Brenner & Rector's The Kidney

Front Matter
Brenner & Rector’s The Kidney
Copyright Page
Dedication
Contributors
Preface
1 Embryology of the Kidney
Chapter Outline
KEY POINTS
Mammalian Kidney Development
Anatomic Overview of the Mammalian Kidney
Development of the Urogenital System
Development of the Metanephros
Ureteric Branching Morphogenesis
Development of the Nephron
The Nephrogenic Zone
Renal Stroma and Interstitial Cell Populations
The Renal Vasculature
Model Systems to Study Kidney Development
The Kidney Organ Culture System
Genetic Mouse Models
Imaging and Lineage Tracing Studies
Nonmammalian Model Systems for Kidney Development
Stem Cell Derived Kidney Organoids
Genetic Analysis of Mammalian Kidney Development
Interaction of the Ureteric Bud and the Metanephric Mesenchyme
Early Lineage Determination of the Metanephric Mesenchyme
Ureteric Bud Induction
Genes Required by the Ureteric Bud
Adhesion Proteins in Early Kidney Development
Positioning of the Ureteric Bud
Formation of the Collecting Duct System
Molecular Genetics of Nephrogenesis
Epithelialization of the Metanephric Mesenchyme
Nephron Segmentation and Tubulogenesis
Cessation of Nephrogenesis
Molecular Genetics of the Stromal Cell Lineage
Molecular Genetics of Vascular Formation
Renin Cells and the Juxtaglomerular Apparatus
Podocyte Development
Glomerular Basement Membrane Development
Development of the Mesangium
Development of the Bowman Capsule
Neural Development
Key References
References
Board Review Questions
2 Anatomy of the Kidney
Chapter Outline
Gross Features
The Nephron
Glomerulus
Endothelial Cells
Glomerular Basement Membrane
Podocytes
Mesangial Cells
Parietal Epithelial Cells
Juxtaglomerular Apparatus
Juxtaglomerular Granular Cells
Extraglomerular Mesangium
Macula Densa
Proximal Tubule
Proximal Convoluted Tubule
Proximal Straight Tubule
Thin Limbs of the Loop of Henle
Distal Tubule
Thick Ascending Limb
Distal Convoluted Tubule
Connecting Segment
Collecting Duct
Cortical Collecting Duct
Outer Medullary Collecting Duct
Inner Medullary Collecting Duct
Papillary Surface Epithelium
Interstitium
Cortical Interstitium
Medullary Interstitium
Lymphatics
Innervation
Acknowledgments
Key References
References
Board Review Questions
3 The Renal Circulations and Glomerular Filtration
Chapter Outline
Key Points
Introduction
Renal Blood Flow and Glomerular Filtration Rate
Major Arteries and Veins
Oxygen Consumption
Hydraulic Pressure Profile and Vascular Resistances
Intrarenal Blood Flow Distribution
Vascular-Tubule Relations
Structural and Functional Aspects of the Glomerular Microcirculation
Determinants of Glomerular Filtration
Permeability of the Glomerular Filtration Barrier
Hydraulic and Oncotic Forces in the Glomerular Capillaries and Bowman’s Space
Determination of the Filtration Coefficient
Determinants of Glomerular Filtration Coefficient in Human Subjects
Selective Alterations in the Primary Determinants of Glomerular Filtration
Glomerular Plasma Flow (QA)
Transcapillary Hydraulic Pressure Difference (ΔP)
Glomerular Capillary Filtration Coefficient (Kf)
Colloid Osmotic Pressure (πA)
Postglomerular Circulation
Peritubular Capillary Dynamics
Medullary Microcirculation
Paracrine and Endocrine Factors Regulating Renal Hemodynamics and Glomerular Filtration Rate
Extrinsic and Intrinsic Regulation of the Renal Microcirculations
Intrinsic Mechanisms: Renal Autoregulation
Cellular Mechanisms Involved in Renal Autoregulation
Myogenic and Tubuloglomerular Feedback Mechanisms
Mechanisms of Tubuloglomerular Feedback Control of Renal Blood Flow and Glomerular Filtration Rate
Connecting Tubule Glomerular Feedback Mechanism
Endothelial Factors and Gaseous Transmitters Controlling Renal Hemodynamics and Glomerular Filtration Rate
Nitric Oxide and Nitric Oxide Synthases
Effects of Heme Oxygenase and Carbon Monoxide on Renal Function
Hydrogen Sulfide
Reactive Oxygen Species
Endothelin
Role of the Renin-Angiotensin-Aldosterone System in the Control of Renal Blood Flow and Glomerular Filtration Rate
Role of Angiotensin II in Glomerular and Tissue Injury
Arachidonic Acid Metabolites Regulating Renal Blood Flow and Glomerular Filtration Rate
Prostaglandins
Leukotrienes and Lipoxins
Cytochrome P450
Neural Regulation of Renal Circulation
Glomerular Hemodynamics in the Aging Kidney
Key References
References
Board Review Questions
4 Glomerular Cell Biology and Podocytopathies
Chapter Outline
Key Points
Glomerular Cell Anatomy and Injury Response Patterns
Podocytes
Structure
Function
Podocyte Pathophysiology
Podocyte Foot Process Effacement
Podocyte Hypertrophy
Podocyte Depletion
Podocyte-Related Mechanisms of Proteinuria
Mesangial Cells
Structure
Function
Pathophysiology
Glomerular Endothelial Cells
Structure
Function
Pathophysiology
Parietal Epithelial Cells
Structure
Function
Pathophysiology
Glomerular Cell Crosstalk
Podocytes and Glomerular Endothelial Cells
Glomerular Endothelial Cells and Mesangial Cells
Podocytes and Mesangial Cells
Podocytes and Parietal Epithelial Cells
Common Mechanisms of Glomerular Diseases
Mechanisms of Injury in Common Podocytopathies
Minimal Change Disease and Focal Segmental Glomeruloschlerosis
Pathophysiologic Concepts of MCD and Primary FSGS
Membranous Nephropathy
Effects of Existing Therapies on Podocytes
Renin Angiotensin System Blockade
Glucocorticoids
Evidence for Direct Actions of Immunosuppressants on Podocytes
Identification of Candidate Therapeutic Approaches for the Future
Summary
Acknowledgments
Key References
References
Board Review Questions
5 Metabolic Basis of Solute Transport
Chapter Outline
Thermodynamic Approach to Metabolism and Transport
Thermodynamic Analysis of Kidney Function
Application of the Laws of Thermodynamics to Kidney Function
Energy and the Sodium Pump
Structure of the Sodium Pump
Other Adenosine Triphosphatases
Pump Leak Process and the Sodium Potential
Harnessing the Sodium Potential for Work
Cell Polarity and Vectorial Transport
Metabolic Substrates Fueling Active Transport Along the Nephron
Metabolism Basics
Whittam Model
Energy Requirements and Substrate Use Along the Nephron
Renal Gluconeogenesis and Lactate Handling
Nephron-Region–Specific Metabolic Considerations
Proximal Tubule
Thick Ascending Limb
Cortical Collecting Dust
Medullary Collecting Duct
Sexual Dimorphic Pattern of Transporters Along the Nephron and Metabolic Considerations
Control of Renal Oxygenation
Renal Blood Flow, Oxygen Consumption, and AV Oxygen Shunting
Tubuloglomerular Feedback
Metabolic Cost of Sodium Reabsorption
Renal Oxygenation and Metabolism During Normal Perturbations and Disease
Physiologic Regulation: Filtration Fraction and Qo2/Tna
Hypoxia and Ischemia
Hypoxia-Inducible Factor
Adenosine Monophosphate–Activated Protein Kinase
Tubular Metabolism
Mitochondrial Disorders
Summary
Key References
References
6 Transport of Sodium, Chloride, and Potassium
Chapter Outline
Introduction to Na, Cl, and K Transport
Sodium and Chloride Transport
Proximal Tubule
Paracellular Na+-Cl− Transport
Transcellular Na+-Cl− Transport
Apical Mechanisms
Basolateral Mechanisms
Regulation of Proximal Tubular Na+-Cl− Transport
Glomerulotubular Balance
Neurohumoral Influences
Regulation of Proximal Tubular Transporters
Loop of Henle
Transport Characteristics of the Descending Thin Limb
Na+-Cl− Transport by the Thin Ascending Limb
Na+-Cl− Transport by the Thick Ascending Limb
Apical Na+-Cl− Transport
Apical K+ Channels
Paracellular Transport
Basolateral Mechanisms
Regulation of Na+-Cl− Transport by the Thick Ascending Limb
Activating Influences
Inhibitory Influences
Uromodulin
Anatomy of the Distal Nephron
Distal Convoluted Tubule
Mechanisms of Na+-Cl− Transport in the Distal Convoluted Tubule
Regulation of Na+-Cl− Transport in the Distal Convoluted Tubule
Connecting Tubules and the Cortical Collecting Duct
Apical Na+ Transport
Cl− Transport
Electroneutral Na+-Cl− Cotransport
Regulation of Na+-Cl− Transport in the Connecting Tubule and Cortical Collecting Duct
Aldosterone
Vasopressin and Other Factors
Potassium Transport
Proximal Tubule
Loop of Henle
Distal Nephron
K+ Secretion
K+ Reabsorption by the Collecting Duct
Regulation of Distal K+ Transport
Modulation of Renal Outer Medullary Potassium Channel Activity
Aldosterone and K+ Loading
K+ Deprivation
Vasopressin
Tissue Kallikrein
Integrated Na+-Cl− and K+ Transport in the Distal Nephron
Key References
References
Board Review Questions
7 The Regulation of Calcium, Magnesium, and Phosphate Excretion by the Kidney
Chapter Outline
Key Points
Calcium Transport in the Kidney
The Role of Calcium in Cellular Processes
Calcium Is Present in Serum in Bound and Free Forms
Regulation of Calcium Homeostasis by the Parathyroid Hormone–Vitamin D Endocrine System
Reabsorption of Calcium Along the Tubule
Ca2+ Reabsorption in the Proximal Tubule
Ca2+ Reabsorption in the Loop of Henle
Ca2+ Reabsorption in the Distal Tubule
Regulation of Ca2+ Transport in the Kidney
Calcium-Regulating Hormones
Extracellular Calcium and Diet
Diuretics
Estrogens
Extracellular Fluid Volume
Metabolic Acidosis and Alkalosis
Regulation of Renal Calcium Transport by Novel Proteins
Klotho
Sclerostin
Magnesium Transport in the Kidney
The Role of Magnesium in Cellular Processes
Magnesium Is Present in Serum in Bound and Free Forms
Regulation of Mg Homeostasis
Reabsorption of Magnesium Along the Tubule
Mg2+ Reabsorption in the Proximal Tubule
Mg2+ Reabsorption in the Thick Ascending Limb
Mg2+ Reabsorption in the Distal Tubule
Regulation of Magnesium Transport in the Kidney
Phosphorus Transport in the Kidney
The Role of Phosphorus in Cellular Processes
Phosphorus Is Present in Blood in Multiple Forms
Regulation of Phosphate Homeostasis—an Integrated View
Reabsorption of Phosphate Along the Nephron
Regulation of Phosphate Transport in the Kidney
Dietary Phosphate
Parathyroid Hormone
Vitamin D and Vitamin D Metabolites
Insulin, Growth Hormone, and Insulin-Like Growth Factor
Renal Nerves, Catecholamines, Dopamine, and Serotonin
Phosphatomins (FGF-23, sFRP-4)
Key References
References
Board Review Questions
8 Renal Handling of Organic Solutes
Chapter Outline
Key Points
Glucose
Physiology of Renal Glucose Transport
A Primary Role for SGLT2 in Renal Glucose Reabsorption
Unmasking a Significant Glucose Transport Capacity of SGLT1 in the Late Proximal Tubule
Molecular Characterization of Proximal Tubular Glucose Transport
Apical Glucose Transporters
Basolateral Glucose Transporters
Renal Formation of Glucose
Renal Glucose Transport in Disease States
Glucose Transport Is Increased in the Diabetic Kidney
Glucose Transporters in the Diabetic Kidney
SGLT2 and GLUT2
SGLT1 and GLUT1
Inhibition of Renal Glucose Reabsorption as a New Antihyperglycemic Therapy
Organic Cations and Anions
Organic Anion Transporters and Organic Cation Transporters
OAT1 (SLC22A6) and OAT3 (SLC22A8)
OAT1 Knockout and OAT3 Knockout Mice
OAT1 and OAT3 Single-Nucleotide Polymorphisms
OCT2 (SLC22A2)
OCT2 Single Nucleotide Polymorphisms
Apical Membrane Proximal Tubule Transporters Involved in the Handling of Organic Anions, Organic Cations, and Organic Zwitterions
Renal Transport of Specific Organic Substrates in Disease
Uremic Toxin Transport
Uric Acid Transport
Creatinine Transport
The Remote Sensing and Signaling Hypothesis: a Framework for Understanding Hyperuricemia and Uremia
Drug–Metabolite Interactions
Amino Acids
Physiology of Renal Amino Acid Transport
Molecular Biology of Renal Amino Acid Transporters
Transporters for Neutral Amino Acids
Apical Transporters
Specific Apical Transporters for Proline and Glycine
Specific Apical Transporters for Β-Amino Acids
Basolateral Transporters
Transporters for Cationic Amino Acids and Cystine
Apical Transporters
Basolateral Transporters
Transporters for Anionic Amino Acids
Structural Information of Amino Acid Transporters
Key References
References
Board Review Question
9 Renal Acidification Mechanisms
Chapter Outline
Key Points
Bicarbonate Reabsorption
Proximal Tubule
General Transport Mechanisms
Proteins Involved in Proximal Tubule Bicarbonate Reabsorption
Na+/H+ Exchangers.
H+-ATPase.
NBCe1 (SLC4A4).
Carbonic Anhydrase.
CA II.
CA IV.
Regulation of Proximal Tubule Bicarbonate Reabsorption
Systemic Acid–Base
Luminal Flow Rate.
AngII.
Potassium.
Endothelin.
PTH.
Calcium Sensing Receptor.
Loop of Henle
Regulation of TAL Bicarbonate Reabsorption
Acid–Base Transporters in the TAL
NBCn1 (SLC4A7)
Distal Convoluted Tubule
Collecting Duct
Collecting Duct Segments
Cell Composition
Type A Intercalated Cell
Type B Intercalated Cell
Non-A, Non-B, or Type C Intercalated Cell
Principal Cells
IMCD Cell
Functional Role of Different Collecting Duct Segments
CNT-ICT
CCD
OMCD
IMCD
Proteins Involved in Collecting Duct H+/Bicarbonate Transport
H+-ATPase
H+-K+-ATPase
Pendrin (SLC26A4)
Carbonic Anhydrase
kAE1
KCC4
Cl– Channel
Other Anion Exchangers
Sodium Bicarbonate Cotransporters
NBCe2 (SLC4A5)
Regulation of Collecting Duct Acid–Base Transport
Acidosis
Alkalosis
Hormonal Regulation of Collecting Duct Acid–Base Transport
Paracrine Regulation
Cellular Adaptations to Acid–Base Perturbations
Bicarbonate Generation
Titratable Acid Excretion
Phosphate as a Titratable Acid
Other Urinary Buffers
Organic Anion Excretion
Citrate Excretion
Other Organic Anions
Ammonia Metabolism
Ammonia Chemistry
Ammonia Production
Glutamine Transport in Ammoniagenesis
Ammonia Transport
Specific Proteins Involved in Renal Ammonia Metabolism
Phosphate-Dependent Glutaminase
Glutamate Dehydrogenase (GDH)
Phosphoenolpyruvate Carboxykinase (PEPCK)
γ-GT
NHE3
Potassium Channels
Na+-K+-2Cl– Cotransport
Na+-K+-ATPase
H+-K+-ATPase
Aquaporins
Carbonic Anhydrase
Rh Glycoproteins
Rhag/RhAG (SLC42A1)
Rhbg/RhBG (SLC42A2)
Rhcg/RhCG
CO2 Transport by Rh Glycoproteins
Sulfatides
Acid–Base Sensors
Acid-/Alkali-Sensing Receptors
GPR4
Insulin Receptor–Related Receptor (InsR-RR)
Kinases
Pyk2/ETB Receptor Pathway
Receptor Tyrosine Kinase
Bicarbonate-Stimulated Adenylyl Cyclase
Diurnal Variation in Acid Excretion
Acknowledgments
Key References
References
Board Review Questions
10 Urine Concentration and Dilution
Chapter Outline
Key Points
Independent Regulation of Water and Salt Excretion
Organization of Structures in the Kidney Relevant to Urinary Concentrating and Diluting Process
Renal Tubule
Loops of Henle
Kidney-Specific Chloride Channel 1 (ClC-K1)
Na-K-2Cl Cotransporter Type 2 (NKCC2) and Na+-H+-Exchanger Isoform Type 3 (NHE3)
Renal Outer Medullary Potassium Channel (ROMK, Kir 1.1)
Distal Tubule Segments in the Cortical Labyrinth
Collecting Duct System
Vasculature
Medullary Interstitium
Renal Pelvis
Vasopressin and the Type 2 Vasopressin Receptor
Vasopressin
Type 2 Vasopressin Receptor
Vasopressin-Regulated Water Transport
Collecting Duct Water Absorption and Osmotic Equilibration
Aquaporin-2: the Vasopressin-Sensitive Collecting Duct Water Channel
Overview of Vasopressin-Regulated AQP2 Trafficking in Collecting Duct Principal Cells
Basolateral Aquaporins in Principal Cells
Aquaporin Knockout Mice
Aquaporin-1 Knockout Mice
Aquaporin-2 Knockout Mice
Aquaporin-3 and Aquaporin-4 Knockout Mice
Mechanisms of Aquaporin-2 Trafficking
Aquaporin-2 Recycling
Role of the Cytoskeleton in Aquaporin-2 Trafficking
Essential Role of Aquaporin-2 Phosphorylation
Role of Phosphorylation in Exocytosis and Endocytosis of Aquaporin-2
Vasopressin-Regulated Urea Transport in the Inner Medulla
Urea Transporter Proteins
Urea Transporter Knockout Mice
UT-A1/A3 Knockout Mice
UT-B and UT-A2 Knockout Mice
Mice Lacking All Urea Transporters
Accumulation of Urea in Renal Inner Medulla
1. Recycling of Urea Through the Ascending Limbs, Distal Tubules, and Collecting Ducts
2. Recycling of Urea Through the Vasa Recta, Short Loops of Henle, and Collecting Ducts
3. Urea Recycling Between Ascending and Descending Limbs of the Loops of Henle
Urine Concentration and Dilution Processes Along the Mammalian Nephron
Sites of Urine Concentration and Dilution
Mechanisms of Tubule Fluid Dilution
Mechanism of Tubule Fluid Concentration
Generation of the Axial NaCl Gradient in the Renal Outer Medulla
Determinants of Concentrating Ability
An Unresolved Question: Concentration of NaCl in the Renal Inner Medulla
1. The “Passive Mechanism”
2. Concentrating Mechanism Driven by External Solute
3. Hyaluronan as a Mechano-osmotic Transducer
Acknowledgments
Key References
References
Board Review Questions
11 Vasoactive Molecules and the Kidney
Chapter Outline
Key Points
Renin–Angiotensin–Aldosterone System
Classical Renin–Angiotensin–Aldosterone System
Angiotensinogen
Renin
Prorenin Activation
Regulation of Renin Secretion
Renal Baroreceptor
Neural Control
Tubule Control
Metabolic Control
Vitamin D Receptor
Other Local Factors
Plasma Prorenin and Renin
Angiotensin-Converting Enzyme
Angiotensin Type 1 Receptor
G Protein–Mediated Signaling
Reactive Oxygen Species
Tyrosine Kinases
Angiotensin Type 1 Receptor Internalization
Angiotensin Type 1 Receptor Dimerization
Ligand-Independent Angiotensin Type 1 Receptor Activation
Physiologic Effects of Angiotensin II in the Kidney
Hemodynamic Actions
Tubule Transport
Sodium
Acid–Base Regulation
Expanded Renin–Angiotensin–Aldosterone System: Enzymes, Angiotensin Peptides, and Receptors
Angiotensin Type 2 Receptor
(Pro)Renin Receptor
Angiotensin-Converting Enzyme 2
Angiotensin Peptides
Angiotensin III, or Angiotensin-(2-8)
Angiotensin IV, or Angiotensin-(3–8)
Angiotensin-(1-7)
Angiotensin-(2-10)
Angiotensin-(1-12)
Angiotensin A and Alamandine
Intrarenal Renin–Angiotensin–Aldosterone System
Intracrine Renin–Angiotensin–Aldosterone System
Renin–Angiotensin–Aldosterone System in Kidney Pathophysiology
Fibrosis
Proteinuria
Inflammation, Immunity, and the Renin–Angiotensin–Aldosterone System
Diabetes Paradox
Endothelin
Structure, Synthesis, and Secretion of the Endothelins
Endothelin Receptors
Physiologic Actions of Endothelin in the Kidney
Role of Endothelin in Essential Hypertension
Role of Endothelin in Renal Injury
The Endothelin System in Chronic Kidney Disease and Diabetic Nephropathy
Preclinical Studies of ET Receptor Antagonists in Diabetic Kidney Disease
Clinical Studies of ET Receptor Antagonists in CKD and Diabetic Nephropathy
Combined ECE and Neprilysin Inhibition
The Endothelin System and Other Kidney Diseases
Sickle Cell Disease-Associated Nephropathy
Renovascular Disease
Acute Kidney Injury
Systemic Lupus Erythematosus
Primary Focal and Segmental Glomerulosclerosis
Scleroderma
Hepatorenal Syndrome
Preeclampsia
Safety Profile of Endothelin Receptor Antagonists
Natriuretic Peptides
Structure and Synthesis of the Natriuretic Peptides
Atrial Natriuretic Peptide
Brain Natriuretic Peptide
C-Type Natriuretic Peptide
Dendroaspis Natriuretic Peptide
Urodilatin
Natriuretic Peptide Receptors
Neprilysin
Actions of the Natriuretic Peptides
Renal Effects of the Natriuretic Peptides
Cardiovascular Effects of the Natriuretic Peptides
Other Effects of the Natriuretic Peptides
Natriuretic Peptides as Biomarkers of Disease
Brain Natriuretic Peptide and N-Terminal Probrain Natriuretic Peptide as Biomarkers of Heart Failure
Role of Brain Natriuretic Peptide and N-Terminal Probrain Natriuretic Peptide as Biomarkers in Renal Disease
Circulating C-Type Natriuretic Peptide Levels as a Biomarker for Risk of Myocardial Infarction
Therapeutic Uses of Natriuretic Peptides
Recombinant Atrial Natriuretic Peptide
Recombinant Brain Natriuretic Peptide
Therapeutic Uses of Other Natriuretic Peptides
Combination Angiotensin Receptor Blockade and Neprilysin Inhibition
Renal Effects of Valsartan/Sacubitril in Patients With Heart Failure and Preserved Ejection Fraction
Other Natriuretic Peptides
Guanylin and Uroguanylin
Adrenomedullin
Kallikrein–Kinin System
Components of the Kallikrein–Kinin System
Kininogen
Kallikrein
Kinins
Bradykinin Receptors
Kallistatin
Kininases
Plasma and Tissue Kallikrein–Kinin System
Renal Kallikrein–Kinin System
Regulation of Tubule Transport by Tissue Kallikrein
The Kallikrein–Kinin System in Renal Disease
Hypertension
Diabetic Nephropathy
Ischemic Renal Injury
Chronic Kidney Disease
Lupus Nephritis/Anti–Glomerular Basement Membrane Disease
Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
Urotensin II
Synthesis, Structure, and Secretion of Urotensin II
Physiologic Role of Urotensin II
Urotensin II in the Kidney
Observational Studies of Urotensin II in Renal Disease
Interventional Studies of Urotensin II in the Kidney
Key References
References
Board Review Questions
12 Aldosterone and Mineralocorticoid Receptors
Chapter Outline
Key Points
General Introduction to Aldosterone and Mineralocorticoid Receptors
Aldosterone Synthesis
Mechanisms of Mineralocorticoid Receptor Function and Gene Regulation
Mineralocorticoid Receptor Function as a Hormone-Regulated Transcription Factor: General Features and Subcellular Localization
Domain Structure of Mineralocorticoid Receptors
DNA-Binding Domain
Ligand/Hormone-Binding Domain
N-Terminal Domain
Mineralocorticoid Receptor Regulation of Transcription Initiation: Coactivators and Corepressors
Regulation of Sodium Absorption and Potassium Secretion
General Model of Aldosterone Action
Aldosterone and Epithelial Sodium Channel Trafficking
Basolateral Membrane Effects of Aldosterone
Activation of the Epithelial Sodium Channel by Proteolytic Cleavage
Potassium Secretion and Aldosterone
Separation of Sodium Absorption and Potassium Secretion by the Aldosterone-Sensitive Distal Nephron
Role of Distal Tubule Fluid Delivery
Independent Regulation of Sodium and Potassium Transporters
Role of Wnks
Role of Chloride Transport Regulation
Differential Regulation of Intercalated Cell Mineralocorticoid Receptor
Aldosterone-Independent Enac-Mediated Sodium Reabsorption in the Distal Nephron
Sites of Mineralocorticoid Receptor Expression and Locus of Action Along the Nephron
Aldosterone-Sensitive Distal Nephron
Other Sites of Expression
Glomerulus
Proximal Convoluted Tubule
Medullary Thick Ascending Limb
Distal Convoluted Tubule
Nonrenal Aldosterone-Responsive Tight Epithelia
Colon
Lung
Exocrine Glands and Sensors
Role of Serum- and Glucocorticoid- Regulated Kinase in Mediating Aldosterone Effects
Induction of SGK1 by Aldosterone
Molecular Mechanisms of SGK1 Action in the Aldosterone-Sensitive Distal Nephron
SGK1 Inhibits the Ubiquitin Ligase Nedd4-2
SGK1 Enhances Epithelial Sodium Channel Activity Independently of Nedd4-2
SGK1 Stimulates the Components of Sodium Transport Machinery
SGK1 Stimulates Potassium Secretion in the Aldosterone-Sensitive Distal Nephron
Alternate Modes of Regulation of ENaC-Mediated Sodium Transport by Aldosterone
11β-Hydroxysteroid Dehydrogenase Type 2
Essential Determinant of Mineralocorticoid Specificity
Sites of Expression
Impact on Mineralocorticoid Receptor Activity
Apparent Mineralocorticoid Excess: a Disease of Defective 11β-Hydroxysteroid Dehydrogenase Type 2
Role in Blood Vessels
Summary of 11β-Hydroxysteroid Dehydrogenase Type 2 Roles
Nongenomic Effects of Aldosterone
Disease States
Primary Aldosteronism
Congestive Heart Failure
Chronic Kidney Disease
Nonepithelial Actions of Aldosterone
Recent Advances in Nonrenal Mineralocorticoid Receptor−Mediated Disease Pathology
Acknowledgments
Key References
References
Board Review Questions
13 Arachidonic Acid Metabolites and the Kidney
Chapter Outline
Key Points
Cellular Origin of Eicosanoids
The Cyclooxygenase Pathway
Molecular Biology
Regulation of COX Gene Expression
Regulation of COX Expression by Antiinflammatory Steroids
Enzymatic Chemistry
Renal COX-1 and COX-2 Expression
COX-2 Expression
COX-2 Expression in the Kidney
COX-2 Expression in the Renal Cortex
COX-2 Expression in the Renal Medulla
COX-1 Expression
COX-1 Expression in the Kidney
Renal Complications of Nonsteroidal Antiinflammatory Drugs
Sodium Retention, Edema, and Hypertension
Hyperkalemia
Papillary Necrosis
Acute Renal Insufficiency
Interstitial Nephritis
Nephrotic Syndrome
Renal Dysgenesis
Cardiovascular Effects of COX-2 Inhibitors
Effects of COX-2 Inhibition on Vascular Tone
Increased Cardiovascular Thrombotic Events
Prostanoids
Prostanoid Synthases
Sources and Nephronal Distribution of COX Products
Thromboxane Synthase
Prostacyclin Synthase
Prostaglandin D Synthase
Prostaglandin F Synthesis
Prostaglandin 9 Ketoreductase
Prostaglandin E Synthases
Prostanoid Receptors
TP Receptors
Prostacyclin Receptors
DP Receptors
FP Receptors
Multiple EP Receptors
EP1 Receptors
EP2 Receptors
EP3 Receptors
EP4 Receptor
Regulation of Renal Function by EP Receptors
Renal Cortical Hemodynamics
Renin Release
Renal Microcirculation
Effects on Salt and Water Transport
Proximal Tubule
Loop of Henle
Collecting Duct System
Water Transport
Prostaglandins
Metabolism of Prostaglandins
15-Ketodehydrogenase
ω/ω-1-Hydroxylation of Prostaglandins
Cyclopentenone Prostaglandins
Nonenzymatic Metabolism of Arachidonic Acid
Prostaglandin Transport and Urinary Excretion
Involvement of Cyclooxygenase Metabolites in Renal Pathophysiology
Experimental and Human Glomerular Injury
Glomerular Inflammatory Injury
Glomerular Noninflammatory Injury
Acute Kidney Injury
Urinary Tract Obstruction
Allograft Rejection and Cyclosporine Nephrotoxicity
Allograft Rejection
Calcineurin Inhibitor Nephrotoxicity
Hepatic Cirrhosis and Hepatorenal Syndrome
Diabetes Mellitus
Pregnancy
Lithium Nephrotoxicity
Role of Reactive Oxygen Species as Mediators of COX-2 Actions
The Lipoxygenase Pathway
Biologic Activities of Lipoxygenase Products in the Kidney
Involvement of Lipoxygenase Products in Renal Pathophysiology
The Cytochrome P450 Pathway
Vasculature
20-Trihydroxyeicosatetraenoic Acid
Epoxides
Autoregulation
Tubuloglomerular Feedback
Tubules
Proximal Tubule
Thick Ascending Limb of Henle
Collecting Duct
Role in Acute and Chronic Kidney Disease
Role in Hypertension
Acknowledgments
Key References
References
Board Review Questions
14 Disorders of Sodium Balance
Chapter Outline
Physiology
Sodium Balance
Effective Arterial Blood Volume
Regulation of Effective Arterial Blood Volume
Afferent Limb: Sensing of Effective Arterial Blood Volume
Sensors of Cardiac Filling
Atrial Sensors.
