relationships Within Subgroups	904
Global Burden of Chronic Kidney Disease	904
Risk Factors for Chronic Kidney Disease	905
Age	905
Sex and Race	906
Social Determinants	906
Comorbid Conditions	906
Issues With Identifying Chronic Kidney Disease	906
Lack of Awareness	906
Imperfect Biomarkers	906
Errors in Urine Albumin Assessment	906
Outcomes of Chronic Kidney Disease	906
Associations With Adverse Outcomes	906
Variation in Absolute Risk for Adverse Outcomes	906
Dialysis Epidemiology	907
Incidence and Prevalence of Chronic Dialysis	907
Dialysis Practice Patterns	908
Outcomes	908
Epidemiologic Concepts	911
Evidence Quality	911
References	911
Self-assessment Questions	912.e1
78 Pathophysiology of Disease Progression in Proteinuric and Nonproteinuric Kidney Disease	913
From Glomerular Hypertension to Loss of Size-Selective Properties	913
Podocyte Response to Protein Trafficking	913
Crosstalk of Podocytes With Mesangial and Endothelial Cells	914
Activation of Parietal Epithelial Cells	914
Proximal Tubular Cell Injury	916
Tubular Cell Apoptosis	916
Tubular Cell Phenotypic Changes	916
Interstitial Inflammation and Fibrosis	918
Resident Monocyte and Lymphocyte Activation	918
Fibroblast Activation and Extracellular Matrix Deposition	919
Chronic Hypoxia	920
Primary Chronic Tubulointerstitial Injury	920
Analgesics and Nonsteroidal Antiinflammatory Drugs	920
Aristolochic Acid	921
Autosomal Dominant Polycystic Kidney Disease	921
Conclusions	921
References	921
Self-assessment Questions	923.e1
79 Retarding Progression of Kidney Disease	924
Level of Glomerular Filtration Rate and the Risk for Natural Progression	924
Proteinuria Magnitude and the Risk for Natural Progression	924
Diagnosis of Natural Progression	924
Monitoring Kidney Disease Progression	924
Monitoring Proteinuria Trends	924
Monitoring Glomerular Filtration Rate Trends	926
Role of Cystatin C in Estimating Glomerular Filtration Rate for Clinical Management	927
Glomerular Filtration Rate Trajectories in Chronic Kidney Disease	927
Therapy for Natural Progression	927
Level 1 Recommendations to Slow Natural Progression	927
Control Blood Pressure	927
Renin-Angiotensin System Blockade	928
Combination Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Therapy	928
Renin Inhibitor Therapy	928
Avoid Dihydropyridine Calcium Channel Blockers	928
Control Protein Intake	931
Level 2 Recommendations to Slow Natural Progression	931
Restrict Salt Intake and Avoid Diuretic Therapy	931
Nondihydropyridine Calcium Channel Blocker Therapy	931
Control Each Component of the Metabolic Syndrome	931
Aldosterone Antagonist Therapy	932
β-Blocker Therapy	932
Control Serum Phosphorous	932
Smoking Cessation	932
Control Hyperuricemia	932
Avoid Anticoagulant-Related Nephropathy	932
Alkali Therapy	932
Monitor Serum Creatinine in Patients Receiving a Proton Pump Inhibitor	933
Correct Vitamin D Deficiency	933
Avoid or Minimize Nonsteroidal Antiinflammatory Drug Use	933
References	933
Self-Assessment Questions	934.e1
80 Clinical Evaluation and Management of Chronic Kidney Disease	935
Definitions	935
Clinical Presentation	935
Evaluation of Chronic Kidney Disease	935
Establishing Chronicity	935
Assessment of Glomerular Filtration Rate	935
Assessment of Proteinuria	936
Kidney Imaging	936
Further Investigations	936
Predicting Prognosis	937
Monitoring and Defining Progression	937
When to Refer to the Nephrologist	937
Prevention of Chronic Kidney Disease Progression	938
Hypertension	938
Dietary Advice	938
Management of Complications of Chronic Kidney Disease	938
Anemia	938
Bone and Mineral Metabolism	939
Metabolic Acidosis	939
Cardiovascular Risk	939
Risk for Infections	939
Care of the Patient With Progressive Chronic Kidney Disease	940
Chronic Kidney Disease and Risk of Acute Kidney Injury	940
Timing the Initiation of Renal Replacement Therapy	940
Conservative Management	940
References	940
Self-Assessment Questions	941.e1
81 Cardiovascular Disease in Chronic Kidney Disease	942
Epidemiology	942
Prevalence of Cardiovascular Complications in Chronic Kidney Disease	942
Cardiovascular Disease Is Present Before the Start of Renal Replacement Therapy	942
Racial and International Differences in Cardiovascular Disease Prevalence	942
Reverse Epidemiology	942
Etiology and Risk Factors	943
Traditional Risk Factors	943
Age, Gender, and Smoking	943
Diabetes Mellitus	943
Hypertension	944
Dyslipidemia	944
Insulin Resistance and Atherosclerosis	946
Nontraditional and Uremia-Specific Risk Factors	946
Oxidative Stress	946
Inflammation	946
Gut Dysbiosis	946
Endothelial Dysfunction	946
Anemia	946
Secondary Hyperparathyroidism and Mineral Metabolism	947
Cardiovascular Calcification	947
Advanced Glycation End-Products	947
Dialysis Modality	948
Clinical Manifestations and Natural History	948
Chest Pain, Coronary Heart Disease, and Acute Myocardial Infarction	948
Peripheral Arterial Disease	949
Cerebrovascular Disease and Atrial Fibrillation	949
Left Ventricular Remodeling and Hypertrophy	949
Extracellular Volume Overload	949
Pericarditis	950
Autonomic Dysfunction	950
Valvular Disease	950
Infective Endocarditis	950
