BOOK
Brenner and Rector's The Kidney E-Book
Karl Skorecki | Glenn M. Chertow | Philip A. Marsden | Maarten W. Taal | Alan S. L. Yu | Valerie Luyckx
(2015)
Additional Information
Book Details
Abstract
Overcome the toughest clinical challenges in nephrology with Brenner & Rector’s The Kidney -- the most well-known nephrology resource in the world. A diverse team of more than 200 international contributors brings you the latest knowledge and best practices on every front in nephrology worldwide. From basic science and pathophysiology to clinical best practices, Brenner & Rector’s The Kidney is your go-to resource for any stage of your career.
- Review of the basic science that underpins clinical nephrology, comprehensive selection of the most important bibliographical sources in nephrology, and Board Review-style questions help you prepare for certification or recertification.
- Coverage of kidney health and disease from pre-conception through fetal and infant health, childhood, adulthood, and into old age. Expanded sections and chapter on global perspective and ethical considerations.
- Uniform terminology and nomenclature in line with emerging consensus in world kidney community.
- More than 700 full-color high-quality photographs as well as carefully chosen figures, algorithms, and tables to illustrate essential concepts, nuances of clinical presentation and technique, and decision making provide a visual grasp and better understanding of critical information.
- Internationally diverse, trusted guidance and perspectives from a team of well-respected global contributors . An editorial team headed by Dr. Skorecki and handpicked by Dr. Brenner ensures the ongoing adherence to previous standards of excellence. All chapters have been extensively updated or entirely rewritten by authorities in their respective fields.
- The latest clinical information including recent clinical trials, genetic causes of kidney disease, cardiovascular and renal risk prediction in chronic kidney disease, new paradigms in fluid and electrolyte management, and pediatric kidney disease, keep you current with the rapid development of care and research worldwide.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| 9780323262590v1_WEB.pdf | 1 | ||
| Front Cover | 1 | ||
| endsheet 2 | 2 | ||
| Brenner & Rector’s The Kidney | 3 | ||
| Copyright Page | 4 | ||
| Dedication | 5 | ||
| Contributors | 6 | ||
| Foreword | 21 | ||
| Preface | 23 | ||
| Table Of Contents | 25 | ||
| I Normal Structure and Function | 29 | ||
| 1 Embryology of the Kidney | 30 | ||
| Chapter Outline | 30 | ||
| Mammalian Kidney Development: Embryology | 30 | ||
| Development of the Urogenital System | 30 | ||
| Development of the Metanephros | 31 | ||
| Development of the Nephron | 32 | ||
| The Nephrogenic Zone | 33 | ||
| Branching Morphogenesis: Development of the Collecting System | 33 | ||
| Renal Stroma and Interstitial Populations | 33 | ||
| Development of the Vasculature | 34 | ||
| Model Systems to Study Kidney Development | 34 | ||
| Organ Culture | 34 | ||
| The Kidney Organ Culture System: Classic Studies | 34 | ||
| Mutant Phenotypic Analyses | 35 | ||
| Antisense Oligonucleotides and siRNA in Organ Culture | 35 | ||
| Organ Culture Microinjection | 37 | ||
| Transgenic and Knockout Mouse Models | 37 | ||
| Imaging and Lineage Tracing Studies | 47 | ||
| Nonmammalian Model Systems for Kidney Development | 47 | ||
| Genetic Analysis of Mammalian Kidney Development | 49 | ||
| Interaction of the Ureteric Bud and the Metanephric Mesenchyme | 49 | ||
| Early Lineage Determination of the Metanephric Mesenchyme | 49 | ||
| Ureteric Bud Induction: Transcriptional Regulation of GDNF | 50 | ||
| Non-GDNF Pathways in the Metanephric Mesenchyme | 51 | ||
| Genes Required by the Ureteric Bud in Early Kidney Development | 51 | ||
| Adhesion Proteins in Early Kidney Development | 53 | ||
| Formation of the Collecting System | 53 | ||
| Positioning of the Ureteric Bud | 55 | ||
| Molecular Analysis of the Nephrogenic Zone | 56 | ||
| Molecular Biology of Nephron Development: Tubulogenesis | 58 | ||
| Molecular Genetics of the Stromal Cell Lineage | 59 | ||
| Molecular Genetics of Vascular Formation | 60 | ||
| The Juxtaglomerular Apparatus and the Renin Angiotensin Aldosterone System | 63 | ||
| Nephron Development and Glomerulogenesis | 64 | ||
| Mesangial Cell Ingrowth | 64 | ||
| Glomerular Epithelial Development | 64 | ||
| Maturation of Glomerular Endothelial Cells and Glomerular Basement Membrane | 67 | ||
| Key References | 68 | ||
| References | 70 | ||
| 2 Anatomy of the Kidney | 82 | ||
| Chapter Outline | 82 | ||
| Gross Features | 82 | ||
| The Nephron | 84 | ||
| Renal Corpuscle | 85 | ||
| Endothelial Cells | 86 | ||
| Glomerular Basement Membrane | 88 | ||
| Visceral Epithelial Cells | 89 | ||
| Mesangial Cells | 91 | ||
| Parietal Epithelial Cells | 92 | ||
| Peripolar Cells | 93 | ||
| Juxtaglomerular Apparatus | 93 | ||
| Juxtaglomerular Granular Cells | 93 | ||
| Extraglomerular Mesangium | 93 | ||
| Macula Densa | 94 | ||
| Autonomic Innervation | 94 | ||
| Tubuloglomerular Feedback | 95 | ||
| Proximal Tubule | 95 | ||
| Pars Convoluta | 95 | ||
| Pars Recta | 100 | ||
| Thin Limbs of the Loop of Henle | 101 | ||
| Distal Tubule | 103 | ||
| Thick Ascending Limb | 103 | ||
| Distal Convoluted Tubule | 105 | ||
| Connecting Tubule | 108 | ||
| Collecting Duct | 109 | ||
| Cortical Collecting Duct | 110 | ||
| Outer Medullary Collecting Duct | 113 | ||
| Inner Medullary Collecting Duct | 114 | ||
| Interstitium | 115 | ||
| Cortical Interstitium | 117 | ||
| Medullary Interstitium | 118 | ||
| Lymphatics | 120 | ||
| Innervation | 120 | ||
| Acknowledgments | 121 | ||
| Key References | 121 | ||
| References | 123 | ||
| 3 The Renal Circulations and Glomerular Ultrafiltration | 131 | ||
| Chapter Outline | 131 | ||
| Major Arteries and Veins | 131 | ||
| Hydraulic Pressure Profile of the Renal Circulation | 133 | ||
| Total Renal Blood Flow | 133 | ||
| Intrarenal Blood Flow Distribution | 135 | ||
| Vascular-Tubule Relations | 135 | ||
| Cortical Blood Flow | 135 | ||
| Peritubular Capillary Dynamics | 137 | ||
| Medullary Blood Flow | 138 | ||
| Medullary Microcirculation | 138 | ||
| Vascular Patterns | 138 | ||
| Vascular-Tubule Relations | 140 | ||
| Medullary Capillary Dynamics | 140 | ||
| Structure of the Glomerular Microcirculation | 140 | ||
| Determinants of Glomerular Ultrafiltration | 142 | ||
| Hydraulic Pressures in the Glomerular Capillaries and Bowman’s Space | 142 | ||
| Glomerular Capillary Hydraulic and Colloid Osmotic Pressure Profiles | 142 | ||
