Seldin and Giebisch's The Kidney (eBook)

Front cover 1
SELDIN AND GEIBISCH’S THE KIDNEY 4
Copyright page 5
Table of contents 8
List of contributors 14
Preface 24
VOLUME 1 26
SECTION I. Epithelial and Nonepithelial Transport and Regulation 26
Chapter 1. Epithelial Cell Structure and Polarity 26
INTRODUCTION 26
NATURE AND PHYSIOLOGIC IMPLICATIONS OF EPITHELIAL POLARITY 26
EPITHELIAL CELL STRUCTURE: MORPHOLOGY AND PHYSIOLOGY 27
BIOGENESIS OF EPITHELIAL POLARITY 34
SORTING PATHWAYS 42
EPITHELIAL CELL POLARITY AND RENAL DISEASE 52
Chapter 2. Mechanisms of Ion Transport Across Cell Membranes and Epithelia 60
INTRODUCTION 60
MECHANISMS OF ION TRANSPORT 62
ION TRANSPORT PROTEINS 68
ION TRANSPORT ACROSS EPITHELIA 74
Chaper 3. Renal Ion-Translocating ATPases: The P-Type Family 82
P-TYPE ATPASES 82
SERCA 85
PMCA 85
Na,K- AND H,K-ATPASE FAMILY 86
Na,K-ATPASE IN THE KIDNEY 96
H,K-ATPASES IN KIDNEY 104
Chapter 4. The Mammalian Transporter Families 116
INTRODUCTION 116
GLUTAMATE–NEUTRAL AMINO ACID TRANSPORTER FAMILY (SLC1) 116
FACILITATED GLUCOSE TRANSPORTER FAMILY (SLC2) 119
SLC3 FAMILY: ACTIVATORS OF CYSTINE, AND DIBASIC AND NEUTRAL AMINO ACID TRANSPORT 120
ANION EXCHANGERS–BICARBONATE COTRANSPORTER FAMILY (SLC4) 121
THE SODIUM–GLUCOSE COTRANSPORTER FAMILY (SLC5) 123
GABA TRANSPORTER FAMILY (SLC6) 125
AMINO ACID PERMEASE FAMILY (SLC7) 126
SODIUM–CALCIUM EXCHANGER FAMILY (SLC8) 128
SODIUM–HYDROGEN EXCHANGER FAMILY (SLC9) 128
SODIUM–BILE ACID COTRANSPORTER FAMILY (SLC10) 130
PROTON–METAL-ION COTRANSPORTER FAMILY (SLC11) 130
ELECTRONEUTRAL CATION–CHLORIDE-COUPLED COTRANSPORTER FAMILY (SLC12) 131
SODIUM CARBOXYLATE–SULFATE COTRANSPORTER FAMILY (SLC13) 133
UREA TRANSPORTER FAMILY (SLC14) 134
PROTON–OLIGOPEPTIDE COTRANSPORTER FAMILY (SLC15) 135
PROTON–MONOCARBOXYLATE COTRANSPORTER FAMILY (SLC16) 137
VESICULAR GLUTAMATE–ORGANIC ANION–PHOSPHATE TRANSPORTER FAMILY (SLC17) 138
VESICULAR MONOAMINE (ACETYLCHOLINE) TRANSPORTER FAMILY (SLC18) 138
FOLATE AND THIAMINE TRANSPORTER FAMILY (SLC19) 139
PIT PHOSPHATE COTRANSPORTER FAMILY (SLC20) 140
ORGANIC ANION TRANSPORTER FAMILY (SLC21) 140
ORGANIC CATION–ANION TRANSPORTER FAMILY (SLC22) 141
Na+–VITAMIN C TRANSPORTER FAMILY (SLC23) 144
SODIUM––CALCIUM–POTASSIUM EXCHANGER FAMILY (SLC24) 145
MITOCHONDRIAL CARRIER FAMILY (SLC25) 145
ANION EXCHANGER FAMILY (SLC26) 148
FATTY ACID TRANSPORTER FAMILY (SLC27) 149
SODIUM NUCLEOSIDE COTRANSPORTER FAMILY (SLC28) 150
FACILITATED NUCLEOSIDE TRANSPORTER FAMILY (SLC29) 151
ZINC TRANSPORTER FAMILY (SLC30) 151
COPPER TRANSPORTER FAMILY (SLC31) 152
VESICULAR GABA TRANSPORTER FAMILY (SLC32) 152
ACETYL-CoA TRANSPORTER FAMILY (SLC33) 153
Na+-COUPLED PHOSPHATE COTRANSPORTER FAMILY (SLC34) 153
NUCLEOTIDE–SUGAR TRANSPORTER FAMILY (SLC35) 154
LYSOSOMAL–PROTON-COUPLED AMINO ACID TRANSPORTER FAMILY (SLC36) 154
GLYCEROL 3–PHOSPHATE PERMEASE FAMILY (SLC37) 155
SODIUM-COUPLED AMINO ACID TRANSPORTER FAMILY (SLC38) 155
METAL ION TRANSPORTER FAMILY (SLC39) 156
BASOLATERAL IRON TRANSPORTER FAMILY (SLC40) 157
MgtE-LIKE MAGNESIUM TRANSPORTER FAMILY (SLC41) 158
Rh AMMONIUM TRANSPORTER FAMILY (SLC42) 158
Na+-INDEPENDENT, SYSTEM-L–LIKE AMINO ACID TRANSPORTER FAMILY (SLC43) 158
Chapte 5. Mechanisms of Water Transport Across Cell Membranes and Epithelia 172
BASIC PRINCIPLES 172
WATER TRANSPORT ACROSS THE CELL MEMBRANE 179
WATER TRANSPORT IN EPITHELIA 185
Chapter 6. Cell Volume Control 194
CELL VOLUME REGULATORY MECHANISMS 194
CHALLENGES AND FUNCTIONS AFFECTING CELL VOLUME 198
Chapter 7. Solute Transport, Energy Consumption, and Production in the Kidney 210
INTRODUCTION 210
ENERGY CONSUMPTION 210
METABOLIC BASIS 216
COUPLING OF TRANSPORT AND METABOLISM 225
BOLD MRI 228
PATHOPHYSIOLOGICAL STATES IN ENERGY PRODUCTION 228
CONCLUSIONS 230
Chapter 8. Electrophysiological Analysis of Transepithelial Transport 236
INTRODUCTION 236
TRANSEPITHELIAL MEASUREMENTS 237
INTRACELLULAR MEASUREMENTS 246
PATCH-CLAMP AND SINGLE-CHANNEL ANALYSIS 255
APPENDIX 1 265
APPENDIX 2 266
APPENDIX 3 267
APPENDIX 4 267
Chapter 9. Exchange of Fluid and Solutes Across Microvascular Walls 272
INTRODUCTION 272
ULTRASTRUCTURE OF MICROVASCULAR WALLS 272
FORMATION OF INTERSTITIAL FLUID BY CONVECTION AND DIFFUSION THROUGH MICROVASCULAR WALLS 286
Chapter 10. External Balance of Electrolytes and Acids and Alkali 300
INTRODUCTION 300
WHY IS BALANCE ALWAYS RESTORED? 300
SPEED OF BALANCE RESTORATION 302
INFINITE GAIN CONTROL MECHANISM 302
MODELS OF EXTERNAL BALANCE 304
COMMON MISCONCEPTIONS AND NEW INSIGHTS 307
EXPLANATION OF DISEASE MANIFESTATIONS IN SELECTED TOPICS 311
EXTERNAL BALANCE OF PROTONS 313
SOURCES OF ACID 314
APPENDIX 319
Chapter 11. Principles of Cell Signaling 322
INTRODUCTION 322
CELL SURFACE RECEPTORS 322
INTRACELLULAR SIGNALING PATHWAYS 335
EXAMPLES OF SIGNALING EFFECTORS IN THE KIDNEY 341
