Seldin and Giebisch's The Kidney - Physiology & Pathophysiology 1-2

Front cover

SELDIN AND GEIBISCH’S THE KIDNEY

Copyright page

Table of contents

List of contributors

Preface

VOLUME 1

SECTION I. Epithelial and Nonepithelial Transport and Regulation

Chapter 1. Epithelial Cell Structure and Polarity

INTRODUCTION

NATURE AND PHYSIOLOGIC IMPLICATIONS OF EPITHELIAL POLARITY

EPITHELIAL CELL STRUCTURE: MORPHOLOGY AND PHYSIOLOGY

BIOGENESIS OF EPITHELIAL POLARITY

SORTING PATHWAYS

EPITHELIAL CELL POLARITY AND RENAL DISEASE

Chapter 2. Mechanisms of Ion Transport Across Cell Membranes and Epithelia

INTRODUCTION

MECHANISMS OF ION TRANSPORT

ION TRANSPORT PROTEINS

ION TRANSPORT ACROSS EPITHELIA

Chaper 3. Renal Ion-Translocating ATPases: The P-Type Family

P-TYPE ATPASES

SERCA

PMCA

Na,K- AND H,K-ATPASE FAMILY

Na,K-ATPASE IN THE KIDNEY

H,K-ATPASES IN KIDNEY

Chapter 4. The Mammalian Transporter Families

INTRODUCTION

GLUTAMATE–NEUTRAL AMINO ACID TRANSPORTER FAMILY (SLC1)

FACILITATED GLUCOSE TRANSPORTER FAMILY (SLC2)

SLC3 FAMILY: ACTIVATORS OF CYSTINE, AND DIBASIC AND NEUTRAL AMINO ACID TRANSPORT

ANION EXCHANGERS–BICARBONATE COTRANSPORTER FAMILY (SLC4)

THE SODIUM–GLUCOSE COTRANSPORTER FAMILY (SLC5)

GABA TRANSPORTER FAMILY (SLC6)

AMINO ACID PERMEASE FAMILY (SLC7)

SODIUM–CALCIUM EXCHANGER FAMILY (SLC8)

SODIUM–HYDROGEN EXCHANGER FAMILY (SLC9)

SODIUM–BILE ACID COTRANSPORTER FAMILY (SLC10)

PROTON–METAL-ION COTRANSPORTER FAMILY (SLC11)

ELECTRONEUTRAL CATION–CHLORIDE-COUPLED COTRANSPORTER FAMILY (SLC12)

SODIUM CARBOXYLATE–SULFATE COTRANSPORTER FAMILY (SLC13)

UREA TRANSPORTER FAMILY (SLC14)

PROTON–OLIGOPEPTIDE COTRANSPORTER FAMILY (SLC15)

PROTON–MONOCARBOXYLATE COTRANSPORTER FAMILY (SLC16)

VESICULAR GLUTAMATE–ORGANIC ANION–PHOSPHATE TRANSPORTER FAMILY (SLC17)

VESICULAR MONOAMINE (ACETYLCHOLINE) TRANSPORTER FAMILY (SLC18)

FOLATE AND THIAMINE TRANSPORTER FAMILY (SLC19)

PIT PHOSPHATE COTRANSPORTER FAMILY (SLC20)

ORGANIC ANION TRANSPORTER FAMILY (SLC21)

ORGANIC CATION–ANION TRANSPORTER FAMILY (SLC22)

Na+–VITAMIN C TRANSPORTER FAMILY (SLC23)

SODIUM––CALCIUM–POTASSIUM EXCHANGER FAMILY (SLC24)

MITOCHONDRIAL CARRIER FAMILY (SLC25)

ANION EXCHANGER FAMILY (SLC26)

FATTY ACID TRANSPORTER FAMILY (SLC27)

SODIUM NUCLEOSIDE COTRANSPORTER FAMILY (SLC28)

FACILITATED NUCLEOSIDE TRANSPORTER FAMILY (SLC29)

ZINC TRANSPORTER FAMILY (SLC30)

COPPER TRANSPORTER FAMILY (SLC31)

VESICULAR GABA TRANSPORTER FAMILY (SLC32)

ACETYL-CoA TRANSPORTER FAMILY (SLC33)

Na+-COUPLED PHOSPHATE COTRANSPORTER FAMILY (SLC34)

NUCLEOTIDE–SUGAR TRANSPORTER FAMILY (SLC35)

LYSOSOMAL–PROTON-COUPLED AMINO ACID TRANSPORTER FAMILY (SLC36)

GLYCEROL 3–PHOSPHATE PERMEASE FAMILY (SLC37)

SODIUM-COUPLED AMINO ACID TRANSPORTER FAMILY (SLC38)

METAL ION TRANSPORTER FAMILY (SLC39)

BASOLATERAL IRON TRANSPORTER FAMILY (SLC40)

MgtE-LIKE MAGNESIUM TRANSPORTER FAMILY (SLC41)

Rh AMMONIUM TRANSPORTER FAMILY (SLC42)

Na+-INDEPENDENT, SYSTEM-L–LIKE AMINO ACID TRANSPORTER FAMILY (SLC43)

Chapte 5. Mechanisms of Water Transport Across Cell Membranes and Epithelia

BASIC PRINCIPLES

WATER TRANSPORT ACROSS THE CELL MEMBRANE

WATER TRANSPORT IN EPITHELIA

Chapter 6. Cell Volume Control

CELL VOLUME REGULATORY MECHANISMS

CHALLENGES AND FUNCTIONS AFFECTING CELL VOLUME

Chapter 7. Solute Transport, Energy Consumption, and Production in the Kidney

INTRODUCTION

ENERGY CONSUMPTION

METABOLIC BASIS

COUPLING OF TRANSPORT AND METABOLISM

BOLD MRI

PATHOPHYSIOLOGICAL STATES IN ENERGY PRODUCTION

CONCLUSIONS

Chapter 8. Electrophysiological Analysis of Transepithelial Transport

INTRODUCTION

TRANSEPITHELIAL MEASUREMENTS

INTRACELLULAR MEASUREMENTS

PATCH-CLAMP AND SINGLE-CHANNEL ANALYSIS

APPENDIX 1

APPENDIX 2

APPENDIX 3

APPENDIX 4

Chapter 9. Exchange of Fluid and Solutes Across Microvascular Walls

INTRODUCTION

ULTRASTRUCTURE OF MICROVASCULAR WALLS

FORMATION OF INTERSTITIAL FLUID BY CONVECTION AND DIFFUSION THROUGH MICROVASCULAR WALLS

Chapter 10. External Balance of Electrolytes and Acids and Alkali

INTRODUCTION

WHY IS BALANCE ALWAYS RESTORED?