| Determination of the Ultrafiltration Coefficient | 144 | ||
| Selective Alterations in the Primary Determinants of Glomerular Ultrafiltration | 145 | ||
| Glomerular Plasma Flow Rate | 145 | ||
| Transcapillary Hydraulic Pressure Difference | 145 | ||
| The Glomerular Capillary Ultrafiltration Coefficient | 146 | ||
| Colloid Osmotic Pressure | 146 | ||
| Regulation of Renal Hemodynamics and Glomerular Filtration | 146 | ||
| Vasomotor Properties of the Renal Microcirculations | 146 | ||
| Role of the Renin-Angiotensin System in the Control of Renal Blood Flow and Glomerular Filtration Rate | 147 | ||
| Endothelial Factors in the Control of Renal Hemodynamics and Glomerular Filtration | 149 | ||
| Nitric Oxide | 149 | ||
| Endothelin | 151 | ||
| Renal Autoregulation | 152 | ||
| Cellular Mechanisms Involved in Renal Autoregulation | 153 | ||
| The Myogenic Mechanism for Autoregulation | 153 | ||
| Autoregulation Mediated by Tubuloglomerular Feedback | 154 | ||
| Mechanisms of Tubuloglomerular Feedback Control of Renal Blood Flow and Glomerular Filtration Rate | 156 | ||
| Autoregulation Mediated By Metabolic Mechanisms | 157 | ||
| Other Factors Involved in Autoregulation | 158 | ||
| Neural Regulation of Glomerular Filtration Rate | 158 | ||
| Key References | 158 | ||
| References | 160 | ||
| 4 The Podocyte | 168 | ||
| Chapter Outline | 168 | ||
| Biologic Functions of Podocytes | 168 | ||
| Ultrastructural and Molecular Anatomy of Podocytes Required for Normal Structure and Function | 169 | ||
| Structure | 169 | ||
| Slit Diaphragm Proteins | 169 | ||
| Cytoskeleton | 169 | ||
| Glomerular Diseases in Which Podocytes are the Primary Glomerular Cell Type Injured | 169 | ||
| Mechanisms of Injury in Common Podocyte Diseases | 170 | ||
| Minimal Change Nephropathy | 170 | ||
| Focal Segmental Glomerulosclerosis | 172 | ||
| Membranous Nephropathy | 172 | ||
| Human Immunodeficiency Virus Nephropathy | 172 | ||
| Diabetic Kidney Disease | 172 | ||
| Responses by Podocytes to Disease-Induced Injury: Linking Structure to Function to Clinical Findings | 173 | ||
| Effacement: A Histologic Change In Podocyte Shape Mediated by the Actin Cytoskeleton | 173 | ||
| Proteinuria Due to Reduced Size and/or Charge Properties | 174 | ||
| Glomerulosclerosis and Reduced Kidney Function: A Correlation with Depletion in Podocyte Number | 174 | ||
| Effects of Existing Therapies on Podocytes | 175 | ||
| Glucocorticosteroids | 175 | ||
| Calcineurin Inhibitors | 175 | ||
| Anti–B Cell Therapy | 175 | ||
| Renin Angiotensin Aldosterone System Inhibitors | 175 | ||
| Identification of Candidate Therapeutic Approaches for the Future | 176 | ||
| Summary | 176 | ||
| Key References | 176 | ||
| References | 178 | ||
| 5 Metabolic Basis of Solute Transport | 181 | ||
| Chapter Outline | 181 | ||
| Thermodynamic Approach to Metabolism and Transport | 182 | ||
| Thermodynamic Analysis of Kidney Function | 182 | ||
| Application of the Laws of Thermodynamics to Kidney Function | 182 | ||
| Energy and the Sodium Pump | 183 | ||
| Structure of the Sodium Pump | 183 | ||
| Other Adenosine Triphosphatases | 183 | ||
| Pump-Leak Process and the Sodium Potential | 183 | ||
| Harnessing the Sodium Potential for Work | 184 | ||
| Cell Polarity and Vectorial Transport | 185 | ||
| Metabolic Substrates Fueling Active Transport Along the Nephron | 185 | ||
| Metabolism Basics | 185 | ||
| Whittam Model | 186 | ||
| Energy Requirements and Substrate Use along the Nephron | 187 | ||
| Renal Gluconeogenesis and Lactate Handling | 189 | ||
| Nephron Region–Specific Metabolic Considerations | 191 | ||
| Proximal Tubule | 191 | ||
| Thick Ascending Limb | 191 | ||
| Cortical Collecting Duct | 192 | ||
| Medullary Collecting Duct | 192 | ||
| Control of Renal Oxygenation | 192 | ||
| Renal Blood Flow and Oxygen Consumption | 192 | ||
| Tubuloglomerular Feedback | 194 | ||
| Metabolic Cost of Sodium Reabsorption | 194 | ||
| Regulation of Metabolic Efficiency of Transport during Normal Perturbations and Disease | 197 | ||
| Physiologic Regulation: Filtration Fraction and Oxygen Consumption | 197 | ||
| Hypoxia and Ischemia | 198 | ||
| Hypoxia-Inducible Factor | 199 | ||
| Adenosine Monophosphate–Activated Protein Kinase | 199 | ||
| Mitochondrial Diseases | 201 | ||
| Summary | 201 | ||
| Key References | 201 | ||
| References | 203 | ||
| 6 Transport of Sodium, Chloride, and Potassium | 207 | ||
| Chapter Outline | 207 | ||
| Sodium and Chloride Transport | 207 | ||
| Proximal Tubule | 207 | ||
| Paracellular Na+-Cl− Transport | 210 | ||
| Transcellular Na+-Cl− Transport | 211 | ||
| Apical Mechanisms | 211 | ||
| Basolateral Mechanisms | 213 | ||
| Regulation of Proximal Tubular Na+-Cl− Transport | 213 | ||
| Glomerulotubular Balance | 213 | ||
| Neurohumoral Influences | 215 | ||
| Regulation of Proximal Tubular Transporters | 217 | ||
| Loop of Henle and Thick Ascending Limb | 219 | ||
| Transport Characteristics of the Descending Thin Limb | 219 | ||
| Na+-Cl− Transport by the Thin Ascending Limb | 219 | ||
| Na+-Cl− Transport by the Thick Ascending Limb | 221 | ||
| Apical Na+-Cl− Transport | 221 | ||
| Apical K+ Channels | 222 | ||
| Paracellular Transport | 223 | ||
| Basolateral Mechanisms | 223 | ||
| Regulation of Na+-Cl− Transport by the Thick Ascending Limb | 225 | ||
| Activating Influences | 225 | ||
| Inhibitory Influences | 227 | ||
| Uromodulin | 228 | ||
| Distal Convoluted Tubule, Connecting Tubule, and Collecting Duct | 228 | ||
| Distal Convoluted Tubule | 229 | ||
| Mechanisms of Na+-Cl− Transport in the Distal Convoluted Tubule | 229 | ||
| Regulation of Na+-Cl− Transport in the Distal Convoluted Tubule | 230 | ||
| Connecting Tubules and the Cortical Collecting Duct | 232 | ||
| Apical Na+ Transport | 232 | ||
| Cl− Transport | 233 | ||
| Electroneutral Na+-Cl− Cotransport | 234 | ||
| Regulation of Na+-Cl− Transport in the Connecting Tubule and Cortical Collecting Duct | 234 | ||
| Aldosterone | 234 | ||
| Vasopressin and Other Factors | 236 | ||
| Potassium Transport | 237 | ||
| Proximal Tubule | 238 | ||
| Loop of Henle and Medullary K+ Recycling | 238 | ||
| K+ Secretion by the Distal Convoluted Tubule, Connecting Tubule, and Cortical Collecting Duct | 239 | ||
| K+ Reabsorption by the Collecting Duct | 241 | ||
| Regulation of Distal K+ Transport | 242 | ||
| Modulation of Renal Outer Medullary Potassium Activity | 242 | ||
| Aldosterone and K+ Loading | 242 | ||
| K+ Deprivation | 243 | ||
| Vasopressin | 245 | ||
| Tissue Kallikrein | 245 | ||
| Integrated Na+-Cl− and K+ Transport in the Distal Nephron | 245 | ||