Chapter 12. Scaffolding Proteins in Transport Regulation 350
INTRODUCTION 350
PDZ-PROTEINS 350
FORM AND FUNCTION OF PDZ PROTEIN FAMILIES IN THE KIDNEY 353
AKAP 361
SUMMARY 362
Chapter 13. The Renin-Angiotensin System 368
THE COMPONENTS OF THE RENIN-ANGIOTENSIN SYSTEM 368
REGULATION OF RENIN 372
Chapter 14. Eicosanoids and the Kidney 384
IN PRINCIPIO 384
RENAL PROSTAGLANDINS: THE EARLY DAYS 385
COX ISOFORMS AND METABOLISM OF AA 386
PROSTAGLANDINS SERVE RENAL ADAPTIVE/PROTECTIVE MECHANISMS 387
RENAL ZONAL REGULATIONS OF COX-2 DIFFER 390
MACULA DENSA: COX-2-/PGI2-DEPENDENT ACTIVATION OF THE RAAS 390
TUBULOGLOMERULAR FEEDBACK: EICOSANOID MEDIATED 392
HYPERCHLOREMIA ACTIVATES COX-AND CYP-DEPENDENT VASCULAR MECHANISMS: THE TGF CONNECTION 393
MACULA DENSA: PGI2 . RENIN .RENOVASCULAR HYPERTENSION 393
RENOVASCULAR HYPERTENSION 393
ENLARGEMENT OF THE AA CASCADE 394
THE TWO BRANCHES OF CYP-AA METABOLISM: 395
INTERACTION OF THE TWO BRANCHES OF CYP-DEPENDENT-AA METABOLISM TAKES TWO FORMS 396
EETS ARE ANTI-INFLAMMATORY AGENTS 397
EETS: ANTIPRESSOR, ANTI-INFLAMMATORY AND RELEASE BY ADENOSINE 397
THE DAHL SALT-SENSITIVE RAT: 20-HETE AND EET DEFICIENCY 398
EICOSANOID SEGMENTAL ANALYSIS: NEPHRON AND MICROVESSELS 398
THE MEDULLA: TONICITY, COX-2, AND PGE2 401
DISTRIBUTION OF PROSTAGLANDIN SYNTHESIS WITHIN THE NEPHRON 401
PROXIMAL TUBULES 402
THE mTAL: CYP- VERSUS COX-DERIVED ARACHIDONATE PRODUCTS 403
COLLECTING TUBULES 404
Chapter 15. Kinins and Endothelin 410
KININS 410
ENDOTHELINS 421
Chapter 16. Adenosine in the Kidney 438
RENAL EFFECTS OF ADENOSINE 438
MECHANISMS OF ADENOSINE PRODUCTION 440
Chapter 17. Extracellular Nucleotides and Renal Function 450
MOLECULAR PHYSIOLOGY OF PURINOCEPTORS 450
NUCLEOTIDE RECEPTORS AND RENAL PHYSIOLOGY 454
CONCLUDING REMARKS 464
Chapter 18. Paracrine Regulation of Renal Function by Dopamine 468
DOPAMINE—A NEUROTRANSMITTER 468
DOPAMINE IN NON-NEURONAL TISSUE 468
DOPAMINE RECEPTORS AND SIGNAL TRANSDUCTION 469
DOPAMINE: AN INTRARENAL HORMONE 472
REGULATION OF RENAL DOPAMINE D1-RECEPTOR RESPONSIVENESS 478
DOPAMINE HAS KEY ROLE IN INTERACTIVE REGULATION OF SODIUM 478
DOPAMINE AND HYPERTENSION 479
DOPAMINE AND RENAL FAILURE 481
FUTURE PERSPECTIVES 482
Chapter 19. Uroguanylin and Guanylin 488
ABSTRACT 488
BACKGROUND 488
DISCOVERY OF GUANYLIN AND UROGUANYLIN 490
A PHYSIOLOGICAL ROLE FOR UROGUANYLIN AND GUANYLIN IN THE KIDNEY 492
EVOLUTION OF TWO GUANYLIN GENES 494
UROGUANYLIN AND BODY SODIUM BALANCE IN MAMMALS 495
LOCAL ACTIONS OF UROGUANYLIN AND GUANYLIN IN THE KIDNEY 497
A NOVEL MECHANISM OF ACTION FOR UROGUANYLIN IN THE KIDNEY 498
TWO DIFFERENT FAMILIES OF NATRIURETIC PEPTIDES: POTENTIAL INTERACTIONS 499
A ROLE FOR THE INTESTINE IN SODIUM BALANCE 501
SECTION II. Structural and Functional Organization of the Kidney 504
Chapter 20. Structural Organization of the Mammalian Kidney 504
KIDNEY TYPES AND RENAL PELVIS 504
RENAL VASCULATURE 506
NEPHRONS AND COLLECTING DUCT SYSTEM 510
INTERSTITIUM AND LYMPHATICS 512
TOPOGRAPHICAL RELATIONSHIPS 519
GLOMERULUS (RENAL CORPUSCLE) 526
STRUCTURAL ORGANIZATION OF RENAL ELECTROLYTE TRANSPORTING EPITHELIA 538
CORRELATION BETWEEN STRUCTURE AND TRANSPORT 541
SEGMENTS DOWNSTREAM THE TAL: DISTAL CONVOLUTED TUBULE, CONNECTING TUBULE, AND COLLECTING DUCT 554
ARCHITECTURAL–FUNCTIONAL RELATIONSHIPS 566
CONCLUSION 577
Chapter 21. Biophysical Basis of Glomerular Filtration 590
INTRODUCTION 590
THE MAGNITUDE OF RENAL BLOOD FLOW AND GLOMERULAR FILTRATION 592
GLOMERULAR HEMODYNAMICS BY INFERENCE 592
GLOMERULAR HEMODYNAMICS AND MICROPUNCTURE 592
THE FILTRATION BARRIER AND FILTRATION OF MACROMOLECULES 599
SUMMARY 610
Chapter 22. Function of the Juxtaglomerular Apparatus: 614
CELLULAR ELEMENTS OF THE JGA 614
MACULA DENSA CONTROL OF VASCULAR TONE 618
MACULA DENSA CONTROL OF RENIN SECRETION 636
Chapter 23. Renal Cortical and Medullary Microcirculations 652
INTRODUCTION 652
ANATOMY OF THE RENAL CIRCULATION 652
TRANSPORT FUNCTIONS AND PROPERTIES 655
INTRARENAL HEMATOCRIT 667
METHODS FOR MEASUREMENT OF REGIONAL BLOOD FLOW TO THE CORTEX AND MEDULLA 667
METHODS FOR DIRECT MEASUREMENTS OF MICROVESSEL REACTIVITY 668
VASOACTIVITY OF THE RENAL MICROCIRCULATION: ION CHANNEL ARCHITECTURE 670
REGULATION OF BLOOD FLOW AND MICROVESSEL CONTRACTION 674
Chapter 24. Molecular and Cellular Mechanisms of Kidney Development 696
OVERVIEW 696
DEVELOPMENT OF THE METANEPHROS 696
EXPERIMENTAL APPROACHES TO KIDNEY DEVELOPMENT 697
MOLECULAR MECHANISMS OF KIDNEY DEVELOPMENT 701
TRANSCRIPTION FACTORS IN METANEPHROGENESIS 701
URETERIC BUD BRANCHING MORPHOGENESIS 704
GLIAL CELL LINE–DERIVED NEUROTROPHIC FACTOR 704
FIBROBLAST GROWTH FACTORS 705
PLEIOTROPHIN 705
WNTS AND RELATED MOLECULES (FRIZZLED-RELATED PROTEINS) 705
TRANSFORMING GROWTH FACTOR ß SUPERFAMILY 705
GREMLIN 706
SLIT-ROBO AND SPROUTY (INTRACELLULAR PROTEIN) 706