Neural Pathways.
Humoral Pathways.
Ventricular and Pulmonary Sensors.
Sensors of Cardiac Output
Carotid and Aortic Baroceptors.
Sensors of Organ Perfusion
Renal Sensors.
Central Nervous System Sensors.
Gastrointestinal Tract Sensors.
Hepatoportal Receptors.
Intestinal Natriuretic Hormones.
Efferent Limb: Effector Mechanisms for Maintaining Effective Arterial Blood Volume
Integration of Changes in Glomerular Filtration Rate and Tubular Reabsorption
Tubuloglomerular Feedback
Glomerulotubular Balance
Peritubular Capillary Starling Forces.
Luminal Composition.
Physical Factors Beyond the Proximal Tubule.
Medullary Hemodynamics and Interstitial Pressure in the Control of Sodium Excretion: Pressure Natriuresis.
Neural Mechanisms: Renal Nerves and Symphathetic Nervous System
Humoral Mechanisms
Renin-Angiotensin-Aldosterone System.
Vasopressin.
Prostaglandins.
Natriuretic Peptides.
Atrial Natriuretic Peptide.
Brain Natriuretic Peptide.
C-Type Natriuretic Peptide.
D-Type Natriuretic Peptide.
Endothelial-Derived Factors.
Endothelin.
Nitric Oxide.
Kinins.
Adrenomedullin.
Urotensin.
Digitalis-Like Factors.
Neuropeptide Y.
Apelin.
Glucagon-Like Peptide-1
Novel Factors
Sodium Balance Disorders
Hypovolemia
Definition
Etiology
Pathophysiology
Absolute Hypovolemia
Extrarenal.
Renal.
Relative Hypovolemia
Extrarenal.
Renal.
Clinical Manifestations
Diagnosis
Laboratory Findings
Hemoglobin and Plasma Albumin.
Plasma Na+ Concentration.
Plasma K+ and Acid-Base Parameters.
Blood Urea and Creatinine Levels.
Urine Biochemical Parameters.
Other Laboratory Parameters.
Treatment
Absolute Hypovolemia
General Principles.
Composition of Replacement Fluids.
Relative Hypovolemia
Hypervolemia
Definition
Etiology
Primary Renal Na+ Retention
Secondary Renal Na+ Retention
Pathophysiology
Local Mechanisms of Edema Formation
Systemic Factors Stimulating Renal Sodium Retention
Reduced Effective Arterial Blood Volume.
Renal Sodium Retention in Heart Failure
Abnormalities of Sensing Mechanisms in Heart Failure.
Abnormalities of Effector Mechanisms in Heart Failure.
Alterations in Glomerular Hemodynamics
Enhanced Tubular Reabsorption of Sodium.
Neurohumoral Mediators.
Vasoconstrictor/Antinatriuretic (Antidiuretic) Systems
Renin-Angiotensin-Aldosterone System
Sympathetic Nervous System
Vasopressin
Endothelin
Vasodilatory/Natriuretic Systems
Natriuretic Peptides
Atrial Natriuretic Peptide.
Brain Natriuretic Peptide.
C-Type Natriuretic Peptide.
Overall Relationship Between Natriuretic and Antinatriuretic Factors in Heart Failure
Nitric Oxide
Protaglandins
Adrenomedullin
Urotensin
Neuropeptides
Apelin
Peroxisome Proliferator-Activated Receptors
Renal Sodium Retention in Cirrhosis With Portal Hypertension.
Peripheral Arterial Vasodilation.
Abnormalities of Sensing Mechanisms in Cirrhosis
Nitric Oxide.
Endocannabinoids.
Afferent Sensing of Intrahepatic Hypertension.
Arterial Underfilling.
Abnormalities of Effector Mechanisms in Cirrhosis.
Vasoconstrictor and Antinatiuretic (Antidiuretic) Systems
Renin-Angiotensin-Aldosterone System
Sympathetic Nervous System
Arginine Vasopressin
Endothelin
Apelin
Vasodilators/Natiuretics
Natriuretic Peptides
Atrial Natriuretic Peptide.
Brain Natriuretic Peptide and C-Type Natriuretic Peptide.
Prostaglandins
Integrated View of the Pathogenesis of Sodium Retention in Cirrhosis
Clinical Manifestations of Hypervolemia
Diagnosis
Treatment
Sodium Restriction
Diuretics
Proximal Tubule Diuretics.
Loop Diuretics.
Distal Tubule Diuretics.
Collecting Duct Diuretics.
Diuretic Resistance.
Extracorpreal Ultrafiltration
Specific Treatments Based on the Pathophysiology of Heart Failure
Inhibition of the Renin-Angiotensin-Aldosterone System
β-Blockade
Nitric Oxide Donor and Reactive Oxygen Species/Peroxynitrate Scavengers
Endothelin Antagonists
Natriuretic Peptides
Neutral Endopeptidase Inhibitors and Vasopeptidase Inhibitors
Vasopressin Receptor Antagonists
Sodium-Glucose Transporter-2 Inhibitors
Specific Treatments Based on the Pathophysiology of Sodium Retention in Cirrhosis
Pharmacologic Treatment
Systemic Vasoconstrictors
Vasopressin V1 Receptor Analogs
Somatostatin Analogs and α-Adrenergic Agonists
Vasopressin V2 Receptor Antagonists
Transjugular Intrahepatic Portosystemic Shunt
Renal and Liver Replacement Therapy
Liver Transplantation
References
15 Disorders of Water Balance
Chapter Outline
Body Fluids: Compartmentalization, Composition, and Turnover
Water Metabolism
Vasopressin Synthesis and Secretion
Structure and Synthesis
Osmotic Regulation
Nonosmotic Regulation
Hemodynamic Stimuli
Drinking
Nausea
Hypoglycemia
Renin-Angiotensin-Aldosterone System
Stress
Hypoxia and Hypercapnia
Drugs
Distribution and Clearance
Thirst
Osmotic Thirst
Hypovolemic Thirst
Anticipatory Thirst
Integration of Vasopressin Secretion and Thirst
Disorders of Insufficient Vasopressin or Vasopressin Effect
Central Diabetes Insipidus
Causes
Pathophysiology
Osmoreceptor Dysfunction
Causes
Pathophysiology
Gestational Diabetes Insipidus
Causes
Pathophysiology
Nephrogenic Diabetes Insipidus
Causes
Pathophysiology
Primary Polydipsia
Causes
Pathophysiology
Clinical Manifestations of Diabetes Insipidus
Differential Diagnosis of Polyuria
Treatment of Diabetes Insipidus
Therapeutic Agents
Arginine Vasopressin
Desmopressin
Chlorpropamide
Prostaglandin Synthase Inhibitors
Natriuretic Agents
Treatment of Different Types of Diabetes Insipidus
Central Diabetes Insipidus
Osmoreceptor Dysfunction
Gestational Diabetes Insipidus
Nephrogenic Diabetes Insipidus
Primary Polydipsia
Disorders of Excess Vasopressin or Vasopressin Effect
Relationship Between Hypoosmolality and Hyponatremia
Variables That Influence Renal Water Excretion
Fluid Delivery From the Proximal Tubule
Dilution of Tubular Fluid
Water Impermeability of the Collecting Duct
Solute Excretion Rate
Pathogenesis and Causes of Hyponatremia
Hyponatremia With Extracellular Fluid Volume Depletion
Hyponatremia With Excess Extracellular Fluid Volume
Congestive Heart Failure
Hepatic Failure
Nephrotic Syndrome
Renal Failure
Hyponatremia With Normal Extracellular Fluid Volume
Syndrome of Inappropriate Antidiuretic Hormone Secretion
Pathophysiology
Clinical Settings
Glucocorticoid Deficiency
Hypothyroidism
Primary Polydipsia
Postoperative Hyponatremia
Endurance Exercise
Pharmacologic Agents
Desmopressin
Chlorpropamide
Antiepileptic Drugs
Psychotropic Drugs
Antineoplastic Drugs
Narcotics
Miscellaneous Agents
Hyponatremia: Symptoms, Morbidity, and Mortality
Hyponatremia Treatment
Current Therapies
Hypertonic Saline
Isotonic Saline
Fluid Restriction
Arginine Vasopressin Receptor Antagonists
Urea
Furosemide and NaCl
Efficacy of Different Treatments for Hyponatremia Due to Syndrome of Inappropriate Antidiuretic Hormone Secretion
Hyponatremia Treatment Guidelines
Levels of Symptoms
Severe Symptoms
Moderate Symptoms
Mild or Absent Symptoms
Monitoring Serum Sodium Concentration in Hyponatremic Patients
Long-Term Treatment of Chronic Hyponatremia
Future of Hyponatremia Treatment
Key References
References
16 Disorders of Acid-Base Balance
Chapter Outline
Acid-Base Homeostasis
Renal Regulation
Systemic Response to Respiratory Acidosis or Alkalosis
Acute Response: Generation of Respiratory Acidosis or Alkalosis
Chronic Response
Systemic Response to Addition of Metabolic Acids
Sources of Endogenous Acids
Hepatic and Renal Roles in Acid-Base Homeostasis
Respiratory Response to Acidemia
Renal Excretion
Systemic Response to Gain of Alkali
Distribution and Cellular Buffering
Respiratory Compensation
Renal Excretion
With Extracellular Volume Expansion
With Extracellular Volume Contraction and Potassium Deficiency
Stepwise Approach to the Diagnosis of Acid-Base Disorders
Clinical and Laboratory Parameters in Acid-Base Disorders
Step 1: Measure Arterial Blood Gas and Electrolyte Values
Step 2: Determine the Compensation to Distinguish Simple From Mixed Acid-Base Disorders
Step 3: Calculate the Anion Gap to Determine the Presence of a High AG Metabolic Acidosis
Step 4: Compare Relative Changes of HCO3− and AG (DELTA/DELTA)
Mixed Acid-Base Disorders
Respiratory Disorders
Respiratory Acidosis
Respiratory Alkalosis
Metabolic Disorders
Metabolic Acidosis
Hyperchloremic (Non-Anion Gap) Metabolic Acidoses
Proximal Renal Tubular Acidosis
Physiology
Pathogenesis – Inherited and Acquired Forms
Clinical Spectrum
Diagnosis
Associated Clinical Features
Treatment
Distal Renal Tubule Acidosis (Classic With Hypokalemia)
Pathophysiology
Inherited and Acquired Defects in Type A Intercalated Cell Acid-Base Transporters Responsible for cDRTA.
Clinical Spectrum and Associated Features
Treatment.
Hyperkalemic Renal Tubular Acidosis, Generalized Distal Nephron Dysfunction (Type 4 RTA)
Clinical Disorders
Primary Mineralocorticoid Deficiency
Hyporeninemic Hypoaldosteronism
Isolated Hypoaldosteronism in Critically Ill Patients
Resistance to Mineralocorticoid and Voltage Defects: Hyperkalemic Distal Renal Tubular Acidosis
Drug-Induced Renal Tubular Secretory Defects
Impaired Renin-Aldosterone Elaboration.
Inhibitors of Potassium Secretion in the Collecting Duct.
Secondary Renal Diseases Associated With Acquired Voltage Defects
Treatment.
Distinguishing the Types of Renal Tubular Acidosis.
Acidosis of Chronic Kidney Disease.
High Anion Gap Acidoses.
Lactic Acidosis
Physiology.
Diagnosis.
Clinical Spectrum.
Associated Clinical Features.
Treatment of l-Lactic Acidosis: General Supportive Care.
Alkali Therapy.
Other Agents.
d-Lactic Acidosis.
Diabetic Ketoacidosis.
Treatment.
Alcoholic Ketoacidosis (AKA).
Treatment.
Starvation Ketoacidosis.
Drug- and Toxin-Induced Acidosis: Salicylate.
Treatment.
Toxins: The Osmolar Gap in Toxin-Induced Acidosis.
Ethylene Glycol.
Methanol.
Paraldehyde.
Pyroglutamic Acid.
Propylene Glycol.
Uremia.
Treatment of Acidosis of Chronic Renal Failure.
Metabolic Alkalosis: Diagnosis of Simple and Mixed Forms of Metabolic Alkalosis.
Exogenous Bicarbonate Loads.
Bicarbonate and Bicarbonate-Precursor Administration.
Milk-Alkali Syndrome.
Loss of Acid: Vomiting and Gastric Aspiration.
Unusual Causes of Diarrhea: Villous Adenoma and Congenital Chloridorrhea.
Renal Loss of Acid: Diuretics.
Edematous States.
Posthypercapnia.
Bartter’s Syndrome.
Gitelman’s Syndrome.
Nonreabsorbable Anions and Magnesium Deficiency.
Potassium Depletion.
Excess Mineralocorticoid Activity (see Table 16.17).
High Renin Levels, Secondary Hyperaldosteronism.
Low Renin Levels, Primary Increased Mineralocorticoids.
Primary Aldosteronism.
Glucocorticoid-Remediable Hyperaldosteronism.
Cushing’s Disease or Syndrome.
Liddle’s Syndrome (Low Renin, Low Aldosterone).
Apparent Mineralocorticoid Excess and Related Conditions.
Symptoms.
Treatment.
Key References
References
17 Disorders of Potassium Balance
Chapter Outline
Potassium Disorders
Normal Potassium Balance
Potassium Transport Mechanisms
Factors Affecting Internal Distribution of Potassium
Insulin
Sympathetic Nervous System
Acid-Base Status
Renal Potassium Excretion
Potassium Transport in the Distal Nephron
Control of Potassium Secretion: Aldosterone
Control of Potassium Secretion: Effect of Potassium Intake
Integrated Regulation of Distal Sodium Absorption and Potassium Secretion
Regulation of Renal Renin and Adrenal Aldosterone
Urinary Indices of Potassium Excretion
Consequences of Hyperkalemia and Hypokalemia
Effects of Hypokalemia
Excitable Tissues: Muscle and Heart
Renal Consequences
Cardiovascular Consequences
Consequences of Hyperkalemia
Excitable Tissues: Muscle and Heart
Renal Consequences
Hypokalemia
Causes of Hypokalemia
Epidemiology
Spurious Hypokalemia
Redistribution and Hypokalemia
Hypokalemic Periodic Paralysis
Nonrenal Potassium Loss
Renal Potassium Loss
Drugs
Hyperaldosteronism
Syndromes of Apparent Mineralocorticoid Excess
Liddle Syndrome
Familial Hypokalemic Alkalosis: Bartter Syndrome
Familial Hypokalemic Alkalosis: Gitelman Syndrome
Renal Tubular Acidosis
Magnesium Deficiency
Clinical Approach to Hypokalemia
Treatment of Hypokalemia
Hyperkalemia
Epidemiology
Pseudohyperkalemia
Excess Intake of Potassium and Tissue Necrosis
Redistribution and Hyperkalemia
Reduced Renal Excretion of Potassium
Hypoaldosteronism
Hyporeninemic Hypoaldosteronism
Acquired Tubular Defects and Potassium Excretion
Hereditary Tubular Defects and Potassium Excretion
Medication-Related Hyperkalemia
Cyclooxygenase Inhibitors
Cyclosporine and Tacrolimus
Epithelial Na+ Channel Inhibition
Angiotensin-Converting Enzyme Inhibitors and Mineralocorticoid and Angiotensin Antagonists
Clinical Approach to Hyperkalemia
Management of Hyperkalemia
Antagonism of Cardiac Effects
Redistribution of K+ Into Cells
Insulin and Glucose
β2-Adrenergic Agonists
Sodium Bicarbonate
Removal of Potassium
Diuretics.
Mineralocorticoids.
Cation Exchange Resins.
Novel Intestinal Potassium Binders.
Dialysis.
Key References
References
18 Disorders of Calcium, Magnesium, and Phosphate Balance
Chapter Outline
Disorders of Calcium Homeostasis
Whole-Body Calcium Homeostasis
Hypercalcemia
Signs and Symptoms
Laboratory Findings
Diagnosis
Causes
Primary Hyperparathyroidism
Malignancy
Familial Primary Hyperparathyroidism Syndromes
Familial Hypocalciuric Hypercalcemia and Neonatal Severe Hyperparathyroidism.
Multiple Endocrine Neoplasia.
Hyperparathyroidism–Jaw Tumor Syndrome.
Nonparathyroid Endocrinopathies
Vitamin D–Mediated Hypercalcemia
Medications
Milk-Alkali Syndrome
Immobilization
Granulomatous Disease
Liver Disease
Acute and Chronic Kidney Disease
Management of Hypercalcemia
Volume Repletion and Loop Diuretics
Inhibition of Bone Resorption
Hypocalcemia
Signs and Symptoms
Laboratory Findings
Diagnosis
Causes
Parathyroid Hormone–Related Disorders: Hypoparathyroidism and Pseudohypoparathyroidism
Genetic Causes of Hypoparathyroidism.
Genetic Syndromes With Resistance to Parathyroid Hormone Action.
Hypomagnesemic Syndromes
Acquired Hypoparathyroidism and Inadequate Parathyroid Hormone Production
Postsurgical Causes.
Magnesium Disorders.
Autoimmune Disease.
Vitamin D–Related Disorders
Low Vitamin D Production.
Vitamin D Resistance.
Miscellaneous Causes
Medications.
Critical Illness.
Other Causes.
Management of Hypocalcemia
Disorders of Magnesium Homeostasis
Hypomagnesemia and Magnesium Deficiency
Causes
Extrarenal Causes
Nutritional Deficiency.
Intestinal Malabsorption.
Diarrhea and Gastrointestinal Fistula.
Cutaneous Losses.
Redistribution to Bone Compartment.
Diabetes Mellitus.
Renal Magnesium Wasting
Polyuria.
Extracellular Fluid Volume Expansion.
Diuretics.
Epidermal Growth Factor Receptor Blockers.
Hypercalcemia.
Tubule Nephrotoxins.
Tubulointerstitial Nephropathies.
Inherited Kidney Magnesium-Wasting Disorders
Primary Magnesium-Wasting Disorders.
Bartter and Gitelman Syndromes.
Calcium-Sensing Disorders.
Clinical Manifestations
Cardiovascular System
Neuromuscular System
Skeletal System
Electrolyte Homeostasis
Other Disorders
Treatment
Intravenous Replacement
Oral Replacement
Potassium-Sparing Diuretics
Hypermagnesemia
Causes
Kidney Disease
Excessive Magnesium Intake
Miscellaneous Causes
Clinical Manifestations
Cardiovascular System
Nervous System
Treatment
Disorders of Phosphate Homeostasis
Hyperphosphatemia
Causes
Decreased Kidney Phosphate Excretion
Reduced Glomerular Filtration Rate.
Hypoparathyroidism and Pseudohypoparathyroidism.
Acromegaly.
Familial Tumoral Calcinosis.
Bisphosphonates.
Exogenous Phosphate Load
Intracellular to Extracellular Shift of Phosphorus
Respiratory Acidosis and Metabolic Acidosis.
Tumor Lysis and Rhabdomyolysis.
Pseudohyperphosphatemia
Clinical Manifestations and Treatment
Hypophosphatemia
Clinical Manifestations
Diagnosis
Causes
Increased Kidney Phosphate Excretion
Hyperparathyroidism.
Increased Production or Activity of Phosphatonins.
X-Linked Hypophosphatemia.
Autosomal Dominant Hypophosphatemic Rickets.
Autosomal Recessive Hypophosphatemic Rickets.
Tumor-Induced Osteomalacia.
Disorders of Proximal Tubule Inorganic Phosphorus Reabsorption
Hereditary Hypophosphatemic Rickets With Hypercalciuria.
Fanconi Syndrome.
Kidney Transplantation.
Drug-Induced Hypophosphatemia.
Miscellaneous Causes.
Decreased Intestinal Absorption
Malnutrition.
Malabsorption.
Vitamin D–Mediated Disorders.
Redistribution of Phosphate.
Respiratory Alkalosis.
Refeeding Syndrome.
Hypophosphatemia Resulting From Multiple Mechanisms
Alcoholism.
Diabetic Ketoacidosis.
Miscellaneous Disorders.