| Key References | 246 | ||
| References | 248 | ||
| 7 The Regulation of Calcium, Magnesium, and Phosphate Excretion by the Kidney | 260 | ||
| Chapter Outline | 260 | ||
| Calcium Transport in the Kidney | 260 | ||
| Role of Calcium in Cellular Processes | 260 | ||
| Calcium Present in Serum in Bound and Free Forms | 261 | ||
| Regulation of Calcium Homeostasis by the Parathyroid Hormone–Vitamin D Endocrine System | 262 | ||
| Reabsorption of Calcium Along the Tubule | 262 | ||
| Ca2+ Reabsorption in the Proximal Tubule | 263 | ||
| Ca2+ Reabsorption in the Loop of Henle | 263 | ||
| Ca2+ Reabsorption in the Distal Tubule | 264 | ||
| Regulation of Ca2+ Transport in the Kidney | 264 | ||
| Calcium-Regulating Hormones | 264 | ||
| Extracellular Calcium | 264 | ||
| Diuretics | 264 | ||
| Estrogens | 266 | ||
| Metabolic Acidosis and Alkalosis | 266 | ||
| Regulation of Renal Calcium Transport by Novel Proteins | 266 | ||
| Klotho | 266 | ||
| Sclerostin | 266 | ||
| Structures of Proteins Involved in the Transport of Calcium | 266 | ||
| Magnesium Transport in the Kidney | 268 | ||
| Role of Magnesium in Cellular Processes | 268 | ||
| Magnesium Present in Serum in Bound and Free Forms | 268 | ||
| Regulation of Magnesium Homeostasis | 268 | ||
| Reabsorption of Magnesium Along the Tubule | 269 | ||
| Regulation of Magnesium Transport in the Kidney | 270 | ||
| Structures of Proteins Involved in the Transport of Magnesium | 270 | ||
| Phosphorus Transport in the Kidney | 271 | ||
| Role of Phosphorus in Cellular Processes | 271 | ||
| Phosphorus Present in Blood in Multiple Forms | 271 | ||
| Regulation of Phosphate Homeostasis: An Integrated View | 272 | ||
| Reabsorption of Phosphate Along the Nephron | 273 | ||
| Regulation of Phosphate Transport in the Kidney | 274 | ||
| Dietary Phosphate | 274 | ||
| Parathyroid Hormone | 275 | ||
| Vitamin D and Vitamin Metabolites | 275 | ||
| Insulin, Growth Hormone, and Insulin-Like Growth Factor | 275 | ||
| Renal Nerves, Catecholamines, Dopamine, and Serotonin | 275 | ||
| Phosphatonins (FGF-23, sFRP-4) | 276 | ||
| Structures of Proteins Involved in the Transport of Phosphorus | 277 | ||
| Key References | 277 | ||
| References | 279 | ||
| 8 Renal Handling of Organic Solutes | 290 | ||
| Chapter Outline | 290 | ||
| Glucose | 290 | ||
| Physiology of Renal Glucose Transport | 290 | ||
| Renal Glucose Handling | 291 | ||
| Molecular Biology of Renal Glucose Transport Proteins | 291 | ||
| Cell Model | 291 | ||
| Apical Entry | 291 | ||
| SGLT1. | 291 | ||
| SGLT2. | 292 | ||
| Basolateral Exit | 293 | ||
| GLUT1 and GLUT2. | 293 | ||
| Renal Glucose Transport in Disease States | 293 | ||
| Monogenic Defects of Glucose Transport | 293 | ||
| Glucose-Galactose Malabsorption | 293 | ||
| Renal Glycosuria | 293 | ||
| Diseases of Glucose Transporters | 295 | ||
| Pharmacologic Manipulation of Sodium-Glucose–Linked Cotransporters | 295 | ||
| Organic Cations | 296 | ||
| Physiology of Renal Organic Cation Transport | 296 | ||
| Renal Organic Cation Secretion | 296 | ||
| Basolateral Organic Cation Entry | 296 | ||
| Apical Organic Cation Exit | 297 | ||
| Organic Cation Reabsorption | 297 | ||
| Molecular Biology of Renal Organic Cation Transport | 297 | ||
| Basolateral Organic Cation Transporters: OCT1, OCT2, and OCT3 | 297 | ||
| Organic Cation Transporter Structure | 299 | ||
| Regulation of OCT-Mediated Transport | 300 | ||
| Apical Organic Cation Transporters: MATE1 and MATE2/2-K | 300 | ||
| MATE Structure | 301 | ||
| Regulation of MATE-Mediated Transport | 301 | ||
| Organic Anions | 301 | ||
| Physiology of Organic Anion Transport | 301 | ||
| Molecular Biology of Organic Anion Transport | 302 | ||
| NaDC Family | 303 | ||
| NaDC1 | 303 | ||
| NaDC3 | 303 | ||
| OAT Family | 304 | ||
| Basolateral OATs | 305 | ||
| Apical OATs | 305 | ||
| OATP Family | 305 | ||
| Clinical Relevance of Organic Anion Transporters | 305 | ||
| Disorders of Citrate Transport | 305 | ||
| Uric Acid | 306 | ||
| Uric Acid Reabsorption | 307 | ||
| Uric Acid Secretion | 307 | ||
| Drugs That Affect Renal Urate Handling | 307 | ||
| Amino Acids | 308 | ||
| Physiology of Renal Amino Acid Transport | 308 | ||
| Molecular Biology of Amino Acid Transport | 308 | ||
| Overview of the Complexity | 308 | ||
| Neutral Amino Acids | 308 | ||
| Apical Transporters | 308 | ||
| B0AT1 (SLC6A19). | 308 | ||
| Hartnup’s Disorder. | 308 | ||
| B0AT3 (SLC6A18). | 310 | ||
| IMINOB (SLC6A20). | 310 | ||
| PAT2 (SLC36A2). | 310 | ||
| Iminoglycinuria. | 310 | ||
| TauT (SLC6A6). | 310 | ||
| Other Transporters of Neutral Amino Acids: ASCT2 (SLC1A5). | 311 | ||
| Ancillary Proteins for B0AT1, B0AT3, and IMINOB. | 311 | ||
| TAT1 (SLC16A10). | 311 | ||
| 4F2hc/LAT2 (SLC3A2/SLC7A9). | 311 | ||
| Other Neutral Amino Acid Transporters | 312 | ||
| Cationic Amino Acids | 312 | ||
| Apical Transporters | 312 | ||
| rBAT/b0,+AT (SLC3A1/SLC7A9). | 313 | ||
| Cystinuria. | 313 | ||
| Oligomeric Structure and Biogenesis of rBAT/b0,+AT. | 313 | ||
| Basolateral Transporters | 314 | ||
| 4F2hc/y+LAT1 (SLC3A2/SLC7A7). | 314 | ||
| Lysinuric Protein Intolerance. | 314 | ||
| Anionic Amino Acids | 314 | ||
| EAAT3 (SLC1A1). | 314 | ||
| Dicarboxylic Aminoaciduria. | 315 | ||
| Basolateral AGT1. | 315 | ||
| Structural Information of Amino Acid Transporters | 315 | ||
| 5 + 5 Inverted Repeat Fold | 315 | ||
| SLC6 Transporters | 315 | ||
| Heteromeric Amino Acid Transporters | 317 | ||
| Key References | 318 | ||
| References | 320 | ||
| 9 Renal Acidification Mechanisms | 329 | ||
| Chapter Outline | 329 | ||
| Bicarbonate Reabsorption | 329 | ||
| Proximal Tubule | 329 | ||
| General Transport Mechanisms | 329 | ||
| Transporters Involved in Proximal Tubule Bicarbonate Reabsorption | 330 | ||
| Na+-H+ Exchangers | 330 | ||
| H+-ATPase | 330 | ||
| Electroneutral Sodium-Bicarbonate Cotransporter | 331 | ||
| Carbonic Anhydrase | 332 | ||
| Carbonic Anhydrase II. | 332 | ||
| Carbonic Anhydrase IV. | 332 | ||
| Regulation of Proximal Tubule Bicarbonate Reabsorption | 332 | ||
| Systemic Acid-Base | 332 | ||
| Luminal Flow Rate | 332 | ||
| Angiotensin II | 332 | ||
| Potassium | 332 | ||
| Endothelin | 332 | ||
| Parathyroid Hormone | 332 | ||
| Calcium-Sensing Receptor | 333 | ||
| Loop of Henle | 333 | ||
| Regulation of Thick Ascending Limb Bicarbonate Reabsorption | 333 | ||
| Acid-Base Transporters in the Thick Ascending Limb | 333 | ||
| Electroneutral Sodium-Bicarbonate Transporter 1 | 333 | ||
| Distal Convoluted Tubule | 333 | ||
| Collecting Duct | 334 | ||