SPEED OF BALANCE RESTORATION

INFINITE GAIN CONTROL MECHANISM

MODELS OF EXTERNAL BALANCE

COMMON MISCONCEPTIONS AND NEW INSIGHTS

EXPLANATION OF DISEASE MANIFESTATIONS IN SELECTED TOPICS

EXTERNAL BALANCE OF PROTONS

SOURCES OF ACID

APPENDIX

Chapter 11. Principles of Cell Signaling

INTRODUCTION

CELL SURFACE RECEPTORS

INTRACELLULAR SIGNALING PATHWAYS

EXAMPLES OF SIGNALING EFFECTORS IN THE KIDNEY

Chapter 12. Scaffolding Proteins in Transport Regulation

INTRODUCTION

PDZ-PROTEINS

FORM AND FUNCTION OF PDZ PROTEIN FAMILIES IN THE KIDNEY

AKAP

SUMMARY

Chapter 13. The Renin-Angiotensin System

THE COMPONENTS OF THE RENIN-ANGIOTENSIN SYSTEM

REGULATION OF RENIN

Chapter 14. Eicosanoids and the Kidney

IN PRINCIPIO

RENAL PROSTAGLANDINS: THE EARLY DAYS

COX ISOFORMS AND METABOLISM OF AA

PROSTAGLANDINS SERVE RENAL ADAPTIVE/PROTECTIVE MECHANISMS

RENAL ZONAL REGULATIONS OF COX-2 DIFFER

MACULA DENSA: COX-2-/PGI2-DEPENDENT ACTIVATION OF THE RAAS

TUBULOGLOMERULAR FEEDBACK: EICOSANOID MEDIATED

HYPERCHLOREMIA ACTIVATES COX-AND CYP-DEPENDENT VASCULAR MECHANISMS: THE TGF CONNECTION

MACULA DENSA: PGI2 . RENIN .RENOVASCULAR HYPERTENSION

RENOVASCULAR HYPERTENSION

ENLARGEMENT OF THE AA CASCADE

THE TWO BRANCHES OF CYP-AA METABOLISM:

INTERACTION OF THE TWO BRANCHES OF CYP-DEPENDENT-AA METABOLISM TAKES TWO FORMS

EETS ARE ANTI-INFLAMMATORY AGENTS

EETS: ANTIPRESSOR, ANTI-INFLAMMATORY AND RELEASE BY ADENOSINE

THE DAHL SALT-SENSITIVE RAT: 20-HETE AND EET DEFICIENCY

EICOSANOID SEGMENTAL ANALYSIS: NEPHRON AND MICROVESSELS

THE MEDULLA: TONICITY, COX-2, AND PGE2

DISTRIBUTION OF PROSTAGLANDIN SYNTHESIS WITHIN THE NEPHRON

PROXIMAL TUBULES

THE mTAL: CYP- VERSUS COX-DERIVED ARACHIDONATE PRODUCTS

COLLECTING TUBULES

Chapter 15. Kinins and Endothelin

KININS

ENDOTHELINS

Chapter 16. Adenosine in the Kidney

RENAL EFFECTS OF ADENOSINE

MECHANISMS OF ADENOSINE PRODUCTION

Chapter 17. Extracellular Nucleotides and Renal Function

MOLECULAR PHYSIOLOGY OF PURINOCEPTORS

NUCLEOTIDE RECEPTORS AND RENAL PHYSIOLOGY

CONCLUDING REMARKS

Chapter 18. Paracrine Regulation of Renal Function by Dopamine

DOPAMINE—A NEUROTRANSMITTER

DOPAMINE IN NON-NEURONAL TISSUE

DOPAMINE RECEPTORS AND SIGNAL TRANSDUCTION

DOPAMINE: AN INTRARENAL HORMONE

REGULATION OF RENAL DOPAMINE D1-RECEPTOR RESPONSIVENESS

DOPAMINE HAS KEY ROLE IN INTERACTIVE REGULATION OF SODIUM

DOPAMINE AND HYPERTENSION

DOPAMINE AND RENAL FAILURE

FUTURE PERSPECTIVES

Chapter 19. Uroguanylin and Guanylin

ABSTRACT

BACKGROUND

DISCOVERY OF GUANYLIN AND UROGUANYLIN

A PHYSIOLOGICAL ROLE FOR UROGUANYLIN AND GUANYLIN IN THE KIDNEY

EVOLUTION OF TWO GUANYLIN GENES

UROGUANYLIN AND BODY SODIUM BALANCE IN MAMMALS

LOCAL ACTIONS OF UROGUANYLIN AND GUANYLIN IN THE KIDNEY

A NOVEL MECHANISM OF ACTION FOR UROGUANYLIN IN THE KIDNEY

TWO DIFFERENT FAMILIES OF NATRIURETIC PEPTIDES: POTENTIAL INTERACTIONS

A ROLE FOR THE INTESTINE IN SODIUM BALANCE

SECTION II. Structural and Functional Organization of the Kidney

Chapter 20. Structural Organization of the Mammalian Kidney

KIDNEY TYPES AND RENAL PELVIS

RENAL VASCULATURE

NEPHRONS AND COLLECTING DUCT SYSTEM

INTERSTITIUM AND LYMPHATICS

TOPOGRAPHICAL RELATIONSHIPS

GLOMERULUS (RENAL CORPUSCLE)

STRUCTURAL ORGANIZATION OF RENAL ELECTROLYTE TRANSPORTING EPITHELIA

CORRELATION BETWEEN STRUCTURE AND TRANSPORT

SEGMENTS DOWNSTREAM THE TAL: DISTAL CONVOLUTED TUBULE, CONNECTING TUBULE, AND COLLECTING DUCT

ARCHITECTURAL–FUNCTIONAL RELATIONSHIPS

CONCLUSION

Chapter 21. Biophysical Basis of Glomerular Filtration

INTRODUCTION

THE MAGNITUDE OF RENAL BLOOD FLOW AND GLOMERULAR FILTRATION

GLOMERULAR HEMODYNAMICS BY INFERENCE

GLOMERULAR HEMODYNAMICS AND MICROPUNCTURE

THE FILTRATION BARRIER AND FILTRATION OF MACROMOLECULES

SUMMARY

Chapter 22. Function of the Juxtaglomerular Apparatus:

CELLULAR ELEMENTS OF THE JGA

MACULA DENSA CONTROL OF VASCULAR TONE

MACULA DENSA CONTROL OF RENIN SECRETION

Chapter 23. Renal Cortical and Medullary Microcirculations

INTRODUCTION

ANATOMY OF THE RENAL CIRCULATION

TRANSPORT FUNCTIONS AND PROPERTIES

INTRARENAL HEMATOCRIT

METHODS FOR MEASUREMENT OF REGIONAL BLOOD FLOW TO THE CORTEX AND MEDULLA

METHODS FOR DIRECT MEASUREMENTS OF MICROVESSEL REACTIVITY

VASOACTIVITY OF THE RENAL MICROCIRCULATION: ION CHANNEL ARCHITECTURE

REGULATION OF BLOOD FLOW AND MICROVESSEL CONTRACTION

Chapter 24. Molecular and Cellular Mechanisms of Kidney Development

OVERVIEW

DEVELOPMENT OF THE METANEPHROS

EXPERIMENTAL APPROACHES TO KIDNEY DEVELOPMENT

MOLECULAR MECHANISMS OF KIDNEY DEVELOPMENT

TRANSCRIPTION FACTORS IN METANEPHROGENESIS

URETERIC BUD BRANCHING MORPHOGENESIS

GLIAL CELL LINE–DERIVED NEUROTROPHIC FACTOR

FIBROBLAST GROWTH FACTORS

PLEIOTROPHIN

WNTS AND RELATED MOLECULES (FRIZZLED-RELATED PROTEINS)