Sudden Cardiac Arrest	950
Diagnosis and Differential Diagnosis	951
Blood Pressure Measurements	951
Electrocardiography and Echocardiography	951
Stress Tests and Screening Renal Transplant Candidates	951
Coronary Angiography	951
Imaging of Vascular Calcification	952
Biomarkers	952
Treatment and Prevention of Cardiovascular Disease	953
Risk Factor Reduction	953
Lifestyle Factors and Smoking	953
Weight and Diet	953
Hypertension and Coronary Heart Disease	953
Diabetes Mellitus	954
Dyslipidemia	954
Volume	954
Anemia	954
Inflammation	954
Oxidative Stress	955
Chronic Kidney Disease–Mineral Bone Disorder	955
Revascularization	955
References	955
Self-Assessment Questions	957.e1
82 Anemia in Chronic Kidney Disease	958
Pathogenesis	958
Epidemiology and Natural History	959
Diagnosis and Differential Diagnosis	959
Clinical Manifestations	960
Treatment	961
Erythropoiesis-Stimulating Agents	961
Epoetin Therapy	961
Darbepoetin Alfa	962
Methoxy Polyethylene Glycol–Epoetin Beta (C.E.R.A.)	962
Adverse Effects of the Erythropoiesis-Stimulating Agents	962
Peginesatide	962
Hypoxia-Inducible Transcription Factor Stabilizers	962
Initiation of and Maintenance Therapy With Erythropoiesis-Stimulating Agents	962
Hyporesponsiveness to Erythropoiesis-Stimulating Agents	963
Iron Management	964
References	965
Self-assessment Questions	966.e1
83 Other Blood and Immune Disorders in Chronic Kidney Disease	967
Immune Dysfunction	967
Bacterial Infections	967
Viral Infections	967
Vaccinations in Chronic Kidney Disease	967
Inflammation	968
Causes of Inflammation	969
Consequences of Inflammation	969
Immune Cell Abnormalities	969
Monocytes	969
T Lymphocytes	970
B Lymphocytes	970
Granulocytes	970
Platelet Dysfunction and Platelet Inhibitors in Chronic Kidney Disease	971
Hemorrhagic Diathesis and Uremic Platelet Dysfunction	971
Treatment of Uremic Platelet Dysfunction	972
Desmopressin	973
Cryoprecipitate	973
Tranexamic Acid	973
Recombinant Activated Factor VII	973
Estrogens	973
Implications for Antiplatelet Agent Therapy	973
Circulating Coagulation Factors	973
Therapeutic Intervention	973
References	977
Self-Assessment Questions	978.e1
84 Bone and Mineral Disorders in Chronic Kidney Disease	979
Definition	979
Epidemiology	979
Pathogenesis	979
Osteitis Fibrosa: Hyperparathyroidism—High-Turnover Renal Bone Disease	979
Abnormalities of Calcium Metabolism	979
Abnormalities of Phosphate Metabolism	979
Abnormalities of Vitamin D Metabolism	981
Abnormalities of Parathyroid Gland Function	982
Abnormal Skeletal Response to Parathyroid Hormone	982
Clinical Manifestations of High-Turnover Renal Osteodystrophy	982
Diagnosis and Differential Diagnosis	982
Serum Biochemistry	982
Parathyroid Hormone	982
Vitamin D Metabolites	983
Markers of Bone Formation and Bone Resorption	983
Radiology of the Skeleton	983
Measurements of Bone Density	983
Bone Biopsy	984
Treatment of High-Turnover Bone Disease	984
Prevention of Hypocalcemia	984
Control of Phosphate	985
Dietary Phosphate Restriction	985
Phosphate Binders	985
Use of Vitamin D Metabolites	986
Role of Calcimimetics	987
Role of Parathyroidectomy	987
Synthesis of Therapeutic Strategies	987
Low-Turnover Renal Bone Disease	988
Pathogenesis of Adynamic Bone Disease	989
Diagnosis and Differential Diagnosis	989
Serum Biochemistry	989
Bone Biopsy	989
Radiology and Measurements of Bone Density	989
Treatment of Adynamic Bone Disease	989
Osteoporosis in Chronic Kidney Disease	990
Pathogenesis of Osteoporosis in Chronic Kidney Disease	990
Diagnosis and Differential Diagnosis	991
Treatment of Osteoporosis in Chronic Kidney Disease	991
β2-Microglobulin–Derived Amyloid	991
Pathogenesis	991
Epidemiology	991
Clinical Manifestations and Diagnosis	991
Diagnosis	992
Treatment and Prevention	992
References	993
Self-assessment Questions	995.e1
85 Neurologic Complications of Chronic Kidney Disease	996
Uremic Encephalopathy	996
Pathogenesis	996
Clinical Manifestations	996
Diagnosis and Differential Diagnosis	997
Treatment	997
Peripheral Neuropathy	998
Autonomic Neuropathy	999
Cranial Neuropathies	999
Sleep Disorders	999
Restless Legs Syndrome (Ekbom Syndrome)	1000
Neurologic Syndromes Associated With Renal Replacement Therapy	1000
References	1000
Self-assessment Questions	1001.e1
86 Gastroenterology and Nutrition in Chronic Kidney Disease	1002
Gastrointestinal Problems in Chronic Kidney Disease	1002
Gastrointestinal Disease in Chronic Kidney Disease	1002
Oral Disease in Chronic Kidney Disease	1002
Gastroesophageal Reflux Disease and Esophagitis	1002
Peptic Ulcer Disease, Gastritis, and Duodenitis	1002
Delayed Gastric Emptying and Gastroparesis	1002
Large Bowel Disorders	1003
Gastrointestinal Pseudoobstruction	1003
Vascular Disease of the Gastrointestinal Tract	1003
Gastrointestinal Hemorrhage	1004
Clostridium difficile Infection	1004
Acute Pancreatitis	1005
Acute Abdomen	1005
Combined Gastrointestinal and Renal Diseases	1005
Diabetes	1005
Systemic Vasculitis	1005
Systemic Amyloidosis	1005
Autosomal Dominant Polycystic Kidney Disease	1005
Inflammatory Bowel Disease	1006
Celiac Disease	1006
Drugs and Gastrointestinal Disease in Chronic Kidney Disease	1006