| Collecting Duct Segments | 334 | ||
| Cell Composition | 334 | ||
| Type A Intercalated Cell | 334 | ||
| Type B Intercalated Cell | 336 | ||
| Non-A, Non-B or Type C Intercalated Cell | 336 | ||
| Principal Cells | 336 | ||
| IMCD Cell | 336 | ||
| Functional Role of Different Collecting Duct Segments | 336 | ||
| Connecting Tubule and Initial Collecting Tubule | 336 | ||
| Cortical Collecting Duct | 337 | ||
| Outer Medullary Collecting Duct | 337 | ||
| Inner Medullary Collecting Duct | 337 | ||
| Proteins Involved in Collecting Duct H+/Bicarbonate Transport | 337 | ||
| H+-ATPase | 337 | ||
| H+-K+-ATPase | 337 | ||
| Carbonic Anhydrase | 338 | ||
| Kidney Anion Exchanger 1 | 338 | ||
| Cl− Channel | 338 | ||
| Other Anion Exchangers | 338 | ||
| Sodium-Bicarbonate Cotransporters | 338 | ||
| Regulation of Collecting Duct Acid-Base Transport | 339 | ||
| Acidosis | 339 | ||
| Alkalosis | 339 | ||
| Hormonal Regulation of Collecting Duct Acid-Base Transport | 339 | ||
| Paracrine Regulation | 340 | ||
| Cellular Adaptations to Acid-Base Perturbations | 340 | ||
| Bicarbonate Generation | 341 | ||
| Titratable Acid Excretion | 341 | ||
| Phosphate as a Titratable Acid | 341 | ||
| Other Urinary Buffers | 342 | ||
| Organic Anion Excretion | 342 | ||
| Citrate Excretion | 342 | ||
| Other Organic Anions | 343 | ||
| Ammonia Metabolism | 343 | ||
| Ammonia Chemistry | 343 | ||
| Ammonia Production | 343 | ||
| Glutamine Transport in Ammoniagenesis | 344 | ||
| Ammonia Transport | 346 | ||
| Specific Proteins Involved in Renal Ammonia Metabolism | 348 | ||
| Phosphate-Dependent Glutaminase | 348 | ||
| Glutamate Dehydrogenase | 348 | ||
| Potassium Channels | 349 | ||
| Na+-K+-2Cl− Cotransport | 349 | ||
| Na+-K+-ATPase | 349 | ||
| H+-K+-ATPase | 349 | ||
| Aquaporins | 349 | ||
| Carbonic Anhydrase | 349 | ||
| Rh Glycoproteins | 350 | ||
| Rhag. | 350 | ||
| Rhbg. | 350 | ||
| Rhcg. | 350 | ||
| CO2 Transport by Rh Glycoproteins. | 350 | ||
| Sulfatides | 350 | ||
| Acid-Base Sensors | 351 | ||
| Acid/Alkali–Sensing Receptors | 351 | ||
| G-Protein–Coupled Receptor 4 | 351 | ||
| Insulin Receptor–Related Receptor | 351 | ||
| Kinases | 351 | ||
| Pyk2/ET-B Receptor Pathway | 351 | ||
| Receptor Tyrosine Kinase | 351 | ||
| Bicarbonate-Stimulated Adenylyl Cyclase | 351 | ||
| Diurnal Variation in Acid Excretion | 351 | ||
| Acknowledgements | 351 | ||
| Key References | 351 | ||
| References | 353 | ||
| 10 Urine Concentration and Dilution | 362 | ||
| Chapter Outline | 362 | ||
| Independent Regulation of Water and Salt Excretion | 362 | ||
| Critical Role of Parallel Organization of Structures in the Renal Medulla to Urinary Concentrating and Diluting Process | 363 | ||
| Renal Tubules | 363 | ||
| Loops of Henle | 363 | ||
| Distal Tubule Segments in the Cortical Labyrinth | 365 | ||
| Collecting Duct System | 366 | ||
| Vasculature | 366 | ||
| Medullary Interstitium | 366 | ||
| Renal Pelvis | 368 | ||
| Urine Concentration and Dilution Processes Along the Mammalian Nephron | 368 | ||
| Sites of Urine Concentration and Dilution | 368 | ||
| Mechanism of Tubule Fluid Dilution | 369 | ||
| Mechanism of Tubule Fluid Concentration | 369 | ||
| Generation of the Axial Sodium Chloride Gradient in the Renal Outer Medulla | 369 | ||
| Accumulation of Urea in the Renal Inner Medulla | 372 | ||
| Collecting Duct Water Absorption and Osmotic Equilibration | 374 | ||
| Determinants of Concentrating Ability | 375 | ||
| An Unresolved Question: Concentration of Sodium Chloride in the Renal Inner Medulla | 375 | ||
| The “Passive Mechanism” | 376 | ||
| Concentrating Mechanism Driven by External Solute | 376 | ||
| Hyaluronan as a Mechano-osmotic Transducer | 377 | ||
| Molecular Physiology of Urinary Concentrating and Diluting Processes | 377 | ||
| Aquaporin-1 Knockout Mice | 377 | ||
| Aquaporin-2 Knockout Mice | 380 | ||
| Aquaporin-3 and Aquaporin-4 Knockout Mice | 380 | ||
| UT-A1/3 Urea Transporter Knockout Mice | 380 | ||
| Na+-H+-Exchanger Isoform 3 and Na-K-2Cl Cotransporter Type 2 Knockout Mice | 382 | ||
| Epithelial Sodium Channel Knockout Mice | 382 | ||
| Kidney-Specific Chloride Channel 1 Knockout Mice | 382 | ||
| Renal Outer Medullary Potassium Channel Knockout Mice | 382 | ||
| Type 2 Vasopressin Receptor Knockout Mice | 382 | ||
| Acknowledgments | 383 | ||
| Key References | 383 | ||
| References | 385 | ||
| 11 The Cell Biology of Vasopressin Action | 390 | ||
| Chapter Outline | 390 | ||
| Vasopressin—the Antidiuretic Hormone | 391 | ||
| The Type 2 Vasopressin Receptor— a G Protein–Coupled Receptor | 391 | ||
| Interaction of Type 2 Vasopressin Receptor with Heterotrimeric G Proteins and β-Arrestin | 391 | ||
| Fate of the Type 2 Vasopressin Receptor after Internalization—Delivery to Lysosomes | 393 | ||
| Diabetes Insipidus (Central and Nephrogenic) | 394 | ||
| Central (Neurohypophyseal) Diabetes Insipidus | 394 | ||
| Nephrogenic Diabetes Insipidus | 394 | ||
| The Aquaporins—a Family of Water Channel Proteins | 395 | ||
| Other Permeability Properties of Aquaporins | 395 | ||
| Aquaporin-2: the Vasopressin-Sensitive Collecting Duct Water Channel | 395 | ||
| An Overview of Vasopressin-Regulated Aquaporin-2 Trafficking in Collecting Duct Principal Cells | 396 | ||
| Use of in Vitro Systems to Examine Aquaporin-2 Trafficking and Function | 397 | ||
| Expression of Aquaporins in Xenopus Oocytes | 397 | ||
| Expression of Aquaporins in Nonepithelial Cells | 397 | ||
| Transfected Polarized Cells Expressing Exogenous Aquaporin-2 | 397 | ||
| Cells Expressing Endogenous Aquaporin-2 | 398 | ||
| Use of Kidney Tissue Slices and Isolated Collecting Duct to Examine Aquaporin-2 Trafficking | 398 | ||
| Expression of Multiple Basolateral Aquaporins (Aquaporin-2, Aquaporin-3, And/or Aquaporin-4) in Principal Cells | 398 | ||
| A Role of Basolateral Aquaporin-2 in Cell Migration and Tubule Morphogenesis | 399 | ||
| Intracellular Pathways of Aquaporin-2 Trafficking | 400 | ||
| Role of Clathrin-Coated Pits in Aquaporin-2 Recycling | 400 | ||
| Aquaporin-2 Localization in Intracellular Compartments during Recycling | 400 | ||
| Aquaporin-2 is a Constitutively Recycling Membrane Protein | 400 | ||
| Regulation of Aquaporin-2 Trafficking | 400 | ||
| Role of Kinases and a-Kinase Anchoring Proteins in Aquaporin-2 Trafficking | 401 | ||
| Importance of the S256 Residue for Aquaporin-2 Membrane Accumulation | 402 | ||
| Other Phosphorylation Sites (S261, S264, S269) are Modified by Vasopressin | 402 | ||
| Role of Phosphorylation in Exocytosis and Endocytosis of Aquaporin-2 | 402 | ||