Treatment
Key References
References
Board Review Questions
19 Epidemiology of Kidney Disease
Chapter Outline
Key Points
Introduction
Consensus Definitions, Conceptual Models, and Classification of Chronic and Acute Kidney Disease
Principles of Epidemiology and Use in Kidney Disease Research
Recent Contributions of Epidemiology to Nephrology
Chronic Kidney Disease
Epidemiology
Prevalence
Incidence
Outcomes
Risk Factors
End-Stage Kidney Disease
Epidemiology
Prevalence
Incidence
Outcomes
Risk Factors
Kidney Transplantation
Prevalence
Incidence
Outcomes
Disparities in Kidney Transplantation
Acute Kidney Injury
Epidemiology
Incidence
Outcomes
Risk Factors
Evidence Gaps and Limitations of the Literature
Conclusion
Key References
References
Board Review Questions
20 Risk Prediction in Chronic Kidney Disease
Chapter Outline
Key Points
Definition of a Risk Factor
Risk Factors and Mechanisms of Chronic Kidney Disease Progression
Demographic Variables
Age
Gender
Ethnicity
Hereditary Factors
Hemodynamic Factors
Decreased Nephron Number
Nephron Endowment
Acquired Nephron Deficit
Acute Kidney Injury
Hypertension
Obesity and Metabolic Syndrome
High Dietary Protein Intake
Pregnancy and Preeclampsia
Multisystem Disorders
Diabetes Mellitus
Primary Renal Disease
Cardiorenal Syndrome
Conventional Biomarkers
Proteinuria
Serum Albumin
Anemia
Dyslipidemia
Serum Uric Acid
Metabolic Acidosis
Novel Biomarkers
Plasma Asymmetric Dimethylarginine
Serum Phosphate and FGF23
Neutrophil Gelatinase-Associated Lipocalin
Kidney Injury Molecule-1
Soluble Urokinase-Type Plasminogen Activator Receptor
Uromodulin
Proteomic Approaches
Other Biomarkers
Environmental Risk Factors
Smoking
Alcohol
Recreational Drugs
Analgesics
Heat Stress
Heavy Metals
Renal Risk Scores
Methods of Renal Risk Score Development
Metrics of Model Performance
Discrimination
Calibration
Reclassification
Clinical Utility
External Validity
Models Predicting Incident Chronic Kidney Disease
Models Predicting Kidney Failure
Kidney Failure Risk Equations
Models Predicting Death and Cardiovascular Disease
Models Predicting Chronic Kidney Disease After Acute Kidney Injury
Clinical Implementation of Risk Models
Primary Care to Nephrology Transition
Interdisciplinary Care
Dialysis Access and Modality Planning
Future Considerations
Key References
References
Board Review Questions
21 Developmental Programming of Blood Pressure and Renal Function Through the Life Course
Chapter Outline
Developmental Programming
Developmental Programming in the Kidney
Plausibility of the Nephron Number Hypothesis
Estimating Nephron Number
Nephron Number and Glomerular Volume
Evidence for Programming in the Kidney
Developmental Programming of Nephron Endowment
Experimental Evidence for Programming of Nephron Endowment
Programming of Nephron Number in Humans
Kidney Size as a Correlate for Nephron Number
Evidence of Additional Programming Effects in the Kidney
Altered Sodium Handling by the Kidney
Renin–Angiotensin System
The Sympathetic Nervous System and Renal Vascular Reactivity
Programming of Renal Function and Disease
Experimental Evidence
Human Evidence
Birth Weight, Preterm Birth, and Blood Pressure
Nephron Number and Blood Pressure
Birth Weight, Preterm Birth, and Kidney Function
Glomerular Filtration Rate
Proteinuria
Neonatal Acute Kidney Injury
Chronic Kidney Disease and End-Stage Kidney Disease
Relative Impact of Being Born Small or Preterm on Renal Programming
Potential Impact of Ethnicity on Renal Programming
Proposed Mechanisms of Developmental Programming in the Kidney
Genetic Variants Associated With Kidney Size and Nephron Number in Humans
Maternal Nutrition
Undernutrition
Overnutrition: Exposure to Maternal Diabetes and Obesity
Maternal and Fetal Exposure to Glucocorticoids
Maternal and Fetal Hypoxia
Fetal Drug and Alcohol Exposure
Obstruction of the Developing Kidney
Molecular Pathways Affected in Fetal Programming of the Kidney
Ureteric Branching Morphogenesis
Apoptosis
Impact of Sex
Potential for Rescue of Nephron Number
Catch-Up Growth
Impact of Early Growth on Kidney Function
Maternal Health and Intergenerational Effects of Programming
Impact of Nephron Endowment in Transplantation
Implications of Nephron Endowment for the Donor
Implications of Nephron Endowment for the Recipient
Global Health Relevance of Renal Programming
Conclusion
Key References
References
Board Review Questions
22 The Physiology and Pathophysiology of the Kidneys in Aging
Chapter Outline
General Overview of the Biology of Aging
Healthy Aging and Age-Related Comorbidity
Differences Between Humans and Other Animals
Anatomic Changes of the Kidneys With Aging
Macroscopic changes
Kidney Size and Volume
Kidney Cortex and Medulla
Kidney Cysts
Other Structural Changes
Microscopic Changes
Glomeruli
Number of Glomeruli
Glomerulosclerosis
Glomerular Hypertrophy
Tubules
Tubular Hypertrophy
Tubular Diverticuli
Arteries and Arterioles
Nephrosclerosis and Interstitial Fibrosis
Functional Changes of the Kidneys With Aging
Glomerular Filtration Rate
Whole-Kidney Glomerular Filtration Rate
Single-Nephron Glomerular Filtration Rate
Other Functional Changes
Renal Plasma Flow
Filtration Fraction
Renal Reserve in Aging
Sexual Dimorphism in Aging
Pathophysiologic Explanations for Aging-Associated Nephrosclerosis
Podocentric Versus Ischemic Hypotheses (Animal and Human Studies).
Contribution of Comorbidities to Renal Aging
Fluid, Electrolyte, and Acid-Base Homeostasis in Aging
Sodium Homeostasis
Potassium Homeostasis
Magnesium Homeostasis
Calcium Homeostasis
Phosphorus Homeostasis
Vitamin D Homeostasis
Acid-Base Homeostasis
Water Homeostasis
Renal Endocrine Changes With Aging
Renin-Angiotensin-Aldosterone System
Erythropoietin
Implications of Normal Physiology on Renal Function
Diagnosis
Prognosis
Cardiovascular Disease and Decline in the Glomerular Filtration Rate With Aging
End-Stage Renal Disease and Aging
Acute Kidney Injury and Diseases of the Kidney and Urinary Tract in Aging
Diseases of the Kidney and Urinary Tract in Aging
Can Renal Aging Be Modified?
Key References
References
Board Review Questions
23 Laboratory Assessment of Kidney Disease: Glomerular Filtration Rate, Urinalysis, and Proteinuria
Chapter Outline
Key Points
Glomerular Filtration Rate
Normal Physiology
Measurement of GFR
Glomerular Filtration Markers
Endogenous Glomerular Filtration Markers
Urea
Serum Creatinine
Sources of Error in Measurement of Creatinine.
Creatinine Clearance.
Cystatin C
Novel Endogenous Filtration Markers
Equations for Estimating GFR
Bias, Precision, and Accuracy.
Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration Equations.
MDRD.
CKD-EPI.
Cockcroft–Gault Equation.
Exogenous Glomerular Filtration Markers
Inulin
Clearance Methods for Other Exogenous Glomerular Filtration Markers
Radiolabeled Markers
Unlabeled Radiocontrast Agents
Specific Circumstances or Populations
Children
Elderly Population
Pregnancy
Acute Kidney Injury
Drug Dosing
Full Age Spectrum Method of eGFR Estimation
Renal Transplant Recipients
Urinalysis
Color
Odor
Relative Density
Urine pH
Bilirubin and Urobilinogen
Leukocyte Esterase and Nitrites
Glucose
Ketones
Hemoglobin and Myoglobin
Proteinuria
Normal Physiology
Types of Proteinuria
Normal Levels of Proteinuria
Categorization of Proteinuria
Sources of Error in Measurement
Advantages of Urinary Albumin Over Total Protein Measurements
Considerations Regarding Measuring Urinary Albumin Rather Than Total Protein
Evidence for CKD Progression Risk and Interventions
Missed Tubular Proteinuria
Diagnostic Utility of Protein Type
Methods to Measure Urinary Total Protein
Methods to Measure Urinary Albumin
Different Laboratory Methods to Measure Albumin in the Urine
Timed Versus Random Collection for Proteinuria Assessment
Translating Urine PCR and ACR Values Into Total Daily Protein Measurements
Correlation Between Ratios and 24-Hour Urine Protein
Variability in Creatinine Excretion
Fluctuations in Protein Excretion
Urinary ACR Versus PCR
Reagent Strip Testing
Albumin-Specific Dipsticks
New Devices for Point-of-Care Protein Testing
Role of Point-of-Care and Reagent Strip Testing
General Population
High-Risk Populations
Proteinuria Measurement in Specific Populations
Pregnant Patients
Children
Kidney Transplant Recipients
Urine Microscopy
Preparation and Method
Cells of the Urinary Sediment
Erythrocytes
Urine Cytology
Leukocytes
Other Cells
Other Elements
Lipids
Casts
Crystals
Microorganisms
Limitations
Summary
Key References
References
Board Review Questions
24 Interpretation of Electrolyte and Acid-Base Parameters in Blood and Urine
Chapter Outline
Water and Sodium
Polyuria
Water Diuresis
Concept 1
Water Channels.
Driving Force.
Concept 2
Distal Delivery of Filtrate.
Residual Water Permeability.
Concept 3
Tools for Assessing Water Diuresis
Urine Flow Rate.
Osmole Excretion Rate.
Urine Osmolality.
Electrolyte-Free Water Balance.
Tonicity Balance.
Clinical Approach to the Patient With Polyuria
Step 1: What Is the Urine Osmolality?
Step 2: Examine the Renal Response to Vasopressin or Desmopressin
Step 3: Establish the Basis for Central Diabetes Insipidus
Step 4: Establish the Basis for Nephrogenic Diabetes Insipidus
Clinical Case 1: What Is “Partial” About Partial Central Diabetes Insipidus?
Questions and Discussion
Clinical Case 2: in a Patient With Central Diabetes Insipidus, Why Did Polyuria Persist After the Administration of Desmopressin?
Questions and Discussion
Osmotic Diuresis
Concept 4
Concept 5
Tools for Evaluation of Osmotic Diuresis
Urine Osmolality.
Osmole Excretion Rate.
Nature of the Urine Osmoles.
Sources of the Urine Osmoles.
Source of Urea.
Source of Glucose.
Clinical Approach to the Patient With an Osmotic Diuresis
Step 1: Calculate the Osmole Excretion Rate
Step 2: Define the Nature of the Excreted Osmoles
Step 3: Identify the Source of the Osmoles in the Urine
Clinical Case 3: Unusually Large Osmotic Diuresis in a Patient With Diabetes Mellitus
Questions and Discussion
Decreased Effective Arterial Blood Volume
Concept 6
Concept 7
Concept 8
Tools for Evaluating Decreased Effective Arterial Blood Volume
Quantitative Assessment of the Extracellular Fluid Volume
Urinary Tests for Low Effective Arterial Blood Volume
Low Rate of Excretion of Sodium and Chloride.
High Rate of Excretion of Sodium but Little Excretion of Chloride.
High Rate of Excretion of Chloride but Little Excretion of Sodium.
Excretions of Sodium and Chloride Are Not Low.
Fractional Excretion of Sodium or Chloride
Determining the Nephron Site Where There Is a Defect in Reabsorption of Sodium
Clinical Case 4: Assessment of the Effective Arterial Blood Volume
Questions and Discussion
Hyponatremia
Concept 9
Concept 10
Tools for Evaluating Hyponatremia
Measurement of Plasma Sodium Concentration
Hyponatremia Due to Hyperglycemia.
Detection of a Low Effective Arterial Blood Volume
Concentrations of Sodium and Chloride in Urine.
Concentrations of Urea and Urate in Plasma.
Other Tests.
Clinical Case 5: Hyponatremia With Brown Spots
Questions and Discussion
Clinical Case 6: Hyponatremia in a Patient on Thiazide Diuretic Therapy
Questions and Discussion
Potassium
Transcellular Distribution of Potassium
Concept 11
Renal Excretion of Potassium
K+ Secretion in the Aldosterone-Sensitive Distal Nephron
Concept 12
Concept 13
Tools for Evaluating a Patient With a Dyskalemia
Assess the Rate of Excretion of Potassium in the Urine
Transtubular Potassium Concentration Gradient
Establishing the Basis for the Abnormal Rate of Excretion of Potassium.
Clinical Approach to the Patient With Hypokalemia
Step 1. Deal With Medical Emergencies That May Be Present on Presentation, and Anticipate and Prevent Risks That May Arise During Therapy
Step 2. Determine Whether the Basis for Hypokalemia Is an Acute Shift of Potassium Into Cells
Step 3. Examine the Acid-Basis Status in the Patient With Chronic Hypokalemia
Subgroup With Metabolic Acidosis.
Subgroup With Metabolic Alkalosis.
Clinical Case 7: Hypokalemia and a Low Rate of Potassium Excretion
Questions and Discussion
Clinical Case 8: Hypokalemia and High Rate of Potassium Excretion
Questions and Discussion
Clinical Approach to the Patient With Hyperkalemia
Step 1. Address Emergencies
Step 2. Determine Whether the Cause of the Hyperkalemia Is an Acute Shift of Potassium Out of Cells in vivo or Pseudohyperkalemia
Destruction of Cells in the Body.
Shift of K+ Out of Cells in the Body.
Pseudohyperkalemia May Be Present.
Step 3. What Is the Rate of Potassium Excretion?
Step 4. What Is the Basis for the Defect in Renal Potassium Excretion?
Does the Patient Have Advanced Chronic Renal Failure?
Is the patient taking drugs that interfere with the renal excretion of potassium?
Does the Patient Have a Disorder That Leads to Diminished Reabsorption of Sodium via ENaC in the ASDN?
Does the Patient Have a Disorder That Increases Electroneutral Sodium Reabsorption in the Distal Convoluted Tubule?
Does the Patient Have a Disorder That Increases Electroneutral Reabsorption of Sodium in the Cortical Collecting Duct?
Step 5. Is a Low Flow Rate in the ASDN Contributing to Hyperkalemia?
Clinical Case 9: Hyperkalemia in a Patient Taking Trimethoprim
Questions and Discussion
Clinical Case 10: Chronic Hyperkalemia in a Patient With Type 2 Diabetes Mellitus
Questions and Discussion
Metabolic Alkalosis
Concept 14
Concept 15
Concept 16
Tools for Assessment of Metabolic Alkalosis
Quantitative Estimate of the Extracellular Fluid Volume
Balance Data for Sodium, Potassium, and Chloride
Clinical Approach to the Patient With Metabolic Akalosis
Clinical Case 11: Metabolic Alkalosis Without Vomiting or Use of Diuretics
Questions and Discussion
Metabolic Acidosis
Concept 17
Tools for Assessment of Metabolic Acidosis
Quantitative Assessment of the Extracellular Fluid Volume
Tools to Assess the Removal of Hydrogen by the Bicarbonate Buffer System
Clinical Approach: Initial Steps
Metabolic Acidosis Due to Added Acids
Concept 18
Tools for Assessing Metabolic Acidosis Due to Added Acids
Detect New Anions in Plasma
Use of the Delta Plasma Anion Gap/Delta Plasma HCO3−.
Detect New Anions in the Urine
Detect Toxic Alcohols
Clinical Approach to the Patient With Metabolic Acidosis Due to Added Acids
Clinical Case 12: Severe Metabolic Acidosis in a Patient With Chronic Alcoholism
Questions and Discussion
Hyperchloremic Metabolic Acidosis
Concept 19
Concept 20
Tools for Assessing Hyperchloremic Metabolic Acidosis
Assess the Rate of Excretion of NH4+ in the Urine
Urine Osmolal Gap.
Determine Why the Rate of Excretion of NH4+ Is Low
Urine pH.
Assess Distal Hydrogen Secretion.
Assessment of Proximal Cell pH
Clinical Approach to the Patient With Hyperchloremic Metabolic Acidosis
Clinical Case 13: Does This Patient Have Distal RTA?
Questions and Discussion
Clinical Case 14: Determine the Cause of Hyperchloremic Metabolic Acidosis
Questions and Discussion
Key References
References
25 Diagnostic Kidney Imaging
Chapter Outline
Key points
Imaging Techniques
Plain Radiograph of the Abdomen
Intravenous Urography
Ultrasonography
Ultrasonography: Normal Anatomy
Computed Tomography
Computed Tomography Technique, Including Urography
Computed Tomography: Normal Anatomy
Iodinated Contrast Media
Postcontrast Acute Kidney Injury (PC-AKI) and Contrast-Induced Nephropathy (CIN)
Screening/evaluation of risk factors
Contrast Administration in Patients With Elevated Creatinine Level
Nephroprotective Strategies
Magnetic Resonance Imaging
Gadolinium-Based Contrast Agents (GBCA) and Nephrogenic Systemic Fibrosis
Diagnostic Magnetic Resonance Imaging Technique
Functional Magnetic Resonance Imaging of the Kidney
Nuclear Medicine
Radiopharmaceuticals
Technetium 99M-Labeled Diethylenetriaminepentaacetic Acid
Iodine 131-Labeled Ortho-Iodohippurate
Technetium 99M-Labeled Mercaptoacetyltriglycine
Technetium 99M-Labeled Dimercaptosuccinic Acid
Fluorine 18 2-Fluoro-2-Deoxy-D-Glucose
Imaging in Clinical Nephrology
Normal Renal Function
Kidney Injury: Acute and Chronic
Unilateral Obstruction
Renal Calcifications and Renal Stone Disease
Renal Infection
Renal Mass: Cysts to Renal Cell Carcinoma
Renal Cancer: Positron Emission Tomography and Positron Emission Tomography-Computed Tomography
Renal Vascular Disease
Nuclear Imaging and Renovascular Disease
Renal Vein Thrombosis
Assessment for Kidney Donation
Assessment of Transplanted Kidneys
Acknowledgments
Key References
References
Board Review Questions
26 The Renal Biopsy
Chapter Outline
Key Points
Introduction
Safety and Complications of Biopsies
Biopsy Handling
Light Microscopy
Staining for Light Microscopy
Examination of the Biopsy by Light Microscopy
Terminology in Description of Glomerular Disease
Immunohistochemistry
Electron Microscopy
Other Studies on the Renal Biopsy
Biopsies of Transplanted Kidneys
The Size of the Biopsy
The Biopsy Report
Conclusion
Key References
References
Board Review Questions
27 Biomarkers in Acute and Chronic Kidney Diseases
Chapter Outline
Key Points
Biomarker Definition
Process of Biomarker Discovery, Assay Validation, and Qualification in a Clinical Context
Phase 1: Discovery of Potential Biomarkers Through Unbiased or Hypothesis-Generating Exploratory Studies
Phase 2: Development and Validation of an Assay for the Measurement or Identification of the Biomarker in Clinical Samples
Phase 3: Demonstration of the Biomarker’s Potential Clinical Utility in Retrospective Studies
Phase 4: Performance of Prospective Screening Studies
Biomarker Qualification Process
Phase 5: Continued Assessment of the Validity of the Biomarker in Routine Clinical Practice
Analysis of Biomarker Performance
Characteristics of an Ideal Biomarker for Kidney Disease
Acute Kidney Injury Markers
Glomerular Injury Markers
Serum Glomerular Filtration Markers
Creatinine
Blood Urea Nitrogen
Cystatin C
Chronic Kidney Disease.
Acute Kidney Injury.
β-Trace Protein
Urinary Glomerular Cell Injury Markers
Podocyte Count
Podocalyxin
Urinary Tubular Injury Markers
Urine Microscopy
α1-Microglobulin
Acute Kidney Injury
Chronic Kidney Disease
β2-Microglobulin
Hepcidin-25
Interleukin-18
Acute Kidney Injury
Chronic Kidney Disease
Kidney Injury Molecule-1
Chronic Kidney Disease
Liver-Type Fatty Acid Binding Protein
Chronic Kidney Disease
Monocyte Chemoattractant Protein-1
Acute Kidney Injury
Chronic Kidney Disease
Neutrophil Gelatinase-Associated Lipocalin
Acute Kidney Injury
Urine Neutrophil Gelatinase-Associated Lipocalin
Plasma Neutrophil Gelatinase-Associated Lipocalin
Chronic Kidney Disease
N-Acetyl-β-D-Glucosaminidase
Proteinuria
Albuminuria
Urinary Cystatin C
Proenkephalin
Acute Kidney Injury
Chronic Kidney Disease
Urine Tissue Inhibitor Metalloproteinase-2 and Insulin-Like Growth Factor–Binding Protein-7
Furosemide Stress Test
Genetic Associations With Acute Kidney Injury Risk
Chronic Kidney Disease Biomarkers
Plasma Asymmetric Dimethylarginine
Fibroblast Growth Factor 23
Soluble Urokinase-Type Plasminogen Activator Receptor
Urinary Renal Fibrosis Markers
Connective Tissue Growth Factor
Transforming Growth Factor-β1
Collagen IV
Tumor Necrosis Factor Receptors
Epidermal Growth Factor
Combinations of Multiple Biomarkers
Critical Path Initiative: A Need for Better Biomarkers
Kidney Health Initiative
Future of Biomarkers
Acknowledgments
Disclosure
Key References
References
Board Review Questions
28 Pathophysiology of Acute Kidney Injury
Chapter Outline
Pathophysiology of Clinical Acute Kidney Injury
Prerenal Acute Kidney Injury
Intrinsic Acute Kidney Injury
Diseases of Large Vessels and Microvasculature
Diseases of the Tubulointerstitium
Interstitial Disease
Tubular Disease—Exogenous Nephrotoxins
Radiocontrast Media–Induced Nephropathy.
Aminoglycoside Nephrotoxicity.
Vancomycin Nephrotoxicity.
Cisplatin Nephrotoxicity.
Acute Phosphate Nephropathy.
Tubular Disease—Endogenous Nephrotoxins
Myoglobin and Hemoglobin.
Immunoglobulin Light Chains.
Uric Acid.
Postrenal Acute Kidney Injury
Pathophysiology of Acute Kidney Injury
Overview of the Pathophysiology of Acute Kidney Injury
Experimental Models
In vivo Models of Acute Kidney Injury
Zebrafish
Three-Dimensional Microfluidic Models and Organoids
Acute Tubular Necrosis
Epithelial Cell Injury
Morphologic Changes
Cytoskeletal and Intracellular Structural Changes
Cell Death Pathways
Necrosis and Regulated Cell Death Pathways.
Apoptosis.
Necroptosis.
Ferroptosis.
Pyroptosis.
Autophagy.
NETosis.
Innate Immunity and Inflammation
Kidney Microenvironment.
Mononuclear Phagocytes in Acute Kidney Injury.
Polymorphonuclear Leukocytes in Acute Kidney Injury.
T Cells in Acute Kidney Injury.
B Lymphocytes.
Inflammation
Complement
Intracellular Mechanisms
Reactive Oxygen Species
Heat Shock Proteins
Iron, Ferritin, and Heme Oxygenase
Heme Oxygenase-1
Repair and Regeneration
Microvascular Function
Vascular Tone.
Acute Kidney Injury to Chronic Kidney Disease Transition
Role of the Endothelium
Epigenetic Modification
Renal Oxidative Stress in Acute Kidney Injury−Chronic Kidney Disease Transition
Cell Cycle Arrest
Inflammation in Acute Kidney Injury−Chronic Kidney Disease Transition
Effects of Organ Crosstalk
Key References
References
Board Review Questions
29 Prevention and Management of Acute Kidney Injury
Chapter Outline
Definition of Acute Kidney Injury
Incidence of Acute Kidney Injury
Categorization of Acute Kidney Injury
Evaluation of Acute Kidney Injury
Clinical Assessment of the Patient
Urine Assessment
Blood and Laboratory Findings
Novel Biomarkers of Kidney Injury
Cystatin C
Neutrophil Gelatinase-Associated Lipocalin
Kidney Injury Molecule 1
Interleukin 18
Liver Fatty Acid−Binding Protein
Tissue Inhibitor of Metalloproteinase 2 and Insulin-Like Growth Factor−Binding Protein 7
Radiologic Evaluation
Kidney Biopsy
Causes of Acute Kidney Injury in Specific Clinical Settings
Acute Kidney Injury in the Setting of Cancer
Acute Kidney Injury in Pregnancy
Acute Kidney Injury in the Setting of Cardiac Surgery
Acute Kidney Injury After Solid Organ or Bone Marrow Transplantation
Acute Kidney Injury Associated With Pulmonary Disease
Acute Kidney Injury in Association With Liver Disease
Acute Kidney Injury and the Nephrotic Syndrome
Complications of Acute Kidney Injury
Potassium Homeostasis
Acid-Base Homeostasis
Mineral and Uric Acid Homeostasis
Volume Overload and Cardiac Complications
Hematologic Complications
Nutritional and Gastrointestinal Complications
Infectious Complications
Other Sequelae of Acute Kidney Injury
Complications During Recovery From Acute Kidney Injury
Management of Acute Kidney Injury
Management of Prerenal Acute Kidney Injury
Intravascular Volume Depletion
Heart Failure
Liver Failure and Hepatorenal Syndrome
Abdominal Compartment Syndrome
Management of Postrenal Acute Kidney Injury
Prevention of Intrinsic Acute Kidney Injury
General Principles
Contrast-Associated Acute Kidney Injury
Prevention of Other Forms of Intrinsic Acute Kidney Injury
Remote Ischemic Preconditioning
Pharmacologic Therapy for Acute Tubular Necrosis
Dopamine
Fenoldopam
Natriuretic Peptides
Loop Diuretics
Mannitol
Management of Other Causes of Intrinsic Acute Kidney Injury
Acute Vasculitis and Acute Glomerular Disease
Acute Kidney Injury in Multiple Myeloma
Acute Interstitial Nephritis
Nondialytic Supportive Management of Acute Kidney Injury−Associated Complications
Extracellular Volume Overload
Hyponatremia and Hypernatremia
Hyperkalemia
Metabolic Acidosis
Disturbances of Calcium, Phosphate, Magnesium, and Uric Acid
Nutritional Management
Anemia
Drug Dosing
Renal Replacement Therapy in Acute Kidney Injury
General Principles
Indications for and Timing of Initiation of Renal Replacement Therapy
Choice of Modality of Renal Replacement Therapy
Intermittent Hemodialysis
Continuous Renal Replacement Therapy
Prolonged Intermittent Renal Replacement Therapy
Peritoneal Dialysis
Summary of Acute Kidney Injury Management
Key References
References
Board Review Questions
30 Pathophysiology of Proteinuria
Chapter Outline
Mechanisms of Proteinuria
Structure and Function of the Glomerular Capillary Wall
Glomerular Capillary Wall Organization
Glomerular Capillary Network
Glomerular Capillary Wall
Ultrastructure of the Glomerular Capillary Membrane
Endothelial Cell Layer
Glomerular Basement Membrane Organization
Epithelial Filtration Slits
Theoretical Models of Glomerular Permselectivity
Heteroporous Models of Glomerular Size Selectivity
Fiber Models of Glomerular Size Selectivity
Models of Glomerular Charge Selectivity
Protein Reabsorption by the Proximal Tubule
Proximal Tubule Structure and Function
Theoretical Models for Tubular Reabsorption
Proteinuria of Glomerular Origin
Glomerular Permselective Dysfunction
Tubular Handling of Excessive Filtered Proteins
Effects of Protein Filtration on Proximal Tubule Cells
Renal Consequences of Proteinuria
Glomerular Damage
Podocytes: Changes in Function and Cell Number
Mesangial Cells: Proliferation and Deposition of Extracellular Matrix
Endothelial Cells: Apoptosis
Parietal Epithelial Cells: Activation
Loss of Glomerular Capillaries: Postglomerular Hypoxia
Tubular Damage
Tubular Cells: Apoptosis and Tubulo Glomerular Disconnection
Tubule Cells: Activation
Interstitial Inflammation and Injury
Resident Monocyte/Dendritic Cells
Macrophages and Lymphocytes
Bone Marrow–Derived Fibrocytes
Fibroblasts: Activation and Deposition of Extracellular Matrix
Chronic Hypoxia
Endogenous Systems of Tissue Repair
Protective Macrophages
Regulatory T Cells
Kidney-Derived Progenitor Cells
Systemic Consequences of Nephrotic-Range Proteinuria
Hypoalbuminemia
Pathogenesis of Hypoalbuminemia
Consequences of Hypoalbuminemia
Edema Formation
Reduced Plasma Oncotic Pressure
Alterations in Blood Volume
Intrarenal Mechanisms
Hyperlipidemia
Pathogenesis of Nephrotic Hyperlipidemia
Clinical Consequences of Hyperlipidemia
Hypercoagulability
Pathogenesis of Hypercoagulability
Clinical Consequence of Hypercoagulability
Susceptability to Infection
Acknowledgments
Key References
References
Board Review Questions
31 Primary Glomerular Disease
Chapter Outline
Key Points
General Description of Glomerular Syndromes
Proteinuria
Recurrent or Persistent Hematuria
Glomerular Diseases That Cause Nephrotic Syndrome and Glomerulonephritis
Nephrotic Syndrome
Minimal Change Disease
Epidemiology
Pathology
Light Microscopy
Immunofluorescence Microscopy
Electron Microscopy
Pathogenesis
Clinical Features and Natural History
Laboratory Findings
Treatment
Steroid-Resistant Minimal Change Disease
Focal Segmental Glomerulosclerosis
Epidemiology
Pathology
Light Microscopy
Immunofluorescence Microscopy
Electron Microscopy
Pathogenesis
Clinical Features and Natural History
Laboratory Findings
Treatment
Angiotensin Inhibitors
Glucocorticoids
Cyclophosphamide
Cyclosporine
Mycophenolate Mofetil
Other Therapies
C1q Nephropathy
Membranous Nephropathy
Epidemiology
Pathology
Electron Microscopy
Immunofluorescence Microscopy
Light Microscopy
Pathogenesis
PLA2R, THSD7A, and Membranous Nephropathy
Clinical Features and Natural History
Laboratory Findings
Treatment
Corticosteroids
Cyclophosphamide or Chlorambucil
Calcineurin Inhibitors
Adrenocorticotropic Hormone
Mycophenolate Mofetil
Rituximab
Other Therapies
Membranoproliferative Glomerulonephritis and C3 Glomerulopathy
Membranoproliferative Glomerulonephritis Type I
Pathology
Light Microscopy.