HEPATOCYTE GROWTH FACTOR 706
EPIDERMAL GROWTH FACTOR RECEPTOR LIGANDS 706
INSULIN-LIKE GROWTH FACTORS 707
TUBULOGENESIS AFTER INDUCTION OF THE METANEPHRIC MESENCHYME 709
VASCULAR AND GLOMERULAR DEVELO PMENT 711
Chapter 25. Molecular and Cellular Mechanisms of Glomerular Capillary Development 716
GLOMERULAR MORPHOGENESIS 716
ORIGIN OF THE GLOMERULAR ENDOTHELIUM 718
ENDOTHELIAL CELL RECRUITMENT AND DIFFERENTIATION 719
DEVELOPMENT OF THE MESANGIUM 721
FACTORS REGULATING PODOCYTE DIFFERENTIATION 722
WT1 722
LMX1B 722
FORMATION OF THE SLIT DIAPHRAGM COMPLEX 723
DEVELOPMENTAL/ORGANIZATIONAL ROLE OF THE GLOMERULAR BASEMENT MEMBRANE 725
RECEPTORS AND RECEPTOR-ASSOCIATED PROTEINS MEDIATING GLOMERULAR CELL INTERACTIONS WITH THE GBM 728
CONCLUDING REMARKS 728
Chapter 26. Postnatal Renal Development 732
INTRODUCTION 732
RENAL BLOOD FLOW AND GLOMERULAR FILTRATION RATE 732
SODIUM CHLORIDE TRANSPORT 733
REGULATION OF SODIUM TRANSPORT 737
RENAL ACIDIFICATION 738
INDUCTION OF NEPHRON MATURATION 741
PHOSPHATE TRANSPORT 741
POTASSIUM TRANSPORT 743
URINARY CONCENTRATING AND DILUTING ABILITY 743
Chapter 27. Renal Hyperplasia and Hypertrophy 748
INTRODUCTION 748
MEASUREMENT OF CELL GROWTH 748
CELL CYCLE AND CELL CYCLE REGULATORY PROTEINS 749
HYPERPLASIA: AN INCREASE IN CELL NUMBER DUE TO PROLIFERATION 752
HYPERTROPHY 758
TUBULAR HYPERTROPHY 760
CONCLUSIONS 764
SECTION III. Fluid and Electrolyte Regulation and Dysregulation 768
Chapter 28. Epithelial Na+ Channels 768
INTRODUCTION 768
STRUCTURAL FEATURES OF ENaC SUBUNITS 773
PORE STRUCTURE 777
ENaC REGULATION 779
CFTR 783
PPARS 785
ENaC AND HUMAN DISORDERS 787
CONCLUSIONS 787
Chapter 29. Anion Channels 794
INTRODUCTION 794
METHODS COMMONLY USED TO STUDY RENAL ANION CHANNEL FUNCTION 794
BIOPHYSICAL AND OTHER FUNCTIONAL CHARACTERISTICS OF RENAL ANION CHANNELS STUDIED IN SITU 796
MOLECULAR IDENTITIES OF RENAL ANION CHANNELS 797
CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR 801
CALCIUM-ACTIVATED CHLORIDE CHANNELS: CLCAS, BESTROPHIN 805
CLCAs 806
ICLN: CHANNEL OR CHANNEL MODULATOR? 807
CLIC/p64: PUTATIVE INTRACELLULAR CHLORIDE CHANNELS 807
BACK TO FUNCTION:LESSONS FROM DISEASE MODELS 809
SUMMARY 812
Chapter 30. Sodium and Chloride Transport 818
INTRODUCTION 818
EPITHELIAL FUNCTION 819
TRANSCELLULAR PATHWAY 824
PARACELLULAR PATHWAY 841
REGULATION OF PROXIMAL NACL TRANSPORT 849
PERSPECTIVE 859
Chapter 31. Sodium Chloride Transport in the Loop of Henle, Distal Convoluted Tubule, and Collecting Duct 874
INTRODUCTION 874
ANATOMIC CONSIDERATIONS 874
NA+ TRANSPORT IN LOOP OF HENLE 875
NA+ TRANSPORT IN DISTAL CONVOLUTED TUBULE AND CONNECTING SEGMENT 893
NA+ TRANSPORT IN COLLECTING DUCT 896
NA+ TRANSPORT IN OUTER MEDULLARY COLLECTING DUCT 901
NA+ TRANSPORT IN INNER MEDULLARY COLLECTING DUCT 901
Chapter 32. Mineralocorticoid Action in the Aldosterone-Sensitive Distal Nephron 914
INTRODUCTION 914
SODIUM TRANSPORT REGULATION BY ALDOSTERONE: HYSIOLOGICAL AND BIOPHYSICAL MECHANISMS 921
SODIUM TRANSPORT REGULATION BY ALDOSTERONE: CELLULAR AND MOLECULAR MECHANISMS 927
HUMAN AND MOUSE DISEASES LINKED TO MR MUTATIONS 938
PHA-1 941
PERSPECTIVES: INTEGRATED PHYSIOLOGICAL 943
CONCLUSIONS 943
Chapter 33. Neural Control of Renal Function 950
INTRODUCTION 950
NEUROANATOMY, PHARMACOLOGY, AND PHYSIOLOGY 950
CONTROL OF RENAL CIRCULATION 952
CONTROL OF RENAL TUBULAR SOLUTE AND WATER TRANSPORT 955
NEURAL CONTROL OF RENIN RELEASE 956
INTEGRATION OF RENAL NERVE ACTIVITY AND FUNCTION 958
RENORENAL REFLEXES 964
SUMMARY 968
Chapter 34. Natriuretic Hormones 972
INTRODUCTION 972
HISTORY OF ATRIAL NATRIURETIC PEPTIDE HORMONES 972
FAMILY OF ATRIAL NATRIURETIC HORMONES: SYNTHESIS OF THREE PROHORMONES 974
PEPTIDE HORMONES ORIGINATING FROM ATRIAL NATRIURETIC PEPTIDE PROHORMONE 974
ORIGINATION OF PEPTIDE HORMONES FROM PROHORMONES 975
MOLECULAR BIOLOGY OF NATRIURETIC HORMONAL SYSTEM 975
PROCESSING OF ATRIAL NATRIURETIC PEPTIDE PROHORMONE IN KIDNEY 978
REGULATION OF ATRIAL NATRIURETIC PEPTIDE PROHORMONE GENE 979
TRANSGENIC KNOCKOUT AND/OR MICE OVEREXPRESSING ATRIAL NATRIURETIC PEPTIDE PROHORMONE GENE 980
HUMAN DISEASES WITH UPREGULATION OF ATRIAL NATRIURETIC PEPTIDE PROHORMONE GENE 980
LOCALIZATION OF ATRIAL NATRIURETIC PEPTIDE PROHORMONE GENE ON CHROMOSOMES 982
ATRIAL NATRIURETIC PEPTIDE PROHORMONE GENE EXPRESSION IN INVERTEBRATES AND PLANTS 982
BRAIN NATRIURETIC PEPTIDE PROHORMONE GENE 983
SECRETION OF NATRIURETIC PEPTIDES 983
BIOLOGIC EFFECTS OF NATRIURETIC HORMONES AND THEIR MECHANISMS OF ACTION 983
NATRIURETIC PEPTIDE RECEPTORS A, B, AND C 990
DEGRADATION OF NATRIURETIC PEPTIDES BY KIDNEY 991
INFLUENCE OF ACUTE RENAL FAILURE ON CIRCULATING CONCENTRATION OF ATRIAL NATRIURETIC PEPTIDES 992
HEMODIALYSIS 992
RENAL TRANSPLANTATION 993
PROTECTIVE AND THERAPEUTIC EFFECTS OF ATRIAL NATRIURETIC PEPTIDES IN ACUTE RENAL FAILURE 993