| Phosphorylation of S256 Modulates Aquaporin-2 Interaction with Endocytotic Proteins | 402 | ||
| Role of the Actin Cytoskeleton in Aquaporin-2 Trafficking | 403 | ||
| Identification of Actin-Associated Proteins Potentially Involved in Aquaporin-2 Trafficking | 403 | ||
| Microtubules and Aquaporin-2 Trafficking | 404 | ||
| SNARE Proteins and Aquaporin-2 Trafficking | 404 | ||
| Long-Term Regulation of Water Balance | 405 | ||
| Acquired Water Balance Disorders | 406 | ||
| Lithium Treatment | 406 | ||
| Electrolyte Abnormalities: Hypokalemia and Hypercalcemia | 408 | ||
| Obstruction of the Urinary Tract | 408 | ||
| Acute and Chronic Renal Injury | 408 | ||
| Liver Cirrhosis and Congestive Heart Failure | 408 | ||
| Novel Approaches for X-Linked Nephrogenic Diabetes Insipidus Therapy | 409 | ||
| Vasopressin Receptor–Independent Membrane Insertion of Aquaporin-2—Potential Strategies for Treating Nephrogenic Diabetes Insipidus | 409 | ||
| Phosphodiesterase Inhibitors | 409 | ||
| Calcitonin and Secretin | 410 | ||
| Statins | 410 | ||
| Prostaglandins | 410 | ||
| Heat Shock Protein 90 | 410 | ||
| Acknowledgments | 411 | ||
| Key References | 411 | ||
| References | 412 | ||
| 12 Aldosterone and Mineralocorticoid Receptors | 421 | ||
| Chapter Outline | 421 | ||
| General Introduction to Aldosterone and Mineralocorticoid Receptors | 422 | ||
| Aldosterone Synthesis | 423 | ||
| Mechanisms of Mineralocorticoid Receptor Function and Gene Regulation | 424 | ||
| Mineralocorticoid Receptor Function as a Hormone-Regulated Transcription Factor: General Features and Subcellular Localization | 424 | ||
| Domain Structure of Mineralocorticoid Receptors | 425 | ||
| DNA-Binding Domain | 425 | ||
| Ligand/Hormone-Binding Domain | 426 | ||
| N-Terminal Domain | 428 | ||
| Mineralocorticoid Receptor Regulation of Transcription Initiation: Coactivators and Corepressors | 428 | ||
| Regulation of Sodium Absorption and Potassium Secretion | 428 | ||
| General Model of Aldosterone Action | 428 | ||
| Aldosterone and Epithelial Sodium Channel Trafficking | 429 | ||
| Basolateral Membrane Effects of Aldosterone | 430 | ||
| Activation of the Epithelial Sodium Channel by Proteolytic Cleavage | 430 | ||
| Potassium Secretion and Aldosterone | 430 | ||
| Separation of Sodium Absorption and Potassium Secretion by the Aldosterone-Sensitive Distal Nephron | 431 | ||
| Role of Distal Tubule Fluid Delivery | 431 | ||
| Independent Regulation of Sodium and Potassium Transporters | 431 | ||
| Electroneutral Versus Electrogenic Sodium Reabsorption | 431 | ||
| Shift to Medullary Collecting Duct | 432 | ||
| Regulation of Chloride Transport | 432 | ||
| Differential Regulation of Intercalated Cell Mineralocorticoid Receptor | 432 | ||
| Aldosterone-Independent ENaC-Mediated Sodium Reabsorption in the Distal Nephron | 432 | ||
| Sites of Mineralocorticoid Receptor Expression and Locus of Action Along the Nephron | 433 | ||
| Aldosterone-Sensitive Distal Nephron | 433 | ||
| Other Sites of Expression | 433 | ||
| Glomerulus | 433 | ||
| Proximal Convoluted Tubule | 433 | ||
| Medullary Thick Ascending Limb | 433 | ||
| Distal Convoluted Tubule | 433 | ||
| Nonrenal Aldosterone-Responsive Tight Epithelia | 433 | ||
| Colon | 434 | ||
| Lung | 435 | ||
| Exocrine Glands and Sensors | 435 | ||
| Role of Serum- and Glucocorticoid-Regulated Kinase in Mediating Aldosterone Effects | 435 | ||
| Induction of SGK1 by Aldosterone | 435 | ||
| Molecular Mechanisms of SGK1 Action in the Aldosterone-Sensitive Distal Nephron | 436 | ||
| SGK1 Inhibits the Ubiquitin Ligase Nedd4-2 | 436 | ||
| SGK1 Enhances Epithelial Sodium Channel Activity Independently of Nedd4-2 | 437 | ||
| SGK1 Stimulates the Components of Sodium Transport Machinery | 437 | ||
| SGK1 Stimulates Potassium Secretion in the Aldosterone-Sensitive Distal Nephron | 437 | ||
| 11β-Hydroxysteroid Dehydrogenase Type 2 | 438 | ||
| 11β-HSD2: An Essential Determinant of Mineralocorticoid Specificity | 438 | ||
| Sites Of 11β-HSD2 Expression | 438 | ||
| Impact of 11β-HSD2 on Mineralocorticoid Receptor Activity | 438 | ||
| Apparent Mineralocorticoid Excess: A Disease of Defective 11β-HSD2 | 438 | ||
| Role of 11β-HSD2 in blood vessels | 438 | ||
| Summary of 11β-HSD2 Roles | 439 | ||
| Nongenomic Effects of Aldosterone | 439 | ||
| Disease States | 439 | ||
| Primary Aldosteronism | 439 | ||
| Congestive Heart Failure | 440 | ||
| Chronic Kidney Disease | 440 | ||
| Nonepithelial Actions of Aldosterone | 440 | ||
| Acknowledgment | 441 | ||
| Key References | 441 | ||
| References | 443 | ||
| 13 Vasoactive Molecules and the Kidney | 452 | ||
| Chapter Outline | 452 | ||
| Renin-Angiotensin-Aldosterone System | 452 | ||
| Classical Renin-Angiotensin- Aldosterone System | 453 | ||
| Angiotensinogen | 453 | ||
| Renin | 453 | ||
| Prorenin Activation | 454 | ||
| Regulation of Renin Secretion | 454 | ||
| Renal Baroreceptor | 454 | ||
| Neural Control | 454 | ||
| Tubular Control | 454 | ||
| Metabolic Control | 455 | ||
| Other Local Factors | 455 | ||
| Plasma Prorenin and Renin | 455 | ||
| Angiotensin-Converting Enzyme | 455 | ||
| Angiotensin Type 1 Receptor | 455 | ||
| G Protein–Mediated Signaling | 456 | ||
| Reactive Oxygen Species | 456 | ||
| Tyrosine Kinases | 456 | ||
| Angiotensin Type 1 Receptor Internalization | 457 | ||
| Angiotensin Type 1 Receptor Dimerization | 457 | ||
| Ligand-Independent Angiotensin Type 1 Receptor Activation | 457 | ||
| Physiologic Effects of Angiotensin II in the Kidney | 457 | ||
| Hemodynamic Actions | 458 | ||
| Tubular Transport | 458 | ||
| Sodium | 458 | ||
| Acid-Base Regulation | 458 | ||
| Expanded Renin-Angiotensin-Aldosterone System: Enzymes, Angiotensin Peptides, and Receptors | 458 | ||
| Angiotensin Type 2 Receptor | 458 | ||
| (Pro)Renin Receptor | 458 | ||
| Angiotensin-Converting Enzyme 2 | 459 | ||
| Angiotensin Peptides | 459 | ||
| Angiotensin III, or Angiotensin-(2-8) | 459 | ||
| Angiotensin IV, or Angiotensin-(3-8) | 459 | ||
| Angiotensin-(1-7) | 460 | ||
| Angiotensin-(2-10) | 460 | ||
| Angiotensin-(1-12) | 460 | ||
| Angiotensin A and Alamandine | 460 | ||
| Intrarenal Renin-Angiotensin- Aldosterone System | 460 | ||
| Intracrine Renin-Angiotensin-Aldosterone System | 460 | ||
| Renin-Angiotensin-Aldosterone System in Kidney Pathophysiology | 461 | ||
| Fibrosis | 461 | ||
| Proteinuria | 461 | ||
| Inflammation, Immunity, and the Renin–Angiotensin-Aldosterone System | 461 | ||
| Diabetes Paradox | 461 | ||
| Endothelin | 462 | ||
| Structure, Synthesis, and Secretion of the Endothelins | 462 | ||
| Endothelin Receptors | 463 | ||