Immunofluorescence Microscopy.
Electron Microscopy.
Pathogenesis
Epidemiology
Clinical Features
Treatment
Membranoproliferative Glomerulonephritis Type III
C3 Glomerulopathies (Dense Deposit Disease and C3 Glomerulonephritis)
Epidemiology
Pathology
Pathogenesis
Clinical Features
Treatment
Acute Poststreptococcal Glomerulonephritis
Epidemiology
Pathology
Light Microscopy
Immunofluorescence Microscopy
Electron Microscopy
Pathogenesis
Clinical Features and Natural History
Laboratory Findings
Treatment
Immunoglobulin A Nephropathy
Epidemiology
Genetics
Pathology
Immunofluorescence Microscopy
Electron Microscopy
Light Microscopy
Pathogenesis
Clinical Features and Natural History
Laboratory Findings
Treatment
Angiotensin II Inhibition
Glucocorticoids
Combinations of Angiotensin II Inhibition and Glucocorticoid Therapy
Combinations of Angiotensin II Inhibition, Glucocorticoid Therapy, and Immunosupprression
Other Treatment Modalities
Omega-3 Fatty Acids.
Fibrillary Glomerulonephritis and Immunotactoid Glomerulopathy
Nomenclature
Fibrillary Glomerulonephritis Pathology
Electron Microscopy
Light Microscopy
Immunofluorescence Microscopy
Immunotactoid Glomerulopathy Pathology
Electron Microscopy
Light Microscopy
Immunofluorescence Microscopy
Pathogenesis
Epidemiology and Clinical Features
Treatment
Rapidly Progressive Glomerulonephritis and Crescentic Glomerulonephritis
Nomenclature and Categorization
Immune Complex–Mediated and C3 Glomerulopathy Crescentic Glomerulonephritis
Epidemiology
Pathology
Light Microscopy
Immunofluorescence Microscopy
Electron Microscopy
Pathogenesis
Treatment
Anti–Glomerular Basement Membrane Glomerulonephritis
Epidemiology
Pathology
Immunofluorescence Microscopy
Light Microscopy
Electron Microscopy
Pathogenesis
Clinical Features and Natural History
Laboratory Findings
Treatment
Pauci-Immune Crescentic Glomerulonephritis
Epidemiology
Pathology
Light Microscopy
Immunofluorescence Microscopy
Electron Microscopy
Pathogenesis
Clinical Features and Natural History
Laboratory Findings
Treatment
Maintenance Treatment
Key References
References
Board Review Questions
32 Secondary Glomerular Disease
Chapter Outline
Systemic Lupus Erythematosus
Epidemiology
Pathogenesis of Systemic Lupus Erythematosus and Lupus Nephritis
Pathology of Lupus Nephritis
Immunofluorescence
Electron Microscopy
Activity and Chronicity
Tubulointerstitial Disease, Vascular Lesions, and Lupus Podocytopathy
Clinical Manifestations
Serologic Tests
Monitoring Clinical Disease
Drug-Induced Lupus
Pregnancy and Systemic Lupus Erythematosus
Dialysis and Transplantation
Course and Prognosis of Lupus Nephritis
Treatment of Lupus Nephritis
Antiphospholipid Syndrome
Treatment
Mixed Connective Tissue Disease
Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
Granulomatosis With Polyangiitis
Pathology
Pathogenesis
Clinical and Laboratory Features
Renal Findings
Course and Treatment
Microscopic Polyangiitis
Pathology
Light Microscopy
Immunofluorescence and Electron Microscopic Findings
Pathogenesis
Clinical Features
Laboratory Tests
Renal Findings
Prognosis and Treatment
Eosinophilic Granulomatosis With Polyangiitis
Pathology
Pathogenesis
Clinical and Laboratory Features
Prognosis, Course, and Treatment
Glomerular Involvement in Other Vasculitides
Polyarteritis Nodosa (Classic Macroscopic Polyarteritis Nodosa)
Pathology
Pathogenesis
Clinical Features
Laboratory Tests
Renal Findings
Prognosis and Treatment
Temporal Arteritis (Giant Cell Arteritis)
Takayasu Arteritis
Treatment
Henoch–Schönlein Purpura
Clinical Findings
Laboratory Features
Pathology
Pathogenesis
Course, Prognosis, and Treatment
Antiglomerular Basement Membrane Disease and Goodpasture Syndrome
Pathogenesis
Clinical Features
Laboratory Findings
Pathology
Course, Treatment, and Prognosis
Sjögren Syndrome
Sarcoidosis
Amyloidosis
AL and AA Amyloidosis
Pathology
Course, Prognosis, and Treatment
End-Stage Kidney Disease in Amyloidosis
Fibrillary Glomerulonephritis and Immunotactoid Glomerulonephritis
Monoclonal Immunoglobulin Deposition Disease
Other Glomerular Diseases and Dysproteinemia
Waldenström Macroglobulinemia
Mixed Cryoglobulinemia
Alport Syndrome
Clinical Features
Pathology
Pathogenesis and Genetics of Hereditary Nephritis
Course and Treatment
Thin Basement Membrane Nephropathy
Clinical Features
Pathology
Pathogenesis
Differential Diagnosis of Familial Hematurias
Nail–Patella Syndrome (Hereditary Osteo-Onychodysplasia)
Clinical Features
Pathology
Pathogenesis
Treatment
Fabry Disease (Angiokeratoma Corporis Diffusum Universale)
Clinical Features
Pathology
Pathogenesis
Diagnosis
Treatment
Sickle Cell Nephropathy
Clinical Features
Pathology
Pathogenesis
Treatment
Lipodystrophy
Lecithin-Cholesterol Acyltransferase Deficiency
Clinical Features
Pathology
Pathogenesis
Diagnosis
Treatment
Lipoprotein Glomerulopathy
Glomerular Involvement With Bacterial Infections
Infectious Endocarditis
Clinical Features
Pathology
Pathogenesis
Treatment
Shunt Nephritis
Visceral Infection
Other Bacterial Infections and Fungal Infections
Glomerular Involvement With Parasitic Diseases
Malaria
Glomerular Involvement With Viral Infections
HIV-Related Glomerulopathies
HIV-Associated Nephropathy
Clinical Features
Pathology
Pathogenesis
Course and Treatment
Other Glomerular Lesions in Patients With HIV Infection
Glomerular Manifestations of Liver Disease
Hepatitis B
Clinical Features
Pathology
Treatment
Hepatitis C
Pathogenesis
Clinical and Pathologic Features
Treatment
Autoimmune Chronic Active Hepatitis
Liver Cirrhosis
Glomerular Lesions Associated With Neoplasia
Clinical and Pathologic Features
Membranous Nephropathy
Minimal Change Disease or Focal Glomerulosclerosis
Proliferative Glomerulonephritides and Vasculitides
Thrombotic Microangiopathy
Glomerular Disease Associated With Drugs
Heroin Nephropathy
Nonsteroidal Antiinflammatory Drug–Induced Nephropathy
Clinical and Pathologic Features
Minimal Change Disease With Interstitial Nephritis
Other Patterns
Pathogenesis.
Antirheumatoid Arthritis Therapy–Induced Glomerulopathy
Other Medications
Miscellaneous Diseases Associated With Glomerular Lesions
Key References
References
33 Treatment of Glomerulonephritis
Chapter Outline
Key Points
Introduction
The Global Impact and Challenges
Personalizing Therapy: Balancing Risks and Benefits
Personalizing Treatment: Disease-Specific Risks and Goals
Membranous Glomerulonephritis
Focal and Segmental Glomerulosclerosis
Iga Nephropathy
Remission in Lupus Nephritis and Vasculitis
Timing of Response
Individualizing Therapy: Mitigating Toxicities of Therapy
Corticosteroids
Major Adverse Effects
Strategies for Reducing Toxicity
Calcineurin Inhibitors
Major Adverse Effects
Strategies for Reducing Toxicity
Alkylating Agents
Major Adverse Effects
Strategies for Reducing Toxicity
Azathioprine
Major Adverse Effects
Strategies for Reducing Toxicity
Mycophenolic Acid
Major Adverse Effects
Strategies for Reducing Toxicity
Rituximab and Ocrelizumab
Major Adverse Effects
Strategies for Reducing Toxicity
Eculizumab
Major Adverse Effects
Strategies for Reducing Toxicity
Adrenocorticotrophic Hormone
Major Adverse Effects
Strategies for Reducing Toxicity
Treatment Algorithms and Considerations
Conclusion
Key References
References
Board Review Questions
34 Thrombotic Microangiopathies
Chapter Outline
Introduction
Classification
Clinical and Laboratory Features
Thrombotic Microangiopathy Pathology
Primary Thrombotic Microangiopathies
Complement-Mediated Atypical Hemolytic Uremic Syndrome
Complement Regulation
Inherited Complement-Mediated Atypical Hemolytic Uremic Syndrome
Complement Factor H
CD46 Membrane Cofactor Protein
Complement Factor I
Complement C3
Complement Factor B
Thrombomodulin
Disease Penetrance
Acquired Primary Complement-Mediated Atypical Hemolytic Uremic Syndrome
Complement Screening in Atypical Hemolytic Uremic Syndrome
Clinical Features of Complement-Mediated Atypical Hemolytic Uremic Syndrome
Treatment of Complement-Mediated Atypical Hemolytic Uremic Syndrome
Plasma Exchange
Eculizumab
Eculizumab Nonresponsive Atypical Hemolytic Uremic Syndrome
Eculizumab Side Effects
Renal Transplantation in Complement-Mediated Atypical Hemolytic Uremic Syndrome
DGKE Thrombotic Microangiopathy
Pathogenesis
Clinical Features
Treatment
Methylmalonic Aciduria and Homocystinuria, Cobalamin C (Cblc)-Type Hemolytic Uremic Syndrome
Clinical Features
Treatment
Thrombotic Thrombocytopenic Purpura
Incidence
Pathogenesis
Clinical Features
Treatment
Infection-Associated Thrombotic Microangiopathies
Shiga Toxin Hemolytic Uremic Syndrome
Microbiology
Source of Infection
Incidence
Clinical Features of Shiga Toxin–Producing Enterohemorrhagic Escherichia Coli–Hemolytic Uremic Syndrome
Extrarenal Manifestations
Long-Term Sequelae
Clinical Features of Shigella Dysenteriae Type 1
Microbiology Testing
Pathogenesis
Role of Complement in the Pathogenesis of STEC-HUS
Treatment
Pneumococcal Hemolytic Uremic Syndrome
Incidence
Pathogenesis
Clinical Features
Treatment
Human Immunodeficiency Virus–Associated Thrombotic Microangiopathies
Other Infections
Secondary Thrombotic Microangiopathies
Pregnancy-Associated Thrombotic Microangiopathies
Drug-Mediated Thrombotic Microangiopathy
Malignancy-Associated Thrombotic Microangiopathy
De Novo Thrombotic Microangiopathy After Solid Organ Transplant
Thrombotic Microangiopathy After Bone Marrow Transplant
Autoimmune and Glomerular Disease–Associated Thrombotic Microangiopathies
Severe Hypertension-Associated Thrombotic Microangiopathy
Summary
Key References
References
35 Tubulointerstitial Diseases
Chapter Outline
Key points
Introduction
Primary Versus Secondary Tubulointerstitial Disease
Mechanisms of Tubulointerstitial Injury
Components of the Tubulointerstitium
Immune-Mediated Tubulointerstitial Disease
Antigens Within the Renal Compartment
Antigen Presentation by Tubular Cells
Cellular Infiltrates
Immunology and Pathogenesis of Drug-Induced Acute Tubulointerstitial Nephritis
Nonimmune-Mediated Tubulointerstitial Disease
Glomerular-Related Events
Proteinuria-Induced Tubular Cell Injury
Glomerular Filtered Growth Factors and Cytokines
Activation of Complement Components
Tubulointerstitial Fibrosis
Epithelial–Mesenchymal Transitions in Fibrosis
Chronic Hypoxia in Fibrosis
Genetic Causes of Tubulointerstitial Diseases
Acute Tubulointerstitial Nephritis
General Features of Acute Tubulointerstitial Nephritis
Incidence/Prevalence
Clinical History
Physical Examination
Laboratory Testing
Serum Creatinine Concentration
Serum Eosinophil Count
Other Serum Tests
Serum Markers of Tubular Dysfunction
Urinalysis
Urine Eosinophil Test
Urine Microscopy and Sediment Examination
Urine Chemistries
Novel Urinary Biomarkers
Lymphocyte Transformation Test
Imaging Tests
Ultrasonography and CT Scanning.
67Gallium Scanning.
FDG-PET Scanning.
Differential Diagnosis
Renal Pathology
Tubulointerstitial Histopathology
Blood Vessels and Glomeruli
General Treatment Principles
Specific Etiologies of ATIN and Their Features
Drug-Induced ATIN
Antimicrobial Agents
Proton Pump Inhibitors
Nonsteroidal Antiinflammatory Agents
Anticancer Agents
Immunosuppressive Therapy of Drug-Induced AIN
Infections
Systemic Diseases
Immunologic Disorders
Tubulointerstitial Nephritis and Uveitis Syndrome
IgG4-Related Kidney Disease
Prognosis
Chronic Tubulointerstitial Diseases
Clinical Features
Differential Diagnosis
Renal Pathology
General Treatment Principles
Specific Etiologies of Chronic Tubulointerstitial Nephritis
Analgesic-Induced Chronic Tubulointerstitial Nephritis (Analgesic Nephropathy)
Aristolochic Acid–Induced Interstitial Nephritis (Balkan and Chinese Herb Nephropathy)
Heavy-Metal–Associated Chronic Tubulointerstitial Nephritis
Lead
Cadmium
Lithium-Induced Chronic Tubulointerstitial Nephritis
Uric Acid Nephropathy
Chronic Kidney Disease of Unknown Etiology
Acknowledgments
Key References
References
Board Review Questions
36 Urinary Tract Infection in Adults
Chapter Outline
Key Points
Definitions
General Concepts
Host Defenses of the Normal Urinary Tract
Immune and Inflammatory Responses to Urinary Tract Infection
Urine Culture
Pharmacokinetic and Pharmacodynamic Considerations for Treatment
Usual Presentations of Urinary Tract Infection
Acute Uncomplicated Urinary Tract Infection: Cystitis
Epidemiology
Pathogenesis
Microbiology
Host Factors
Diagnosis
Treatment
Other Investigations
Recurrent Infection
Acute Nonobstructive Pyelonephritis
Epidemiology
Pathogenesis
Diagnosis
Diagnostic Imaging
Treatment
Complicated Urinary Tract Infection
Epidemiology
Pathogenesis
Microbiology
Host Factors
Clinical Presentations
Laboratory Diagnosis
Antimicrobial Treatment
Other Interventions
Management of Recurrent Infection
Asymptomatic Bacteriuria
Epidemiology
Pathogenesis
Microbiology
Host Factors
Diagnosis
Treatment
Prostatitis
Urinary Tract Infection in Unique Patient Populations
Renal Transplant Recipients
Persons With Renal Failure
Persons With Urinary Stones
Other Infections of the Urinary Tract
Renal and Perinephric Abscesses
Infected Renal Cysts
Emphysematous Cystitis and Pyelonephritis
Xanthogranulomatous Pyelonephritis
Pyocystis
Uncommon Organisms
Genitourinary Tuberculosis
Bacillus Calmette–Guérin Infection
Fungal Urinary Tract Infection
Viral Infections
Parasitic Infestations of the Urinary Tract
Key References
References
Board Review Questions
37 Urinary Tract Obstruction
Chapter Outline
Key Points
Prevalence and Incidence
Classification
Etiology
Congenital Causes of Obstruction
Acquired Causes of Obstruction
Intrinsic Causes
Extrinsic Causes
Clinical Aspects
Diagnosis
History and Physical Examination
Biomarkers for Evaluation of Urinary Tract Obstruction
Biochemical Evaluation of Blood and Urine
Evaluation by Medical Imaging
Ultrasonography
Antenatal Ultrasonography
Duplex Doppler Ultrasonography
Intravenous Urography
Computed Tomography
Isotopic Renography
Positron Emission Tomography
Magnetic Resonance Imaging
Whitaker Test
Retrograde and Antegrade Pyelography
Pathophysiology of Obstructive Nephropathy
Effects of Obstruction on Renal Blood Flow and Glomerular Filtration
The Early, Hyperemic Phase
The Late, Vasoconstrictive Phase
Regulation of the Glomerular Filtration Rate in Response to Obstruction
Recovery of Glomerular Function After Relief of Obstruction
Effects of Obstruction on Tubule Function
Effects of Obstruction on Tubular Sodium Reabsorption
Effects of Obstruction on Urinary Concentration and Dilution
Effects of Relief of Obstruction on Urinary Acidification
Effects of Relief of Obstruction on Excretion of Potassium
Effects of Relief of Obstruction on Excretion of Phosphate and Divalent Cations
Pathophysiology of Recovery of Tubular Epithelial Cells From Obstruction or of Tubulointerstitial Fibrosis
Fetal Urinary Tract Obstruction
Treatment of Urinary Tract Obstruction and Recovery of Renal Function
Estimating Renal Damage and Potential for Recovery
Recovery of Renal Function After Prolonged Obstruction
Postobstructive Diuresis
Key References
References
Board Review Questions
38 Urolithiasis
Chapter Outline
Introduction
Epidemiology
General Points
Kidney Stones in Adults: 1976−1994
Kidney Stones in Adults: 2007 to 2010
Calcium Stones
Prevalence of Calcium Stones
Calcium Intake
Vitamin D Intake
Oxalate Intake
Protein Consumption
Uric Acid Stones
Prevalence of Uric Acid Stones
Genetic and Dietary Factors
Data on Stone Incidence
Histopathology
Randall’s Plaque
Idiopathic Calcium Oxalate Stones
Calcium Phosphate Stones and Stones in Renal Tubular Acidosis
Stones in Enteric Hyperoxaluria
Pathophysiology
Physical Chemistry of Urinary Saturation
General Concepts
Factors Influencing Saturation
Urine Saturation Measurements in vitro
Upper Limits of Metastability and Formation Product
Activity Product Ratio
Concentration Product Ratio
Urine Saturation Estimation in Silico
Relative Supersaturation Ratio
Supersaturation Index
Urine Saturation in Stone Formers
Assessment of Nucleation
Assessment of Crystal Growth and Aggregation
Inhibition of Crystal Agglomeration
Cell-Crystal Interactions
Inhibitors
Concept
Magnesium
Citrate
Pyrophosphate
Macromolecules
Osteopontin
Tamm-Horsfall Protein
Urinary Prothrombin Fragment 1
Bikunin
Glycosaminoglycans
Matrix-Gla Protein
Urinary Trefoil Factor 1
Calcium Stones
Hypercalciuria
Intestinal Hyperabsorption of Calcium
1,25-Dihydroxyvitamin D−Dependent Absorptive Hypercalciuria
1,25-Dihydroxyvitamin D−Independent Absorptive Hypercalciuria
Increased Abundance of Vitamin D Receptor
Genetic Hypercalciuric Stone-Forming Rat Model of Hypercalciuria
Renal Leak Hypercalciuria
Resorptive Hypercalciuria
Parathyroid Hormone-Dependent Resorptive Hypercalciuria
Parathyroid Hormone−Independent Resorptive Hypercalciuria
Hyperuricosuria
Pathophysiologic Mechanism of Hyperuricosuria
Physicochemical Mechanism of Hyperuricosuria-Induced Calcium Stones
Hypocitraturia
Role of Acid-Base Factors
Other Factors
Clinical Conditions
Actions of Citrate
Hyperoxaluria
Increased Hepatic Production
Dietary Intake and Bioavailability
Intestinal Absorption
Role of Anion Exchanger Slc26a6
Role of Oxalobacter Formigenes
Renal Excretion
Clinical Hyperoxaluria
Physicochemical Effects of Hyperoxaluria
Alterations of Urinary pH
Uric Acid Stones
Physicochemistry of Uric Acid
Pathophysiology of Uric Acid Stones
Hyperuricosuria
Low Urinary Volume
Low Urinary pH
Origin of Low Urinary pH
Increased Acid Load to Kidneys
Impaired NH4+ Excretion
Role of Renal Lipotoxicity
Cystine Stones
Overview
Molecular Biology and Genetics
Clinical Presentation
Management
Pharmacologic Therapy
Infection Stones
Pathophysiology
Uncommon Stones
Genetic Causes
Acquired Causes
Genetics
Human Genetics
Familial Clustering
Ethnicity
Human Genetic Studies
Twin Studies
Candidate Genes
Genome-Wide Association Studies
Monogenic Causes of Urolithiasis
Polygenic Animal Model
Nephrolithiasis as a Systemic Disorder
Obesity, Weight Gain, Diabetes Mellitus, and Risk for Nephrolithiasis
Association Between Metabolic Syndrome and Nephrolithiasis
Nephrolithiasis, Cardiovascular Disease, and Hypertension
Kidney Stone Disease and Chronic Kidney Disease
Urinary Tract Cancers and Kidney Stones
Calcium Stones and Bone Disease
Epidemiology
Pathophysiologic Mechanisms Linking Osteoporosis and Kidney Stones
Dietary Factors
Genetic Factors
Hormones and Local Cytokines
Evaluation
Clinical Presentation
Symptoms and Signs
Environmental, Lifestyle, and Medical History
Family History
Laboratory Evaluation
Serum Chemistry
Urine Chemistry
Spot Urinalysis
Simplified Metabolic Evaluation
Extensive Metabolic Evaluation
Spot and Fasting Urine Specimen
Urinary Supersaturation Estimation
Stone Analysis
Imaging Studies
Kidneys, Ureters, and Bladder X-Ray
Ultrasound
Computed Tomography
Intravenous Pyelography
Magnetic Resonance Imaging
Digital Tomosynthesis
Management of Stones
Acute Management
Management of Renal Colic
Medical Expulsive Therapy
Chronic Management
Lifestyle and Dietary Management
Fluid Intake
Dietary Adjustment
Calcium Intake.
Dietary Oxalate.
Animal Protein.
Ascorbic Acid.
Dietary Intervention in Cystinuria.
Other Dietary Interventions.