TREATMENT OF OTHER DISEASES WITH ABNORMAL BLOOD VOLUME 995
ANTIPROLIFERATIVE AND ANTICANCER PROPERTIES OF ATRIAL NATRIURETIC PEPTIDES 996
SUMMARY AND FUTURE DIRECTIONS 997
Chapter 35. Classical and Novel Hormonal Influences on Renal Tubular Transport, and the Emerging Concept of Intracrine Regulation 1004
INTRODUCTION 1004
CLASSICAL HORMONES 1004
NOVEL BRAIN–GUT PEPTIDES 1017
CONCEPT OF A RENAL INTRACRINE SYSTEM 1020
Chapter 36. Physiology and Pathophysiology of Sodium Retention and Wastage 1030
INTRODUCTION 1030
SODIUM INTAKE AND SODIUM BALANCE 1030
PRIMARY AND SECONDARY EDEMA 1030
CONCEPT OF EFFECTIVE ARTERIAL BLOOD VOLUME 1031
AFFERENT LIMB VOLUME CONTROL 1032
RENAL MECHANISMS FOR SODIUM RETENTION 1035
EFFECTOR MECHANISM REGULATING RENAL SODIUM HANDLING 1038
CONGESTIVE HEART FAILURE 1042
CIRRHOSIS 1048
NEPHROTIC SYNDROME 1061
SODIUM WASTAGE 1066
Chapter 37. Physiology and Pathophysiology of Diuretic Action 1076
DIURETIC-SENSITIVE SALT TRANSPORT 1077
OSMOTIC DIURETICS 1077
PROXIMAL TUBULE DIURETICS 1080
LOOP DIURETICS 1084
DISTAL CONVOLUTED TUBULE DIURETICS 1090
CORTICAL COLLECTING TUBULE DIURETICS 1097
AQUARETICS (VASOPRESSIN RECEPTOR ANTAGONISTS) 1101
GENERAL PRINCIPLES OF DIURETIC ACTION 1102
DIURETIC ADAPTATIONS AND DIURETIC RESISTANCE 1104
Chapter 38. Aquaporin Water Channels in Mammalian Kidney 1120
DISCOVERY OF AQP1 1120
STRUCTURE AND FUNCTION OF AQUAPORINS 1121
DISTRIBUTION OF AQP1 IN KIDNEY AND OTHER TISSUES 1125
AQP1 DEFICIENCY 1126
ADDITIONAL FUNCTIONS OF AQP1 1127
AQUAPORINS IN KIDNEY 1127
AQUAGLYCEROPORINS 1130
VASOPRESSIN REGULATION OF KIDNEY AQUAPORINS 1131
DYSREGULATION OF RENAL AQUAPORINS IN WATER BALANCE DISORDERS 1137
URINARY CONCENTRATING DEFECTS 1137
WATER RETENTION 1139
Chapter 39. Thirst and Vasopressin 1148
VASOPRESSIN AND RELATED PEPTIDES 1149
REGULATION OF SECRETION 1152
DISTRIBUTION AND CLEARANCE 1160
THIRST 1160
ROLE OF VASOPRESSIN AND THIRST IN OSMOREGULATION 1163
Chapter 40. The Urine Concentrating Mechanism and Urea Transporters 1168
KIDNEY STRUCTURE 1169
TRANSPORT PROPERTIES OF INDIVIDUAL NEPHRON SEGMENTS 1172
GENERAL FEATURES OF URINARY CONCENTRATION AND DILUTION 1179
COUNTERCURRENT MULTIPLICATION:HISTORY AND THEORY 1181
OSMOPROTECTIVE OSMOLYTES 1191
ROLE OF UREA 1192
LONG-TERM REGULATION OF UREA TRANSPORTERS 1194
UREA RECYCLING 1196
DEVELOPMENT OF URINE CONCENTRATING ABILITY 1196
SUMMARY 1197
Chapter 41. Hyponatremia 1204
THE PLASMA SODIUM CONCENTRATION AND BODY FLUID TONICITY 1204
PHYSIOLOGIC CONTROL OF WATER EXCRETION 1204
HYPOTONIC HYPONATREMIA:CLASSIFICATION AND PATHOGENESIS 1205
WATER INTOXICATION WITH MAXIMALLY DILUTE URINE 1206
VASOPRESSIN-INDEPENDENT DEFECTS IN WATER EXCRETION 1207
VASOPRESSIN-DEPENDENT DEFECTS IN WATER EXCRETION 1208
HEMODYNAMIC CAUSES OF VASOPRESSIN-MEDIATED HYPONATREMIA 1208
INAPPROPRIATE VASOPRESSIN SECRETION 1210
ADAPTATIONS TO HYPOTONIC HYPONATREMIA 1215
RAPID CORRECTION OF HYPONATREMIA AND OSMOTIC DEMYELINATION 1218
TREATMENT OF HYPOTONIC HYPONATREMIA 1219
NONHYPOTONIC HYPONATREMIA 1221
Chapter 42. Hypernatremic States 1228
REGULATION OF WATER HOMEOSTASIS 1228
DEFENSE MECHANISMS AGAINST WATER DEPLETION 1229
CELLULAR RESPONSE TO HYPERNATREMIA 1231
ETIOLOGY OF HYPERNATREMIC STATES 1237
CLASSIFICATION OF HYPERNATREMIA BASED ON TOTAL-BODY SODIUM: 1238
CLINICAL FEATURES IN HYPERNATREMIA 1243
THERAPY FOR HYPERNATREMIA 1243
CLINICAL STUDIES AND OUTCOME 1245
Chapter 43. Polyuria and Diabetes Insipidus 1250
ARGININE VASOPRESSIN 1250
THE BRATTLEBORO RAT WITH AUTOSOMAL RECESSIVE NEUROGENIC DIABETES INSIPIDUS 1257
KNOCKOUT MICE WITH URINARY CONCENTRATION DEFECTS 1257
QUANTITATING RENAL WATER EXCRETION 1257
CLINICAL CHARACTERISTICS OF DIABETES INSIPIDUS DISORDERS 1257
RARE FORMS 1258
SYNDROME OF HYPERNATREMIA AND HYPODIPSIA 1259
LOSS-OF-FUNCTION MUTATIONS OF AVPR2 1260
LOSS-OF-FUNCTION MUTATIONS OF AQP2 (OMIM 222000, 125800, 107777) 1262
COMPLEX POLYUROPOLYDIPSIC SYNDROME 1263
ACQUIRED NEPHROGENIC DIABETES INSIPIDUS 1263
INVESTIGATION OF A PATIENT WITH POLYURIA 1265
RADIOIMMUNOASSAY OF AVP AND OTHER LABORATORY DETERMINATIONS 1267
MAGNETIC RESONNANCE IMAGING IN PATIENTS WITH DIABETES INSIPIDUS 1268
TREATMENT 1268
Chapter 44. The Molecular Biology of Renal Potassium Channels 1274
THE MOLECULAR BIOLOGY OF ROMK (KIR1), A DISTAL K+ SECRETORY CHANNEL 1274
OTHER RENAL POTASSIUM CHANNELS 1286
SUMMARY AND CONCLUSIONS 1288
Chapter 45. Expression, Function, and Regulation of H+,K+-ATPase in the Kidney 1294
FUNCTIONAL PROPERTIES, PHARMACOLOGY, AND PHYSIOLOGY 1294
EXPRESSION IN THE KIDNEY 1295
REGULATION 1297
OTHER FUNCTIONS OF RENAL H+,K+-ATPases 1299
ASSOCIATED DISEASES 1299
SUMMARY 1299
Chapter 46. Extrarenal Potassium Metabolism 1302
POTASSIUM DEPLETION AND REPLETION 1303
INSULIN 1304
GLUCAGON 1306
CATECHOLAMINES 1306