| Physiologic Actions of Endothelin in the Kidney | 463 | ||
| Role of Endothelin in Essential Hypertension | 463 | ||
| Role of Endothelin in Renal Injury | 464 | ||
| Endothelin System in Chronic Kidney Disease and Diabetic Nephropathy | 464 | ||
| Endothelin System and Other Kidney Diseases | 465 | ||
| Endotoxemia | 465 | ||
| Systemic Lupus Erythematosus | 465 | ||
| Hepatorenal Syndrome | 465 | ||
| Preeclampsia | 465 | ||
| Safety Profile of Endothelin Receptor Antagonists | 465 | ||
| Natriuretic Peptides | 466 | ||
| Structure and Synthesis of the Natriuretic Peptides | 466 | ||
| Atrial Natriuretic Peptide | 466 | ||
| Brain Natriuretic Peptide | 467 | ||
| C-Type Natriuretic Peptide | 467 | ||
| Dendroaspis Natriuretic Peptide | 467 | ||
| Urodilatin | 468 | ||
| Natriuretic Peptide Receptors | 468 | ||
| Neutral Endopeptidase | 468 | ||
| Actions of the Natriuretic Peptides | 469 | ||
| Renal Effects of the Natriuretic Peptides | 469 | ||
| Cardiovascular Effects | 469 | ||
| Other Effects of the Natriuretic Peptides | 469 | ||
| Natriuretic Peptides as Biomarkers of Disease | 470 | ||
| Brain Natriuretic Peptide and N-Terminal Pro–Brain Natriuretic Peptide as Biomarkers of Heart Failure | 470 | ||
| Role of Brain Natriuretic Peptide and N-Terminal Pro–Brain Natriuretic Peptide as Biomarkers in Renal Disease | 470 | ||
| Therapeutic Uses of Natriuretic Peptides | 471 | ||
| Recombinant Atrial Natriuretic Peptide | 471 | ||
| Recombinant Brain Natriuretic Peptide | 471 | ||
| Therapeutic Uses of Other Natriuretic Peptides | 471 | ||
| Neutral Endopeptidase Inhibition | 472 | ||
| Vasopeptidase Inhibitors | 472 | ||
| Combination Angiotensin Receptor Blockers and Neutral Endopeptidase Inhibitors | 472 | ||
| Other Natriuretic Peptides | 473 | ||
| Guanylin and Uroguanylin | 473 | ||
| Adrenomedullin | 473 | ||
| Kallikrein-Kinin System | 473 | ||
| Components of the Kallikrein-Kinin System | 473 | ||
| Kininogen | 473 | ||
| Kallikrein | 473 | ||
| Kinins | 474 | ||
| Bradykinin Receptors | 474 | ||
| Kallistatin | 474 | ||
| Kininases | 474 | ||
| Plasma and Tissue Kallikrein-Kinin System | 474 | ||
| Renal Kallikrein-Kinin System | 475 | ||
| Regulation of Tubular Transport by Tissue Kallikrein | 476 | ||
| Kallikrein-Kinin System in Renal Disease | 476 | ||
| Hypertension | 476 | ||
| Diabetic Nephropathy | 476 | ||
| Ischemic Renal Injury | 477 | ||
| Chronic Kidney Disease | 477 | ||
| Lupus Nephritis/Anti–Glomerular Basement Membrane Disease | 477 | ||
| Antineutrophil Cytoplasmic Antibody–Associated Vasculitis | 477 | ||
| Urotensin II | 478 | ||
| Synthesis, Structure, and Secretion of Urotensin II | 478 | ||
| Physiologic Role of Urotensin II | 478 | ||
| Urotensin II in the Kidney | 479 | ||
| Observational Studies of Urotensin II in Renal Disease | 479 | ||
| Interventional Studies of Urotensin II in the Kidney | 479 | ||
| Key References | 479 | ||
| References | 481 | ||
| 14 Arachidonic Acid Metabolites and the Kidney | 492 | ||
| Chapter Outline | 492 | ||
| Cellular Origin of Eicosanoids | 493 | ||
| Cyclo-Oxygenase Pathway | 493 | ||
| Molecular Biology | 493 | ||
| Regulation of Cyclo-Oxygenase Gene Expression | 495 | ||
| Regulation of Cyclo-Oxygenase Expression By Antiinflammatory Steroids | 495 | ||
| Enzymatic Chemistry | 495 | ||
| Renal COX-1 and COX-2 Expression | 495 | ||
| COX-2 Expression in the Kidney | 495 | ||
| COX-2 Expression in the Renal Cortex | 495 | ||
| COX-2 Expression in the Renal Medulla | 498 | ||
| COX-1 Expression in the Kidney | 499 | ||
| Renal Complications of Nonsteroidal Antiinflammatory Drugs | 499 | ||
| Na+ Retention, Edema, and Hypertension | 499 | ||
| Hyperkalemia | 500 | ||
| Papillary Necrosis | 500 | ||
| Acute Kidney Injury | 500 | ||
| Interstitial Nephritis | 501 | ||
| Nephrotic Syndrome | 501 | ||
| Renal Dysgenesis | 501 | ||
| Cardiovascular Effects of COX-2 Inhibitors | 501 | ||
| Effects of COX-2 Inhibition on Vascular Tone | 501 | ||
| Increased Cardiovascular Thrombotic Events | 501 | ||
| Prostanoid Synthases | 502 | ||
| Sources and Nephronal Distribution of Cyclo-Oxygenase Products | 502 | ||
| Thromboxane Synthase | 503 | ||
| Prostacyclin Synthase | 503 | ||
| Prostaglandin D Synthase | 503 | ||
| Prostaglandin F Synthesis | 503 | ||
| Prostaglandin 9-Ketoreductase | 503 | ||
| Prostaglandin E Synthases | 504 | ||
| Prostanoid Receptors | 504 | ||
| TP Receptors | 504 | ||
| IP Receptors | 507 | ||
| DP Receptors | 507 | ||
| FP Receptors | 507 | ||
| Multiple EP Receptors | 508 | ||
| EP1 Receptors | 508 | ||
| EP2 Receptors | 508 | ||
| EP3 Receptors | 509 | ||
| EP4 Receptor | 510 | ||
| Regulation of Renal Function by EP Receptors | 510 | ||
| Renal Cortical Hemodynamics | 510 | ||
| Renin Release | 510 | ||
| Renal Microcirculation | 511 | ||
| Effects of COX-1 and COX-2 Metabolites on Salt and Water Transport | 511 | ||
| Proximal Tubule | 511 | ||
| Loop of Henle | 511 | ||
| Collecting Duct System | 512 | ||
| Water Transport | 512 | ||
| Metabolism of Prostaglandins | 512 | ||
| 15-Ketodehydrogenase | 512 | ||
| ω/ω-1 Hydroxylation of Prostaglandins | 512 | ||
| Cyclopentenone Prostaglandins | 512 | ||
| Nonenzymatic Metabolism of Arachidonic Acid | 513 | ||
| Prostaglandin Transport and Urinary Excretion | 513 | ||
| Involvement of Cyclo-Oxygenase Metabolites in Renal Pathophysiology | 513 | ||
| Experimental and Human Glomerular Injury | 513 | ||
| Glomerular Inflammatory Injury | 513 | ||
| Glomerular Noninflammatory Injury | 514 | ||
| Acute Kidney Injury | 515 | ||
| Urinary Tract Obstruction | 515 | ||
| Allograft Rejection and Cyclosporine Nephrotoxicity | 516 | ||
| Allograft Rejection | 516 | ||
| Calcineurin Inhibitor Nephrotoxicity | 516 | ||
| Hepatic Cirrhosis and Hepatorenal Syndrome | 516 | ||
| Diabetes Mellitus | 516 | ||
| Pregnancy | 516 | ||
| Lithium Nephrotoxicity | 517 | ||
| Role of Reactive Oxygen Species as Mediators of COX-2 Actions | 517 | ||
| Lipoxygenase Pathway | 517 | ||
| Biologic Activities of Lipoxygenase Products in the Kidney | 519 | ||
| Involvement of Lipoxygenase Products in Renal Pathophysiology | 519 | ||
| Cytochrome P450 Pathway | 520 | ||
| Vasculature | 521 | ||
| 20-Hydroxyeicosatetraenoic Acid | 521 | ||
| Epoxides | 521 | ||
| Autoregulation | 522 | ||
| Tubuloglomerular Feedback | 522 | ||
| Tubules | 522 | ||
| Proximal Tubule | 522 | ||
| Thick Ascending Limb of the Loop of Henle | 523 | ||
| Collecting Duct | 523 | ||
| Role in Acute And Chronic Kidney Disease | 523 | ||
| Role in Hypertension | 523 | ||
| Acknowledgments | 523 | ||
| Key References | 524 | ||