Pharmacologic Treatment
Pharmacologic Agents Used
Thiazide Diuretics
Alkali Treatment
Combined Pharmacologic Treatment
Xanthine Oxidase Inhibitors
Magnesium Treatment
Cystine Chelation Therapy
Pharmacotherapy of Infection-Related Stones
Antibiotics
Dissolution Therapy
Urease Inhibitors
Urinary Acidification
Surgical Management of Infection-Related Stones
Acknowledgments
Key References
References
Board Review Questions
39 Epidemiology of Diabetic Kidney Disease
Chapter Outline
Key Points
Definition, Measurement, and Classification
Epidemiology
Prevalence
Incidence
Secular Trends
Youth-Onset Type 2 Diabetes and Its Impact on Kidney Disease
Regression of Albuminuria and Nonalbuminuric DKD
Risk Factors
Duration of Diabetes
Hyperglycemia
Hypertension
Hyperfiltration
Lipids
Dietary Protein
Obesity
Insulin Resistance
Pregnancy
Intrauterine Factors
Smoking
Peridontal Disease
Cardiac Autonomic Neuropathy
Familial and Genetic Factors
Epigenetic Factors
Biomarkers of DKD
Clinical Course
Prognosis
Extrarenal Complications in DKD
Pathology of the Kidney in Diabetes
Classic Lesions of Diabetic Kidney Disease
Structural-Functional Relationships of Diabetic Kidney Disease in Type 1 Diabetes
Comparisons of Diabetic Kidney Disease in Type 1 Versus Type 2 Diabetes
Structure-Function Relationships in Type 2 Diabetes
Nondiabetic Lesions in Diabetic Patients
Classification of Pathologic Lesions in Diabetic Kidney Disease
Reversability of Diabetic Kidney Disease Lesions
Clinical Indications for Kidney Biopsy in Diabetic Kidney Disease
Systems Biology in Diabetic Kidney Disease
Pathophysiology
Selective Glomerular Permeability
Glomerular Hemodynamic Function
Primary Cell Targets
Treatment
Blood Pressure CONTROL for the Treatment of Diabetic Kidney Disease
Renin-Angiotensin-Aldosterone System Blockers
Combination of Angiotensin- Converting Enzyme Inhibitors With Angiotensin-Receptor Blockers
Aldosterone Antagonists in Addition to Renin-Angiotensin-Aldosterone System Blockers
Endothelin Receptor Antagonists
Blood Pressure CONTROL for the Primary Prevention of Diabetic Kidney Disease
Glycemic CONTROL for the Treatment of Diabetic Kidney Disease
Impact of Targeting Glycemia With Different Agents in Diabetic Kidney Disease
Hypoglycemia
Lipid-Lowering Therapy
Dietary Protein Restriction
Multifactorial Intervention
New Compounds Under Investigation
End-Stage Kidney Disease
Epidemiology
Definitions of End-Stage Kidney Disease in People With Diabetes
Prevalence of End-Stage Kidney Disease
Incidence of End-Stage Kidney Disease
Acute and Acute-on-Chronic Renal Failure
Management of Patients With End-Stage Kidney Disease
Initiation of Renal Replacement Therapy
Hemodialysis
Cardiovascular Problems
Intradialytic Blood Pressure
Glycemic CONTROL
Monitoring of Glycemic CONTROL in Patients on Dialysis
Peritoneal Dialysis
Transplantation
Cardiovascular Disease Before Kidney Transplantation
Cardiovascular Disease After Kidney Transplantation
Islet Cell Transplantation
Stem Cell Transplantation
Acknowledgments
Key References
References
Board Review Questions
40 Cardiorenal Syndromes
Chapter Outline
Key Points
Introduction
Terminology of Cardiorenal Syndrome
Epidemiology and Prognosis
Pathophysiology of Concomitant Heart Failure and Chronic Kidney Disease
Shared Risk Factors
Renal Hemodynamics
Renal Blood Flow
Central and Renal Venous Pressure
Cardiorenal Connectors
Worsening Renal Function and Change in Renal Function
Deterioration of Cardiac Function
Albuminuria
Tubulointerstitial Damage in Heart Failure
Treatment of Heart Failure in Patients With Concomitant Renal Dysfunction
Key References
References
Board Review Questions
41 Kidney Cancer
Chapter Outline
Key Points
Biology of Renal Cell Carcinoma
Renal Cell Carcinoma: a Metabolic Disease
Biology and Rationale of Current Therapeutics
Renal Cell Carcinoma Histology and Genetics
Clear Cell Renal Cell Carcinoma
Papillary Renal Cell Carcinoma
Chromophobe Renal Cell Carcinoma
Presentation
Cystic Diseases and Renal Cell Carcinoma
Acquired Cystic Kidney Disease and Chronic Kidney Disease
Acquired Cystic Kidney Disease and Renal Cell Carcinoma
Polycystic Kidney Disease and Renal Cell Carcinoma
Prognosis of Renal Cell Carcinoma in the End-Stage Renal Disease Population
Renal Cell Carcinoma Risk and Kidney Function
Acquired Cystic Kidney Disease, Renal Cell Carcinoma, and Renal Transplantation
Evaluation and Prognostic Assessment of Renal Masses
Radiologic Evaluation of Renal Masses
Differentiation of Benign Tumors From Renal Cell Carcinoma
Tumor Staging and Grading
Treatment
Localized Renal Masses
Preoperative Considerations: Chronic Kidney Disease Burden
Postoperative Chronic Kidney Disease Risk
Renal Pathology
Surgical Treatment
Preoperative Clinical Evaluation
Renal Mass Excision and Nephron-Sparing Therapies
Posttreatment Surveillance of Localized Tumors
Advanced Renal Cell Carcinoma and Systemic Therapy
Introduction to New Therapeutic Approaches
Immunotherapy
Targeted Molecular Therapy
Vascular Endothelial Growth Factor
PI3K/mTOR
Novel Targeted Therapies
Key References
References
Board Review Questions
42 Onconephrology
Chapter Outline
Key Points
Acute Kidney Injury in Patients With Cancer
Epidemiology
Causes of Acute Kidney Injury in Patients With Cancer
Tumor Lysis Syndrome
Lysozymuria
Tumor Infiltration of the Kidneys
Thrombotic Microangiopathy
Light-Chain Cast Nephropathy and Acute Kidney Injury Associated With Myeloma
Urinary Tract Obstruction
Decision Making in the Patient With Cancer and Acute Kidney Injury
Chronic Kidney Disease in Patients With Cancer
Epidemiology
Outcomes and Prognosis
Cancer and Chronic Kidney Disease: Bidirectional Relationship
Effect of Chronic Kidney Disease on Cancer
Assessment of Kidney Function
Drug Dosing in Chronic Kidney Disease and End-Stage Renal Disease
Cancer Screening in End-Stage Renal Disease
Screening Tests for Cancer in the End-Stage Renal Disease Patient
Outcomes of Cancer Therapy in End-Stage Renal Disease Patients
Recommendations for Cancer Screening in End-Stage Renal Disease Patients
Glomerular Diseases Associated With Cancer
Membranous Nephropathy
Other Glomerular Diseases Associated With Solid Tumors
Hematologic Malignancy−Associated Glomerular Diseases
Hodgkin Disease
Chronic Lymphocytic Leukemia and B-Cell Lymphomas
Plasma Cell Dyscrasia
Fluid and Electrolyte Abnormalities Associated With Malignancies
Hyponatremia
Hypokalemia
Hyperkalemia
Hypercalcemia
Hypophosphatemia
Hypomagnesemia
Kidney Disease Associated With Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cell Transplantation−Associated Acute Kidney Injury
Marrow Infusion Syndrome
Hepatic Sinusoidal Obstruction Syndrome
Acute Thrombotic Microangiopathy
Graft-Versus-Host Disease
Hematopoietic Stem Cell Transplantation−Associated Chronic Kidney Disease
Anticancer Drugs and Kidney Disease
Conventional Chemotherapeutic Agents
Gemcitabine
Cisplatin
Ifosfamide
Methotrexate
Immunotherapies
Interferon
Interleukin-2
Immune Checkpoint Inhibitors
Targeted Therapies
Antiangiogenesis Drugs
Epidermal Growth Factor Receptor Inhibitors
B-RAF Inhibitors
Anaplastic Lymphoma Kinase Inhibitors
Miscellaneous Agents
Bisphosphonates
Key References
References
Board Review Questions
43 Inherited Disorders of the Glomerulus
Chapter Outline
Introduction
Disorders of the Podocyte
Mendelian Diseases of the Podocyte
Congenital Nephrotic Syndromes
Nephrin (NPHS1)
Podocin (NPHS2)
ACTN4
INF2
TRPC6
Other Forms of Monogenic Steroid-Resistant Nephrotic Syndrome
Cyoskeleton
Actin-Binding Proteins
Cytoskeletal Regulators
Slit Diaphragm
CD2AP
FAT1
MAGI-2
Podocyte-Matrix Adhesion
Mitochondria
Nuclear Pore Proteins
Transcription Factors
LMX1B
WT1
Other Transcription Factors
Other Genes
Common Genetic Factors
APOL1 Nephropathy
Other Common Genetic Factors
Immunoglobulin a Nephropathy
Membranous Nephropathy
Diseases of the Glomerular Basement Membrane
Alport Syndrome and Collagen IV−Related Renal Disease
Genetics of Alport Syndrome and Collagen IV−Associated Renal Disease
Clinicopathologic Presentation of Alport Syndrome and Collagen IV−Related Kidney Disease
Treatment of Alport Syndrome
Pierson Syndrome
LAMA5
Systemic Diseases With Glomerular Components
Fabry Disease
Galloway-Mowat Syndrome
Nonglomerular Diseases Appearing as Primary Glomerulopathies
Genetic Testing Considerations
Key References
References
44 Inherited Disorders of the Renal Tubule
Chapter Outline
Inherited Disorders Associated With Generalized Dysfunction of the Proximal Tubule (Renal Fanconi Syndrome)
Pathogenesis
Clinical Presentation of Renal Fanconi Syndrome
Aminoaciduria
Phosphaturia and Bone Disease
Renal Tubular Acidosis
Glucosuria
Polyuria, Sodium, and Potassium Wasting
Proteinuria
Hypercalciuria
Dent Disease
Pathogenesis
Clinical Presentation
Treatment
Oculocerebrorenal Dystrophy (Lowe Syndrome)
Pathogenesis
Clinical Presentation
Treatment
Mistargeting to Mitochondria of Peroxisomal EHHADH, an Enzyme Involved in Peroxisomal Oxidation of Fatty Acids
Idiopathic Causes of Renal Fanconi Syndrome
Cystinosis
Pathogenesis
Clinical Presentation
Treatment
Glycogenosis (Von Gierke Disease, OMIM #232200)
Pathogenesis
Clinical Presentation
Treatment
Tyrosinemia
Pathogenesis
Clinical Presentation
Treatment
Galactosemia
Pathogenesis
Clinical Presentation
Treatment
Wilson Disease
Pathogenesis
Clinical Presentation
Treatment
Hereditary Fructose Intolerance
Inherited Disorders of Renal Amino Acid Transport
Cystinuria
Pathogenesis
Clinical Presentation
Treatment
Diet
Decreasing Urine Cystine Saturation
Penicillamine
Surgical Management
Lysinuric Protein Intolerance
Pathogenesis
Clinical Presentation
Treatment
Hartnup Disorder
Pathogenesis
Clinical Presentation
Treatment
Iminoglycinuria
Dicarboxylic Aminoaciduria
Inherited Disorders of Renal Phosphate Transport
Renal Phosphate Excretion
Renal Phosphate Transporters
X-Linked Hypophosphatemic Rickets
Pathogenesis
Clinical Presentation
Treatment
Autosomal Dominant Hypophosphatemic Rickets
Autosomal Recessive Hypophosphatemic Rickets
Hereditary Hypophosphatemic Rickets With Hypercalciuria
Familial Tumoral Calcinosis
Hereditary Selective Deficiency of 1α,25(OH)2D3
Hereditary Generalized Resistance to 1α,25(OH)2D3
Resistance to Parathormone Action
Inherited Disorder of Urate Transport
Familial Renal Hypouricemia
Inherited Disorders of Renal Glucose Transport
Renal Glucosuria
Glucose–Galactose Malabsorption
Inherited Disorders of Acid–Base Transporters
Proximal Renal Tubular Acidosis
Sodium–Bicarbonate Symporter Mutations
Carbonic Anhydrase II Deficiency
Distal Renal Tubular Acidosis
Chloride–Bicarbonate Exchanger Mutations
Proton Atpase Subunit Mutations
Bartter and Gitelman Syndromes
Bartter Syndrome
Pathogenesis
Clinical Presentation
Treatment
Gitelman Syndrome
Pathogenesis
Clinical Presentation
Treatment
Inherited Disorders With Hypertension and Hypokalemia
Congenital Adrenal Hyperplasia
11β-Hydroxylase Deficiency
17α-Hydroxylase Deficiency
Liddle Syndrome
Pathogenesis
Clinical Presentation
Treatment
Apparent Mineralocorticoid Excess
Pathogenesis
Clinical Presentation
Treatment
Autosomal Dominant Early Onset Hypertension With Severe Exacerbation During Pregnancy
Glucocorticoid-Remediable Hyperaldosteronism
Pathogenesis
Clinical Presentation
Treatment
Familial Hyperaldosteronism Type II
Pseudohypoaldosteronism
Pseudohypoaldosteronism Type I
Pathogenesis
Clinical Presentation
Treatment
Pseudohypoaldosteronism Type II
Pathogenesis
Clinical Presentation
Treatment
Inherited Disorders of Renal Magnesium Processing
Familial Hypomagnesemia With Hypercalciuria and Nephrocalcinosis
Familial Hypomagnesemia With Secondary Hypocalcemia
Isolated Dominant Hypomagnesemia With Hypocalciuria
Ca2+/Mg2+-Sensing Receptor–Associated Disorders
Isolated Recessive Hypomagnesemia With Normocalciuria
Dominant and Recessive Hypomagnesemia
Diabetes Insipidus
Pathogenesis
The AVP–AVPR2–AQP Shuttle Pathway
Clinical Presentation and History of X-Linked Nephrogenic Diabetes Insipidus
Loss-of-Function Mutations of AQP2 (OMIM #107777)
Polyuria, Polydipsia, Electrolyte Imbalance, and Dehydration in Cystinosis
Polyuria in Hereditary Hypokalemic Salt-Losing Tubulopathies
Carrier Detection, Perinatal Testing, and Treatment
Key References
References
Board Review Questions
45 Cystic Diseases of the Kidney
Chapter Outline
Classification of Renal Cystic Diseases
Development of Renal Epithelial Cysts
Hereditary Cystic Kidney Disorders
Autosomal Dominant Polycystic Kidney Disease
Epidemiology
Genetics and Genetic Mechanisms
Pathogenesis
Pathology
Diagnosis
Renal Manifestations
Cyst Development and Growth
Renal Function Abnormalities
Hypertension
Pain
Chronic Kidney Disease and Renal Failure
Extrarenal Manifestations
Polycystic Liver Disease
Cysts in Other Organs
Vascular Manifestations
Cardiac Manifestations
Diverticular Disease
Bronchiectasis
Treatment
Hypertension
Pain
Cyst Hemorrhage
Cyst Infection
Nephrolithiasis
End-Stage Kidney Disease
Polycystic Liver Disease
Intracranial Aneurysm
Novel Therapies
Vasopressin V2 Receptor Antagonists.
Somatostatin Analogs.
Rapalogs.
Other Agents.
Clinical Trials and Renal Function
Autosomal Recessive Polycystic Kidney Disease
Epidemiology
Genetics
Pathogenesis
Pathology
Diagnosis
Manifestations
Treatment
Polycystic Kidney and/or Liver Diseases Associated With Altered Maturation of PKD Proteins in the Endoplasmic Reticulum
Tuberous Sclerosis Complex
Epidemiology
Genetics
Pathogenesis
Diagnosis
Manifestations
Treatment
Von Hippel–Lindau Syndrome
Epidemiology
Genetics
Pathogenesis
Diagnosis
Manifestations
Treatment
Autosomal Dominant Tubulointerstitial Kidney Disease
Autosomal Dominant Tubulointerstitial Kidney Disease-Hepatocyte Nuclear Factor-1Β–(ADTKD-HNF1B)
Familial Renal Hamartomas Associated With Hyperparathyroidism–Jaw Tumor Syndrome
Autosomal Recessive Ciliopathies With Interstitial Nephritis and Renal Cystic Disease
Nephronophthisis
Joubert Syndrome
Meckel Syndrome
Bardet–Biedl Syndrome
Alström Syndrome
Nephronophthisis Variants Associated With Skeletal Defects (Skeletal Ciliopathies)
Oro-Facial-Digital Syndrome Type 1
Renal Cystic Dysplasia
Multicystic Dysplastic Kidney
Other Cystic Kidney Disorders
Simple Cysts
Prevalence
Pathogenesis
Pathology
Diagnosis
Manifestations
Treatment
Localized or Unilateral Renal Cystic Disease
Medullary Sponge Kidney
Epidemiology
Pathogenesis
Pathology
Diagnosis
Manifestations
Treatment
Acquired Cystic Kidney Disease
Epidemiology
Pathogenesis
Pathology
Diagnosis
Manifestations
Treatment
Renal Cystic Neoplasms
Cystic Renal Cell Carcinoma
Multilocular Cystic Nephroma
Cystic Partially Differentiated Nephroblastoma
Mixed Epithelial and Stromal Tumor
Renal Cysts of Nontubular Origin
Cystic Disease of the Renal Sinus
Perirenal Lymphangiomas
Subcapsular and Perirenal Urinomas (Uriniferous Pseudocysts)
Pyelocalyceal Cysts
Key References
References
46 Primary and Secondary Hypertension
Chapter Outline
Hypertension Definitions
Evolution of Blood Pressure Goals
Epidemiology
Age and Hypertension
Gender and Hypertension
Race and Ethnicity and Hypertension
Blood Pressure Control Rates
Economics of Hypertension
Pathophysiology
Pressure Natriuresis and Salt Sensitivity
Genetics of Hypertension
Nonosmotic Sodium Storage
Renin-Angiotensin-Aldosterone System
Sympathetic Nervous System
Obesity
Natriuretic Peptides
The Endothelium
Arterial Stiffness in Hypertension
Role of the Immune System in Hypertension
Other Metabolic Peptides and Hypertension
Gut Microbiome
Clinical Evaluation
History and Physical Examination
Blood Pressure Measurement
Office Blood Pressure Measurement
Orthostatic Blood Pressure Measurement
Office Versus Out-of-Office Blood Pressure
Clinical Use of Ambulatory and Home Blood Pressure Monitoring
Integrating Out-of-Office Blood Pressure Into Clinical Practice
Laboratory and Other Complementary Tests
Echocardiography
Evaluation of Sodium and Potassium Intake
Renin Profiling
Systemic Hemodynamics and Extracellular Fluid Volume
Secondary Hypertension
Risk Factors and Epidemiology
Evaluation of Secondary Hypertension
Exacerbation of Preexisting Hypertension Attributed to Lifestyle Factors
Intrinsic Kidney Disease
Primary Hyperaldosteronism
Hyperaldosteronism Associated With Sleep-Disordered Breathing
Apparent Mineralocorticoid Excess States
Renovascular Hypertension
Pheochromocytoma
Hypercortisolism
Thyroid Dysfunction
Hyperparathyroidism, Calcium Intake, Vitamin D, and Hypertension
Coarctation of the Aorta
Acromegaly
Sleep Deprivation and Sleep-Disordered Breathing
Drug-Induced Hypertensiom
Hypertensive Urgency and Emergency
Goals of Antihypertensive Therapy
Blood Pressure Control and Chronic Kidney Disease Progression
Nondiabetic Chronic Kidney Disease
Modification of Diet in Renal Disease Study
African American Study of Kidney Disease and Hypertension
Ramipril Efficacy in Nephropathy Trial (REIN-2)
Systolic Blood Pressure Intervention Trial
Diabetic Kidney Disease
Antihypertensive Therapy in Older Adults
Clinical Trials in Older Adults
Nonpharmacologic Intervention in Older Adults
Pharmacologic Intervention in Older Adults
Blood Pressure Management in Patients Undergoing Dialysis
Management of Hypertension in Chronic Kidney Disease
Resistant Hypertension
References
Board Review Questions
47 Renovascular Hypertension and Ischemic Nephropathy
Chapter Outline
Introduction
Historical Perspective
Pathophysiology of Renovascular Hypertension and Ischemic Nephropathy
Renal Artery Stenosis Versus Renovascular Hypertension
Role of the Renin-Angiotensin System in One-Kidney and Two-Kidney Renovascular Hypertension
Mechanisms Sustaining Renovascular Hypertension
Renin-Angiotensin System
Phases of Development of Renovascular Hypertension
Mechanisms of Ischemic Nephropathy
Adaptive Mechanisms to Reduced Renal Perfusion
Mechanisms of Tissue Injury in Azotemic Renovascular Disease
Consequences of Restoring Renal Blood Flow
Renal Reperfusion Injury
Epidemiology of Renal Artery Stenosis and Renovascular Hypertension
Clinical Features
Renovascular Hypertension: Fibromuscular Disease Versus Atherosclerosis
Renal Artery Stenosis
Progressive Vascular Occlusion
Developments in Medical and Antihypertensive Drug Therapy
Changing Population Demographics
Role of Concurrent Diseases
Diagnostic Testing for Renovascular Hypertension and Ischemic Nephropathy
Goals of Evaluation
Diagnostic Tests
Imaging of the Renal Vasculature
Noninvasive Imaging
Doppler Ultrasound of the Renal Arteries.
Computed Tomography Angiography.
Magnetic Resonance Angiography.
Captopril Renography.
Invasive Imaging
Physiologic and Functional Studies of the Renin-Angiotensin System
Studies of Individual Renal Function.