THYROID 1310
ACID-BASE 1310
ALDOSTERONE 1313
RENAL FAILURE 1314
MAGNESIUM 1315
DRUGS 1316
OTHER FACTORS 1317
Chaper 47. Regulation of Potassium Excretion 1326
OVERVIEW OF POTASSIUM DISTRIBUTION AND EXCRETION: INTERNAL AND EXTERNAL BALANCE 1326
INTERNAL POTASSIUM BALANCE 1326
EXTERNAL POTASSIUM BALANCE: THE ROLE OF THE KIDNEY 1326
POTASSIUM TRANSPORT BY INDIVIDUAL NEPHRON SEGMENTS 1329
POTASSIUM REABSORPTION 1344
CONTROL OF RENAL POTASSIUM TRANSPORT 1346
Chapter 48. Potassium Deficiency 1374
ETIOLOGY OF POTASSIUM DEFICIENCY 1374
SYSTEMIC CHANGES RELEVANT TO RENAL FUNCTION 1382
RENAL CHANGES IN POTASSIUM DEFICIENCY 1385
TREATMENT OF CLINICAL POTASSIUM DEFICIENCY: GENERAL PRINCIPLES 1406
Chapter 49. Clinical Disorders of Hyperkalemia 1412
REGULATION OF POTASSIUM HOMEOSTASIS 1413
ACUTE CONTROL OF THE PK 1413
CLINICAL TOOLS TO ASSESS THE CONTROL OF THE RENAL EXCRETION OF POTASSIUM 1417
CLINICAL APPROACH TO THE PATIENT WITH HYPERKALEMIA 1419
SPECIFIC CAUSES OF HYPERKALEMIA 1421
THERAPY OF HYPERKALEMIA 1427
Chapter 50. The Effects of Electrolyte Disorders on Excitable Membranes 1432
THE NATURE OF EXCITABILITY 1432
ION CHANNELS 1436
EXCITABLE TISSUES 1443
DISORDERED EXCITABILITY 1446
SUMMARY 1450
VOLUME 2. Regulation and Disorders of Acid-Base Homeostasis 1454
SECTION III. Fluid and Electrolyte Regulation and Dysregulation 1454
Chapter 51. Control of Intracellular pH 1454
ELUCIDATING THE COMPLEXITY OF pHi REGULATION 1454
UNDERSTANDING THE MOLECULAR MECHANISMS OF pHi REGULATION 1455
SCOPE OF THIS CHAPTER 1455
METHODS FOR MEASURING pHi 1455
pH-SENSITIVE MICROELECTRODES 1455
DISTRIBUTION OF WEAK ACIDS AND BASES 1456
pH-SENSITIVE DYES 1457
NUCLEAR MAGNETIC RESONANCE 1460
FORCES AFFECTING THE PASSIVE MOVEMENT OF H+ AND OTHER CHARGED ACIDS AND BASES 1461
EFFECTS OF WEAK ACIDS AND BASES ON pHi 1463
EFFECTS OF NH3 AND OTHER NEUTRAL WEAK BASES 1465
INTRACELLULAR BUFFERING 1467
MECHANISMS OF INTRACELLULAR BUFFERING 1468
MEASUREMENT OF INTRACELLULAR BUFFERING POWER 1470
ACID-BASE TRANSPORT SYSTEMS 1471
ACID-LOADING MECHANISMS 1472
ACID-EXTRUSION MECHANISMS 1476
THE REGULATION OF pHi 1484
FACTORS INFLUENCING pHi 1486
Chapter 52. Sodium-Coupled Bicarbonate Transporters 1506
INTRODUCTION 1506
OVERVIEW OF THE SLC4 FAMILY 1506
THE ELECTROGENIC Na+-COUPLED HCO-3 TRANSPORTERS 1510
THE ELECTRONEUTRAL Na+-COUPLED HCO-3 TRANSPORTERS 1513
NCBE (SLC4A10) 1516
ROLES IN HEALTH AND DISEASE 1517
CONCLUSION 1519
Chapter 53. The SLC4 Anion Exchanger Gene Family 1524
THE AE ANION EXCHANGERS AMONG THE SLC4 AND SLC26 SUPERFAMILIES 1524
SLC4 ANION EXCHANGE DOMAIN STRUCTURE AND ALTERNATIVE TRANSCRIPTS 1525
LOCALIZATION AND FUNCTION OF ANION EXCHANGERS IN TISSUES 1526
AE1 N-TERMINAL CYTOPLASMIC DOMAIN STRUCTURE AND BINDING PROTEINS 1529
AE1 C-TERMINAL TRANSMEMBRANE DOMAIN STRUCTURE AND BINDING PROTEINS 1531
MECHANISMS OF SLC4/AE ANION TRANSPORT 1533
PHARMACOLOGY OF SLC4/AE ANION EXCHANGERS 1539
THE ANION TRANSLOCATION PATHWAY OF AE1 1539
ANION CONDUCTANCE ASSOCIATED WITH AE1 1540
THE AE1 C-TERMINAL CYTOPLASMIC TAIL:CARBONIC ANHYDRASE BINDING, ANION SELECTIVITY, AND OTHER FUNCTIONS 1541
ACUTE REGULATION OF ANION EXCHANGERS 1542
AE1 DEFICIENCY DISEASES OF ERYTHROCYTES 1545
KNOCKOUT MOUSE MODELS OF DEFICIENCY OF AE2/SLC4A2 AND AE3/SLC4A3 1552
CONCLUSION 1554
Chapter 54. Cellular Mechanisms of Renal Tubular Acidification 1564
PROXIMAL TUBULE 1564
LOOP OF HENLE AND THICK ASCENDING LIMB 1585
DISTAL NEPHRON 1587
Chapter 55. Chemoreceptors, Breathing, and pH 1612
INTRODUCTION 1612
CO2 1612
PERIPHERAL CHEMORECEPTORS 1613
CENTRAL CHEMORECEPTORS 1613
PARADOX: CENTRAL CHEMORECEPTORS LOCATED IN AN ENVIRONMENT WITH TIGHT PH REGULATION 1620
BREATHING AND PH REGULATION 1622
SUMMARY 1623
Chapter 56. Renal Ammonium Ion Production and Excretion 1626
INTRODUCTION 1626
ROLE OF RENAL AMMONIUM ION PRODUCTION AND EXCRETION IN THE MAINTENANCE OF ACID–BASE BALANCE 1626
PATHWAYS OF RENAL AMMONIAGENESIS 1628
ACUTE REGULATION OF RENAL AMMONIAGENESIS 1628
CHRONIC ADAPTATIONS TO METABOLIC ACIDOSIS 1629
SIGNAL TRANDSDUCTION PATHWAYS THAT MEDIATE ADAPTIVE RESPONSES TO ACIDOSIS 1635
COUNTERCURRENT TRANSPORT OF AMMONIUM IONS 1637
EXCRETION OF AMMONIUM IONS 1639
PATHOPHYSIOLOGY 1640
FUTURE DIRECTIONS 1641
Chapter 57. The Acid–Base Effects of the Contemporary Western Diet: An Evolutionary Perspective 1646
INTRODUCTION 1646
METABOLIC ACIDOSIS AND ALKALOSIS:DEFINITIONS 1647
DETERMINANTS OF BLOOD ACIDITY AND PLASMA [HCO3] SET-POINT REGULATION IN “NORMAL” SUBJECTS 1648
ACIDOSIS VERSUS ACID RETENTION 1650
PATHOPHYSIOLOGICAL CONSEQUENCES OF DIET-INDUCED, AGE-AMPLIFIED METABOLIC ACIDOSIS IN HUMANS 1652
DIET-INDUCED POTASSIUM-REPLETE CHLORIDE-SUFFICIENT CHRONIC LOW-GRADE METABOLIC ALKALOSIS AS NATURALLY SELECTED OPTIMAL SYSTEMIC ACID–BASE STATE OF HUMANS 1659
IMPLICATIONS FOR FURTHER RESEARCH 1664