| References | 526 | ||
| II Disorders of Body Fluid Volume and Composition | 539 | ||
| 15 Disorders of Sodium Balance | 540 | ||
| Chapter Outline | 540 | ||
| Physiology | 540 | ||
| Sodium Balance | 541 | ||
| Effective Arterial Blood Volume | 543 | ||
| Regulation of Effective Arterial Blood Volume | 544 | ||
| Afferent Limb: Sensing of Effective Arterial Blood Volume | 544 | ||
| Sensors of Cardiac Filling | 544 | ||
| Atrial Sensors. | 544 | ||
| Neural Pathways. | 545 | ||
| Humoral Pathways. | 545 | ||
| Ventricular and Pulmonary Sensors. | 545 | ||
| Sensors of Cardiac Output | 546 | ||
| Carotid and Aortic Baroceptors. | 546 | ||
| Sensors of Organ Perfusion | 546 | ||
| Renal Sensors. | 546 | ||
| Central Nervous System Sensors. | 547 | ||
| Gastrointestinal Tract Sensors. | 547 | ||
| Hepatoportal Receptors. | 547 | ||
| Intestinal Natriuretic Hormones: Guanylin Peptides. | 547 | ||
| Efferent Limb: Effector Mechanisms for Maintaining Effective Arterial Blood Volume | 548 | ||
| Integration of Changes in Glomerular Filtration Rate and Tubular Reabsorption | 548 | ||
| Tubuloglomerular Feedback | 549 | ||
| Glomerulotubular Balance | 550 | ||
| Peritubular Capillary Starling Forces. | 550 | ||
| Luminal Composition. | 552 | ||
| Physical Factors Beyond the Proximal Tubule. | 552 | ||
| Medullary Hemodynamics and Interstitial Pressure in the Control of Sodium Excretion: Pressure Natriuresis. | 552 | ||
| Neural Mechanisms: Renal Nerves and Sympathetic Nervous System | 555 | ||
| Humoral Mechanisms | 557 | ||
| Renin-Angiotensin-Aldosterone System. | 557 | ||
| Vasopressin. | 559 | ||
| Prostaglandins. | 561 | ||
| Natriuretic Peptides. | 563 | ||
| Atrial Natriuretic Peptide. | 563 | ||
| Brain Natriuretic Peptide. | 564 | ||
| C-Type Natriuretic Peptide. | 564 | ||
| D-Type Natriuretic Peptide. | 565 | ||
| Endothelium-Derived Factors. | 565 | ||
| Endothelin. | 565 | ||
| Nitric Oxide. | 566 | ||
| Kinins. | 567 | ||
| Adrenomedullin. | 568 | ||
| Urotensin. | 568 | ||
| Digitalis-Like Factors. | 569 | ||
| Neuropeptide Y. | 569 | ||
| Apelin. | 569 | ||
| Glucagon-Like Peptide-1 | 570 | ||
| Novel Factors | 570 | ||
| Sodium Balance Disorders | 571 | ||
| Hypovolemia | 571 | ||
| Definition | 571 | ||
| Etiology | 571 | ||
| Pathophysiology | 571 | ||
| Absolute Hypovolemia | 571 | ||
| Extrarenal. | 571 | ||
| 9780323262590v2_WEB | 1805 | ||
| Front Cover | 1805 | ||
| endsheet 2 | 1806 | ||
| Brenner & Rector’s The Kidney | 1807 | ||
| Copyright Page | 1808 | ||
| Dedication | 1809 | ||
| Contributors | 1810 | ||
| Foreword | 1825 | ||
| Preface | 1827 | ||
| Table of Contents | 1829 | ||
| V Disorders of Kidney Structure and Function | 1832 | ||
| 40 Urolithiasis | 1832 | ||
| Chapter Outline | 1832 | ||
| Epidemiology | 1832 | ||
| General Points | 1832 | ||
| Kidney Stones in Adult Population: 1976-1994 | 1832 | ||
| Kidney Stones in the Adult Population: 2007-2010 | 1833 | ||
| Calcium Stones | 1833 | ||
| Prevalence of Calcium Stones | 1833 | ||
| Calcium Intake | 1834 | ||
| Oxalate Intake | 1834 | ||
| Protein Consumption | 1834 | ||
| Uric Acid Stones | 1834 | ||
| Prevalence of Uric Acid Stones | 1834 | ||
| Genetic and Dietary Factors | 1834 | ||
| Data on Stone Incidence | 1834 | ||
| Histopathology | 1835 | ||
| Idiopathic Calcium Oxalate Stones | 1835 | ||
| Calcium Phosphate Stones | 1835 | ||
| Stones in Enteric Hyperoxaluria | 1835 | ||
| Pathophysiology | 1835 | ||
| Physical Chemistry of Urinary Saturation | 1835 | ||
| General Concepts | 1835 | ||
| Factors Influencing Saturation | 1837 | ||
| Urine Saturation Measurements | 1837 | ||
| Upper Limit of Metastability and Formation Product | 1837 | ||
| Activity Product Ratio | 1837 | ||
| Concentration Product Ratio | 1838 | ||
| Use of Software | 1838 | ||
| Urine Saturation in Stone Formers | 1838 | ||
| Assessment of Nucleation | 1838 | ||
| Assessment of Crystal Growth and Aggregation | 1839 | ||
| Cell-Crystal Interactions | 1839 | ||
| Kidney Stone Inhibitors | 1839 | ||
| Magnesium | 1839 | ||
| Citrate | 1840 | ||
| Pyrophosphate | 1840 | ||
| Macromolecules | 1840 | ||
| Osteopontin | 1840 | ||
| Tamm-Horsfall Protein | 1840 | ||
| Urinary Prothrombin Fragment 1 | 1840 | ||
| Bikunin | 1840 | ||
| Glycosaminoglycans | 1841 | ||
| Matrix-Gla Protein | 1841 | ||
| Urinary Trefoil Factor 1 | 1841 | ||
| Calcium Stones | 1841 | ||
| Hypercalciuria | 1841 | ||
| Intestinal Hyperabsorption of Calcium | 1841 | ||
| 1,25-Dihydroxyvitamin D Dependence. | 1841 | ||
| 1,25-Dihydroxyvitamin D–Independent Absorptive Hypercalciuria. | 1842 | ||
| Increased Abundance of Vitamin D Receptor. | 1843 | ||
| Genetic Hypercalciuric Rat Model of Hypercalciuria | 1843 | ||
| Renal Leak Hypercalciuria | 1844 | ||
| Resorptive Hypercalciuria | 1845 | ||
| Parathyroid Hormone–Dependent Resorptive Hypercalciuria. | 1845 | ||
| Parathyroid Hormone–Independent Resorptive Hypercalciuria. | 1845 | ||
| Hyperuricosuria | 1845 | ||
| Pathophysiologic Mechanism of Hyperuricosuria | 1845 | ||
| Physicochemical Mechanism of Hyperuricosuria-Induced Calcium Stones | 1846 | ||
| Hypocitraturia | 1846 | ||
| Role of Acid-Base Status | 1846 | ||
| Other Factors | 1847 | ||
| Clinical Conditions | 1847 | ||
| Actions of Citrate | 1847 | ||
| Hyperoxaluria | 1847 | ||
| Increased Hepatic Production | 1847 | ||
| Dietary Intake and Bioavailability | 1849 | ||
| Intestinal Absorption | 1849 | ||
| Role of Anion Exchanger Slc26a6 | 1849 | ||
| Role of Oxalobacter formigenes | 1849 | ||
| Renal Excretion | 1850 | ||
| Clinical Hyperoxaluria | 1850 | ||
| Physicochemical Effects of Hyperoxaluria | 1850 | ||
| Alterations of Urinary pH | 1850 | ||
| Uric Acid Stones | 1851 | ||
| Physicochemistry of Uric Acid | 1851 | ||
| Pathophysiology of Uric Acid Stones | 1852 | ||
| Hyperuricosuria | 1852 | ||
| Low Urinary Volume | 1853 | ||
| Low Urinary pH | 1853 | ||
| Origin of Low Urinary pH. | 1853 | ||
| Increased Acid Load to Kidneys. | 1853 | ||
| Impaired NH4+ Excretion. | 1854 | ||
| Role of Renal Lipotoxicity | 1854 | ||
| Cystine Stones | 1855 | ||
| Overview | 1855 | ||
| Molecular Biology and Genetics | 1855 | ||
| Clinical Presentation | 1856 | ||
| Infection Stones | 1856 | ||
| Pathophysiology | 1856 | ||
| Uncommon Stones | 1857 | ||
| Genetic Causes | 1857 | ||
| Acquired Causes | 1857 | ||
| Genetics | 1858 | ||
| Human Genetics | 1858 | ||
| Familial Clustering | 1858 | ||
| Ethnicity | 1858 | ||
| Human Genetic Studies | 1858 | ||
| Twin Studies | 1858 | ||
| Candidate Genes | 1858 | ||
| Genomewide Association Studies | 1858 | ||