Management of Renal Artery Stenosis and Ischemic Nephropathy
Overview
Medical Therapy of Renovascular Disease
Renal Artery Stenosis
Unilateral Versus Bilateral Renal Artery Stenosis
Unilateral Renal Artery Stenosis
Progressive Renal Artery Stenosis in Medically Treated Patients
Endovascular Renal Angioplasty and Stenting
Angioplasty for Fibromuscular Disease
Angioplasty and Stenting for Atherosclerotic Renal Artery Stenosis
Prospective Treatment Trials
Medical Therapy Compared With Angioplasty Plus Stents
Stents for Progression of Renal Insufficiency and Cardiovascular Outcomes
Complications of Renal Artery Angioplasty and Stenting
Renal Denervation
Surgical Treatment of Renovascular Hypertension and Ischemic Nephropathy
Predictors of Likely Benefit Regarding Renal Revascularization
Future Research in Renovascular Disease
Summary
Key References
References
Board Review Questions
48 Pregnancy and Kidney Disease
Chapter Outline
Key Points
Introduction
Physiologic Changes of Pregnancy
Hemodynamic and Vascular Changes of Normal Pregnancy
Renal Adaptation to Pregnancy
Respiratory Alkalosis of Pregnancy
Diabetes Insipidus of Pregnancy
Mechanism of Vasodilation in Pregnancy
Preeclampsia and HELLP Syndrome
Epidemiology and Risk Factors
Preeclampsia: Diagnosis and Clinical Features
Hypertension
Proteinuria
Edema
Uric Acid
Clinical Features of Severe Preeclampsia
Eclampsia
HELLP Syndrome
Maternal and Neonatal Mortality
Postpartum Recovery
Long-Term Cardiovascular and Renal Outcomes
Pathogenesis of Preeclampsia
The Role of the Placenta
Placental Vascular Remodeling
Maternal Endothelial Dysfunction
Hemodynamic Changes
Renal Changes
Cerebral Changes
Oxidative Stress and Inflammation
Immunologic Intolerance
Angiogenic Imbalance
Angiotensin-1 Receptor Autoantibodies
Screening
Prevention of Preeclampsia
Antiplatelet Agents
Calcium for the Prevention of Preeclampsia
Antioxidants and Nutritional Interventions
Low-Molecular-Weight Heparin
Management and Treatment of Preeclampsia
Timing of Delivery
Blood Pressure Management
Magnesium and Seizure Prophylaxis
Management of the HELLP Syndrome
Novel Therapies for Preeclampsia
Chronic Hypertension and Gestational Hypertension
Secondary Hypertension in Pregnancy
Approach to Management of Chronic Hypertension in Pregnancy
Goals of Therapy
Gestational Hypertension
Management of Hypertension in Pregnancy
Choice of Agents
Intravenous Agents for Urgent Blood Pressure Control
Antihypertensive Drugs in Breastfeeding
Acute Kidney Injury in Pregnancy
Acute Tubular Injury and Renal Cortical Necrosis
Acute Kidney Injury and Thrombotic Microangiopathy
Severe Preeclampsia
Acute Fatty Liver of Pregnancy
Thrombotic Thrombocytopenic Purpura
Hemolytic Uremic Syndrome
Obstructive Uropathy and Nephrolithiasis
Urinary Tract Infection and Acute Pyelonephritis
Chronic Kidney Disease in Pregnancy
Diabetic Nephropathy
Lupus Nephritis and Pregnancy
Kidney Biopsy in Pregnancy
Pregnancy in End-Stage Kidney Disease
Pregnancy in the Kidney Transplant Recipient
Fetal and Neonatal Outcomes
Timing of Pregnancy After Transplantation
Effect of Pregnancy on Renal Allograft Function
Management of Immunosuppressive Therapy in Pregnancy
Management of Acute Rejection in Pregnancy
Breastfeeding and Immunosuppressive Agents
Pregnancy Outcome Following Kidney Donation
Conclusion
Key References
References
Board Review Questions
49 Antihypertensive Therapy
Chapter Outline
Pharmacology of the Nondiuretic Antihypertensive Drugs
Angiotensin-Converting Enzyme Inhibitors
Class Mechanisms of Action
Class Members
Sulfhydryl Angiotensin-Converting Enzyme Inhibitors
Carboxyl Angiotensin-Converting Enzyme Inhibitors
Phosphinyl Angiotensin-Converting Enzyme Inhibitor
Class Renal Effects
Class Efficacy and Safety
Angiotensin II Type 1 Receptor Antagonists
Class Mechanisms of Action
Class Members
Biphenyl Tetrazole and Oxadiazole Derivatives
Nonbiphenyl Tetrazole Derivatives
Nonheterocyclic Derivatives
Class Renal Effects
Class Efficacy and Safety
β-Adrenergic Receptor Antagonists
Class Mechanisms of Action
Nonselective β-Adrenergic Antagonists
β1-Selective Adrenergic Antagonists
Nonselective β-Adrenergic Antagonists With α-Adrenergic Antagonism or Other Mechanisms of Antihypertensive Action
Class Renal Effects
Class Efficacy and Safety
Calcium Channel Blockers
Class Mechanisms of Action
Class Members
Benzothiazepines
Diphenylalkylamine
Dihydropyridines
Class Renal Effects
Class Efficacy and Safety
Central Adrenergic Agonists
Class Mechanisms of Action
Class Members
Class Renal Effects
Class Efficacy and Safety
Central and Peripheral Adrenergic Neuronal Blocking Agent
Mechanisms of Action and Class Member
Renal Effects
Efficacy and Safety
Direct-Acting Vasodilators
Class Mechanisms of Action
Class Members
Class Renal Effects
Class Efficacy and Safety
Endothelin Receptor Antagonists
Class Mechanism of Action and Class Members
Class Renal Effects
Moderately Selective Peripheral α1-Adrenergic Antagonists
Class Mechanisms of Action
Class Members
Class Renal Effects
Class Efficacy and Safety
Peripheral Α1-Adrenergic Antagonists
Class Mechanisms of Action
Class Members
Class Renal Effects
Class Efficacy and Safety
Renin Inhibitors
Class Mechanism of Action and Class Member
Class Renal Effects
Class Efficacy and Safety
Selective Aldosterone Receptor Antagonists
Class Mechanism and Class Members
Class Renal Effects
Class Efficacy and Safety
Tyrosine Hydroxylase Inhibitor
Mechanisms of Action
Class Member
Renal Effects
Efficacy and Safety
Selection of Antihypertensive Drug Therapy
Determination of Blood Pressure Goal
Single-Pill Combination Therapy
Choice of Appropriate Agents
Treatment of Older Patients
Treatment Based on Sex
Race and Ethnicity
Obese Patients
Treatment of Patients With Cardiovascular or Kidney Disease
Cardiovascular Disease
Kidney Disease
Strategies for Selecting the Optimal Combination Antihypertensive Therapy
Preferred Combinations
Renin–Angiotensin–Aldosterone System Inhibitors and Calcium Channel Blockers
Renin–Angiotensin–Aldosterone System Inhibitors and Thiazide-Type Diuretics
Acceptable Combinations
β-Blockers and Thiazide-Like Diuretics
Calcium Channel Blockers and Thiazide-Like Diuretics
Calcium Channel Blockers and β-Blockers
Dual Calcium Channel Blockade
Unacceptable or Ineffective Combinations
Dual Renin–Angiotensin Blockade
β-Blockers and Central Adrenergic Agonists
Bedtime Antihypertensive Dosing Versus Morning Dosing
Resistant Hypertension
Drug Treatment of Hypertensive Urgencies and Emergencies
Parenteral Direct-Acting Vasodilators
β1-Selective Adrenergic Antagonist
α1- and β-Adrenergic Antagonists
Central α2-Adrenergic Agonist
Angiotensin-Converting Enzyme Inhibitor
α-Adrenergic Antagonist
Calcium Channel Blockers
Dopamine D1–Like Receptor Agonist
Rapid-Acting Oral Drugs
Clinical Considerations in the Rapid Reduction of Blood Pressure
Acknowledgments
Key References
References
Board Review Questions
50 Diuretics
Chapter Outline
Key Points
Individual Classes of Diuretics
Carbonic Anhydrase Inhibitors
Sites and Mechanisms of Action
Pharmacokinetics
Clinical Indications
Adverse Effects
Osmotic Diuretics
Sites and Mechanisms of Action
Pharmacokinetics and Dosage
Clinical Indications
Adverse Effects
Loop Diuretics
Sites and Mechanisms of Action
Pharmacokinetics and Differences Between Drugs
Clinical Indications
Adverse Effects
Thiazides and Thiazide-Like Diuretics (Distal Convoluted Tubule Diuretics)
Sites and Mechanisms of Action
Pharmacokinetics of and Differences Among Thiazides
Clinical Indications and Adverse Effects
Distal Potassium-Sparing Diuretic Agents
Sites and Mechanisms of Action
Pharmacokinetics
Clinical Indications
Adverse Effects and Drug Interactions
Miscellaneous Agents
Dopaminergic Agents
Vasopressin Receptor Antagonists
Adenosine Type I Receptor Antagonists
Nesiritide
Neprilysin Inhibitors
Sodium Glucose-Linked Transporter 2 (SGLT2) Inhibitors
Novel Diuretics in Preclinical Development
Adaptation to Diuretic Therapy
Diuretic Braking Phenomenon
Humoral and Neuronal Modulators of the Response to Diuretics
Renin-Angiotensin-Aldosterone System
Eicosanoids
Arginine Vasopressin
Catecholamines and Sympathetic Nervous System
Atrial Natriuretic Peptide
Diuretic Resistance
Diuretic Combinations
Loop Diuretics and Thiazides
Loop Diuretics or Thiazides and Distal Potassium-Sparing Diuretics
Clinical Uses of Diuretics
Edematous Conditions
Heart Failure
Acute Decompensated Heart Failure
Acute Decompensated Heart Failure in Acute Coronary Syndrome
Chronic Heart Failure
Right Ventricular Failure
Cirrhosis of the Liver
Nephrotic Syndrome
Idiopathic Edema
Nonedematous Conditions
Hypertension
Acute Kidney Injury
Chronic Kidney Disease
Renal Tubular Acidosis
Hypercalcemia
Nephrolithiasis
Osteoporosis
Gitelman Syndrome
Diabetes Insipidus
Adverse Effects of Diuretics
Fluid and Electrolyte Abnormalities
Extracellular Volume Depletion and Azotemia
Hyponatremia
Hypokalemia
Hyperkalemia
Hypomagnesemia
Hypercalcemia
Acid-Base Changes
Metabolic Abnormalities
Hyperglycemia
Hyperlipidemia
Hyperuricemia
Other Adverse Effects
Impotence
Ototoxicity
Hazards in Pregnancy and Newborns
Vitamin B Deficiency
Drug Allergy
Malignancy
Adverse Drug Interactions
Key References
References
Board Review Questions
51 Mechanisms of Progression in Chronic Kidney Disease
Chapter Outline
Key Points
Introduction
Structural and Functional Adaptation of the Kidney to Nephron Loss
Alterations in Glomerular Physiology
Mediators of the Glomerular Hemodynamic Responses to Nephron Loss
Renin-Angiotensin-Aldosterone System
Endothelins
Natriuretic Peptides
Eicosanoids
Nitric Oxide
Bradykinin
Urotensin II
Adjustments in Renal Autoregulatory Mechanisms
Interaction of Multiple Factors
Renal Hypertrophic Responses to Nephron Loss
Whole-Kidney Hypertrophic Responses
Glomerular Enlargement
Mechanisms of Renal Hypertrophy
Solute Load
Renotropic Factors
Endocrine Effects
Growth Factors
Mesangial Cell Responses, a Unifying Hypothesis
Tubule Cell Responses
Adaptation of Specific Tubule Functions in Response to Nephron Loss
Adaptation in Proximal Tubule Solute Handling
Loop of Henle and Distal Nephron
Glomerulotubular Balance
Sodium Excretion and Extracellular Fluid Volume Regulation
Urinary Concentration and Dilution
Potassium Excretion
Acid-Base Regulation
Calcium and Phosphate
Long-Term Adverse Consequences of Adaptations to Nephron Loss
Hemodynamic Factors
Mechanisms of Hemodynamically Induced Injury
Mechanical Stress
Endothelial Cells
Mesangial Cells
Podocytes
Cellular Infiltration in Remnant Kidneys
Nonhemodynamic Factors in the Development of Nephron Injury Following Extensive Renal Mass Ablation
Proteinuria
Tubulointerstitial Fibrosis
Molecular Mediators of Renal Fibrosis
Hepatocyte Growth Factor
Bone Morphogenetic Protein-7
Micro Rnas
Oxidative Stress
Acidosis
Hypertrophy
Angiotensin II
Aldosterone
A Unified Hypothesis of Chronic Kidney Disease Progression
Insights From Modifiers of Chronic Kidney Disease Progression
Pharmacologic Inhibition of the Renin-Angiotensin- Aldosterone System
Arterial Hypertension
Dietary Protein Intake
Gender Differences
Nephron Endowment
Race and Ethnicity
Obesity and Metabolic Syndrome
Sympathetic Nervous System
Dyslipidemia
Calcium and Phosphate Metabolism
Hyperphosphatemia
Renal Calcium Deposition
Hyperparathyroidism
Activated Vitamin D Deficiency
Fibroblast Growth Factor 23
Anemia
Tobacco Smoking
Acute Kidney Injury
Future Directions
Key References
References
Board Review Questions
52 The Pathophysiology of Uremia
Chapter Outline
Solutes Cleared by the Kidney and Retained in Uremia
Individual Uremic Solutes
Urea
d–Amino Acids
Peptides and Proteins
Guanidines
Phenols and Other Aromatic Compounds
Indoles and Other Tryptophan Metabolites
Aliphatic Amines
Other Uremic Solutes
Solute Removal by Different Forms of Renal Replacement Therapy
Original Middle Molecule Hypothesis
Large Solutes—Changing Definition of “Middle Molecules”
Protein-Bound Solutes
Sequestered Solutes
Effects of Diet and Gastrointestinal Function
Solute Clearance by Organic Transport Systems
Metabolic Effects of Uremia
Oxidant Stress and the Modification of Protein Structure
Effects of Uremia
On Resting Energy Expenditure
On Carbohydrate Metabolism
On Lipid Metabolism
On Amino Acid and Protein Metabolism
Overall Nutrition
Signs and Symptoms of Uremia
Well-Being and Physical Function
Neurologic Function
Appetite, Taste, and Smell
Cellular Functions
Why Is the Glomerular Filtration Rate so Large?
Key References
References
53 Chronic Kidney Disease–Mineral Bone Disorder
Chapter Outline
Key Points
Pathophysiology of Chronic Kidney Disease-Mineral and Bone Disorder
Phosphorus and Calcium Homeostasis
Phosphorus Balance and Homeostasis
Calcium Balance and Homeostasis
Calcium-Sensing Receptor
Hormonal Regulation of Chronic Kidney Disease-Mineral and Bone Disorder
Parathyroid Hormone
Vitamin D
FGF-23 and Klotho
Bone Biology
Pathophysiology of Vascular Calcification
Cellular Transformation
Matrix Vesicles and Apoptosis
Inhibitors of Vascular Calcification
Fetuin-A
Matrix Gamma-Carboxyglutamate (GLA) Protein
Pyrophosphate
Osteoprotegerin
Integrated Regulation of Phosphorus and Calcium
PTH–FGF-23–Calcitriol Loop
Pi–PTH–FGF-23 Loop
Calcium–PTH–FGF-23 Loop
Diagnosis of Chronic Kidney Disease-Mineral and Bone Disorder
Measurement of the Biochemical Abnormalities in CKD-MBD
Parathyroid Hormone
Vitamin D
FGF-23
Soluble Klotho
Sclerostin
Bone-Specific Alkaline Phosphatase
Collagen-Based Bone Biomarkers
Tartrate-Resistant ACID Phosphatase 5b
Bone Biopsy Assessment of Bone in Chronic Kidney Disease-Mineral and Bone Disorder
Histomorphometry in Patients With CKD
The Spectrum of Bone Histomorphometry in CKD
TMV Classification
Noninvasive Assessment of Bone
Dual-Energy X-Ray Absorptiometry
Quantitative Computerized Tomography Techniques
Microcomputed Tomography and Micromagnetic Resonance Imaging
Assessment of Vascular Calcification
Clinical Consequences of the Abnormalities in Chronic Kidney Disease-Mineral and Bone Disorder
Biochemical Abnormalities
Phosphorus and Calcium
Parathyroid Hormone
Combination of Abnormalities of Calcium, Phosphorus, and Parathyroid Hormone
Fibroblast Growth Factor 23
Nutritional Vitamin D Deficiency
Fracture
Extraskeletal Calcification
Vascular Calcification in Patients With Chronic Kidney Disease
Chronic Kidney Disease-Mineral and Bone Disorder in Kidney Transplant Recipients
Biochemical Changes After Transplantation
Bone Changes After Transplantation
Vascular Calcification Changes After Transplantation
Summary
Key References
References
Board Review Questions
54 Cardiovascular Aspects of Kidney Disease
Chapter Outline
Introduction
Spectrum of Cardiovascular Pathology in Chronic Kidney Disease
Arterial Disease
Arterial Wall Thickening
Arterial Stiffening
Endothelial Dysfunction
Arterial Calcification
Cardiac Disease
Altered Cardiac Geometry
Impaired Angiogenesis
Myocardial Fibrosis
Changes to Left Ventricular Function
Valvular Diseases
Dysrhythmia
Clinical Manifestations of Cardiovascular Disease in Chronic Kidney Disease
Epidemiology of Cardiovascular Disease in Cardiovascular Disease
Association Between Kidney Function and Cardiovascular Disease
Association Between Albuminuria and Cardiovascular Disease
Kidney Disease as a Cause of Cardiovascular Disease
Blood Pressure
Dyslipidemia
Other Direct Risk Factors
Coagulation Defects
Anemia
Homocysteine
Chronic Kidney Disease and Mineral Bone Disorders
Phosphate
Fibroblast Growth Factor 23
Vitamin D
Parathyroid Hormone
Oxidative Stress and Inflammation
Uric Acid
Indirect Risk Factors: Causes of Kidney and Cardiovascular Disease
Diabetes Mellitus
Obesity
Cardiovascular Risk Prediction
Basic Risk Prediction Scores
Role of Estimated GFR in Risk Prediction
Use of Imaging and Other Assessments of Cardiovascular Function in Risk Prediction
Cardiovascular Risk Prevention
Smoking Cessation
Blood Pressure
Dyslipidemia
Tight Glycemic Control
Anemia
Homocysteine
Chronic Kidney Disease and Mineral Bone Disorders
Reducing Serum Phosphate
Vitamin D
Calcimimetics
Antiplatelet Therapy
Mineralocorticoid Antagonism
Dialysis Delivery
Conclusions
Key References
References
Board Review Questions
55 Hematologic Aspects of Kidney Disease
Chapter Outline
Key Points
Anemia of Kidney Disease
Definition and Prevalence of Anemia in Chronic Kidney Disease
Pathobiology of Anemia in Chronic Kidney Disease
Normal Erythropoiesis
Erythropoietin
The Roles of Iron, Folate, and Vitamin B12 in Erythropoiesis
Anemia of Chronic Kidney Disease
Erythropoietin Production and Kidney Disease
Shortened Red Cell Survival
Blood Loss
Uremic “Inhibitors” of Erythropoiesis
Iron Metabolism, Hepcidin, and Anemia of Chronic Disease
Inflammation and Anemia of Chronic Disease
Folic Acid, Vitamin D, and Zinc Deficiency
Aluminum Overload
Hormones, Parathyroid Hormone, and Marrow Fibrosis
Drugs
Association of Anemia With Adverse Outcomes
Erythrocytosis of Patients With Kidney Diseases
(Poly)Cystic Kidney Disease
Posttransplantation Erythrocytosis
Renal Artery Stenosis
Renal Tumors
Treatment of Renal Anemia
Erythropoiesis-Stimulating Agents
Epoetin
Darbepoetin Alfa
Methoxypolyethylene Glycol Epoetin Beta
Other Erythropoiesis-Stimulating Agents
Hypoxia-Inducible Factor Stabilizers
Initiation and Maintenance of Therapy
Iron Management
Markers of Iron Status
Serum Ferritin.
Serum Iron, Transferrin, and Transferrin Saturation.
Serum Transferrin Receptor.
Erythrocyte Ferritin Concentration
Erythrocyte Zinc Protoporphyrin Concentration.
Percentage of Hypochromic Red Blood Cells.
Reticulocyte Hemoglobin Content.
Bone Marrow Iron.
Liver Magnetic Resonance Imaging.
Iron Balance Considerations.
Intravenous Iron Therapy
Lower Molecular Weight Iron Dextran.
Iron Sucrose.
Ferric Gluconate.
Ferric Carboxymaltose.
Ferumoxytol.
Ferric Isomaltoside.
Side Effects of Intravenous Iron
Infection Risk and Intravenous Iron Therapy.
Iron Therapy in Patients With Chronic Kidney Disease.
Efficacy and Safety of Anemia Management With Erythropoiesis-Stimulating Agents and Iron
Trial Overview
Large Randomized Controlled Trials
Risk-Benefit Relationship and Target Hemoglobin Recommendations
Ferric Citrate–Based Phosphate Binding and Iron Metabolism in Chronic Kidney Disease
Red Blood Cell Transfusion
Disorders of Hemostasis in Chronic Kidney Disease
Bleeding and Chronic Kidney Disease
Pathophysiology
Diagnostic Studies
Treatment
Hypercoagulability and Chronic Kidney Disease
Evidence for Hypercoagulability in Chronic Kidney Disease
Pharmacologic Interventions
Heparin-Induced Thrombocytopenia
White Cell Function in Chronic Kidney Disease
Leukocyte (Monocyte) Activation
Leukocyte Functional Impairment
Markers of Leukocyte Activation
Key References
References
Board Review Questions
56 Endocrine Aspects of Chronic Kidney Disease
Chapter Outline
Pancreatic Hormonal Disorders: Insulin Resistance
Causes of Uremic Insulin Resistance
Insulin Resistance as a Risk Factor for Chronic Kidney Disease
Insulin Resistance and Cardiovascular Risk
Treatment of Insulin Resistance in Chronic Kidney Disease
Hypothalamopituitary Axis
Thyroid Hormonal Alterations
Causes of Thyroid Hormone Disturbances in Chronic Kidney Disease
Clinical Implications and Consequences of Thyroid Hormone Alterations in Chronic Kidney Disease
Growth Hormone
Resistance to Growth Hormone in Chronic Kidney Disease
Growth Failure in Children With Chronic Kidney Disease
Growth Hormone Treatment in Adult Patients With Chronic Kidney Disease
Growth Hormone/Insulin-Like Growth Factor-1 System and Kidney Function
Prolactin
Adrenal Glands
Adrenocorticotropic Hormone
Aldosterone and Cortisol
Adrenal Androgens
Gonadal Dysfunction
In Women
Endocrine Abnormalities
Clinical Manifestations
Treatment
Female Sex Hormones and Progression of Chronic Kidney Disease
In Men
Endocrine Abnormalities
Clinical Manifestations
Treatment
Male Sex Hormones and Progression of Chronic Kidney Disease
Vitamin D, Parathyroid Hormone, and Kidney Disease
Vitamin D and Parathyroid Hormone: Metabolism and Actions in Chronic Kidney Disease
Vitamin D Deficiency in Chronic Kidney Disease
Vitamin D Supplementation in Chronic Kidney Disease
Key References
References
Board Review Questions
57 Neurologic Aspects of Kidney Disease
Chapter Outline
Stroke
Epidemiology of Stroke in Patients With Chronic Kidney Disease and End-Stage Kidney Disease, and in Kidney Transplant Recipients
Stroke Prevention in Chronic Kidney Disease and End-Stage Kidney Disease
Hypertension
Diabetes Mellitus
Proteinuria
Atrial Fibrillation
Dyslipidemia
Nutritional Factors
Anemia
Disordered Mineral Metabolism
Homocysteine
Antiplatelet Agents
Carotid Stenosis
Dialysis-Associated Factors
Management of Acute Stroke in Chronic Kidney Disease and End-Stage Kidney Disease
Initial Evaluation
Neuroimaging
Intravenous Thrombolysis
Supportive Care
Disorders of Cognitive Function
Delirium Syndromes
Uremic Encephalopathy
Clinical Features
Pathophysiology
Treatment
Dialysis Disequilibrium
Clinical Features
Pathophysiology
Syndromes of Chronic Cognitive Impairment
Dialysis Dementia
Chronic Cognitive Impairment
Epidemiology
Risk Factors and Mechanisms
Evaluation
Management
Seizures
Epidemiology of Seizures in Patients With ESKD
Differential Diagnosis of Seizure in Patients With End-Stage Kidney Disease
Uremic Encephalopathy
Dialysis Disequilibrium
Posterior Reversible Encephalopathy Syndrome
Drugs and Intoxications
Use of Antiepileptic Drugs
First-Generation Antiepileptic Drugs
Second-Generation Antiepileptic Drugs
Neuropathy
Uremic Polyneuropathy
Mononeuropathy
Autonomic Neuropathy
Sleep Disorders
Prevalence of Sleep Complaints
Sleep Apnea
Epidemiology
Pathophysiology
Treatment
Restless Legs Syndrome
Periodic Limb Movements of Sleep
Key References
References
58 Dermatologic Conditions in Kidney Disease
Chapter Outline
Key Points
Skin Manifestations Secondary to Kidney Dysfunction
Signs and Symptoms
Pruritus
Xerosis
Acquired Ichthyosis
Pigmentary Alteration
Manifestations Somewhat Specific to Kidney Disease
Acquired Perforating Dermatosis
Calciphylaxis (Calcific Uremic Arteriolopathy)
Metastatic Calcification
Porphyria Cutanea Tarda
Pseudoporphyria
Eruptive Xanthomas
Pseudo–Kaposi Sarcoma
Iododerma
Manifestations Specific to Kidney Disease
Nephrogenic Systemic Fibrosis
Dialysis-Associated Steal Syndrome
Metastatic Renal Cell Carcinoma
Dialysis-Related Amyloidosis
Arteriovenous Shunt Dermatitis
Nail Changes Associated With Kidney Disease
Lindsay (Half-and-Half) Nail
Selected Conditions With Skin and Renal Involvement
Lupus Erythematosus
Leukocytoclastic Vasculitis
Henoch–Schönlein Purpura
Genodermatoses
Dermatologic Conditions That May Later Involve the Kidneys
Impetigo and Streptococcal Skin Infection
Key References
References
Board Review Questions
59 Classification and Management of Chronic Kidney Disease
Chapter Outline