ADDENDUM ADDED IN PROOF 1669
Chapter 58. Clinical Syndromes of Metabolic Alkalosis 1670
INTRODUCTION 1670
DEFENSE AGAINST EXCESS ECF HCO3 1670
MECHANISMS OF METABOLIC ALKALOSIS 1674
CLINICAL SYNDROMES OF METABOLIC ALKALOSIS 1679
CONCLUDING REMARKS 1687
Chapter 59. Clinical Syndromes of Metabolic Acidosis 1692
INTRODUCTION 1692
DEFINITION OF METABOLIC ACIDOSIS 1692
SYSTEMIC AND RENAL ACID–BASE HOMEOSTASIS 1693
CLINICAL CONSEQUENCES 1697
CLINICAL DISORDERS 1704
Chapter 60. Respiratory Alkalosis and Acidosis 1746
INTRODUCTION 1746
RESPIRATORY ALKALOSIS 1748
RESPIRATORY ACIDOSIS 1757
Chapter 61. Mechanisms and Disordersof Magnesium Metabolism 1772
INTRODUCTION 1772
PHYSIOLOGY OF RENAL MAGNESIUM HANDLING 1772
PATHOPHYSIOLOGY OF RENAL MAGNESIUM HANDLING 1779
Chapter 62. Calcium Channels 1794
INTRODUCTION 1794
EPITHELIAL Ca2+ CHANNELS:TRPV5 AND TRPV6 1796
REGULATION OF EPITHELIAL Ca2+ CHANNELS 1801
CHARACTERIZATION OF TRPV5 KNOCKOUT MICE 1806
Chapter 63. The Calcium-Sensing Receptor 1810
LIGAND BINDING:THE CaSR IS A Ca2+/Mg2+ AND AN “EXTRACELLULAR ENVIRONMENT” SENSOR 1810
CALCIUM-SENSING RECEPTOR FUNCTION IN THE PARATHYROID GLAND 1812
MODULATION OF THE CALCIUM-SENSING RECEPTOR IN SECONDARY HYPERPARATHYROIDISM 1814
CALCIUM-SENSING RECEPTOR AND KIDNEY FUNCTION 1816
Chapter 64. Vitamin D 1828
INTRODUCTION 1828
METABOLISM OF VITAMIN D 1829
TRANSPORT OF VITAMIN D METABOLITES 1834
MECHANISM OF ACTION OF VITAMIN D 1835
CLASSICAL ACTIONS OF VITAMIN D 1841
NONCLASSICAL VITAMIN D ACTIONS 1845
CLINICAL DISORDERS OF VITAMIN D METABOLISM 1853
VITAMIN D THERAPY IN CHRONIC KIDNEY DISEASE 1861
Chapter 65. Renal Calcium Metabolism 1876
INTRODUCTION 1876
CALCIUM CHEMISTRY 1876
CALCIUM TRANSPORT ALONG THE NEPHRON 1878
REGULATION OF RENAL CALCIUM TRANSPORT 1889
CELLULAR MECHANISMS OF TRANSEPITHELIAL CALCIUM TRANSPORT 1903
Chapter 66. The Hormonal Regulation of Calcium Metabolism 1916
INTRODUCTION 1916
CALCIUM BALANCE 1916
VITAMIN D ENDOCRINE SYSTEM 1917
PARATHYROID HORMONE ENDOCRINE SYSTEM 1924
CALCITONIN 1927
CONCLUSION 1928
Chapter 67. Disorders of Calcium Metabolism 1936
INTRODUCTION 1936
GENERAL CONSIDERATIONS 1936
CALCIUM HOMEOSTASIS 1937
DEFENSES AGAINST HYPERCALCEMIA AND HYPOCALCEMIA 1940
HYPERCALCEMIA 1941
HYPOCALCEMIA 1954
Chapter 68. Pathogenesis and Treatment of Nephrolithiasis 1970
STONES AND THEIR DISEASE STONES, CLINICAL SYNDROMES, AND NATURAL HISTORY
PRIMARY PROCESS OF CRYSTALLIZATION 1972
PHYSICAL CELLULAR MECHANISMS IN STONE FORMATION 1979
INHIBITORS OF CRYSTALLIZATION AND CELL CRYSTAL INTERACTIONS 1988
DISORDERS OF CALCIUM STONE FORMATION 1990
URIC ACID IN STONES 1998
CYSTINURIA AND CYSTINE STONES 1998
INFECTION (STRUVITE) STONES 1999
Chapter 69. Proximal Tubular Handling of Phosphate 2004
PROXIMAL TUBULAR REABSORPTION OF PHOSPHATE 2004
GENE PRODUCTS INVOLVED IN PROXIMAL TUBULAR PHOSPHATE REABSORPTION 2005
ALTERATIONS OF PROXIMAL TUBULAR REABSORPTION OF PI 2008
Chapter 70. Clinical Disturbances of Phosphate Homeostasis 2014
THE IMPORTANCE OF PHOSPHORUS IN BIOLOGICAL SYSTEMS 2014
THE REGULATION OF PHOSPHATE BALANCE 2014
THE PHYSIOLOGY OF PHOSPHATE IN THE KIDNEY 2015
FACTORS REGULATING RENAL PHOSPHATE EXCRETION 2016
ACUTE AND CHRONIC HYPOPHOSPHATEMIA 2022
ACUTE AND CHRONIC HYPERPHOSPHATEMIA 2025
Chapter 71. Glucose Reabsorption in the Kidney 2032
TRANSPORT OF GLUCOSE AT THE BASOLATERAL MEMBRANE 2033
TRANSPORT OF GLUCOSE AT THE LUMINAL MEMBRANE 2033
THE HIGH-AFFINITY Na+/D-GLUCOSE COTRANSPORTER 2034
THE LOW-AFFINITY Na+/D-GLUCOSE COTRANSPORTER 2034
MOLECULAR ORGANIZATION AND ENERGETICS OF RENAL TUBULAR GLUCOSE REABSORPTION 2035
ABNORMALITIES OF TUBULAR GLUCOSE REABSORPTION 2036
MOLECULAR CHARACTERIZATION OF THE HIGH-AFFINITY Na+/D-GLUCOSE COTRANSPORTER 2037
MEMBRANE TOPOLOGY OF SGLT1 2038
STRUCTURE/FUNCTION STUDIES OF SGLT1 2038
Na+-GLUCOSE COUPLING AND STRUCTURAL RELATIONSHIP OF THE Na+ AND GLUCOSE DOMAINS 2041
CONCLUSION 2043
Chapter 72. Amino Acids, Oligopeptides, and Hyperaminoacidurias 2046
AMINO ACIDS 2046
WHICH NEPHRON SEGMENTS ARE RESPONSIBLE FOR RESORPTION? 2046
THE “WRONG” WAY? PERITUBULAR UPTAKE AND TRANSCELLULAR SECRETION 2051
RECENT ADVANCES IN MOLECULAR CHARACTERIZATION OF RENAL AMINO ACID TRANSPORTERS 2055
AGT1 2056
PRINCIPLE MECHANISMS OF HYPERAMINOACIDURIA 2060
OLIGOPEPTIDES 2062
Chapter 73. Organic Anion and Cation Transporters in Renal Elimination of Drugs 2070
ORGANIC ANION TRANSPORT SYSTEMS 2070
OVERVIEW OF TRANSPORTERS INVOLVED IN TRANSPORT OF ANIONIC DRUGS 2082
ORGANIC CATION TRANSPORTERS 2086
OCT1 2087
OCT2 2087
OCT3 2087
OCTN1 (SLC22A4) 2095
OCTN2 (SLC22A5) 2095
OCTN3 (Slc22a9) 2097
CONCLUSIONS AND OUTLOOK 2097
Chapter 74. Renal Filtration, Transport, and Metabolism of Albumin and Albuminuria 2106
INTRODUCTION 2106
ALBUMIN METABOLISM 2107
GLOMERULAR SIEVING COEFFICIENT 2110