TRANSFORMING GROWTH FACTOR ß SUPERFAMILY

GREMLIN

SLIT-ROBO AND SPROUTY (INTRACELLULAR PROTEIN)

HEPATOCYTE GROWTH FACTOR

EPIDERMAL GROWTH FACTOR RECEPTOR LIGANDS

INSULIN-LIKE GROWTH FACTORS

TUBULOGENESIS AFTER INDUCTION OF THE METANEPHRIC MESENCHYME

VASCULAR AND GLOMERULAR DEVELO PMENT

Chapter 25. Molecular and Cellular Mechanisms of Glomerular Capillary Development

GLOMERULAR MORPHOGENESIS

ORIGIN OF THE GLOMERULAR ENDOTHELIUM

ENDOTHELIAL CELL RECRUITMENT AND DIFFERENTIATION

DEVELOPMENT OF THE MESANGIUM

FACTORS REGULATING PODOCYTE DIFFERENTIATION

WT1

LMX1B

FORMATION OF THE SLIT DIAPHRAGM COMPLEX

DEVELOPMENTAL/ORGANIZATIONAL ROLE OF THE GLOMERULAR BASEMENT MEMBRANE

RECEPTORS AND RECEPTOR-ASSOCIATED PROTEINS MEDIATING GLOMERULAR CELL INTERACTIONS WITH THE GBM

CONCLUDING REMARKS

Chapter 26. Postnatal Renal Development

INTRODUCTION

RENAL BLOOD FLOW AND GLOMERULAR FILTRATION RATE

SODIUM CHLORIDE TRANSPORT

REGULATION OF SODIUM TRANSPORT

RENAL ACIDIFICATION

INDUCTION OF NEPHRON MATURATION

PHOSPHATE TRANSPORT

POTASSIUM TRANSPORT

URINARY CONCENTRATING AND DILUTING ABILITY

Chapter 27. Renal Hyperplasia and Hypertrophy

INTRODUCTION

MEASUREMENT OF CELL GROWTH

CELL CYCLE AND CELL CYCLE REGULATORY PROTEINS

HYPERPLASIA: AN INCREASE IN CELL NUMBER DUE TO PROLIFERATION

HYPERTROPHY

TUBULAR HYPERTROPHY

CONCLUSIONS

SECTION III. Fluid and Electrolyte Regulation and Dysregulation

Chapter 28. Epithelial Na+ Channels

INTRODUCTION

STRUCTURAL FEATURES OF ENaC SUBUNITS

PORE STRUCTURE

ENaC REGULATION

CFTR

PPARS

ENaC AND HUMAN DISORDERS

CONCLUSIONS

Chapter 29. Anion Channels

INTRODUCTION

METHODS COMMONLY USED TO STUDY RENAL ANION CHANNEL FUNCTION

BIOPHYSICAL AND OTHER FUNCTIONAL CHARACTERISTICS OF RENAL ANION CHANNELS STUDIED IN SITU

MOLECULAR IDENTITIES OF RENAL ANION CHANNELS

CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

CALCIUM-ACTIVATED CHLORIDE CHANNELS: CLCAS, BESTROPHIN

CLCAs

ICLN: CHANNEL OR CHANNEL MODULATOR?

CLIC/p64: PUTATIVE INTRACELLULAR CHLORIDE CHANNELS

BACK TO FUNCTION:LESSONS FROM DISEASE MODELS

SUMMARY

Chapter 30. Sodium and Chloride Transport

INTRODUCTION

EPITHELIAL FUNCTION

TRANSCELLULAR PATHWAY

PARACELLULAR PATHWAY

REGULATION OF PROXIMAL NACL TRANSPORT

PERSPECTIVE

Chapter 31. Sodium Chloride Transport in the Loop of Henle, Distal Convoluted Tubule, and Collecting Duct

INTRODUCTION

ANATOMIC CONSIDERATIONS

NA+ TRANSPORT IN LOOP OF HENLE

NA+ TRANSPORT IN DISTAL CONVOLUTED TUBULE AND CONNECTING SEGMENT

NA+ TRANSPORT IN COLLECTING DUCT

NA+ TRANSPORT IN OUTER MEDULLARY COLLECTING DUCT

NA+ TRANSPORT IN INNER MEDULLARY COLLECTING DUCT

Chapter 32. Mineralocorticoid Action in the Aldosterone-Sensitive Distal Nephron

INTRODUCTION

SODIUM TRANSPORT REGULATION BY ALDOSTERONE: HYSIOLOGICAL AND BIOPHYSICAL MECHANISMS

SODIUM TRANSPORT REGULATION BY ALDOSTERONE: CELLULAR AND MOLECULAR MECHANISMS

HUMAN AND MOUSE DISEASES LINKED TO MR MUTATIONS

PHA-1

PERSPECTIVES: INTEGRATED PHYSIOLOGICAL

CONCLUSIONS

Chapter 33. Neural Control of Renal Function

INTRODUCTION

NEUROANATOMY, PHARMACOLOGY, AND PHYSIOLOGY

CONTROL OF RENAL CIRCULATION

CONTROL OF RENAL TUBULAR SOLUTE AND WATER TRANSPORT

NEURAL CONTROL OF RENIN RELEASE

INTEGRATION OF RENAL NERVE ACTIVITY AND FUNCTION

RENORENAL REFLEXES

SUMMARY

Chapter 34. Natriuretic Hormones

INTRODUCTION

HISTORY OF ATRIAL NATRIURETIC PEPTIDE HORMONES

FAMILY OF ATRIAL NATRIURETIC HORMONES: SYNTHESIS OF THREE PROHORMONES

PEPTIDE HORMONES ORIGINATING FROM ATRIAL NATRIURETIC PEPTIDE PROHORMONE

ORIGINATION OF PEPTIDE HORMONES FROM PROHORMONES

MOLECULAR BIOLOGY OF NATRIURETIC HORMONAL SYSTEM

PROCESSING OF ATRIAL NATRIURETIC PEPTIDE PROHORMONE IN KIDNEY

REGULATION OF ATRIAL NATRIURETIC PEPTIDE PROHORMONE GENE

TRANSGENIC KNOCKOUT AND/OR MICE OVEREXPRESSING ATRIAL NATRIURETIC PEPTIDE PROHORMONE GENE

HUMAN DISEASES WITH UPREGULATION OF ATRIAL NATRIURETIC PEPTIDE PROHORMONE GENE

LOCALIZATION OF ATRIAL NATRIURETIC PEPTIDE PROHORMONE GENE ON CHROMOSOMES

ATRIAL NATRIURETIC PEPTIDE PROHORMONE GENE EXPRESSION IN INVERTEBRATES AND PLANTS

BRAIN NATRIURETIC PEPTIDE PROHORMONE GENE

SECRETION OF NATRIURETIC PEPTIDES

BIOLOGIC EFFECTS OF NATRIURETIC HORMONES AND THEIR MECHANISMS OF ACTION

NATRIURETIC PEPTIDE RECEPTORS A, B, AND C

DEGRADATION OF NATRIURETIC PEPTIDES BY KIDNEY

INFLUENCE OF ACUTE RENAL FAILURE ON CIRCULATING CONCENTRATION OF ATRIAL NATRIURETIC PEPTIDES

HEMODIALYSIS

RENAL TRANSPLANTATION

PROTECTIVE AND THERAPEUTIC EFFECTS OF ATRIAL NATRIURETIC PEPTIDES IN ACUTE RENAL FAILURE

TREATMENT OF OTHER DISEASES WITH ABNORMAL BLOOD VOLUME

ANTIPROLIFERATIVE AND ANTICANCER PROPERTIES OF ATRIAL NATRIURETIC PEPTIDES

SUMMARY AND FUTURE DIRECTIONS

Chapter 35. Classical and Novel Hormonal Influences on Renal Tubular Transport, and the Emerging Concept of Intracrine Regulation