Specific Gastrointestinal Complications of Renal Replacement Therapy	1006
Idiopathic Dialysis-Related Ascites	1006
Peritoneal Dialysis–Related Gastrointestinal Conditions	1006
Dialysis-Related Amyloidosis	1006
Transplantation and Gastrointestinal Disturbance	1006
Nutrition in Chronic Kidney Disease	1007
Malnutrition: Protein-Energy Wasting	1007
Obesity Paradox in Chronic Kidney Disease	1007
Assessment of Nutritional Status	1007
Estimation of Intake	1007
Body Mass Index	1008
Body Composition	1008
Visceral Protein	1008
Tools to Diagnose Protein-Energy Wasting and Assess Nutritional Status	1008
Nutritional Guidelines	1008
Hyperlipidemia	1008
Hypertension	1009
Vitamins, Minerals, and Trace Elements	1009
Monitoring and Treatment	1010
Enteral Supplementation	1010
Supplementation of Dialysate Fluids	1010
Appetite Stimulants	1010
Gut-Targeted Therapeutics	1010
Metabolic Acidosis	1011
Exercise	1011
Potassium Binders	1011
References	1011
Self-Assessment Questions	1012.e1
87 Dermatologic Manifestations of Chronic Kidney Disease	1013
Uremic Pruritus	1013
Clinical Manifestations	1013
Pathogenesis	1013
Treatment	1013
Optimizing Dialysis and Mineral Metabolism Therapy	1013
Skin Emollients	1014
Antihistaminic Drugs	1014
Phototherapy	1015
5-Hydroxytryptamine Antagonist	1015
Opioid Receptor Agonists	1015
Gabapentin	1015
Immunomodulators and Immunosuppressive Agents	1016
Long-Chain Essential Fatty Acids	1016
Capsaicin	1016
Oral Activated Charcoal	1016
Miscellaneous	1016
Bullous Dermatoses	1016
Calcific Uremic Arteriolopathy (Calciphylaxis)	1016
Definition	1016
Epidemiology, Pathogenesis, and Risk Factors	1016
Clinical Manifestations	1017
Pathology	1017
Diagnosis and Differential Diagnosis	1017
Natural History	1017
Prevention and Treatment	1017
Nephrogenic Systemic Fibrosis	1018
Definition	1018
Pathogenesis	1018
Epidemiology	1019
Clinical Manifestations and Natural History	1019
Pathology	1019
Diagnosis and Differential Diagnosis	1019
Treatment and Prevention	1020
References	1020
Self-Assessment Questions	1021.e1
88 Acquired Cystic Kidney Disease and Malignant Neoplasms	1022
Definition	1022
Pathogenesis	1022
Epidemiology	1022
Clinical Manifestations	1022
Acquired Cystic Kidney Disease–Associated Renal Cell Carcinoma	1022
Pathology	1023
Diagnosis and Differential Diagnosis	1024
Natural History	1024
Treatment	1025
Cancer in Dialysis Patients	1026
References	1027
Self-assessment Questions	1027.e1
XVII Geriatric and Palliative Nephrology	1028
89 Geriatric Nephrology	1028
Aging-Associated Structural Changes	1028
Anatomic Changes	1028
Glomerular Changes	1028
Tubular and Interstitial Changes	1028
Vascular Changes	1028
Aging-Associated Changes in Renal Function	1028
Glomerular Filtration Rate	1028
Renal Plasma Flow	1028
Assessment of Renal Function in the Elderly	1029
Albuminuria	1029
Hematuria	1029
Prevalence of Chronic Kidney Disease in the Elderly	1030
Risk Factors for Chronic Kidney Disease in the Elderly	1030
Pathogenesis of Age-Related Chronic Kidney Disease	1031
Fluid and Electrolytes in Aging	1031
Sodium Balance and Hypertension	1031
Osmoregulation and Water Handling	1032
Other Tubular Defects and Electrolyte Problems	1032
Endocrine Function and Renal Hormones	1032
Clinical Manifestations	1032
General Considerations	1032
Glomerular Diseases	1032
Renovascular and Atheroembolic Disease	1032
Diabetic Nephropathy	1033
Acute Kidney Injury	1033
Nephrotoxicity and Drug Dosage	1033
End-Stage Renal Disease and Renal Replacement Therapy	1033
Depression in Elderly Patients With Kidney Diseases	1034
References	1034
Self-assessment Questions	1035.e1
XVIII Dialytic Therapies	1036
90 Approach to Renal Replacement Therapy	1036
Prediction of End-Stage Renal Disease	1036
Multidisciplinary Care in Advanced Chronic Kidney Disease	1036
Predialysis Education Programs	1036
Education About Transplantation	1037
When Should Dialysis Be Started?	1037
Limitations of a Purely Clinical Approach to the Initiation of Dialysis	1038
Limitations of a Purely Laboratory Results–Based Approach to the Initiation of Dialysis	1038
The Choice Between Peritoneal Dialysis and Hemodialysis	1039
Contraindications to Peritoneal Dialysis	1040
Fresh Intraabdominal Foreign Body	1040
Body Size Limitations and Intolerance of Intraabdominal Fluid Volume	1040
Bowel Disease and Other Sources of Infection	1041
Severe Malnutrition or Morbid Obesity	1042
Contraindications to Hemodialysis	1042
Home Hemodialysis	1042
Hemodialysis or Hemodiafiltration	1042
Patient Choice of Hemodialysis or Peritoneal Dialysis	1042
Economic Factors	1042
Physician Preference	1043
The Importance of Dialysis Access	1043
The Decision Whether to Offer Renal Replacement Therapy	1043
The Availability of Dialysis Facilities	1043
Selection of Patients by Physicians and Nephrologists	1044
Rationing Versus Rational Dialysis Treatment	1044
Predictive Factors	1044
Advising Patients About Prognosis on Dialysis	1045
Conservative Kidney Care	1045
The Patient Who Does Not Want Dialysis	1045
Disagreement About a Decision to Dialyse	1046
Management of Disruptive Patients on Dialysis	1047