| Monogenic Causes of Urolithiasis | 1859 | ||
| Polygenic Animal Model | 1859 | ||
| Urolithiasis as a Systemic Disorder | 1860 | ||
| Obesity, Weight Gain, Diabetes Mellitus, and Risk for Urolithiasis | 1860 | ||
| Association between Metabolic Syndrome and Nephrolithiasis | 1860 | ||
| Urolithiasis and Risk for Cardiovascular Disease | 1861 | ||
| Urolithiasis and Hypertension | 1861 | ||
| Kidney Stone Disease and Chronic Kidney Disease | 1862 | ||
| Urinary Tract Cancers and Kidney Stones | 1862 | ||
| Calcium Stones and Bone Disease | 1862 | ||
| Epidemiology | 1862 | ||
| Pathophysiologic Mechanisms Linking Osteoporosis and Kidney Stones | 1862 | ||
| Dietary Factors | 1864 | ||
| Genetic Factors | 1864 | ||
| Hormones and Local Cytokines | 1865 | ||
| Clinical Evaluation | 1865 | ||
| Presentation | 1865 | ||
| Symptoms and Signs | 1865 | ||
| Environment, Lifestyle, and Medical History | 1865 | ||
| Family History | 1865 | ||
| Laboratory Evaluation | 1866 | ||
| Serum Chemistry | 1866 | ||
| Urine Chemistry | 1866 | ||
| Spot Urinalysis | 1866 | ||
| Simplified Metabolic Evaluation | 1866 | ||
| Extensive Metabolic Evaluation | 1866 | ||
| Urinary Supersaturation Estimation | 1867 | ||
| Stone Analysis | 1869 | ||
| Imaging Studies | 1869 | ||
| Kidneys, Ureters, and Bladder X-Ray | 1869 | ||
| Ultrasound | 1869 | ||
| Computed Tomography | 1869 | ||
| Intravenous Pyelography | 1869 | ||
| Magnetic Resonance Imaging | 1869 | ||
| Management OF Stones | 1870 | ||
| Acute Management | 1870 | ||
| Renal Colic | 1870 | ||
| Medical Expulsive Therapy | 1870 | ||
| Chronic Management | 1871 | ||
| Lifestyle and Dietary Treatment | 1871 | ||
| Fluid Intake | 1871 | ||
| Dietary Adjustment | 1871 | ||
| Calcium Intake. | 1871 | ||
| Dietary Oxalate. | 1871 | ||
| Ascorbic Acid. | 1871 | ||
| Dietary Intervention in Cystinuria. | 1871 | ||
| Other Dietary Interventions. | 1872 | ||
| Pharmacologic Treatment | 1872 | ||
| Thiazide Diuretics | 1872 | ||
| Alkali Treatment | 1872 | ||
| Xanthine Oxidase Inhibitors | 1874 | ||
| Cystine Chelation Therapy | 1875 | ||
| Pharmacotherapy of Infection-Related Stones | 1875 | ||
| Antibiotics. | 1875 | ||
| Dissolution Therapy. | 1875 | ||
| Urease Inhibitors. | 1875 | ||
| Urinary Acidification. | 1875 | ||
| Surgical Management of Infection-Related Stones | 1876 | ||
| Acknowledgments | 1876 | ||
| Key References | 1876 | ||
| References | 1878 | ||
| 41 Kidney Cancer | 1896 | ||
| Chapter Outline | 1896 | ||
| Benign Neoplasms of the Kidney | 1896 | ||
| Benign Epithelial Tumors | 1896 | ||
| Renal Cortical Adenoma | 1896 | ||
| Oncocytoma | 1896 | ||
| Metanephric Adenoma | 1896 | ||
| Benign Mesenchymal Tumors | 1896 | ||
| Angiomyolipoma | 1896 | ||
| Leiomyoma | 1897 | ||
| Juxtaglomerular Cell Tumor | 1897 | ||
| Renomedullary Interstitial Cell Tumor | 1897 | ||
| Hemangioma | 1897 | ||
| Other Rare Benign Mesenchymal Tumors | 1897 | ||
| Benign Cystic Neoplasms | 1897 | ||
| Multilocular Cystic Nephroma and Mixed Epithelial Stromal Tumor | 1897 | ||
| Malignant Neoplasms of the Kidney | 1898 | ||
| Renal Cell Carcinoma | 1898 | ||
| Epidemiology | 1898 | ||
| Pathology and Cytogenetics | 1899 | ||
| Molecular Biology and Hereditary Disorders | 1900 | ||
| Clinical and Laboratory Features | 1902 | ||
| Radiologic Diagnosis | 1903 | ||
| Staging and Prognosis | 1905 | ||
| Surgical Treatment | 1907 | ||
| Nephrectomy | 1907 | ||
| Nephron-Sparing Surgery | 1907 | ||
| Impact of Surgical Treatment for Renal Cell Carcinoma on Kidney Function | 1908 | ||
| Energy-Based Tissue Ablation | 1908 | ||
| Surveillance | 1908 | ||
| Lymph Node Dissection | 1908 | ||
| Vena Caval Involvement | 1909 | ||
| Cytoreductive Nephrectomy | 1909 | ||
| Resection of Metastatic Disease | 1909 | ||
| Systemic Therapy | 1909 | ||
| Adjuvant Therapy | 1909 | ||
| Neoadjuvant Therapy | 1910 | ||
| Targeted Agents | 1910 | ||
| Sunitinib. | 1910 | ||
| Sorafenib. | 1910 | ||
| Pazopanib. | 1911 | ||
| Axitinib. | 1911 | ||
| Bevacizumab. | 1912 | ||
| Temsirolimus. | 1912 | ||
| Everolimus. | 1912 | ||
| Vaccines | 1912 | ||
| Chemotherapy | 1913 | ||
| Immunotherapy | 1913 | ||
| Interferon alfa | 1913 | ||
| Interleukin-2 | 1913 | ||
| Renal Pelvic Tumors | 1913 | ||
| Clinical Features and Diagnostic Evaluation | 1914 | ||
| Staging and Grading of Renal Pelvic Tumors | 1914 | ||
| Treatment | 1914 | ||
| Other Kidney Tumors | 1914 | ||
| Renal Sarcomas | 1914 | ||
| Wilms’ Tumor | 1914 | ||
| Genetics | 1915 | ||
| Pathology and Staging | 1915 | ||
| Clinical Features | 1915 | ||
| Multimodality Treatment | 1915 | ||
| Key References | 1915 | ||
| References | 1917 | ||
| 42 Onco-Nephrology: | 1924 | ||
| Chapter Outline | 1924 | ||
| Acute Kidney Injury | 1925 | ||
| Multiple Myeloma | 1925 | ||
| Pathogenesis | 1925 | ||
| Kidney Involvement and Pathology | 1926 | ||
| Cast Nephropathy | 1926 | ||
| Light-Chain Deposition Disease | 1926 | ||
| Amyloid Light-Chain Amyloidosis | 1927 | ||
| Other Disorders in Multiple Myeloma | 1927 | ||
| Treatment of Cast Nephropathy | 1927 | ||
| General Measures | 1927 | ||
| Chemotherapy and Stem Cell Transplantation | 1927 | ||
| Extracorporeal Removal of Free Light Chains | 1927 | ||
| Therapeutic Plasma Exchange. | 1928 | ||
| High-Cutoff Hemodialysis. | 1928 | ||
| Hematopoietic Stem Cell Transplantation | 1928 | ||
| Acute Kidney Injury | 1929 | ||
| Chronic Kidney Disease | 1929 | ||
| Specific Kidney Diseases after Hematopoietic Stem Cell Transplantation | 1929 | ||
| Marrow Infusion Syndrome | 1929 | ||
| Sinusoidal Occlusion Syndrome | 1929 | ||
| Transplantation-Associated Thrombotic Microangiopathy | 1930 | ||
| Graft-Versus-Host Disease–Related Chronic Kidney Disease | 1930 | ||
| Tumor Lysis Syndrome | 1930 | ||
| Definitions | 1931 | ||
| Pathophysiology | 1931 | ||
| Treatment | 1931 | ||
| Chemotherapeutic Agents | 1932 | ||
| Cisplatin | 1932 | ||
| Ifosfamide | 1932 | ||
| Cyclophosphamide | 1932 | ||
| Methotrexate | 1933 | ||
| Biologic Agents | 1933 | ||
| Anti-Angiogenic Agents | 1933 | ||
| Cetuximab | 1933 | ||
| Miscellaneous Agents | 1933 | ||
| Calcineurin Inhibitors | 1933 | ||
| Bisphosphonates | 1934 | ||
| Hypercalcemia of Malignancy | 1934 | ||
| Radiation-Associated Kidney Injury | 1935 | ||
| Pathogenesis | 1935 | ||
| Epidemiology | 1935 | ||
| Total-Body Irradiation and Transplantation | 1935 | ||
| Clinical Presentation | 1936 | ||
| History | 1936 | ||
| Laboratory Findings | 1936 | ||
| Diagnosis | 1936 | ||
| Treatment | 1936 | ||
| Prognosis | 1936 | ||
| Leukemia and Lymphoma | 1936 | ||
| Lymphoma | 1937 |