FACTORS CONTROLLING GLOMERULAR CAPILLARY WALL PERMEABILITY AND SIEVING COEFFICIENT 2113
STRUCTURAL AND CELLULAR COMPONENTS AFFECTING ALBUMINURIA/PROTEINURIA 2117
MECHANISTIC PATHWAYS THAT CONTROL ALBUMIN PROCESSING 2121
MOLECULAR FACTORS AFFECTING ALBUMINURIA/PROTEINURIA 2126
ALBUMINURIA IN DIFFERENT DISEASED STATES 2129
CONCLUDING REMARKS 2131
SECTION IV. Pathophysiology of Renal Disease 2138
Chapter 75. Physiologic Principles in the Clinical Evaluation of Electrolyte, Water, and Acid-Base Disorders 2138
CONCEPT OF EXTERNAL BALANCE AND STEADY STATE 2138
URINARY CONSTITUENTS AS CLINICAL INDICES: GENERAL CONSIDERATIONS 2140
EVALUATION OF DISORDERS OF WATER EXCRETION 2144
EVALUATION OF POTASSIUM DISORDERS 2152
EVALUATION OF METABOLIC ACIDOSIS 2157
Chapter 76. Pathophysiology of Acute Kidney Injury 2168
CLINICAL OVERVIEW 2168
MODELS OF ACUTE KIDNEY INJURY AND TECHNIQUES OF EARLY DIAGNOSIS 2175
PATHOPHYSIOLOGY OF ACUTE KIDNEY INJURY 2178
APOPTOSIS AND NECROSIS 2193
CELLULAR REPAIR, REGENERATION, AND RECOVERY 2199
TGF-ß 2200
CLINICAL COURSE AND DIAGNOSTIC TESTS IN ACUTE KIDNEY INJURY 2202
CLINICAL OUTCOMES AND PROGNOSIS 2206
PATHOPHYSIOLOGIC BASIS OF THERAPY OF ACUTE RENAL FAILURE 2207
EVOLVING MANAGEMENT OF ACUTE KIDNEY INJURY 2207
CONCLUSION 2210
Chapter 77. Ischemic Renal Disease 2218
ATHEROSCLEROTIC RENAL ARTERY STENOSIS:A COMMON DISORDER WITH INCREASING CLINICAL RECOGNITION AND PUBLIC HEALTH IMPORTANCE 2218
CLINICAL PRESENTATIONS OF ISCHEMIC NEPHROPATHY 2219
DIAGNOSIS OF ISCHEMIC NEPHROPATHY 2220
CLINICAL SIGNIFICANCE OF ATHEROSCLEROTIC RENAL ARTERY STENOSIS 2221
PATHOPHYSIOLOGY OF RENAL UNDERPERFUSION AND ISCHEMIC NEPHROPATHY 2223
ADAPTIVE RESPONSES TO RENAL UNDERPERFUSION 2224
PATHOPHYSIOLOGY OF ISCHEMIC NEPHROPATHY 2225
PATHOLOGY OF THE KIDNEY IN ISCHEMIC NEPHROPATHY 2229
NATURAL HISTORY OF ISCHEMIC NEPHROPATHY 2229
TREATMENT OF ISCHEMIC NEPHROPATHY 2231
MEDICAL MANAGEMENT 2232
SUMMARY 2237
Chapter 78. Pathophysiology and Pathogenesis of Diabetic Nephropathy 2240
EPIDEMIOLOGY 2240
CLINICAL COURSE OF DIABETIC NEPHROPATHY IN TYPE 1 AND TYPE 2 DIABETES 2241
PATHOLOGY OF KIDNEY DISEASE IN DIABETES MELLITUS 2243
THE CENTRAL ROLE OF PODOCYTES IN THE PATHOPHYSIOLOGY OF DIABETIC PROTEINURIA 2244
CELLULAR AND MOLECULAR MECHANISMS IN THE PATHOPHYSIOLOGY OF DIABETIC NEPHROPATHY 2245
METABOLIC SYNDROME/OBESITY AND RENAL DISEASE 2252
REGRESSION 2253
SUMMARY AND OUTLOOK 2254
Chapter 79. Renal Failure in Cirrhosis 2260
DEFINITION 2260
EPIDEMIOLOGY 2260
PATHOGENESIS 2260
CLINICAL AND LABORATORY FINDINGS 2262
DIFFERENTIAL DIAGNOSIS 2266
MANAGEMENT 2267
Chapter 80. Obstructive Uropathy 2272
DEFINITIONS 2272
INCIDENCE AND PREVALENCE 2272
CLASSIFICATION 2272
RENAL FUNCTION 2272
SODIUM AND WATER REABSORPTION 2279
ENDOTHELIN SYSTEM 2288
CAUSES OF OBSTRUCTIVE UROPATHY 2289
DIAGNOSTIC APPROACH 2293
TREATMENT 2298
ARGININE AND NITRIC OXIDE 2302
Chapter 81. Autosomal Dominant Polycystic Kidney Disease and Inherited Cystic Diseases 2308
CLINICAL FEATURES OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE 2308
GENETICS OF ADPKD 2312
PROPERTIES OF CYSTS 2316
THE PKD GENES AND THEIR PROTEIN PRODUCTS 2317
CILIA AND THE SPECTRUM OF INHERITED CYSTIC DISEASE 2321
CELLULAR PATHWAYS AFFECTED BY POLYCYSTINS 2323
PROSPECTS FOR THERAPY IN ADPKD 2331
Chapter 82. Immunologic Mechanisms of Vasculitis 2340
IMMUNOPATHOLGIC CATEGORIES OF VASCULITIS 2340
BASIC PATHOGENIC EVENTS IN SMALL-VESSEL VASCULITIS 2342
IMMUNE COMPLEX–MEDIATED VASCULITIS 2349
PAUCI-IMMUNE ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODY VASCULITIS 2354
Chapter 83. Renal Physiology and Disease in Pregnancy 2364
ANATOMICAL CHANGES 2364
RENAL HEMODYNAMICS 2366
RENAL TUBULAR FUNCTION 2372
OSMOREGULATION AND RENAL WATER HANDLING 2375
VOLUME HOMEOSTASIS 2379
RENAL DISORDERS AND GESTATION 2384
CHRONIC PARENCHYMAL RENAL DISEASE 2388
HYPERTENSION 2396
Chapter 84. Immune-Mediated and Other Glomerular Diseases 2424
IMMUNOGLOBULIN A NEPHROPATHY 2424
MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS 2428
ANTI–GLOMERULAR BASEMENT MEMBRANE DISEASE AND GOODPASTURE SYNDROME 2434
ACUTE POSTINFECTIOUS GLOMERULONEPHRITIS 2437
PRIMARY RENAL DISEASES CAUSING NEPHROTIC SYNDROME 2439
SYSTEMIC DISEASES ASSOCIATED WITH THE NEPHROTIC SYNDROME 2448
MALIGNANCY-ASSOCIATED GLOMERULAR DISEASES 2454
DRUG-INDUCED GLOMERULAR DISEASES 2455
Chapter 85. Genetic Abnormalities in Glomerular Function 2472
INTRODUCTION 2472
DISORDERS OF EXTRACELLULAR MATRIX 2472
STORAGE DISORDERS 2483
DISORDERS OF THE PODOCYTE SLIT DIAPHRAGM 2487
DISORDERS OF PODOCYTE CYTOSKELETON 2490
FSGS1 2490
FSGS2 2491
FSGS3 2491
MYH9-RELATED DISORDERS (EPSTEIN AND FECHTNER SYNDROMES) 2491
DISORDERS OF PODOCYTE GENE REGULATION 2491
Chapter 86. Immunological Mechanisms of Interstitial Disease 2502
INTRODUCTION 2502