Resuscitation and Withdrawal of Dialysis	1047
Cardiopulmonary Resuscitation	1047
Withdrawal of Dialysis	1047
References	1048
Self-assessment Questions	1049.e1
91 Vascular Access for Dialytic Therapies	1050
Evaluation of the Patient for Vascular Access	1050
Primary Autogenous Vascular Access	1050
Radiocephalic Arteriovenous Fistula	1050
Nonmaturation of Radiocephalic Arteriovenous Fistula	1051
Secondary Autogenous Vascular Access	1051
Forearm Cephalic and Basilic Vein Transposition and Elevation	1051
Elbow and Upper Arm Cephalic Vein Arteriovenous Fistula	1051
Upper Arm Basilic Vein Arteriovenous Fistula	1051
Nonautogenous Prosthetic Vascular Access	1052
Measures to Improve Graft Patency	1053
Pharmacologic Approaches for Access Patency	1053
Lower Limb Vascular Access	1054
Vascular Access Complications	1054
Nonmaturation of Arteriovenous Fistulas	1054
Stenosis and Thrombosis	1054
Autogenous Fistula Stenosis or Thrombosis	1055
Arteriovenous Graft Stenosis or Thrombosis	1055
Central Venous Obstruction	1055
Endovascular Intervention	1055
Surgical Intervention	1055
Vascular Access–Induced Ischemia	1055
Diagnosis of Ischemia	1056
Endovascular and Surgical Management of Ischemia	1056
Central Venous Catheter Access	1057
Nontunneled Catheters	1057
Tunneled Catheters	1057
Catheter Infection	1057
Infections Involving Temporary Catheters	1058
Exit Site Versus Tunnel Tract Infections	1058
Catheter-Associated Bacteremia	1058
Catheter Removal	1059
Prevention of Infection	1059
Catheter Obstruction	1059
References	1059
Self-assessment Questions	1061.e1
92 Diagnostic and Interventional Nephrology	1062
Ultrasound	1062
Applications and Limitations of Ultrasound	1062
Chronic Kidney Disease	1062
Acute Kidney Injury	1062
Renal Transplantation	1062
Renal Biopsy	1062
Urinary Bladder	1062
Hemodialysis Access	1062
Renovascular Ultrasound	1063
Equipment	1063
Procedure	1063
Training and Certification	1063
Peritoneal Dialysis Catheters	1063
Catheter Insertion	1063
Burying (Embedding) the Peritoneal Dialysis Catheter	1066
Complications of Peritoneal Dialysis Catheter Insertion	1066
Catheter Repositioning	1066
Removal of Peritoneal Dialysis Catheters	1067
Training and Certification	1067
Tunneled Hemodialysis Catheters	1067
Tunneled Catheter Insertion	1067
Catheter Dysfunction	1068
Catheter Exchange and Fibrin Sheath Removal	1068
Training and Certification	1068
Procedures on Arteriovenous Fistulas and Grafts	1068
Percutaneous Balloon Angioplasty	1069
Percutaneous Thrombectomy	1069
Stents	1069
Training and Certification	1070
References	1070
Self-Assessment Questions	1072.e1
93 Hemodialysis	1073
Dialysis System	1073
Dialyzer Designs and Membranes	1073
Safety Monitors	1073
Anticoagulation	1073
Dialysate Fluid	1074
Water and Water Treatment	1074
Dialysate Solution	1075
Biocompatibility	1076
Hemofiltration and Hemodiafiltration	1076
Modes of Hemofiltration and Hemodiafiltration	1076
Postdilution Hemodiafiltration	1076
Predilution Hemodiafiltration	1076
Mixed Dilution Hemodiafiltration	1076
Middilution Hemodiafiltration	1077
Uremic Toxins and Their Removal by Hemodialysis	1077
Additional Devices and Technologies	1077
Relative Blood Volume Monitoring	1077
Ultrafiltration Profiling	1078
Sodium Profiling	1079
Online Clearance Monitoring	1079
Blood Temperature Monitoring and Dialysate Cooling	1079
Intradialytic Oxygen Measurement	1079
Bioimpedance	1080
Home Hemodialysis	1080
Dialysis Machine Choice and Other Equipment	1080
Water Preparation, Standards, and Plumbing	1080
Safety	1080
Wearable Artificial Kidney	1080
References	1080
Self-assessment Questions	1081.e1
94 Hemodialysis	1082
Assessment of Dialysis Dose	1082
Markers of Uremic Toxin Removal by Renal Replacement Therapy	1082
Urea Removal	1082
Intradialytic Urea Kinetics	1082
Urea Reduction Ratio	1082
Single-Pool Kt/V (spKt/V) and Equilibrated Double-Pool Kt/V (eKt/V)	1083
Weekly Dialysis Dose and Weekly Standard: Kt/V (stdKt/V)	1084
Middle Molecule Removal	1084
Phosphate Removal	1084
Prescription of Hemodialysis	1085
Hemodialysis Dose	1085
Hemodiafiltration Dose	1085
Treatment Time and Frequency	1086
Dialysate Composition	1086
Sodium	1086
Potassium	1086
Calcium	1086
Bicarbonate	1086
Magnesium	1086
Fluid Status and Ultrafiltration Rate	1087
Dialysis Adequacy	1087
Prevention of Intradialytic Hypotension	1087
Preservation of Residual Renal Function	1087
Maintenance or Improvement of Nutritional Status	1087
Dialysis Adequacy in the Elderly	1087
References	1088
Self-Assessment Questions	1089.e1
95 Acute Complications During Hemodialysis	1090
Cardiovascular Complications	1090
Intradialytic Hypotension	1090
Intradialytic Hypertension	1090
Cardiac Arrhythmias	1091
Sudden Death	1092
Pericarditis	1092
Dialysis-Associated Steal Syndrome	1092
Neuromuscular Complications	1093
Muscle Cramps	1093
Restless Legs Syndrome	1093
Dialysis Disequilibrium Syndrome	1093
Seizures	1093
Headache	1094
Hematologic Complications	1094
Complement Activation and Dialysis-Associated Neutropenia	1094
Intradialytic Hemolysis	1094
Hemorrhage	1095
Thrombocytopenia	1095
Pulmonary Complications	1095