INTRODUCTION

CLASSICAL HORMONES

NOVEL BRAIN–GUT PEPTIDES

CONCEPT OF A RENAL INTRACRINE SYSTEM

Chapter 36. Physiology and Pathophysiology of Sodium Retention and Wastage

INTRODUCTION

SODIUM INTAKE AND SODIUM BALANCE

PRIMARY AND SECONDARY EDEMA

CONCEPT OF EFFECTIVE ARTERIAL BLOOD VOLUME

AFFERENT LIMB VOLUME CONTROL

RENAL MECHANISMS FOR SODIUM RETENTION

EFFECTOR MECHANISM REGULATING RENAL SODIUM HANDLING

CONGESTIVE HEART FAILURE

CIRRHOSIS

NEPHROTIC SYNDROME

SODIUM WASTAGE

Chapter 37. Physiology and Pathophysiology of Diuretic Action

DIURETIC-SENSITIVE SALT TRANSPORT

OSMOTIC DIURETICS

PROXIMAL TUBULE DIURETICS

LOOP DIURETICS

DISTAL CONVOLUTED TUBULE DIURETICS

CORTICAL COLLECTING TUBULE DIURETICS

AQUARETICS (VASOPRESSIN RECEPTOR ANTAGONISTS)

GENERAL PRINCIPLES OF DIURETIC ACTION

DIURETIC ADAPTATIONS AND DIURETIC RESISTANCE

Chapter 38. Aquaporin Water Channels in Mammalian Kidney

DISCOVERY OF AQP1

STRUCTURE AND FUNCTION OF AQUAPORINS

DISTRIBUTION OF AQP1 IN KIDNEY AND OTHER TISSUES

AQP1 DEFICIENCY

ADDITIONAL FUNCTIONS OF AQP1

AQUAPORINS IN KIDNEY

AQUAGLYCEROPORINS

VASOPRESSIN REGULATION OF KIDNEY AQUAPORINS

DYSREGULATION OF RENAL AQUAPORINS IN WATER BALANCE DISORDERS

URINARY CONCENTRATING DEFECTS

WATER RETENTION

Chapter 39. Thirst and Vasopressin

VASOPRESSIN AND RELATED PEPTIDES

REGULATION OF SECRETION

DISTRIBUTION AND CLEARANCE

THIRST

ROLE OF VASOPRESSIN AND THIRST IN OSMOREGULATION

Chapter 40. The Urine Concentrating Mechanism and Urea Transporters

KIDNEY STRUCTURE

TRANSPORT PROPERTIES OF INDIVIDUAL NEPHRON SEGMENTS

GENERAL FEATURES OF URINARY CONCENTRATION AND DILUTION

COUNTERCURRENT MULTIPLICATION:HISTORY AND THEORY

OSMOPROTECTIVE OSMOLYTES

ROLE OF UREA

LONG-TERM REGULATION OF UREA TRANSPORTERS

UREA RECYCLING

DEVELOPMENT OF URINE CONCENTRATING ABILITY

SUMMARY

Chapter 41. Hyponatremia

THE PLASMA SODIUM CONCENTRATION AND BODY FLUID TONICITY

PHYSIOLOGIC CONTROL OF WATER EXCRETION

HYPOTONIC HYPONATREMIA:CLASSIFICATION AND PATHOGENESIS

WATER INTOXICATION WITH MAXIMALLY DILUTE URINE

VASOPRESSIN-INDEPENDENT DEFECTS IN WATER EXCRETION

VASOPRESSIN-DEPENDENT DEFECTS IN WATER EXCRETION

HEMODYNAMIC CAUSES OF VASOPRESSIN-MEDIATED HYPONATREMIA

INAPPROPRIATE VASOPRESSIN SECRETION

ADAPTATIONS TO HYPOTONIC HYPONATREMIA

RAPID CORRECTION OF HYPONATREMIA AND OSMOTIC DEMYELINATION

TREATMENT OF HYPOTONIC HYPONATREMIA

NONHYPOTONIC HYPONATREMIA

Chapter 42. Hypernatremic States

REGULATION OF WATER HOMEOSTASIS

DEFENSE MECHANISMS AGAINST WATER DEPLETION

CELLULAR RESPONSE TO HYPERNATREMIA

ETIOLOGY OF HYPERNATREMIC STATES

CLASSIFICATION OF HYPERNATREMIA BASED ON TOTAL-BODY SODIUM:

CLINICAL FEATURES IN HYPERNATREMIA

THERAPY FOR HYPERNATREMIA

CLINICAL STUDIES AND OUTCOME

Chapter 43. Polyuria and Diabetes Insipidus

ARGININE VASOPRESSIN

THE BRATTLEBORO RAT WITH AUTOSOMAL RECESSIVE NEUROGENIC DIABETES INSIPIDUS

KNOCKOUT MICE WITH URINARY CONCENTRATION DEFECTS

QUANTITATING RENAL WATER EXCRETION

CLINICAL CHARACTERISTICS OF DIABETES INSIPIDUS DISORDERS

RARE FORMS

SYNDROME OF HYPERNATREMIA AND HYPODIPSIA

LOSS-OF-FUNCTION MUTATIONS OF AVPR2

LOSS-OF-FUNCTION MUTATIONS OF AQP2 (OMIM 222000, 125800, 107777)