Key Points
Introduction
Classification of Chronic Kidney Disease
Mechanisms of Disease Progression and the Rationale for Interventions to Achieve Renoprotection
Interventions for Slowing Progression of Chronic Kidney Disease
Lifestyle Interventions
Smoking Cessation
Weight Loss
Dietary Sodium Restriction
Dietary Protein Restriction
Glycemic Control in Persons With Diabetes
Antihypertensive Therapy
Antihypertensive Drugs
Trials of Low Versus Usual Targets for Lowering Blood Pressure
Pharmacologic Inhibition of the Renin–Angiotensin–Aldosterone System
Angiotensin-Converting Enzyme Inhibitors
Diabetic Kidney Disease
Nondiabetic Chronic Kidney Disease
Angiotensin Receptor Blockers
Diabetic Kidney Disease
Nondiabetic Chronic Kidney Disease
Angiotensin-Converting Enzyme Inhibitors Versus Angiotensin Receptor Blocker Treatment
Combination Treatment With Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers
Aldosterone Antagonism
DIRECT Renin Inhibitors
Sodium Glucose Cotransporter 2 (SGLT2) Inhibitors
Hyperuricemia
Treatment of Metabolic Acidosis
Proteinuria as a Therapeutic Target
Time Course for Proteinuria Response
Monitoring and Safety Considerations
Renal Dysfunction and Hyperkalemia Induced by Inhibitors of the Renin–Angiotensin–Aldosterone System
Strategy for Maximal Renoprotection: Aiming for Remission of Chronic Kidney Disease
Interventions to Reduce Cardiovascular Risk Associated With Chronic Kidney Disease
Interventions to Manage Complications of Chronic Kidney Disease
Anemia
Mineral and Bone Disorder
A Stepped Care Approach to Chronic Kidney Disease
Stages 1 and 2
Stage 3
Stage 4
Hepatitis B Vaccination
Preemptive Renal Transplantation
Stage 5
Key References
References
Board Review Questions
60 Dietary Approaches to Kidney Diseases
Chapter Outline
Key Points
Introductory Points
Diet Is a Key Component of the Management of Chronic Kidney Disease
Dietary Contributions to the Main Syndromes Which Cause CKD: Diabetes and Hypertension
Diabetes
Hypertension
Dietary Contributions to CKD Incidence and Progression
Dietary Factors Associated With Initiation of CKD
Dietary Factors Associated With Progression of Established CKD
Potential Mechanisms for Diet-Related Kidney Injury
Dietary Contributions to Increased CKD-Related Mortality
Component Considerations in the Dietary Management of CKD
Nutritional Components to Consider When Designing Dietary Management of CKD Patients
Overall Diet Considerations in the Management of CKD
Dietary Approaches to Prevention of the Conditions That Most Commonly Cause CKD in Developed Societies, Diabetes and Hypertension
Dietary Approaches to Minimizing the Risk for Initiation of CKD in Susceptible Individuals/Populations
Dietary Approaches to Minimizing the Risk for Progression of Established CKD to ESKD
Dietary Approaches to Reducing Mortality in Established CKD
General Dietary Management of Patients With CKD
Dietary Approaches to Managing Some CKD-Related Complications
Considerations for Enabling CKD Patients to Eat a More Plant-Based Diet
Future Research Directions
Key References
References
Board Review Questions
61 Drug Dosing Considerations in Patients With Acute Kidney Injury and Chronic Kidney Disease
Chapter Outline
Key Points
Effects of AKI and CKD on Drug Disposition
Absorption
Distribution
Metabolism
Alterations of Cytochrome P450 Enzyme Activity
Renal Excretion
Pharmacogenomics
Pharmacodynamics
Assessment of Kidney Function
Chronic Kidney Disease
Pediatrics
Acute Kidney Injury
Patients Receiving Dialysis
Drug Dosing Considerations
Patients With Chronic Kidney Disease
Goals of Therapy
Individualization of the Drug Dosage Regimen
Measurement of Therapeutic Drug Levels
Patients With Acute Kidney Injury
Loading Dose
Maintenance Dose
Patients Undergoing Hemodialysis
Assessment of the Impact of Hemodialysis
Patients Receiving Continuous Renal Replacement Therapy
Patients Undergoing Peritoneal Dialysis
Clinical Bottom Line
Key References
References
Board Review Questions
62 Supportive Care in Advanced Chronic Kidney Disease
Chapter Outline
Key Points
Defining Kidney Supportive Care
Key Components of Kidney Supportive Care
Culturally Competent Shared Decision Making
Prognostication
Symptom Assessment and Management
Chronic Pain Management
Special Considerations at the End of Life
Advance Care Planning
Conservative Kidney Management
Palliative Dialysis
Withdrawal of Dialysis
Early Identification of Patients Most Likely to Benefit From Supportive Care Services
Summary
Key References
References
Board Review Questions
63 Hemodialysis
Chapter Outline
The Hemodialysis Population
Incidence and Prevalence
Causes of End-Stage Kidney Disease
Mortality
Transition From Chronic Kidney Disease, Stage 5
Vascular Access
Background
Types of Vascular Access
Arteriovenous Fistulas
Arteriovenous Grafts
Central Venous Catheters
Maintenance of Vascular Access Function
Monitoring and Surveillance
Prophylactic Therapy for Access Maintenance
Vascular Access Timing and Decision Making
General Principles of Hemodialysis: Physiology and Biomechanics
Native Kidney Versus Artificial Kidney
Clearance
Clearance Versus Removal Rate
Serum Urea Concentration Versus Urea Clearance
Factors That Affect Clearance in a Flowing System
Dialysance
Determinants of Clearance
Dialyzer Clearance Versus Whole-Body Clearance
Effect of Red Blood Cells Passing Through the Dialyzer
Sequestration in Remote Compartments
Components of the Extracorporeal Circuit
Blood Circuit
Hemodialyzers
Membrane Composition
Membrane Biocompatibility
Membrane Permeability and Surface Area
High-Efficiency and High-Flux Dialyzers
Convection Versus Diffusion
Dialysate Circuit
Online Monitoring
Monitoring Clearance
Monitoring Hematocrit and Relative Blood Volume
Computer Controls
Dialysate
Water Treatment
Hazards Associated With Dialysis Water
Essential Components of Water Purification
Microbiology of Hemodialysis Systems
Monitoring Water Quality
Hemodialysis Adequacy
Historical Perspectives
Uremia: the Syndrome Reversed by Dialysis Therapy
Measuring Hemodialysis Adequacy
Importance of the Postdialysis Concentration
Solute Generation
Urea Volume
Treatment Time
Alternative Measures of Dialysis
Urea Reduction Ratio
Conductivity Clearance
Comparison of Hemodialysis and Peritoneal Dialysis Doses
Standard Clearance and Standard Kt/V
Nocturnal Hemodialysis and Home Hemodialysis
Short Daily Hemodialysis
Accounting for Native Kidney Function
The Dialysis Prescription
Goals of Hemodialysis
Hemodialysis Session Length and Frequency
Dialyzer Choice
Blood and Dialysate Flow Rates
Anticoagulation
Dialysate Composition
Sodium
Potassium
Calcium
Magnesium
Bicarbonate
Glucose
Dialysate Temperature
Ultrafiltration Rate and Dry Weight
Reuse
Management of Patients on Maintenance Hemodialysis
End-Stage Kidney Disease
Anemia
Principles of Erythropoiesis-Stimulating Agent Use
Hemoglobin Target
Iron Therapy
Hyporesponsiveness to Erythropoiesis-Stimulating Agent Therapy
Nutrition
Markers of Nutrition
Management of Protein Energy Wasting
Vitamins and Trace Elements
Mineral Metabolism–Related Issues
Vascular Calcification
Calcific Uremic Arteriolopathy
Cardiovascular Disease
Traditional Cardiovascular Risk Factors
Nontraditional Cardiovascular Risk Factors
Diagnosis and Treatment
Hypertension
Immune Disorders and Infection
Role of the Vascular Access and Hemodialysis Procedure
Uremia-Induced Immune Disorder
Infections and Response to Vaccination
Primary Care Management
Complications for Patients on Maintenance Hemodialysis
Hypotension
Ultrafiltration
Dialysate Factors
Management
Muscle Cramps
Dialysis Disequilibrium Syndrome
Cardiac Events
Arrhythmias, Myocardial Stunning, and Death
Pericardial Disease
Reactions to Dialyzers
Other Complications
Key References
References
64 Peritoneal Dialysis
Chapter Outline
Peritoneal Membrane Anatomy and Structure
Peritoneal Transport Physiology
Evaluation of Peritoneal Solute and Water Transfer Rate
The Peritoneal Catheter and Access
Catheter-Related Complications
Peritoneal Dialysis Solutions
Icodextrin PD Solution
Low Glucose-Degradation Product Glucose-Based Solutions
Bicarbonate-Based PD Solution
Glucose-Sparing Regimens
Peritoneal Dialysis Modalities
Dialysis Adequacy
Indicators to Evaluate Dialysis Adequacy
Determinants of Solute Clearance and Fluid Removal in Peritoneal Dialysis
Patient-Related Factors
Volume of Distribution and Body Surface Area
Peritoneal Transport Type
Prescription-Related Factors
Frequency of Exchanges
Increase in Volume Exchange
Increase in Solution Osmolality
Clearance Targets and Clinical Outcomes
Nutrition and Peritoneal Dialysis
Nutritional Counseling and Nutrient Supplements
Dialysis Solutions With Amino Acids
Reversible Causes of Anorexia
Metabolic Acidosis
Anabolic Hormones
L-Carnitine
Inflammation and Peritoneal Dialysis
Residual Kidney Function and Peritoneal Dialysis
Measures to Preserve Residual Kidney Function
Cardiovascular Disease in Peritoneal Dialysis
Management of Cardiovascular Disease in Peritoneal Dialysis
Peritonitis
Definition, Diagnosis, and Clinical Course
Peritonitis Treatment
Initial Empiric Therapy
Route and Schedule of Administration
Specific Antibiotic Treatment
Gram-Positive Bacteria
Gram-Negative Bacteria
Polymicrobial Peritonitis
Fungal Peritonitis
Mycobacterial Peritonitis
Catheter Removal in Peritonitis
Peritonitis Prevention
Noninfectious Complications of Peritoneal Dialysis
Mechanical Complications
Metabolic Complications
Encapsulating Peritoneal Sclerosis
Patient Outcomes With Peritoneal Dialysis
Economics and Cost Effectiveness of Peritoneal Dialysis
Key References
References
Board Review Questions
65 Critical Care Nephrology
Chapter Outline
Key Points
Acute Kidney Injury in the Context of Critical Illness
Liver Failure
Acute Respiratory Distress Syndrome
Heart Failure
Sepsis
Fluid Management and Its Impact on Acute Kidney Injury
RENAL Replacement Therapy in the Intensive Care Unit
Goals of Care
Indications for Commencing RENAL Replacement Therapy
RENAL Replacement Therapy Modality
Intermittent Hemodialysis
Continuous RENAL Replacement Therapy
Sustained Low-Efficiency Dialysis
Impact of Modality on Clinical Outcomes
Continuous RENAL Replacement Therapy Versus Intermittent Hemodialysis
Continuous RENAL Replacement Therapy Versus Sustained Low-Efficiency Dialysis
Mode of Clearance
Intensity of RENAL Replacement Therapy
Anticoagulation
Fluid Balance, Ultrafiltration, and Maintenance of Hemodynamic Stability
Vascular Access Considerations
Drug Dosing Considerations
Key References
References
Board Review Questions
66 Plasmapheresis
Chapter Outline
Key Points
Clinical Relevance
Historical Perspective
General Principles of Therapeutic Plasma Exchange
Plasmapheresis Use in Renal Disease
Anti–Glomerular Basement Membrane Disease
Rapidly Progressive Glomerulonephritis
Lupus Nephritis
Mixed Cryoglobulinemia
Kidney Failure Associated With Multiple Myeloma and Other Hematologic Disorders
Syndromes of Thrombotic Microangiopathy
Kidney Transplantation
Recurrent Focal Segmental Glomerulosclerosis
ABO-Incompatible Kidney Transplantation
Positive T Cell Crossmatch
Acute Humoral Rejection
Other Renal Diseases
Therapeutic Plasma Exchange and Nonrenal Disease
Guillain-Barré Syndrome
Chronic Inflammatory Demyelinating Polyneuropathy
Myasthenia Gravis
Familial Hypercholesterolemia
Toxins and Drugs
Pregnancy and Therapeutic Plasma Exchange
Technical Aspects
Plasma Separation Techniques
Other Separation Modalities
Venous Access
Anticoagulation
Replacement Fluid
Complications
Conclusion
Key References
References
Board Review Questions
67 Enhanced Elimination of Poisons
Chapter Outline
Overview of Corporeal Treatments for Enhanced Elimination of Poisons
Forced Diuresis
Urinary Alkalinization
Fecal Elimination Enhancement
Principles and Factors Influencing Poison Removal During Extracorporeal Treatments
Poison-Related Factors
Molecular Size
Protein Binding
Endogenous Clearance
Volume of Distribution
Available Extracorporeal Treatments to Enhance Elimination of Poisons
Intermittent Hemodialysis
Hemoperfusion
Hemofiltration
Combined Therapies
Continuous Renal Replacement Therapy
Peritoneal Dialysis
Therapeutic Plasma Exchange and Plasmapheresis
Exchange Transfusion
Extracorporeal Liver Assist Devices (Albumin Dialysis)
General Indications for Extracorporeal Removal of Poisons
Technical Considerations
Vascular Access
Choice of Hemodialyzer, Filter, and Adsorber
Anticoagulation
Blood, Dialysate, and Effluent Flow
Dialysate Composition
Duration of Extracorporeal Treatment
Patient Disposition
Rebound
Poisons Amenable to Extracorporeal Elimination
Toxic Alcohols: Ethylene Glycol, Methanol, Isopropanol
Toxicology and Toxicokinetics
Clinical Presentation
Diagnostic Testing
Treatment
Salicylic Acid
Toxicology and Toxicokinetics
Clinical Presentation and Diagnostic Testing
Treatment
Lithium
Toxicology and Toxicokinetics
Clinical Presentation and Diagnostic Testing
Treatment
Valproic Acid
Toxicology and Toxicokinetics
Clinical Presentation and Diagnostic Testing
Treatment
Carbamazepine
Toxicology and Toxicokinetics
Clinical Presentation and Diagnostic Testing
Treatment
Barbiturates
Toxicology and Toxicokinetics
Clinical Presentation and Diagnostic Testing
Treatment
Phenytoin
Toxicology and Toxicokinetics
Clinical Presentation and Diagnostic Testing
Treatment
Metformin
Toxicology and Toxicokinetics
Clinical Presentation and Diagnostic Testing
Treatment
Paraquat
Toxicology and Toxicokinetics
Clinical Presentation and Diagnostic Testing
Treatment
Theophylline
Toxicology and Toxicokinetics
Clinical Presentation and Diagnostic Testing
Treatment
Acetaminophen
Toxicology and Toxicokinetics
Clinical Presentation and Diagnostic Testing
Treatment
Methotrexate
Toxicology and Toxicokinetics
Clinical Presentation and Diagnostic Testing
Treatment
Other Factors
Conclusion
Key References
References
Board Review Questions
68 Interventional Nephrology
Chapter Outline
Introduction
Overview of Vascular Access for Dialysis
Interventional Nephrology in Maintenance of Hemodialysis Vascular Access
Biology and Pathogenesis of Vascular Access Stenosis in AV Fistulas and AV Grafts
Preoperative Vascular Mapping
Technical Procedure: Sonographic Preoperative Vascular Mapping
Procedures Involving AV Grafts
Surveillance for Graft Stenosis
Angioplasty of AV Graft Stenosis
Technical Procedure: Percutaneous Graft Angioplasty
Thrombectomy of Arteriovenous Grafts
Technical Procedure: Percutaneous ArterioVenous Graft Thrombectomy
Deployment of Stents for AV Graft Stenosis/Thrombosis
Technical Procedure: Percutaneous Deployment of Stent
Procedures Involving AV Fistulas
Salvage of Immature AV Fistulas
Technical Procedure: Salvage of Immature AV Fistulas
a. Angioplasty of Stenotic Lesions
b. Ligation of Accessory Veins
Percutaneous Transluminal Angioplasty (PTA) of AV Fistulas
Technical Procedure: Angioplasty of AV Fistulas
Percutaneous Mechanical Thrombectomy and Thrombolysis of AV Fistulas
Technical Procedure: Percutaneous Thrombectomy of AV Fistulas
Novel Techniques for Treatment of Severe Stenotic Lesions
Cutting Balloon
Cryoplasty Balloon
Local Perivascular Modalities
Endovascular Proximal Forearm Arteriovenous Fistula for Hemodialysis Access
Central Vein Stenosis
Access-Induced Hand Ischemia
Indwelling Hemodialysis Catheters
Non-Tunneled Temporary Hemodialysis Catheters
Technical Procedure: Insertion of Temporary Dialysis Catheters
Tunneled Hemodialysis Catheters
Technical Procedure: Insertion of Tunneled Hemodialysis Catheters
Less Common Locations for Tunneled Hemodialysis Catheters
Exchange of Tunneled Hemodialysis Catheters
Peritoneal Dialysis Catheter Procedures
Technical Procedure: Insertion of Peritoneal Catheters by Fluoroscopic and Ultrasound Technique
Technical Procedure: Insertion of Peritoneal Catheters by Peritoneoscopic Technique
Technical Procedure: Insertion of Peritoneal Catheters by PreSternal Catheter Placement
Percutaneous Kidney Biopsy (see also Chapter 26)
Technical Procedure: Percutaneous Kidney Biopsy Under Real-Time Ultrasound Guidance
Radiation and Personal Safety
Key References
References
Board Review Questions
69 The Immunobiology of Transplantation
Chapter Outline
Key Points
Mechanisms Involved in Allorecognition
Antigen Presentation Pathways
Direct Pathway
Indirect Pathway
Semidirect Pathway and Cross-Dressing
T-Cell Cosignaling Pathways
T-Cell Phenotypes
B Cells and Antibody Production
Antihuman Leukocyte Antigen Antibodies and Graft Injury
Complement Activation
Antibody-Dependent Cytotoxicity
Endothelial Activation
Other Transplant-Relevant Antigens and Antibodies
Interactions Between Ischemia-Reperfusion and Autoantibodies
Interactions Between Alloantibodies and Autoantibodies
Mechanistic Effect of Non–Human Leukocyte Antigen Antibodies
Histocompability Testing for the Kidney Transplant Candidate and Recipient
Human Leukocyte Antigen Typing
Context
Human Leukocyte Antigens
Human Leukocyte Antigen Typing Methods
Serologic Methods
Molecular Methods
Interpreting Human Leukocyte Antigens Typing Results
Nomenclature—Alleles and Antigens
Matching and Mismatching of Alleles, Antigens and Epitopes
Limitations of Human Leukocyte Antigen Typing Methods
Using Human Leukocyte Antigen Typing Results in Kidney Transplantation
Interpreting the Transplant Candidate’s Antibody Profile
Clinical Estimate of Immunogenicity of Human Leukocyte Antigen Mismatches
Avoidance of Unacceptable Donor Antigens/Alleles
Donor Data Supporting Calculated Panel Reactive Antibody Calculators
Human Leukocyte Antigen Antibody Screening and Identification
Context
Antibody Detection and Identification Methods
Serology
Solid-Phase Human Leukocyte Antigen Antibody Screening
Solid-Phase Human Leukocyte Antigen Antibody-Specificity Testing
Complement-Binding Solid-Phase Assays
Non-Human Leukocyte Antigen Antibodies
Interpreting Solid-Phase Human Leukocyte Antigen Antibody Tests
General Interpretation
Antibodies Reported at the Antigen Level
Allele-Specific Antibodies
Alpha/Beta Antibodies
Calculated Panel Reactive Antibody (or Equivalent) Determination
Limitations of Human Leukocyte Antigen Antibody Testing
Defining a Positive Bead
Defining Immunologic Relevance
Naturally Occurring Antibodies
Antibody Can Be Bound to the Allograft
Complement Fixing Assays
Generalizability of Calculated Panel Reactive Antibody
Using Human Leukocyte Antigen Antibody Testing in Kidney Transplantation
On the Waitlist
At the Time of Transplant Offer: Virtual Crossmatching
Posttransplant Antibody Monitoring
Donor-Specific (Cell-Based) Crossmatching
Context
Crossmatch Methods
Complement-Dependent Cytotoxicity
Antihuman Globulin Enhanced Complement-Dependent Cytotoxicity
Flow Cytometry Crossmatch
Interpreting Cell-Based Crossmatch Results
Limitations of Cell-Based Crossmatch
Complement Dependence for Detecting Human Leukocyte Antigen Antibodies
Immunologically Irrelevant Non–Human Leukocyte Antigen Targets on Cells
Drug Interference
B-Cell False-Positive Crossmatch
Increasing Sensitivity May Reduce Predictive Value
Laboratory Variability
Using the Cell-Based Crossmatch in the Modern Era
The Evolving Role of Histocompatibility Consultation
Kidney Allograft Rejection
Acute Cellular and Antibody-Mediated Rejection
Chronic Allograft Injury
Chronic Active Cellular and Antibody-Mediated Rejection
Mechanisms of Action of Immunosuppressive Drugs
Induction Agents
Polyclonal Antibodies
Monoclonal Antibodies
Anti-IL-2R Antibodies
Alemtuzumab
Maintenance Immunosuppressive Drugs
Calcineurin Inhibitors
Differences Between Taccolimus and Cyclosporine
Mycophenolic Acid
Azathioprine
Mammalian Target of Rapamycin Inhibitors
Corticosteroids
Belatacept
Other Immunosuppressive Agents Used in the Field of Kidney Transplantation
Rituximab
Bortezomib
Eculizumab
Tocilizumab
Concluding Remarks
Key References
References
Board Review Questions
70 Clinical Management of the Adult Kidney Transplant Recipient
Chapter Outline
The Transplant Surgery Procedure
Live Donor Nephrectomy
Handling and Preservation of the Donor Kidney
Surgical Complications of the Transplant Procedure
Vascular Complications
Hemorrhage
Arterial Thrombosis
Venous Thrombosis
Lymphocele
Currently Used Immunosuppressive Agents in Kidney Transplantation
Overview
Induction Therapies
Lymphocyte-Depleting Agents
Polyclonal T-Cell Depleting Antibodies
Monoclonal T-Cell Depleting Antibody
Anti-CD52 Antibody
Interleukin-2 Receptor Antagonist (IL-2-RA)
Anti-CD20 Antibodies
Intravenous Immunoglobulin (IVIg)
Maintenance Immunosuppressive Agents
Calcineurin Inhibitors (CNIs)
Cyclosporine
Tacrolimus
Calcineurin-Inhibitor Target Levels
AntiProliferative Agents
Azathioprine
Mycophenolate Acid
Target-of-Rapamycin Inhibitors
Co-Stimulatory Signal Blockers
Corticosteroids
Immunosuppression at Our Institution
PreFormed Donor-Specific Antibody With a Negative Flow Crossmatch
Desensitization
ABO Incompatible Transplantation
Evaluation of the Recipient Immediately Before the Transplant
Assessing Compatibility and Immunological Risk
Donor Immune Status and Crossmatch
Medical Status
Evaluation of the Recipient Immediately After the Transplant
Management of Allograft Dysfunction
Immediate Posttransplant Period (First Week)
Delayed Graft Function
Causes of Delayed Graft Function
Ischemic Acute Tubular Necrosis
Hyperacute Rejection
Accelerated Rejection Superimposed on Acute Tubular Necrosis
Acute Cyclosporine or Tacrolimus Nephrotoxicity Superimposed on Acute Tubular Necrosis
Vascular and Urologic Complications of Surgery
Outcome and Significance of Delayed Graft Function
Early Posttransplant Period (First Six Months)
Prerenal Renal Dysfunction in the Early Posttransplant Period
Hypovolemia and Drugs
Renal Vessel Thrombosis
Intrarenal Dysfunction in the Early Posttransplant Period
Acute Rejection
T-Cell Mediated Rejection.
Refractory T-Cell Mediated Rejection.
Active Antibody-Mediated Rejection.
Significance of Acute Rejection
Acute Calcineurin Inhibitor Nephrotoxicity.
Distinguishing Acute Calcineurin Inhibitor Nephrotoxicity and Acute Rejection.
Monitoring.
Acute Thrombotic Microangiopathy
Acute Pyelonephritis
Acute Allergic Interstitial Nephritis
Early Recurrence of Primary Disease
Primary Focal Segmental Glomerulosclerosis.
Antiglomerular Basement Membrane Disease.
Hemolytic-Uremic Syndrome/Thrombotic Thrombocytopenia Purpura (HUS/TTP).
Postrenal Dysfunction in the Early Posttransplant Period
Urine Leaks
Urinary Tract Obstruction
Late Posttransplant Period
Late Acute Allograft Dysfunction
Late Acute Rejection
Late Acute Calcineurin Inhibitor Nephrotoxicity
Transplant Renal Artery Stenosis
Renal Artery Stenosis.
Infections Causing Late Acute Allograft Dysfunction
Human Polyomavirus Infection.
Hepatitis C.
Drug and Radiocontrast Nephrotoxicity
Late Allograft Dysfunction and Late Allograft Loss
Chronic ABMR.
Calcineurin Inhibitor Toxicity.