Dialysis-Associated Hypoxemia	1095
Technical Malfunctions	1096
Air Embolism	1096
Incorrect Dialysate Composition	1096
Hypernatremia	1096
Hyponatremia	1096
Metabolic Acidosis	1097
Metabolic Alkalosis	1097
Temperature Monitor Malfunction	1097
Blood Loss	1097
Clotting of Dialysis Circuit	1097
Dialysis Reactions	1097
Anaphylactic and Anaphylactoid Reactions	1097
Clinical Presentation	1097
First-Use Reactions	1098
Reuse Reactions	1098
Bradykinin-Mediated Reactions	1098
Drug-Induced Reactions	1099
Treatment and Prevention	1099
Mild Reactions	1099
Fever and Pyrogenic Reactions	1099
Investigation of a Dialysis Pyrogenic Outbreak	1100
Miscellaneous Complications	1100
Postdialysis Fatigue	1100
Pruritus	1100
Genitourinary Problems	1100
Hearing and Visual Loss	1101
References	1101
Self-assessment Questions	1102.e1
96 Peritoneal Dialysis	1103
Advantages and Limitations of Peritoneal Dialysis	1103
Principles of Peritoneal Dialysis	1103
Three-Pore Model	1103
Fluid Kinetics	1104
Effective Peritoneal Surface Area	1104
Peritoneal Access	1106
Techniques of Peritoneal Dialysis	1107
Peritoneal Dialysis Fluids	1108
Electrolyte Concentration	1108
Osmotic Agents	1108
Assessments of Peritoneal Solute Transport and Ultrafiltration	1108
Small-Solute Removal	1108
Large-Solute Removal	1109
Ultrafiltration	1109
Peritoneal Membrane Function	1109
Peritoneal Equilibration Test	1109
Mini–Peritoneal Equilibration Test	1109
Double–Mini–Peritoneal Equilibration Test	1109
Residual Renal Function	1109
Adequacy	1110
Small-Solute Clearance	1110
Fluid Balance	1111
Management of Fluid Overload	1111
Nutrition	1111
Outcome of Peritoneal Dialysis	1112
References	1112
Self-assessment Questions	1113.e1
97 Complications of Peritoneal Dialysis	1114
Catheter Malfunction	1114
Optimal Timing and Placement of the Peritoneal Dialysis Catheter	1114
Catheter Function: Inflow	1114
Catheter Function: Outflow	1114
Fibrin in the Dialysate	1114
Fluid Leaks	1114
External Leaks	1115
Internal Leaks	1115
Hydrothorax	1115
Pain Related to Peritoneal Dialysis	1116
Inflow Pain	1116
Outflow Pain	1116
Blood-Stained Dialysate	1116
Infectious Complications	1116
Peritonitis	1116
Diagnosis of Peritonitis	1117
Treatment of Peritonitis	1117
Fungal Peritonitis	1118
Relapsing Peritonitis	1118
Culture-Negative Peritonitis	1118
Exit Site Infection	1118
Reduced Ultrafiltration and Ultrafiltration Failure	1119
Definition and Significance of Ultrafiltration Failure	1119
Establishing the Causes of Ultrafiltration Failure	1119
Fast Peritoneal Solute Transport Rate–Related Ultrafiltration Failure: Diagnosis and Management	1119
Low Osmotic Conductance–Related Ultrafiltration Failure: Diagnosis and Management	1120
Changes in Peritoneal Structure and Function	1120
Preventing Membrane Injury	1120
Encapsulating Peritoneal Sclerosis	1120
Nutritional and Metabolic Complications	1121
Undernutrition	1121
Acid-Base Status	1122
Lipids and Obesity	1122
References	1122
Self-assessment Questions	1123.e1
98 Extracorporeal Therapies for Drug Overdose and Poisoning	1124
When Should Extracorporeal Removal Be Considered?	1124
Molecular Weight	1124
Protein Binding	1124
Volume of Distribution	1125
Solute Compartmentalization	1125
Contribution of Extracorporeal Toxin Relative to Endogenous Clearance	1126
Treatment Modalities	1126
Intermittent Hemodialysis, Hemofiltration, and Hemodiafiltration	1126
Peritoneal Dialysis	1126
Continuous Renal Replacement Therapy	1127
Hemoperfusion	1128
Other Modalities	1129
Extracorporeal Therapy for Specific Drugs and Poisons	1129
Alcohols	1129
β-Blockers	1129
Lithium	1130
Metformin	1130
Salicylates	1130
Theophylline	1130
Valproate	1130
Tricyclic Antidepressant Drugs	1130
Thallium	1130
Barbiturates	1130
Acetaminophen	1130
Carbamazepine	1130
Phenytoin	1131
Digoxin	1131
References	1131
Self-Assessment Questions	1131.e1
99 Plasma Exchange	1132
Techniques	1132
Complications	1135
Mechanisms of Action	1135
Indications for Plasma Exchange	1136
Anti–Glomerular Basement Membrane Antibody Disease (Goodpasture Disease)	1136
XIX Transplantation	1141
100 Immunologic Principles in Kidney Transplantation	1141
Ischemia/Reperfusion Injury	1141
Antigen Presentation	1141
Antigen-Presenting Cells	1141
T Cell Ontogeny and Major Histocompatibility Complex Specificity	1142
Pathways of Allorecognition	1143
Major Histocompatibility Complex	1143
Human Leukocyte Antigen Typing and Transplantation	1144
Human Leukocyte Antigen Inheritance	1144
Non–Major Histocompatibility Antigens	1144
T Cell Activation	1144
T Cell Receptor	1144
CD4 and CD8 Coreceptors	1145
T Cell Receptor Engagement of Antigen: Signal 1	1145
T Cell Costimulation: Signal 2	1145
T Cell Clonal Expansion and Differentiation	1146
Memory Cells	1147
Effector Functions	1147
Cytologic T Lymphocyte Differentiation and Function	1148
Macrophage Activation	1148
The Humoral Immune Response	1148
Natural Killer Lymphocytes	1149
Termination of the Immune Response	1149
Allograft Rejection	1149
Recruitment of Cells into the Interstitium of Kidney Allografts	1149
Acute T Cell–Mediated Rejection	1150
Acute Antibody-Mediated Rejection	1151
Chronic Rejection	1151