COMPLEX POLYUROPOLYDIPSIC SYNDROME

ACQUIRED NEPHROGENIC DIABETES INSIPIDUS

INVESTIGATION OF A PATIENT WITH POLYURIA

RADIOIMMUNOASSAY OF AVP AND OTHER LABORATORY DETERMINATIONS

MAGNETIC RESONNANCE IMAGING IN PATIENTS WITH DIABETES INSIPIDUS

TREATMENT

Chapter 44. The Molecular Biology of Renal Potassium Channels

THE MOLECULAR BIOLOGY OF ROMK (KIR1), A DISTAL K+ SECRETORY CHANNEL

OTHER RENAL POTASSIUM CHANNELS

SUMMARY AND CONCLUSIONS

Chapter 45. Expression, Function, and Regulation of H+,K+-ATPase in the Kidney

FUNCTIONAL PROPERTIES, PHARMACOLOGY, AND PHYSIOLOGY

EXPRESSION IN THE KIDNEY

REGULATION

OTHER FUNCTIONS OF RENAL H+,K+-ATPases

ASSOCIATED DISEASES

SUMMARY

Chapter 46. Extrarenal Potassium Metabolism

POTASSIUM DEPLETION AND REPLETION

INSULIN

GLUCAGON

CATECHOLAMINES

THYROID

ACID-BASE

ALDOSTERONE

RENAL FAILURE

MAGNESIUM

DRUGS

OTHER FACTORS

Chaper 47. Regulation of Potassium Excretion

OVERVIEW OF POTASSIUM DISTRIBUTION AND EXCRETION: INTERNAL AND EXTERNAL BALANCE

INTERNAL POTASSIUM BALANCE

EXTERNAL POTASSIUM BALANCE: THE ROLE OF THE KIDNEY

POTASSIUM TRANSPORT BY INDIVIDUAL NEPHRON SEGMENTS

POTASSIUM REABSORPTION

CONTROL OF RENAL POTASSIUM TRANSPORT

Chapter 48. Potassium Deficiency

ETIOLOGY OF POTASSIUM DEFICIENCY

SYSTEMIC CHANGES RELEVANT TO RENAL FUNCTION

RENAL CHANGES IN POTASSIUM DEFICIENCY

TREATMENT OF CLINICAL POTASSIUM DEFICIENCY: GENERAL PRINCIPLES

Chapter 49. Clinical Disorders of Hyperkalemia

REGULATION OF POTASSIUM HOMEOSTASIS

ACUTE CONTROL OF THE PK

CLINICAL TOOLS TO ASSESS THE CONTROL OF THE RENAL EXCRETION OF POTASSIUM

CLINICAL APPROACH TO THE PATIENT WITH HYPERKALEMIA

SPECIFIC CAUSES OF HYPERKALEMIA

THERAPY OF HYPERKALEMIA

Chapter 50. The Effects of Electrolyte Disorders on Excitable Membranes

THE NATURE OF EXCITABILITY

ION CHANNELS

EXCITABLE TISSUES

DISORDERED EXCITABILITY

SUMMARY

VOLUME 2. Regulation and Disorders of Acid-Base Homeostasis

SECTION III. Fluid and Electrolyte Regulation and Dysregulation

Chapter 51. Control of Intracellular pH

ELUCIDATING THE COMPLEXITY OF pHi REGULATION

UNDERSTANDING THE MOLECULAR MECHANISMS OF pHi REGULATION

SCOPE OF THIS CHAPTER

METHODS FOR MEASURING pHi

pH-SENSITIVE MICROELECTRODES

DISTRIBUTION OF WEAK ACIDS AND BASES

pH-SENSITIVE DYES

NUCLEAR MAGNETIC RESONANCE

FORCES AFFECTING THE PASSIVE MOVEMENT OF H+ AND OTHER CHARGED ACIDS AND BASES

EFFECTS OF WEAK ACIDS AND BASES ON pHi

EFFECTS OF NH3 AND OTHER NEUTRAL WEAK BASES

INTRACELLULAR BUFFERING

MECHANISMS OF INTRACELLULAR BUFFERING

MEASUREMENT OF INTRACELLULAR BUFFERING POWER

ACID-BASE TRANSPORT SYSTEMS

ACID-LOADING MECHANISMS

ACID-EXTRUSION MECHANISMS

THE REGULATION OF pHi

FACTORS INFLUENCING pHi

Chapter 52. Sodium-Coupled Bicarbonate Transporters

INTRODUCTION

OVERVIEW OF THE SLC4 FAMILY

THE ELECTROGENIC Na+-COUPLED HCO-3 TRANSPORTERS

THE ELECTRONEUTRAL Na+-COUPLED HCO-3 TRANSPORTERS

NCBE (SLC4A10)

ROLES IN HEALTH AND DISEASE

CONCLUSION

Chapter 53. The SLC4 Anion Exchanger Gene Family

THE AE ANION EXCHANGERS AMONG THE SLC4 AND SLC26 SUPERFAMILIES

SLC4 ANION EXCHANGE DOMAIN STRUCTURE AND ALTERNATIVE TRANSCRIPTS

LOCALIZATION AND FUNCTION OF ANION EXCHANGERS IN TISSUES

AE1 N-TERMINAL CYTOPLASMIC DOMAIN STRUCTURE AND BINDING PROTEINS

AE1 C-TERMINAL TRANSMEMBRANE DOMAIN STRUCTURE AND BINDING PROTEINS

MECHANISMS OF SLC4/AE ANION TRANSPORT

PHARMACOLOGY OF SLC4/AE ANION EXCHANGERS

THE ANION TRANSLOCATION PATHWAY OF AE1

ANION CONDUCTANCE ASSOCIATED WITH AE1

THE AE1 C-TERMINAL CYTOPLASMIC TAIL:CARBONIC ANHYDRASE BINDING, ANION SELECTIVITY, AND OTHER FUNCTIONS

ACUTE REGULATION OF ANION EXCHANGERS

AE1 DEFICIENCY DISEASES OF ERYTHROCYTES

KNOCKOUT MOUSE MODELS OF DEFICIENCY OF AE2/SLC4A2 AND AE3/SLC4A3

CONCLUSION

Chapter 54. Cellular Mechanisms of Renal Tubular Acidification

PROXIMAL TUBULE

LOOP OF HENLE AND THICK ASCENDING LIMB

DISTAL NEPHRON

Chapter 55. Chemoreceptors, Breathing, and pH

INTRODUCTION

CO2

PERIPHERAL CHEMORECEPTORS

CENTRAL CHEMORECEPTORS

PARADOX: CENTRAL CHEMORECEPTORS LOCATED IN AN ENVIRONMENT WITH TIGHT PH REGULATION

BREATHING AND PH REGULATION

SUMMARY

Chapter 56. Renal Ammonium Ion Production and Excretion

INTRODUCTION

ROLE OF RENAL AMMONIUM ION PRODUCTION AND EXCRETION IN THE MAINTENANCE OF ACID–BASE BALANCE

PATHWAYS OF RENAL AMMONIAGENESIS

ACUTE REGULATION OF RENAL AMMONIAGENESIS

CHRONIC ADAPTATIONS TO METABOLIC ACIDOSIS

SIGNAL TRANDSDUCTION PATHWAYS THAT MEDIATE ADAPTIVE RESPONSES TO ACIDOSIS

COUNTERCURRENT TRANSPORT OF AMMONIUM IONS

EXCRETION OF AMMONIUM IONS

PATHOPHYSIOLOGY

FUTURE DIRECTIONS

Chapter 57. The Acid–Base Effects of the Contemporary Western Diet: An Evolutionary Perspective

INTRODUCTION

METABOLIC ACIDOSIS AND ALKALOSIS:DEFINITIONS

DETERMINANTS OF BLOOD ACIDITY AND PLASMA [HCO3] SET-POINT REGULATION IN “NORMAL” SUBJECTS

ACIDOSIS VERSUS ACID RETENTION

PATHOPHYSIOLOGICAL CONSEQUENCES OF DIET-INDUCED, AGE-AMPLIFIED METABOLIC ACIDOSIS IN HUMANS

DIET-INDUCED POTASSIUM-REPLETE CHLORIDE-SUFFICIENT CHRONIC LOW-GRADE METABOLIC ALKALOSIS AS NATURALLY SELECTED OPTIMAL SYSTEMIC ACID–BASE STATE OF HUMANS