Recurrence of Primary Disease
IgA Glomerulonephritis
Lupus Nephritis
Granulomatosis With Polyangiitis and Microscopic Polyangiitis
Membranoproliferative Glomerulonephritis (MPGN)
Membranous Nephropathy
Comparative Transplant Outcomes in Patients With ESRD From Glomerulonephritides
Diabetic Nephropathy
Assessing Outcomes in Kidney Transplantation
Actual and Actuarial Allograft and Patient Survival
Survival Benefits of Kidney Transplantation
Short-Term Outcomes in Kidney Transplantation
Long-Term Outcomes in Kidney Transplantation
Factors Affecting Kidney Allograft Survival
Donor-Recipient Factors
Delayed Graft Function
Human Leukocyte Antigen Matching
Cytomegalovirus Status of Donor and Recipient
Timing of Transplantation
Center Effect
Donor Factors
Donor Source: Deceased Versus Living Donor
Donor Age
Donor Sex
Donor Race/Ethnicity
Donor Nephron Mass
Cold Ischemia Time
Expanded Criteria Donors and Kidney Donor Profile Index
Donation After Cardiac Death
Recipient Factors
Recipient Age
Recipient Race/Ethnicity
Recipient Sex
Recipient Sensitization
Acute Rejection
Recipient Immunosuppression
Recipient Compliance
Recipient Body Size
Recipient Diabetes Mellitus
Recipient History of Hepatitis C
Improving Kidney Allograft Outcomes: Matching Kidney and Recipient Risk
Medical Management of the Transplant Recipient
Electrolyte Disorders
Hypercalcemia and Hypophosphatemia
Hyperkalemia
Metabolic Acidosis
Other Electrolyte Abnormalities
Bone Disorders After Kidney Transplantation
Hyperparathyroidism
Gout
Calcineurin Inhibitor–Associated Bone Pain
Osteonecrosis
Osteoporosis
Posttransplant Diabetes Mellitus
Cardiovascular Disease
Smoking
Hypertension
Proteinuria
Hyperlipidemia
Hyperhomocysteinemia
Cancer After Kidney Transplantation
Skin and Lip Cancers
Anogenital Cancers
Kaposi’s Sarcoma
Posttransplant Lymphoproliferative Disorder
Cancer Screening
Infectious Complications of Kidney Transplantation
Infections in the First Month
Infections From 1 to 6 Months After Transplant
Infections More Than 6 Months After Transplant
Cytomegalovirus
Pneumocystosis
Immunization in Kidney Transplant Recipients
Summary
Transplant Issues in Specific Patient Groups
Transplantation in Patients With Diabetes
Kidney-Pancreas Transplantation
Kidney Transplantation in Patients With Human Immunodeficiency Virus Infection
Pregnancy in the Kidney Transplant Recipient
Surgery in the Kidney Transplant Recipient
Allograft Nephrectomy
Nontransplant-Related Surgery or Hospitalization
The Patient With the Failing Kidney
Transplantation/Immunosuppression: the Future
Conclusion
Key References
References
Board Review Questions
71 Considerations in Living Kidney Donation
Chapter Outline
Key Points
Introduction
Considerations for the Kidney Transplant Recipient
Evaluation and Selection of the Living Kidney Donor Candidate
Kidney Function
Albuminuria
Hematuria
Kidney Stones
Hyperuricemia, Gout, and Metabolic Bone Disease
Blood Pressure
Metabolic and Lifestyle Risk Factors
Screening for Transmissible Infections
Cancer Screening
Genetic Kidney Diseases
Pregnancy
Psychosocial Assessment
Kidney Paired Donation and Incompatible Living Donor Transplants
Donor Nephrectomy Approaches
Laparoscopic Versus Open Donor Nephrectomy
Left Versus Right Donor Nephrectomy
Living Kidney Donor Follow-Up
Risks and Outcomes of Living Kidney Donation
Perioperative Mortality and Complications
Long-Term Mortality
Kidney Function
End-Stage Kidney Disease
Proteinuria
Hypertension
Cardiovascular Events
Maternal and Fetal Complications
Ethical, Legal, and Policy Considerations
Key References
References
Board Review Questions
72 Diseases of the Kidney and Upper Urinary Tract in Children
Chapter Outline
The Spectrum of Kidney and Urinary Tract Disorders in Children
Evaluation of Kidney Function in Children
Congenital Anomalies of the Kidney and Urinary Tract
Clinical Classification of Kidney Malformation
Epidemiology of Congenital Anomalies of the Kidney and Urinary Tract
Pathogenesis of Congenital Anomalies of the Kidney and Urinary Tract
Mechanisms of Inheritance
Molecular Pathogenesis
Ureteric Budding, ROBO2, and BMP4
Ureteric Branching, PAX2, and RET
Control of GDNF Expression in the Metanephric Mesenchyme: SALL1, EYA1, and SIX1
Hedgehog Signaling, GLI3 Repressor, and Congenital Anomalies of the Kidney and Urinary Tract
The Medulla and Glypican-3
TCF2, MODY5, and Sporadic Forms of Congenital Anomalies of the Kidney and Urinary Tract
Tubular Dysgenesis and Mutations of Ras System Elements
CHD1L, CHD7, and CHARGE Syndrome
DSTYK and Congenital Anomalies of the Kidney and Urinary Tract
Copy Number Variants, Congenital Anomalies of the Kidney and Urinary Tract, and Neuropsychiatric Disorders
The Environment in Utero and Congenital Anomalies of the Kidney and Urinary Tract
Functional Consequences of Congenital Anomalies of the Kidney and Urinary Tract
Clinical Presentation of Congenital Anomalies of the Kidney and Urinary Tract
Clinical Presentation in the Fetus
Clinical Presentation of Specific Forms of Congenital Anomalies of the Kidney and Urinary Tract
Renal Agenesis
Renal Dysplasia
Double Collecting System
Renal Ectopy
Renal Fusion
Clinical Management of Congenital Anomalies of the Kidney and Urinary Tract
Overall Approach to Management of Congenital Anomalies of the Kidney and Urinary Tract in Utero and in the Immediate Postnatal Period
Management of Specific Types of Congenital Anomalies of the Kidney and Urinary Tract
Renal Dysplasia
Renal Ectopy and Fusion
Long-Term Outcomes of Renal Malformation
Glomerular Diseases
Nephritic Syndrome and Related Diseases
Differential Diagnosis of Glomerular Hematuria
Alport Syndrome and Thin Basement Membrane Nephropathy
Pathogenesis
Clinical Manifestations
Thin Basement Membrane Nephropathy
Establishing the Diagnosis of Alport Syndrome and Thin Basement Membrane Nephropathy
Treatment
Nephrotic Syndrome
Clinical Classification and Definitions
Epidemiology
Pathogenesis
Clinical Presentation
Consideration of Renal Biopsy
Histological Classification
Treatment of Nephrotic Syndrome
Steroid-Sensitive Nephrotic Syndrome
Steroid-Dependent and Frequent Relapsing Nephrotic Syndrome
Steroid-Resistant Nephrotic Syndrome
Outcome
Complement-Associated Kidney Diseases
Complement System
Immune Complex Membranoproliferative Glomerulonephritis and C3 Glomerulopathy
Pathogenesis
Clinical Manifestations
Diagnosis
Treatment
Postinfectious (Poststreptococcal) Glomerulonephritis
Pathogenesis
Clinical Manifestations
Treatment
Membranous Nephropathy
Epidemiology
Pathogenesis
Clinical Manifestations
Treatment
Outcomes
Thrombotic Microangiopathy
Diagnosis
Infectious Forms of Thrombotic Microangiopathy
STEC–HUS
Pathogenesis
Clinical Manifestations
Treatment
Pneumococcal HUS
Pathogenesis
Clinical Manifestations
Treatment
Noninfectious, Noncomplement-Mediated Forms of Thrombotic Microangiopathy
Diacylglycerol Kinase Epsilon Thrombotic Microangiopathy
Pathogenesis
Clinical Manifestations
Treatment
Cobalamin C–Associated Thrombotic Microangiopathy
Pathogenesis
Clinical Manifestations
Treatment
INF2-Mediated Thrombotic Microangiopathy
Noninfectious, Complement- Mediated Thrombotic Microangiopathy
Atypical HUS
Pathogenesis
Clinical Manifestations
Treatment
Secondary Forms of Thrombotic Microangiopathy With Possible Complement Contribution
Transplant-Associated Thrombotic Microangiopathy
Recurrent Atypical HUS After Renal Transplantation
De Novo Thrombotic Microangiopathy After Renal Transplantation
AMR-Associated Thrombotic Microangiopathy
Bone Marrow/Stem Cell Transplant–Associated Thrombotic Microangiopathy
Glomerulopathy and Vasculitis- Associated Thrombotic Microangiopathy
SLE-Associated Thrombotic Microangiopathy
APS-Associated Thrombotic Microangiopathy
IC-MPGN/C3G-Associated Thrombotic Microangiopathy
ANCA-Associated Vasculitis-Associated Thrombotic Microangiopathy
Malignant Hypertension–Associated Thrombotic Microangiopathy
Drug-Associated Thrombotic Microangiopathy
Thrombotic Thrombocytopenic Purpura
Pathogenesis
Clinical Manifestations
Treatment
Systemic Diseases With Renal Involvement
Henoch–Schönlein Purpura and Iga Nephropathy
Introduction
Epidemiology
Pathophysiology
Clinical Presentation
Laboratory Evaluation
Treatment
Outcome
Renal Diseases With Vasculitis
Medium Vessel Vasculitides
Kawasaki Disease
Polyarteritis Nodosa
Small Vessel Vasculitides
Granulomatosis With Polyangiitis (Wegener Granulomatosis)
Microscopic Polyangiitis
Eosinophilic Granulomatosis With Polyangiitis (Churg–Strauss Syndrome)
Anti-Glomerular Basement Membrane (Anti-GBM) Disease
Systemic Lupus Erythematosus Nephritis
Tubular Disorders
Fanconi Syndromes—With Emphasis on Cystinosis
Etiology
Presentation
Diagnosis
Treatment
Disorders of Renal Tubular Nacl Transport
Bartter Syndrome
Etiology
Presentation
Diagnosis
Treatment
Gitelman Syndrome
EAST Syndrome
Pseudohypoaldosteronism
PHA Type I
PHA Type II
Liddle Syndrome
Renal Tubular Acidosis
Type I, Distal Renal Tubular Acidosis
Type II, Proximal Renal Tubular Acidosis
Type IV, Hyperkalemic Renal Tubular Acidosis
A Note on Type III, Renal Tubular Acidosis
Nephrogenic Diabetes Insipidus
Etiology
Presentation
Diagnosis
Treatment
Urolithiasis and Nephrocalcinosis in Children
Epidemiology
Risk Factors
Hypercalciuria
Hypocitraturia
Hyperuricosuria
Hyperoxaluria
Altered Urinary Flow and Infections
Presentation
Diagnosis
Treatment
Genetics of Pediatric Urolithiasis and Nephrocalcinosis
Hypercalciuria-Inducing Conditions
Williams Syndrome
Dent Disease/Oculocerebral Syndrome of Lowe
Bartter Syndromes
Autosomal Dominant Hypocalcemia With Hypercalciuria
Familial Hypomagnesemia Hypercalciuria and Nephrocalcinosis
Distal Renal Tubular Acidosis
Hereditary Hypophosphatemic Rickets With Hypercalciuria
Noncalcium Wasting Disorders
Cystinuria
Hyperuricosuria (Including 2,8-Dihydroxyadenine Urolithiasis)
Primary Hyperoxalurias
Hyperoxaluria Type 1
Hyperoxaluria Type 2
Hyperoxaluria Type 3
Pediatric Aspects of Chronic Kidney Disease
Growth, Nutrition, and Development
Prevention and Treatment of Growth Failure in Chronic Kidney Disease
Cardiovascular Comorbidity in Pediatric Chronic Kidney Disease
Hypertension
Anemia
Intermediate Cardiovascular Endpoints in Children With Chronic Kidney Disease
Progression of Chronic Renal Failure in Children
Course of Renal Function in Children With Chronic Kidney Disease
Risk Factors for Progression of Renal Failure
Key References
References
Board Review Questions
73 Fluid, Electrolyte, and Acid-Base Disorders in Children
Chapter Outline
Sodium and Water Disorders
Normal Metabolism of Water and Sodium Specific to Pediatrics
Hyperosmolality and Hypernatremia: Pathogenesis and Classification
Dehydration
Hypernatremic Dehydration
The Exclusively Breast-Fed Baby.
Nephrogenic Diabetes Insipidus.
Presentation.
Fluid Management.
Secondary Forms.
Hypernatremia From Excess Salt
Hypoosmolality and Hyponatremia: Pathogenesis and Classification
Treatment of Hyponatremia
Syndrome of Inappropriate Antidiuretic Hormone Secretion
Hyponatremia in Hospitalized Children
Nephrogenic Syndrome of Inappropriate Antidiuresis
Basis of Fluid Therapy for Dehydration in Children
Potassium Disorders
Hypokalemia
Inherited Disorders Associated With Hypokalemia
Hypokalemic Alkalosis Without Hypertension
Bartter Syndrome
Antenatal Presentation.
Classic Presentation.
Gitelman Syndrome.
EAST Syndrome.
Claudin 10.
Hypokalemic Alkalosis With Hypertension
Disorders Associated With Hypokalemia and Acidosis.
Hyperkalemia
Disorders Associated With Hyperkalemia
Pseudohypoaldosteronism
Pseudohypoaldosteronism Type 1.
Pseudohypoaldosteronism Type 2.
Hydrogen Ion Disorders
Acid-Base Equilibrium in Children
Renal Tubular Acidosis
Proximal Type 2 Renal Tubular Acidosis
Primary Distal Type 1 Renal Tubular Acidosis
Clinical Presentation
Treatment
Hyperkalemic Type 4 Renal Tubular Acidosis
Magnesium Disorders
Hypomagnesemia
Clinical Manifestations
Hypercalciuric Hypomagnesemia: Familial Hypomagnesemia With Hypercalciuria and Nephrocalcinosis
Gitelman-Like Hypomagnesemia
Mitochondrial Hypomagnesemia
Other Hypomagnesemias: Familial Hypomagnesemia With Secondary Hypocalcemia
Calcium and Phosphate Disorders
Calcium and Phosphate Concentrations in Serum
Vitamin D, Parathyroid Hormone, Calcitonin, and Fibroblast Growth Factor 23
Vitamin D
Calcitonin, Fibroblast Growth Factor 23, and Parathyroid Hormone
Hypocalcemia
Types and Causes
Early Neonatal Hypocalcemia
Late Neonatal Hypocalcemia
Infusions of Lipid or Citrate Blood Products
Alkalosis
Diagnostic Workup for Hypocalcemia
Treatment of Hypocalcemia
Monitoring Hypocalcemia
Hypercalcemia
Idiopathic Infantile Hypercalcemia
Williams-Beuren Syndrome
Familial Hypocalciuric Hypercalcemia
Neonatal Severe Hyperparathyroidism
Diagnostic Workup for Hypercalcemia
Treatment of Hypercalcemia
Hypophosphatemia
Diagnostic Workup for Hypophosphatemia
Imaging Studies in Chronic Hypophosphatemia
Treatment of Hypophosphatemia
Hyperphosphatemia
Diagnostic Workup for Hyperphosphatemia
Imaging Studies in Hyperphosphatemia
Treatment of Hyperphosphatemia
Summary and Conclusion
Key References
References
Board Review Questions
74 Renal Replacement Therapy (Dialysis and Transplantation) in Pediatric End-Stage Kidney Disease
Chapter Outline
Key Points
Epidemiology of End-Stage Kidney Disease
Etiology
Clinical Consequences of Pediatric End-Stage Kidney Disease
Nutrition and Weight
Linear Growth
Electrolyte Imbalance
Metabolic Acidosis
Anemia
Chronic Kidney Disease–Mineral Bone Disease
Cardiovascular
Hypertension
Vascular Calcification
Cardiac Pathology
Left Ventricular Hypertrophy
Diastolic Dysfunction
Arrhythmia
Valvular Disease
Neurodevelopment
Quality of Life
Mortality
Cardiovascular Mortality
Medications
Renal Replacement Therapy
Advantages of Renal Transplantation Over Chronic Dialysis in Children
Survival
Quality of Life
Neurodevelopment
Exhaustion of Access Sites
Cost
Comparing Hemodialysis With Peritoneal Dialysis
Hemodialysis
Vascular Access
Dialysis Apparatus
Tubing
Dialyzer
Hemodialysis Machine
Blood Flow
Dose of Dialysis
Fluid Removal
Complications
Hypotension
Disequilibrium Syndrome
Hypothermia
Hypophosphatemia
Hypoglycemia
Peritoneal Dialysis
Access
Peritoneal Dialysis Prescription
Types of Peritoneal Dialysis
Peritoneal Dialysis Solutions
Exchange Volume
Dwell Time
Adequacy of Dialysis
Complications
Infection
Technique Failure
Catheter Malfunction
Ultrafiltration Failure
Fluid Leaks
Encapsulating Peritoneal Sclerosis
Adherence to Treatment
World Disparities
Change of Dialysis Modality
Renal Replacement Therapy for Children With Inborn Errors of Metabolism
Continuous Renal Replacement Therapy
Indications
Comparison With Hemodialysis and Peritoneal Dyalysis
Technical Considerations
Dosing of Continuous Renal Replacement Therapy
Continuous Renal Replacement Therapy Outcomes
Pediatric Kidney Transplantation
Incidence, Prevalence, and Allocation
Preparation of the Recipient for Transplantation
Choice of Donor
Timing
Contraindications
Recipient Evaluation
Infection
Malignancy
Urological Issues
Cardiovascular Issues
Risk of Recurrence
Sensitization
Transplant Immunology
HLA Matching and Sensitization
ABO Compatibility
Immunosuppression
Induction Immunosuppression
Maintenance Immunosuppression
Calcineurin Inhibitors
Cyclosporine
Tacrolimus
Antimetabolites
Azathioprine
Mycophenolate
Corticosteroids
Mammalian Target of Rapamycin Inhibitors
Sirolimus
Everolimus
Other Immunosuppressive Medications
Immunosuppression Combinations
Perioperative Management
Immediate Postoperative Period
Early Complications of Kidney Transplantation
Delayed Graft Function
Acute Rejection
Infections
Urinary Tract Infection
Cytomegalovirus
Epstein–Barr Virus Infection
BK Virus Infection
Varicella
Other Infections
Respiratory Viruses
Cutaneous Warts
Pneumocystis jirovecii Pneumonia
Infectious Diarrhea
Recurrence of Primary Renal Disease
Chronic Allograft Nephropathy
Patient Survival
Graft Survival
Long-Term Follow-Up of Children With Kidney Transplant
Hypertension
Cardiovascular Disease
Metabolic Syndrome and Diabetes Mellitus
Cancer
Anemia
Bone Health and Growth
Urological Issues
Puberty and Reproduction
Nonadherence
Transition
Rehabilitation and Quality of Life
Key References
References
Board Review Questions
75 Global Challenges and Initiatives in Kidney Health
Chapter Outline
Key Points
Global Challenges in Kidney Health
Awareness of Kidney Disease as an Important Public Health Issue
Renal Replacement Therapy and the Challenges of Limited Access
Dilemmas Posed by Lack of Sustainable Renal Replacement Therapy in Low-Resource Settings
Policy Development and Access to Renal Replacement Therapy
Global Initiatives for Kidney Health
Global Burden of Disease Study
Mortality and Morbidity Due to Chronic Kidney Disease
Mortality and Morbidity Due to Cardiovascular Disease Driven by Low Glomerular Filtration Rate
Scope of Amenable Chronic Kidney Disease Mortality Amenable to Intervention
Drivers of Epidemiologic Transition for Chronic Kidney Disease
Acute Kidney Injury and the 0by25 Initiative
Saving Young Lives Initiative
The Global Kidney Health Atlas
Awareness of Kidney Health as a Government Priority, Strategies, Guidelines, and Advocacy
Infrastructure for Treatment of Acute Kidney Injury and Chronic Kidney Disease
Availability of Chronic Kidney Disease Monitoring and Management Services
Availability of Renal Replacement Therapy Services
Dialysis.
Kidney Transplantation.
Workforce for Care Delivery
Capacity for Kidney Research
Public Health Initiatives and Policies to Improve Kidney Health and Access to Care
Heath in All Policies and Sustainable Development Goals
Health Technology Assessment: the Example of Thailand
Conclusion
Acknowledgments
Key References
References
Board Review Questions
76 Latin America
Chapter Outline
Key Points
Introduction
Tropical Diseases and Kidney Injury
Dengue Fever
Kidney Involvement in Dengue Fever
Yellow Fever
Kidney Involvement in Yellow Fever
Malaria
Kidney Involvement in Malaria
Leptospirosis
Kidney Involvement in Leptospirosis
Nephrotoxicity Due to Venoms
Spiders
Kidney Involvement in Loxoscelism
Lonomia Caterpillars
Renal Involvement in Lonomia Accidents
Snakes
Crotalus Snakes
Kidney Involvement in Crotalus Bites
Bothrops Snakes
Kidney Involvement in Bothrops Bites
Chronic Kidney Disease in Latin America
Prevalence of Chronic Kidney Disease
Risk Factors for Chronic Kidney Disease
Mesoamerican Nephropathy—Chronic Kidney Disease of Unknown Cause
End-Stage Kidney Disease in Latin America
Transplantation
Trends and the Future
Key References
References
Board Review Questions
77 Global Considerations in Kidney Disease
Chapter Outline
KEY POINTS
Introduction
Human Resources for Nephrology
Acute Kidney Injury
Acute Kidney Injury in Human Immunideficiency Virus Infection
Acute Kidney Injury and Malaria
Acute Kidney Injury and Toxins
Pregnancy-Related Acute Kidney Injury
Therapeutic Challenges
Chronic Kidney Disease
Issues in the Diagnosis of Chronic Kidney Disease
Chronic Kidney Disease Prevalence in African Countries
Common Causes of Chronic Kidney Disease and End-Stage Renal Disease
Diabetic Nephropathy
Glomerulonephritis
Kidney Disease Associated With Human Immunodeficiency Virus Infection
Glomerular Disease Associated With Hepatitis B Virus Infection
Postinfectious Glomerulonephritis
Lupus Nephritis
Schistosomiasis
Renal Stones
Sickle Cell Disease
Hypertensive Renal Disease
Genetic Disorders
The Role of Consanguineous Marriage
Cystic Kidney Disease
Metabolic Diseases
Tubular Disorders
Glomerular Diseases
Chronic Kidney Disease of Uncertain Etiology
Screening and Prevention of Chronic Kidney Disease
End-Stage Renal Disease and Renal Replacement Therapy
Concluding Remarks
Key References
References
Board Review Questions
78 Near and Middle East
Chapter Outline
Key Points
Acute Kidney Injury
Causes
Chronic Kidney Disease
Epidemiology
Causes
Genetic Disorders
Cystic Kidney Diseases
Genetic Glomerular Diseases
Genetic Metabolic Diseases and Inherited Tubular Disorders
Familial Mediterranean Fever
Clinical Spectrum and Renal Disease.
Treatment of Familial Mediterranean Fever.
Familial Mediterranean Fever and End-Stage Kidney Disease.
Management of End-Stage Kidney Disease in the Middle East
Dialysis
Peritoneal Dialysis
Hemodialysis
Management of End-Stage Kidney Disease With Viral Hepatitis
Dialysis-Related Outcomes
Kidney Transplantation
Commercial Kidney Transplantation
Pharmacologic Treatment of Kidney Transplant Recipients
Posttransplantation Complications
Summary
Acknowledgment
Key References
References
Board Review Questions
79 Indian Subcontinent
Chapter Outline
Key Points
Acute Kidney Injury
Pregnancy-Associated Acute Kidney Injury
Acute Kidney Injury Associated With Surgical Causes
Acute Kidney Injury Due to Infections
Diarrheal Diseases
Hemolytic-Uremic Syndrome
Malaria
Clinical Features
Histologic Features
Pathogenesis
Treatment
Leptospirosis
Clinical Features
Histologic Features
Pathogenesis
Treatment
Zygomycosis
Dengue Fever
Acute Kidney Injury Due to Snake Bite and Insect Stings
Snake Bite
Clinical Features
Histologic Features
Acute Tubular Necrosis.
Acute Cortical Necrosis.
Pathogenesis
Treatment
Bee, Wasp, and Hornet Stings
Acute Kidney Injury Due to Chemical Toxins
Copper Sulfate Poisoning
Ethylene Glycol Poisoning
Ethylene Dibromide Poisoning
Chromic Acid Poisoning
Hair Dye–Related Acute Kidney Injury
Acute Kidney Injury Due to Intravascular Hemolysis and Glucose-6-Phosphate Dehydrogenase Deficiency
Acute Cortical Necrosis
Acute Peritoneal Dialysis for Acute Kidney Injury
Chronic Kidney Disease
Incidence and Prevalence of Chronic Kidney Disease
Demographics of Chronic Kidney Disease and End-Stage Kidney Disease
Chronic Kidney Disease Due to Glomerulonephritis
Chronic Kidney Disease Due to Vascular Disorders
Chronic Kidney Disease Due to Renal Calculi
Chronic Kidney Disease Due to Indigenous Therapies
Herbal Medicine Toxicity
Toxicity of Natural Medicines From Animal Sources
Chronic Kidney Disease of Uncertain Cause
End-Stage Kidney Disease
Financial and Reimbursement Issues
Hemodialysis
Peritoneal Dialysis
Kidney Transplantation
Summary
Key References
References
Board Review Questions
80 The Far East
Chapter Outline
Key Points
Introduction
Traditional Medicine
Acute Kidney Injury and Chronic Kidney Disease
Acute Kidney Injury
Chronic Kidney Disease
Specific Kidney Diseases
IgA Nephropathy
Lupus Nephritis
Diabetic Nephropathy
Aristolochic Acid Nephropathy
ANCA-Associated Vasculitides
Hepatitis B/C-Associated Renal Diseases
Kidney Injury Related to Infections
Leptospirosis
Dengue Viral Infection
Malaria
Scrub Typhus
Severe Fever With Thrombocytopenia Syndrome
Hantaviruses and Hemorrhagic Fever With Renal Syndrome
Dialysis in Asia
Peritoneal Dialysis
Hemodialysis
Kidney Transplantation—Special Issues in Asia
Kidney Transplantation Across ABO Blood Group Barrier
Hepatitis B in Kidney Transplant Recipients
Concluding Statements
Key References
References
Board Review Questions
81 Oceania Region
Chapter Outline
Key Points
Introduction
Australia
Burden of Disease
Dialysis
Kidney Transplantation
Nondialysis Supportive Care for ESKD
Acute Kidney Injury
Indigenous Australians
Ethnic Inequities
Domains of Kidney Disease Care in Australia
Health Finance
Essential Medications and Technology Access
Detection and Monitoring of Kidney Disease
Health Workforce
Health Information Systems and Statistics
Strategies and Policy Frameworks
Capacity for Research and Development
New Zealand
Access to Health Care
Burden of Chronic Kidney Disease
Inequity Based on Ethnicity
Dialysis
Transplantation
Nondialysis Supportive Care for ESKD
Acute Kidney Injury
Kidney Disease Care in New Zealand
Health Finance
Essential Medications and Technology Access
Detection and Monitoring of Kidney Disease
Health Workforce
Health Information Systems and Statistics
Strategies and Policy Frameworks
Capacity for Research and Development
Samoa
New Zealand Dependencies (Cook Islands, Niue, Tokelau)
Papua New Guinea
Pacific Islands
French Protectorates (French Polynesia, New Caledonia, Wallis and Futuna)
US Protectorates (American Samoa, Guam)
Norfolk Island (Australian Protectorate)
Pitcairn Island (British Colony)
Fiji
Conclusion
Acknowledgments
Key References
References
Board Review Questions
82 Ethical Dilemmas Facing Nephrology
Chapter Outline
Key Points
Past: the Evolution of Dialysis and Transplant Ethics in the United States
Nephrology’s Contribution to the Birth of Bioethics
Rationing of Hemodialysis and Patient Selection Criteria at the Beginning of Chronic Dialysis in the United States
US Health-Care Coverage for Dialysis and an Expanding Dialysis Patient Demographic
Withdrawal From Dialysis
Present
Advance Directives and Dialysis Patients
Financing Dialysis Centers and Conflicts of Interest
CKD Care and Dialysis of the Older and/or Multimorbid Patient
Ethical Issues in ESRD End-of-Life Care
Shared Decision-Making and Clinical Practice Guideline on Appropriate Use of Dialysis
Access to Renal Transplantation in the United States
The “Difficult” Dialysis Patient and Conflict Management
Future
Financial Stresses and Cost-Containment Strategies in Nephrology
ESCOs and Cherry Picking of Dialysis Patients
Professional Ethics in Dialysis
A Global Perspective on Nephrology Health Care
Ethical Challenges Posed by Genetic Advances in CKD
Conclusion
Key References
References
Board Review Questions
83 Health Disparities in Nephrology
Chapter Outline
Key Points
Disparity
Health Justice
Social Origins of Disparities in Nephrology
Prenatal Environment and Disparities in Risk Factors for Kidney Diseases
Postnatal Environment and Disparities in Risk Factors for Kidney Diseases
Race, Social Conditions, and Disparities in Incident Kidney Diseases
Biologic Origins of Disparities in Nephrology
Health System and Disparities in Nephrology
Unequal Health System Access and Surveillance
Importance of Health System Structure
Disparities in the Treatment of Chronic Kidney Diseases
Disparities in the Treatment of End-Stage Kidney Disease
Dialysis: Process and Outcome
Kidney Transplantation: Process
Kidney Transplantation: Outcomes
Moving Toward More Equitable Care
Initiatives to Reduce Disparities
Summary and Challenges
Key References
References
Board Review Questions
84 Care of the Older Adult With Chronic Kidney Disease
Chapter Outline
Key Points
Introduction
Chronic Kidney Disease and Age-Related Changes in Estimated Glomerular Filtration Rate
Evaluation of Renal Function in Older Adults
Normal Aging Versus Disease: Is There a Need for Change in How We Define Chronic Kidney Disease?
Comorbidities and Geriatric Syndromes Among Older Individuals With Chronic Kidney Disease
Frailty
Functional Impairment
Falls
Depression
Polypharmacy
Malnutrition and Protein-Energy Wasting
Cognitive Impairment
Controversies and Complexity in the Management of Older Patients With Chronic Kidney Disease
Hypertension in the Frail Older Patient With Chronic Kidney Disease: Targeting Blood Pressure
The Role of Statins in Octogenarians
Anticoagulation in Atrial Fibrillation
Antiresorptive Treatment: Bone Health
Vascular Access Creation
Care for Older Adults With End-Stage Renal Disease
Dialysis
Dialysis Modality Selection
Kidney Transplantation
Comprehensive Conservative Renal Care
Importance of Shared Decision Making in End-Stage Renal Disease
Dialysis Treatments Unique to Older Patients
Dialysis and Geriatric Rehabilitation Programs
Palliative Dialysis
Conclusion
Key References
References
Board Review Questions
85 Stem Cells, Kidney Regeneration, and Gene and Cell Therapy in Nephrology
Chapter Outline
Key Points
Kidney Stem Cells
Pluripotent Stem Cells (ES and iPS)
Nephron Progenitor Cells and Organoids
Adult Stem Cells
Kidney Regeneration
Stem Cell Therapy
Bioartificial Kidneys
Metanephric Implants
Xenotransplants and Chimeras
Gene Therapy
Preimplantation Genetic Diagnosis
Gene Transfer
Gene Editing
Designer Therapeutics
Conclusion
Acknowledgments
Key References
References
Board Review Questions