Transplantation Tolerance	1152
References	1152
Self-Assessment Questions	1153.e1
101 Immunosuppressive Medications in Kidney Transplantation	1154
Small-Molecule Drugs	1154
Corticosteroids	1154
Mechanism of Action	1154
Pharmacokinetics	1154
Side Effects	1154
Calcineurin Inhibitors	1154
Mechanism of Action	1156
Pharmacokinetics, Monitoring, and Drug Interactions	1156
Side Effects	1157
Mycophenolate	1157
Mechanism of Action	1157
Pharmacokinetics	1157
Side Effects	1158
Azathioprine	1158
Mammalian Target of Rapamycin Inhibitors	1158
Mechanism of Action	1158
Pharmacokinetics	1158
Side Effects	1159
Dihydroorotate Dehydrogenase Inhibitors	1159
Biologic Agents	1159
Polyclonal Antilymphocyte Sera	1160
Humanized Monoclonal Anti-CD52 Antibody	1160
Monoclonal Anti-CD25 Antibody	1160
B Cell–Depleting Monoclonal Anti-CD20 Antibody	1160
Intravenous Immunoglobulin	1160
Belatacept	1160
Other Agents Used in Transplantation	1161
Bortezomib	1161
Eculizumab	1162
References	1162
Self-assessment Questions	1162.e1
102 Evaluation and Preoperative Management of Kidney Transplant Recipient and Donor	1163
Recipient Evaluation	1163
Cardiovascular Disease	1163
Coronary Heart Disease and Left Ventricular Dysfunction	1163
Cerebrovascular Disease	1163
Peripheral Vascular Disease	1164
Cancer	1164
Infectious Complications	1165
Obesity	1166
Recurrent Disease	1166
Gastrointestinal Disease	1166
Genitourinary Disorders	1166
Pulmonary Disease	1166
Psychosocial Issues	1166
Presence of Multiple Comorbidities	1166
Reevaluation of Patients on the Waiting List	1166
Donor Evaluation	1167
Deceased Donors	1167
Classification of the Deceased Donor	1167
Evaluation of the Deceased Donor	1168
Deceased Donor Management Before Transplantation	1168
Living Donors	1168
Mortality and Morbidity	1169
Evaluation of the Living Donor	1169
Assessment of Renal Function	1169
Hypertension and Proteinuria in the Living Donor	1170
Obesity and Abnormal Glucose Tolerance in the Living Donor	1170
Renal Abnormalities in the Living Donor	1170
Malignancy	1171
Cardiovascular and Pulmonary Disease	1171
Compatibility and Immunologic Considerations	1171
Blood Group Compatibility	1171
Human Leukocyte Antigen Compatibility	1171
Assessing Human Leukocyte Antigen Sensitization	1171
References	1172
Self-Assessment Questions	1173.e1
103 Kidney Transplantation Surgery	1174
Sources of Kidneys for Transplantation	1174
Donation Before Cardiac Death Donors	1174
Donation After Cardiac Death Donors	1174
Donation After Cardiac Death Protocol	1174
Uncontrolled Donation After Cardiac Death Donors	1174
Controlled Donation After Cardiac Death Donors	1175
Living Kidney Donors	1175
Preoperative Imaging	1175
Minimal Access (Laparoscopic) Donor Nephrectomy	1175
Transperitoneal Laparoscopic Donor Nephrectomy	1176
Hand-Assisted Laparoscopic Donor Nephrectomy	1177
Retroperitoneoscopic Operative Technique	1177
Contraindications to Minimal Access Donor Nephrectomy	1177
Effect of Pneumoperitoneum	1177
Graft Function and Acute Rejection	1177
Technical Issues	1177
Postoperative Recovery	1177
Choice of Donor Operative Technique	1177
Renal Preservation	1177
Renal Transplantation Procedure	1177
Vascular Anastomosis	1178
Urinary Drainage	1178
Alternative Techniques of Urinary Reconstruction	1179
Drainage and Wound Closure	1179
Postoperative Course	1179
Surgical Complications of Renal Transplantation	1179
Wound Infection	1179
Wound Dehiscence	1179
Vascular Complications	1179
Bleeding From Vessels in the Renal Hilum	1180
Anastomotic Hemorrhage	1180
Renal Artery Thrombosis	1180
Renal Vein Thrombosis	1181
Transplant Renal Artery Stenosis	1181
Lymphocele	1181
Urologic Complications	1182
Urinary Leaks	1182
Ureteral Obstruction	1182
Complications in the Transplant Bed	1184
Transplant Nephrectomy	1184
References	1184
Self-assessment Questions	1185.e1
104 Prophylaxis and Treatment of Kidney Transplant Rejection	1186
Definition	1186
Antibody-Mediated Rejection	1186
T Cell–Mediated Rejection	1187
Borderline Rejection	1188
Clinical Manifestations	1188
Prophylaxis and Prevention	1188
Prophylaxis	1188
Prevention of Acute T Cell–Mediated Rejection: Induction Therapy	1188
Prevention of Acute Antibody-Mediated Rejection: Desensitization	1191
Maintenance Therapy for Prevention of Acute Rejection	1192
Calcineurin Inhibitors in the Prevention of Acute Rejection	1192
Antiproliferative Agents in the Prevention of Acute Rejection	1193
Acute Rejection Rates in Calcineurin-Sparing and Corticosteroid-Sparing Immunosuppression Regimens	1193
Treatment	1194
Acute T Cell–Mediated Rejection	1194
Acute Antibody-Mediated Rejection	1195
Chronic Rejection (T Cell–Mediated and/or Antibody-Mediated)	1195
Prognosis	1195
Summary and Recommendations	1195
References	1196
Self-assessment Questions	1197.e1
105 Medical Management of the Kidney Transplant Recipient	1198
Infectious Diseases	1198
Immunizations Before and After Transplantation	1198
Infectious Causes	1198
Risk Factors for Post-Transplant Infectious Complications	1198
Donor-Derived Infections	1198
Month 1 After Transplantation	1199
Months 1 to 6	1199
After 6 Months	1200