FUNCTIONAL SIGNIFICANCE OF TUBULOINTERSTITIAL INJURY 2502
TUBULOINTERSTITIAL ANTIGENS 2503
DRUG–HAPTEN CONJUGATES AS NEPHRITOGENIC ANTIGENS 2505
ANTIGENS BASED ON MOLECULAR MIMICRY 2505
IMMUNE RESPONSE GENES 2506
T CELLS IN INTERSTITIAL INJURY 2508
REGULATION OF T CELLS 2510
MACROPHAGES IN INTERSTITIAL INJURY 2511
ANTIBODY-MEDIATED NEPHRITOGENIC RESPONSES 2512
TRAFFICKING OF INFLAMMATORY CELLS 2514
FIBROBLASTS AND FIBROSIS 2521
CONCLUSION 2523
Chapter 87. Cellular Mechanisms of Drug Nephrotoxicity 2532
INTRODUCTION 2532
CYCLOSPORIN A 2543
PHENACETIN ACETAMINOPHEN NEPHROTOXICITY 2547
AMINOGLYCOSIDES 2549
CISPLATIN 2550
LITHIUM 2551
CONCLUSION 2552
Chapter 88. Role of Glomerular Pressure in Progression 2562
INTRODUCTION 2562
ADAPTATION OF RENAL FUNCTION LEADING TO GLOMERULAR HYPERTENSION AND HYPERFILTRATION 2562
MECHANISMS OF GLOMERULAR INJURY 2568
NEPHRON NUMBER AS A FACTOR PREDISPOSING TO PROGRESSION 2571
APPROACHES TO PREVENT PROGRESSION BASED ON RATIONALE OF REDUCING GLOMERULAR HYPERTENSION 2571
Chapter 89. Role of Proteinuria in Progression 2588
INTRODUCTION 2588
HISTORICAL PERSPECTIVE 2588
TUBULAR HANDLING OF PROTEINS 2590
PROTEIN OVERLOAD ACTIVATES PHENOTYPIC CHANGES IN CULTURED PROXIMAL TUBULAR CELLS 2591
INTRACELLULAR SIGNALING OF PROTEIN OVERLOAD 2593
IN VIVO EVIDENCE FOR PROINFLAMMATORY PATHWAYS AND SIGNALING IN TUBULAR CELLS ACTIVATED BY PROTEINURIA 2594
PATHOGENIC ROLE OF COMPLEMENT PROTEINS IN TUBULAR AND INTERSTITIAL INJURY 2595
ROLE OF PROTEIN-BOUND LIPIDS 2597
PROFIBROGENIC SIGNALING FROM PROXIMAL TUBULAR CELLS LOADED WITH FILTERED PROTEINS 2597
ROLE OF PROTEINURIA IN TUBULAR APOPTOSIS 2598
Chapter 90. The Inflammatory Response to Ischemic Acute Renal Injury 2602
LEUKOCYTES IN INJURED, ISCHEMIC TISSUES: FRIEND OR FOE? 2602
THE RIGHT STUFF IN THE WRONG PLACE:THE PRO-INFLAMMATORY EFFECTS OF INTRACELLULAR MOLECULES RELEASED INTO THE EXTRA CELLULAR SPACE BY NECROTIC CELLS. 2604
WHEN DEATH IS NO ACCIDENT: NECROSIS AS A PROGRAMMED EVENT 2607
DOES AUTOPHAGY LEAD TO PROGRAMMED NECROSIS? 2608
ADDITIONAL EXAMPLES OF PROGRAMMED NECROSIS IN VIVO 2608
SUMMARY: DEATH AND INJURY ELICIT INFLAMMATION 2609
Chapter 91. The Role of Dyslipidemias in the Progression of Chronic Kidney Disease 2616
WHAT IS THE HYPOTHESIS? 2616
HOW CAN WE TEST THE HYPOTHESIS? 2616
ASSOCIATIONS BETWEEN LIPOPROTEIN ABNORMALITIES AND CKD PROGRESSION 2619
EVIDENCE FROM RETROSPECTIVE ANALYSES OF RANDOMIZED CONTROLLED TRIALS 2619
DIRECT EVIDENCE FROM RANDOMIZED CONTROLLED TRIALS 2620
THE ROLE OF DYSLIPIDEMIAS IN RENAL ALLOGRAFT INJURY 2621
CURRENT TREATMENT RECOMMENDATIONS 2621
THE STUDY OF HEART AND RENAL PROTECTION (SHARP) 2622
SUMMARY 2622
Chapter 92. Oxidants in Progressive Kidney Disease 2626
ROLE OF OXIDANTS IN NONDIABETIC GLOMERULAR DISEASE 2628
OXIDANT MECHANISMS IN DIABETES 2633
ROLE OF OXIDANTS AND IRON IN PROGRESSIVE KIDNEY DISEASE 2635
CONCLUSIONS 2635
Chapter 93. Chronic Kidney Disease: Pathophysiology and Influence of Dietary Protein 2640
INTRODUCTION 2640
MEASUREMENT AND NATURAL HISTORY OF CKD 2640
PATHOPHYSIOLOGY OF CKD 2653
INFLUENCE OF DIETARY THERAPY IN PATIENTS WITH CHRONIC KIDNEY DISEASE 2670
DIETARY PROTEIN RESTRICTION AND PROGRESSION OF RENAL INSUFFICIENCY 2677
CONCLUSION 2683
Chapter 94. Management of Calcium and Bone Disease in Renal Patients 2696
INTRODUCTION 2696
MOLECULAR TARGETS FOR SUPPRESSING PARATHYROID GLAND FUNCTION IN CKD 2696
CLINICAL MANIFESTATIONS OF DISORDERED MINERAL METABOLISM IN CKD 2697
VASCULAR CALCIFICATIONS, DISORDERED MINERAL METABOLISM, AND CARDIOVASCULAR DISEASE 2698
TREATMENT GOALS:K/DOQI GUIDELINES FOR MINERAL METABOLISM IN CKD 2698
TREATMENT STRATEGIES 2699
Chapter 95. Hematopoiesis and the Kidney 2706
INTRODUCTION 2706
ERYTHROPOIESIS 2706
THROMBOCYTOPOIESIS 2732
GRANULOCYTOPOIESIS 2735
FUTURE ASPECTS 2736
Chapter 96. Electrolyte Disturbances in Dialysis 2744
INTRODUCTION 2744
SODIUM 2744
POTASSIUM 2748
ACID–BASE 2751
CALCIUM 2754
MAGNESIUM 2757
DIALYSATE PHOSPHATE 2758
Chapter 97. Homeostasis of Solute and Water by the Transplanted Kidney 2762
INTRODUCTION 2762
INTRINSIC CAPACITY OF THE DENERVATED TRANSPLANTED ISOGRAFT 2763
ISCHEMIA ATTENDANT TO HARVEST, PRESERVATION, AND ENGRAFTMENT 2764
ALLOGRAFT IN THE AZOTEMIC SOLUTE-LOADED RECIPIENT 2765
SOLUTE REGULATION DURING REJECTION 2768
RENAL TUBULAR ACIDOSIS ASSOCIATED WITH ISCHEMIA AND REJECTION 2769
SYNDROMES OF POTASSIUM HANDLING 2771
MINERAL METABOLISM STATES AFTER TRANSPLANT 2772
HANDLING OF URATE AFTER TRANSPLANT 2774
RENAL TRANSPORT AND IMMUNOSUPPRESSIVE DRUGS 2775
Chapter 98. Disposition and Dose Requirements of Drugs in Renal Insufficiency 2788
INTRODUCTION 2788
ROLE OF THE KIDNEY IN DRUG DISPOSITION 2789
INFLUENCE OF RENAL DISEASE ON RESPONSE TO DRUGS 2804
DOSING RECOMMENDATIONS IN PATIENTS WITH RENAL INSUFFICIENCY 2804
Index 2818