IMPLICATIONS FOR FURTHER RESEARCH

ADDENDUM ADDED IN PROOF

Chapter 58. Clinical Syndromes of Metabolic Alkalosis

INTRODUCTION

DEFENSE AGAINST EXCESS ECF HCO3

MECHANISMS OF METABOLIC ALKALOSIS

CLINICAL SYNDROMES OF METABOLIC ALKALOSIS

CONCLUDING REMARKS

Chapter 59. Clinical Syndromes of Metabolic Acidosis

INTRODUCTION

DEFINITION OF METABOLIC ACIDOSIS

SYSTEMIC AND RENAL ACID–BASE HOMEOSTASIS

CLINICAL CONSEQUENCES

CLINICAL DISORDERS

Chapter 60. Respiratory Alkalosis and Acidosis

INTRODUCTION

RESPIRATORY ALKALOSIS

RESPIRATORY ACIDOSIS

Chapter 61. Mechanisms and Disordersof Magnesium Metabolism

INTRODUCTION

PHYSIOLOGY OF RENAL MAGNESIUM HANDLING

PATHOPHYSIOLOGY OF RENAL MAGNESIUM HANDLING

Chapter 62. Calcium Channels

INTRODUCTION

EPITHELIAL Ca2+ CHANNELS:TRPV5 AND TRPV6

REGULATION OF EPITHELIAL Ca2+ CHANNELS

CHARACTERIZATION OF TRPV5 KNOCKOUT MICE

Chapter 63. The Calcium-Sensing Receptor

LIGAND BINDING:THE CaSR IS A Ca2+/Mg2+ AND AN “EXTRACELLULAR ENVIRONMENT” SENSOR

CALCIUM-SENSING RECEPTOR FUNCTION IN THE PARATHYROID GLAND

MODULATION OF THE CALCIUM-SENSING RECEPTOR IN SECONDARY HYPERPARATHYROIDISM

CALCIUM-SENSING RECEPTOR AND KIDNEY FUNCTION

Chapter 64. Vitamin D

INTRODUCTION

METABOLISM OF VITAMIN D

TRANSPORT OF VITAMIN D METABOLITES

MECHANISM OF ACTION OF VITAMIN D

CLASSICAL ACTIONS OF VITAMIN D

NONCLASSICAL VITAMIN D ACTIONS

CLINICAL DISORDERS OF VITAMIN D METABOLISM

VITAMIN D THERAPY IN CHRONIC KIDNEY DISEASE

Chapter 65. Renal Calcium Metabolism

INTRODUCTION

CALCIUM CHEMISTRY

CALCIUM TRANSPORT ALONG THE NEPHRON

REGULATION OF RENAL CALCIUM TRANSPORT

CELLULAR MECHANISMS OF TRANSEPITHELIAL CALCIUM TRANSPORT

Chapter 66. The Hormonal Regulation of Calcium Metabolism

INTRODUCTION

CALCIUM BALANCE

VITAMIN D ENDOCRINE SYSTEM

PARATHYROID HORMONE ENDOCRINE SYSTEM

CALCITONIN

CONCLUSION

Chapter 67. Disorders of Calcium Metabolism

INTRODUCTION

GENERAL CONSIDERATIONS

CALCIUM HOMEOSTASIS

DEFENSES AGAINST HYPERCALCEMIA AND HYPOCALCEMIA

HYPERCALCEMIA

HYPOCALCEMIA

Chapter 68. Pathogenesis and Treatment of Nephrolithiasis

STONES AND THEIR DISEASE; STONES, CLINICAL SYNDROMES, AND NATURAL HISTORY

PRIMARY PROCESS OF CRYSTALLIZATION

PHYSICAL CELLULAR MECHANISMS IN STONE FORMATION

INHIBITORS OF CRYSTALLIZATION AND CELL CRYSTAL INTERACTIONS

DISORDERS OF CALCIUM STONE FORMATION

URIC ACID IN STONES

CYSTINURIA AND CYSTINE STONES

INFECTION (STRUVITE) STONES

Chapter 69. Proximal Tubular Handling of Phosphate

PROXIMAL TUBULAR REABSORPTION OF PHOSPHATE

GENE PRODUCTS INVOLVED IN PROXIMAL TUBULAR PHOSPHATE REABSORPTION

ALTERATIONS OF PROXIMAL TUBULAR REABSORPTION OF PI

Chapter 70. Clinical Disturbances of Phosphate Homeostasis

THE IMPORTANCE OF PHOSPHORUS IN BIOLOGICAL SYSTEMS

THE REGULATION OF PHOSPHATE BALANCE

THE PHYSIOLOGY OF PHOSPHATE IN THE KIDNEY

FACTORS REGULATING RENAL PHOSPHATE EXCRETION

ACUTE AND CHRONIC HYPOPHOSPHATEMIA

ACUTE AND CHRONIC HYPERPHOSPHATEMIA

Chapter 71. Glucose Reabsorption in the Kidney

TRANSPORT OF GLUCOSE AT THE BASOLATERAL MEMBRANE

TRANSPORT OF GLUCOSE AT THE LUMINAL MEMBRANE

THE HIGH-AFFINITY Na+/D-GLUCOSE COTRANSPORTER

THE LOW-AFFINITY Na+/D-GLUCOSE COTRANSPORTER

MOLECULAR ORGANIZATION AND ENERGETICS OF RENAL TUBULAR GLUCOSE REABSORPTION

ABNORMALITIES OF TUBULAR GLUCOSE REABSORPTION

MOLECULAR CHARACTERIZATION OF THE HIGH-AFFINITY Na+/D-GLUCOSE COTRANSPORTER

MEMBRANE TOPOLOGY OF SGLT1

STRUCTURE/FUNCTION STUDIES OF SGLT1

Na+-GLUCOSE COUPLING AND STRUCTURAL RELATIONSHIP OF THE Na+ AND GLUCOSE DOMAINS

CONCLUSION

Chapter 72. Amino Acids, Oligopeptides, and Hyperaminoacidurias

AMINO ACIDS

WHICH NEPHRON SEGMENTS ARE RESPONSIBLE FOR RESORPTION?