Management and Prophylactic Therapy for Selected Infections	1201
Cytomegalovirus Infection	1201
Clinical Manifestations	1201
Immunomodulating Effects of Cytomegalovirus Infection	1201
Risk Factors for Cytomegalovirus Infection	1201
Prevention	1201
Treatment	1202
Candida Infections	1202
BK Virus Infection	1202
Other Infections	1205
Gastrointestinal Disease	1205
Drug-Related Gastrointestinal Complications	1205
Infections	1206
Cytomegalovirus Infection	1207
Herpes Simplex Virus Infection	1207
Fungal Infections	1207
Helicobacter Infection	1207
Diarrhea and Colon Disorders	1207
Transplant-Associated Malignancy	1207
Post-Transplant Lymphoproliferative Disorder	1208
Risk Factors	1209
Type of organ transplant.	1209
Age.	1209
Type of immunosuppression	1209
Calcineurin inhibitors.	1209
mTOR inhibitors.	1209
Antimetabolites.	1209
Induction agents.	1209
Belatacept.	1209
Viral infection	1209
Epstein-Barr virus.	1209
Hepatitis C virus.	1209
Miscellaneous.	1209
Clinical Manifestations	1209
Treatment	1210
Viral Load Monitoring and Preemptive Strategies	1210
Skin Cancer	1210
Management of Immunosuppressive Therapy in Post-Transplantation Malignancy	1210
References	1211
Self-Assessment Questions	1212.e1
106 Medical Management of the Kidney Transplant Recipient	1213
Cardiovascular Disease	1213
Conventional Cardiovascular Disease Risk Factors	1213
Post-Transplantation Hypertension	1213
Post-Transplantation Dyslipidemia	1214
Statin Therapy	1214
Nonstatin Drug Therapy	1216
Management of Hypertriglyceridemia	1216
Drug therapy for Hypertriglyceridemia	1216
Fibrates.	1216
Ezetimibe.	1216
Bile acid resins.	1216
Niacin.	1216
Summary	1216
Post-Transplantation Diabetes Mellitus (New-Onset Diabetes After Transplantation)	1216
Risk Factors	1216
Management of Post-Transplantation Diabetes Mellitus	1216
Therapeutic Interventions	1217
Nonpharmacologic Management	1217
Modification of Immunosuppression	1217
Pharmacologic Treatment	1217
Cigarette Smoking	1218
Obesity	1218
Unconventional Cardiovascular Disease Risk Factors	1218
Proteinuria	1218
Belatacept Use	1219
Common Laboratory Abnormalities	1219
Anemia	1219
Leukopenia and Thrombocytopenia	1219
Erythrocytosis	1219
Hyperkalemia	1220
Hypophosphatemia	1220
Hypercalcemia	1220
Hypomagnesemia	1221
Abnormal Liver Function Tests	1221
Bone and Mineral Metabolism After Kidney Transplantation	1221
Osteoporosis	1222
Avascular Necrosis	1222
Prevention and Management of Post-Transplantation Bone Diseases	1222
Gout	1223
Outpatient Care	1224
References	1224
Self-Assessment Questions	1225.e1
107 Chronic Allograft Injury	1226
Definitions and Epidemiology	1226
Pathogenesis: Nonimmunologic Factors	1226
Donor Age, Donor Gender, and Donor-Recipient Size Mismatching	1226
Ischemia/Reperfusion Injury and Delayed Graft Function	1226
BK Virus Nephropathy	1227
Calcineurin Inhibitor Toxicity	1227
Recurrent and De Novo Glomerular Diseases	1227
Cardiovascular Risk Factors	1229
Pathogenesis: Immunological Factors	1229
T Cell–Mediated Rejection	1229
Antibody-Mediated Rejection	1229
Insufficient Immunosuppression and Nonadherence to Medication	1231
Clinical Manifestations	1232
Pathology	1232
Diagnosis and Differential Diagnosis	1233
Prevention of Antibody-Mediated Allograft Injury	1233
Treatment of Chronic Allograft Injury	1234
References	1234
Self-Assessment Questions	1235.e1
108 Recurrent Disease in Kidney Transplantation	1236
Definitions	1236
Recurrent Glomerulonephritis	1236
Recurrence of Specific Glomerular Diseases	1238
Immunoglobulin A Nephropathy and IgA Vasculitis (Henoch-Schonlein Purpura)	1238
Membranous Nephropathy	1240
Focal Segmental Glomerulosclerosis	1240
Membranoproliferative Glomerulonephritis	1241
Membranoproliferative Glomerulonephritis Type I	1242
C3 Glomerulopathy	1242
Membranoproliferative Glomerulonephritis Type III	1242
Congenital Nephrotic Syndrome	1242
Antineutrophil Cytoplasmic Antibody–Associated Pauci-immune Vasculitis	1242
Anti–Glomerular Basement Membrane Disease	1242
Lupus Nephritis	1242
Thrombotic Microangiopathy and Hemolytic Uremic Syndrome	1243
Scleroderma	1243
Amyloid, Light-Chain Disease, and Fibrillary and Immunotactoid Glomerulopathies	1243
Amyloidosis	1243
Light-Chain Nephropathy	1244
Fibrillary and Immunotactoid Glomerulopathies	1244
Recurrence of Metabolic Diseases Affecting the Kidney Transplant	1244
Diabetes Mellitus	1244
Primary Hyperoxaluria	1244
Fabry Disease	1244
Recurrence of Virus-Associated Nephropathies and Tumors in the Transplanted Kidney	1244
References	1245
Self-Assessment Questions	1246.e1
109 Outcomes of Renal Transplantation	1247
Methods of Measurement and Analysis	1247
Types of Outcome Analyses	1247
Survival Analyses	1247
Half-Life Analysis	1247
Graft Survival	1247
Randomized Controlled Trials	1249
Cohort Studies	1249
Meta-Analyses	1249
Case Reports	1249
Expert Opinion Guidelines	1250
Qualitative Studies	1250
Economic Analysis	1250
Types of Data Collection	1250
Registries	1251
International Statistical Collections	1251
Randomized Controlled Trials: Data Collection	1251
Structured Reviews	1252
Variables Affecting the Outcomes of Transplantation	1252