THE “WRONG” WAY? PERITUBULAR UPTAKE AND TRANSCELLULAR SECRETION

RECENT ADVANCES IN MOLECULAR CHARACTERIZATION OF RENAL AMINO ACID TRANSPORTERS

AGT1

PRINCIPLE MECHANISMS OF HYPERAMINOACIDURIA

OLIGOPEPTIDES

Chapter 73. Organic Anion and Cation Transporters in Renal Elimination of Drugs

ORGANIC ANION TRANSPORT SYSTEMS

OVERVIEW OF TRANSPORTERS INVOLVED IN TRANSPORT OF ANIONIC DRUGS

ORGANIC CATION TRANSPORTERS

OCT1

OCT2

OCT3

OCTN1 (SLC22A4)

OCTN2 (SLC22A5)

OCTN3 (Slc22a9)

CONCLUSIONS AND OUTLOOK

Chapter 74. Renal Filtration, Transport, and Metabolism of Albumin and Albuminuria

INTRODUCTION

ALBUMIN METABOLISM

GLOMERULAR SIEVING COEFFICIENT

FACTORS CONTROLLING GLOMERULAR CAPILLARY WALL PERMEABILITY AND SIEVING COEFFICIENT

STRUCTURAL AND CELLULAR COMPONENTS AFFECTING ALBUMINURIA/PROTEINURIA

MECHANISTIC PATHWAYS THAT CONTROL ALBUMIN PROCESSING

MOLECULAR FACTORS AFFECTING ALBUMINURIA/PROTEINURIA

ALBUMINURIA IN DIFFERENT DISEASED STATES

CONCLUDING REMARKS

SECTION IV. Pathophysiology of Renal Disease

Chapter 75. Physiologic Principles in the Clinical Evaluation of Electrolyte, Water, and Acid-Base Disorders

CONCEPT OF EXTERNAL BALANCE AND STEADY STATE

URINARY CONSTITUENTS AS CLINICAL INDICES: GENERAL CONSIDERATIONS

EVALUATION OF DISORDERS OF WATER EXCRETION

EVALUATION OF POTASSIUM DISORDERS

EVALUATION OF METABOLIC ACIDOSIS

Chapter 76. Pathophysiology of Acute Kidney Injury

CLINICAL OVERVIEW

MODELS OF ACUTE KIDNEY INJURY AND TECHNIQUES OF EARLY DIAGNOSIS

PATHOPHYSIOLOGY OF ACUTE KIDNEY INJURY

APOPTOSIS AND NECROSIS

CELLULAR REPAIR, REGENERATION, AND RECOVERY

TGF-ß

CLINICAL COURSE AND DIAGNOSTIC TESTS IN ACUTE KIDNEY INJURY

CLINICAL OUTCOMES AND PROGNOSIS

PATHOPHYSIOLOGIC BASIS OF THERAPY OF ACUTE RENAL FAILURE

EVOLVING MANAGEMENT OF ACUTE KIDNEY INJURY

CONCLUSION

Chapter 77. Ischemic Renal Disease

ATHEROSCLEROTIC RENAL ARTERY STENOSIS:A COMMON DISORDER WITH INCREASING CLINICAL RECOGNITION AND PUBLIC HEALTH IMPORTANCE

CLINICAL PRESENTATIONS OF ISCHEMIC NEPHROPATHY

DIAGNOSIS OF ISCHEMIC NEPHROPATHY

CLINICAL SIGNIFICANCE OF ATHEROSCLEROTIC RENAL ARTERY STENOSIS

PATHOPHYSIOLOGY OF RENAL UNDERPERFUSION AND ISCHEMIC NEPHROPATHY

ADAPTIVE RESPONSES TO RENAL UNDERPERFUSION

PATHOPHYSIOLOGY OF ISCHEMIC NEPHROPATHY

PATHOLOGY OF THE KIDNEY IN ISCHEMIC NEPHROPATHY

NATURAL HISTORY OF ISCHEMIC NEPHROPATHY

TREATMENT OF ISCHEMIC NEPHROPATHY

MEDICAL MANAGEMENT

SUMMARY

Chapter 78. Pathophysiology and Pathogenesis of Diabetic Nephropathy

EPIDEMIOLOGY

CLINICAL COURSE OF DIABETIC NEPHROPATHY IN TYPE 1 AND TYPE 2 DIABETES

PATHOLOGY OF KIDNEY DISEASE IN DIABETES MELLITUS

THE CENTRAL ROLE OF PODOCYTES IN THE PATHOPHYSIOLOGY OF DIABETIC PROTEINURIA

CELLULAR AND MOLECULAR MECHANISMS IN THE PATHOPHYSIOLOGY OF DIABETIC NEPHROPATHY

METABOLIC SYNDROME/OBESITY AND RENAL DISEASE

REGRESSION

SUMMARY AND OUTLOOK

Chapter 79. Renal Failure in Cirrhosis

DEFINITION

EPIDEMIOLOGY

PATHOGENESIS

CLINICAL AND LABORATORY FINDINGS

DIFFERENTIAL DIAGNOSIS

MANAGEMENT

Chapter 80. Obstructive Uropathy

DEFINITIONS

INCIDENCE AND PREVALENCE

CLASSIFICATION

RENAL FUNCTION

SODIUM AND WATER REABSORPTION

ENDOTHELIN SYSTEM

CAUSES OF OBSTRUCTIVE UROPATHY

DIAGNOSTIC APPROACH

TREATMENT

ARGININE AND NITRIC OXIDE

Chapter 81. Autosomal Dominant Polycystic Kidney Disease and Inherited Cystic Diseases

CLINICAL FEATURES OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

GENETICS OF ADPKD

PROPERTIES OF CYSTS

THE PKD GENES AND THEIR PROTEIN PRODUCTS

CILIA AND THE SPECTRUM OF INHERITED CYSTIC DISEASE

CELLULAR PATHWAYS AFFECTED BY POLYCYSTINS

PROSPECTS FOR THERAPY IN ADPKD

Chapter 82. Immunologic Mechanisms of Vasculitis

IMMUNOPATHOLGIC CATEGORIES OF VASCULITIS

BASIC PATHOGENIC EVENTS IN SMALL-VESSEL VASCULITIS

IMMUNE COMPLEX–MEDIATED VASCULITIS

PAUCI-IMMUNE ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODY VASCULITIS

Chapter 83. Renal Physiology and Disease in Pregnancy

ANATOMICAL CHANGES

RENAL HEMODYNAMICS

RENAL TUBULAR FUNCTION

OSMOREGULATION AND RENAL WATER HANDLING

VOLUME HOMEOSTASIS

RENAL DISORDERS AND GESTATION

CHRONIC PARENCHYMAL RENAL DISEASE

HYPERTENSION

Chapter 84. Immune-Mediated and Other Glomerular Diseases

IMMUNOGLOBULIN A NEPHROPATHY

MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS

ANTI–GLOMERULAR BASEMENT MEMBRANE DISEASE AND GOODPASTURE SYNDROME

ACUTE POSTINFECTIOUS GLOMERULONEPHRITIS

PRIMARY RENAL DISEASES CAUSING NEPHROTIC SYNDROME

SYSTEMIC DISEASES ASSOCIATED WITH THE NEPHROTIC SYNDROME

MALIGNANCY-ASSOCIATED GLOMERULAR DISEASES

DRUG-INDUCED GLOMERULAR DISEASES

Chapter 85. Genetic Abnormalities in Glomerular Function

INTRODUCTION

DISORDERS OF EXTRACELLULAR MATRIX

STORAGE DISORDERS

DISORDERS OF THE PODOCYTE SLIT DIAPHRAGM

DISORDERS OF PODOCYTE CYTOSKELETON

FSGS1

FSGS2

FSGS3

MYH9-RELATED DISORDERS (EPSTEIN AND FECHTNER SYNDROMES)

DISORDERS OF PODOCYTE GENE REGULATION

Chapter 86. Immunological Mechanisms of Interstitial Disease

INTRODUCTION

FUNCTIONAL SIGNIFICANCE OF TUBULOINTERSTITIAL INJURY

TUBULOINTERSTITIAL ANTIGENS

DRUG–HAPTEN CONJUGATES AS NEPHRITOGENIC ANTIGENS

ANTIGENS BASED ON MOLECULAR MIMICRY

IMMUNE RESPONSE GENES

T CELLS IN INTERSTITIAL INJURY

REGULATION OF T CELLS

MACROPHAGES IN INTERSTITIAL INJURY

ANTIBODY-MEDIATED NEPHRITOGENIC RESPONSES

TRAFFICKING OF INFLAMMATORY CELLS

FIBROBLASTS AND FIBROSIS

CONCLUSION

Chapter 87. Cellular Mechanisms of Drug Nephrotoxicity

INTRODUCTION

CYCLOSPORIN A

PHENACETIN ACETAMINOPHEN NEPHROTOXICITY

AMINOGLYCOSIDES

CISPLATIN

LITHIUM

CONCLUSION

Chapter 88. Role of Glomerular Pressure in Progression

INTRODUCTION

ADAPTATION OF RENAL FUNCTION LEADING TO GLOMERULAR HYPERTENSION AND HYPERFILTRATION

MECHANISMS OF GLOMERULAR INJURY

NEPHRON NUMBER AS A FACTOR PREDISPOSING TO PROGRESSION

APPROACHES TO PREVENT PROGRESSION BASED ON RATIONALE OF REDUCING GLOMERULAR HYPERTENSION

Chapter 89. Role of Proteinuria in Progression

INTRODUCTION

HISTORICAL PERSPECTIVE

TUBULAR HANDLING OF PROTEINS

PROTEIN OVERLOAD ACTIVATES PHENOTYPIC CHANGES IN CULTURED PROXIMAL TUBULAR CELLS

INTRACELLULAR SIGNALING OF PROTEIN OVERLOAD

IN VIVO EVIDENCE FOR PROINFLAMMATORY PATHWAYS AND SIGNALING IN TUBULAR CELLS ACTIVATED BY PROTEINURIA

PATHOGENIC ROLE OF COMPLEMENT PROTEINS IN TUBULAR AND INTERSTITIAL INJURY

ROLE OF PROTEIN-BOUND LIPIDS

PROFIBROGENIC SIGNALING FROM PROXIMAL TUBULAR CELLS LOADED WITH FILTERED PROTEINS

ROLE OF PROTEINURIA IN TUBULAR APOPTOSIS

Chapter 90. The Inflammatory Response to Ischemic Acute Renal Injury

LEUKOCYTES IN INJURED, ISCHEMIC TISSUES: FRIEND OR FOE?

THE RIGHT STUFF IN THE WRONG PLACE:THE PRO-INFLAMMATORY EFFECTS OF INTRACELLULAR MOLECULES RELEASED INTO THE EXTRA CELLULAR SPACE BY NECROTIC CELLS.

WHEN DEATH IS NO ACCIDENT: NECROSIS AS A PROGRAMMED EVENT

DOES AUTOPHAGY LEAD TO PROGRAMMED NECROSIS?

ADDITIONAL EXAMPLES OF PROGRAMMED NECROSIS IN VIVO

SUMMARY: DEATH AND INJURY ELICIT INFLAMMATION

Chapter 91. The Role of Dyslipidemias in the Progression of Chronic Kidney Disease

WHAT IS THE HYPOTHESIS?

HOW CAN WE TEST THE HYPOTHESIS?

ASSOCIATIONS BETWEEN LIPOPROTEIN ABNORMALITIES AND CKD PROGRESSION

EVIDENCE FROM RETROSPECTIVE ANALYSES OF RANDOMIZED CONTROLLED TRIALS

DIRECT EVIDENCE FROM RANDOMIZED CONTROLLED TRIALS

THE ROLE OF DYSLIPIDEMIAS IN RENAL ALLOGRAFT INJURY

CURRENT TREATMENT RECOMMENDATIONS

THE STUDY OF HEART AND RENAL PROTECTION (SHARP)

SUMMARY

Chapter 92. Oxidants in Progressive Kidney Disease

ROLE OF OXIDANTS IN NONDIABETIC GLOMERULAR DISEASE

OXIDANT MECHANISMS IN DIABETES

ROLE OF OXIDANTS AND IRON IN PROGRESSIVE KIDNEY DISEASE

CONCLUSIONS

Chapter 93. Chronic Kidney Disease: Pathophysiology and Influence of Dietary Protein

INTRODUCTION

MEASUREMENT AND NATURAL HISTORY OF CKD

PATHOPHYSIOLOGY OF CKD

INFLUENCE OF DIETARY THERAPY IN PATIENTS WITH CHRONIC KIDNEY DISEASE

DIETARY PROTEIN RESTRICTION AND PROGRESSION OF RENAL INSUFFICIENCY

CONCLUSION

Chapter 94. Management of Calcium and Bone Disease in Renal Patients

INTRODUCTION

MOLECULAR TARGETS FOR SUPPRESSING PARATHYROID GLAND FUNCTION IN CKD

CLINICAL MANIFESTATIONS OF DISORDERED MINERAL METABOLISM IN CKD

VASCULAR CALCIFICATIONS, DISORDERED MINERAL METABOLISM, AND CARDIOVASCULAR DISEASE

TREATMENT GOALS:K/DOQI GUIDELINES FOR MINERAL METABOLISM IN CKD

TREATMENT STRATEGIES

Chapter 95. Hematopoiesis and the Kidney

INTRODUCTION

ERYTHROPOIESIS

THROMBOCYTOPOIESIS

GRANULOCYTOPOIESIS

FUTURE ASPECTS

Chapter 96. Electrolyte Disturbances in Dialysis

INTRODUCTION

SODIUM

POTASSIUM

ACID–BASE

CALCIUM

MAGNESIUM

DIALYSATE PHOSPHATE

Chapter 97. Homeostasis of Solute and Water by the Transplanted Kidney

INTRODUCTION

INTRINSIC CAPACITY OF THE DENERVATED TRANSPLANTED ISOGRAFT

ISCHEMIA ATTENDANT TO HARVEST, PRESERVATION, AND ENGRAFTMENT

ALLOGRAFT IN THE AZOTEMIC SOLUTE-LOADED RECIPIENT

SOLUTE REGULATION DURING REJECTION

RENAL TUBULAR ACIDOSIS ASSOCIATED WITH ISCHEMIA AND REJECTION

SYNDROMES OF POTASSIUM HANDLING

MINERAL METABOLISM STATES AFTER TRANSPLANT

HANDLING OF URATE AFTER TRANSPLANT

RENAL TRANSPORT AND IMMUNOSUPPRESSIVE DRUGS

Chapter 98. Disposition and Dose Requirements of Drugs in Renal Insufficiency

INTRODUCTION

ROLE OF THE KIDNEY IN DRUG DISPOSITION

INFLUENCE OF RENAL DISEASE ON RESPONSE TO DRUGS

DOSING RECOMMENDATIONS IN PATIENTS WITH RENAL INSUFFICIENCY

Index