Deceased Donor Variables	1252
Living Donor Variables	1253
Other Donor Variables	1253
Recipient Variables	1253
Effects of Immunosuppression on Transplant Outcome	1254
Transplant Center Variables	1254
Transplantation Matching Variables	1255
Outcomes Inform the Recipient Decision	1256
References	1256
Self-Assessment Questions	1257.e1
110 Pancreas and Islet Transplantation	1258
Patient Selection Criteria for Pancreas or Islet Transplantation	1258
Indications for Transplantation	1258
Medical Evaluation	1259
Pancreas Transplantation	1260
Patient and Graft Survival	1260
Surgical Procedure	1260
Immunosuppression	1261
Graft Monitoring	1261
Antimicrobial Prophylaxis	1263
Metabolic Monitoring	1263
Surgical Complications	1263
Nonsurgical Complications	1263
Urologic Complication	1264
Urinary Tract Infections	1265
Enteric Conversion	1265
Late Complications	1265
Impact of Pancreas Transplantation on Diabetic Complications	1265
Hypoglycemia	1265
Hyperglycemia	1266
Microvascular Complications	1266
Retinopathy	1266
Neuropathy	1266
Nephropathy	1266
Vascular Disease	1266
Quality of Life and Social Issues	1266
Pregnancy After Pancreas Transplantation	1266
Islet Transplantation	1267
Islet After Kidney Transplantation	1267
Technique of Islet Transplantation	1267
Medical Complications	1267
Glycemic Control and Insulin Independence	1268
Immunosuppressive Regimens	1268
References	1270
Self-assessment Questions	1271.e1
111 Kidney Disease in Liver, Cardiac, Lung, and Hematopoietic Stem Cell Transplantation	1272
Generic Issues of Kidney Disease in Nonrenal Solid Organ Transplantation	1272
Use of Serum Creatinine and Derived Equations to Estimate Glomerular Filtration Rate	1272
Nephrotoxicity of Calcineurin Inhibitors	1272
Acute Kidney Injury in the Immediate Pretransplant Period	1272
Acute Kidney Injury in the Early Post-Transplant Period	1273
Acute Kidney Injury in the Late Post-Transplantation Period	1273
Chronic Kidney Disease	1273
Management of Chronic Kidney Disease	1275
BK Virus Nephropathy	1275
Kidney Disease in Liver Transplantation	1275
Kidney Disease Before Cardiac Transplantation	1276
Kidney Disease in Lung Transplantation	1276
Kidney Disease in Hematopoietic Stem Cell Transplantation	1277
Acute Kidney Injury After Hematopoietic Stem Cell Transplantation	1277
Hepatic Sinusoidal Obstructive Syndrome	1278
Management of Acute Kidney Injury After Hematopoietic Stem Cell Transplantation	1278
Chronic Kidney Disease After Hematopoietic Stem Cell Transplantation	1278
Thrombotic Microangiopathy	1278
Calcineurin Inhibitor and Sirolimus Nephrotoxicity	1279
Glomerular Disease	1279
Management of Hematopoietic Stem Cell Transplantation–Related Chronic Kidney Disease	1279
References	1280
Self-assessment Questions	1281.e1
XX Palliative Nephrology	1282
112 Palliative Nephrology	1282
Prognosis	1282
Communication and Shared Decision Making	1282
Conservative Care	1285
Dialysis Withdrawal	1286
Symptom Control and Management of Last Days	1287
References	1287
Self-Assessment Questions	1288.e1
Answers	e.1
Chapter 1	e.1
Chapter 2	e.2
Chapter 3	e.3
Chapter 4	e.4
Chapter 5	e.5
Chapter 6	e.6
Chapter 7	e.7
Chapter 8	e.8
Chapter 9	e.9
Chapter 10	e.10
Chapter 11	e.11
Chapter 12	e.12
Chapter 13	e.13
Chapter 14	e.14
Chapter 15	e.15
Chapter 16	e.16
Chapter 17	e.17
Chapter 18	e.18
Chapter 19	e.19
Chapter 21	e.20
Chapter 23	e.21
Chapter 24	e.22
Chapter 25	e.23
Chapter 26	e.24
Chapter 27	e.25
Chapter 28	e.26
Chapter 29	e.27
Chapter 30	e.28
Chapter 32	e.29
Chapter 33	e.30
Chapter 34	e.32
Chapter 35	e.33
Chapter 36	e.34
Chapter 37	e.35
Chapter 38	e.36
Chapter 39	e.37
Chapter 40	e.38
Chapter 41	e.39
Chapter 42	e.40
Chapter 43	e.41
Chapter 44	e.42
Chapter 45	e.43
Chapter 46	e.44
Chapter 47	e.45
Chapter 48	e.46
Chapter 49	e.47
Chapter 50	e.48
Chapter 51	e.49
Chapter 52	e.50
Chapter 53	e.51
Chapter 54	e.52
Chapter 55	e.53
Chapter 56	e.54
Chapter 57	e.55
Chapter 58	e.56
Chapter 59	e.57
Chapter 60	e.58
Chapter 61	e.59
Chapter 62	e.60
Chapter 63	e.61
Chapter 64	e.62
Chapter 65	e.63
Chapter 66	e.64
Chapter 68	e.65
Chapter 69	e.66
Chapter 70	e.67
Chapter 71	e.68
Chapter 72	e.69
Chapter 73	e.70
Chapter 74	e.71
Chapter 75	e.72
Chapter 76	e.73
Chapter 77	e.74
Chapter 78	e.75
Chapter 79	e.76
Chapter 80	e.77
Chapter 81	e.78
Chapter 82	e.79
Chapter 83	e.80
Chapter 84	e.81
Chapter 85	e.82
Chapter 86	e.83
Chapter 87	e.84
Chapter 88	e.85
Chapter 89	e.86
Chapter 90	e.87
Chapter 91	e.88
Chapter 92	e.89
Chapter 93	e.90
Chapter 94	e.90
Chapter 95	e.91
Chapter 96	e.92
Chapter 97	e.93
Chapter 98	e.94
Chapter 99	e.95
Chapter 100	e.96
Chapter 101	e.97
Chapter 102	e.98
Chapter 103	e.99
Chapter 104	e.100
Chapter 105	e.101
Chapter 106	e.102
Chapter 107	e.103
Chapter 108	e.104
Chapter 109	e.105
Chapter 110	e.106
Chapter 111	e.107
Chapter 112	e.108
Index	1289
A	1289
B	1294
C	1295
D	1300
E	1302
F	1304
G	1305
H	1307
I	1310
J	1312
K	1312
L	1314
M	1315
N	1318
O	1319
P	1320
Q	1324
R	1324
S	1327
T	1329
U	1331
V	1332
W	1333
X	1333
Y	1333
Z	1333
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SPEC - Comprehensive Clinical Nephrology

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