Textbook of Nephro-Endocrinology, 1st Edition

Cover Page......Page 1
List of Contributors......Page 2
Preface......Page 6
Erythropoiesis......Page 7
Growth Factors Important for Hematopoiesis and Erythropoiesis......Page 8
Intracellular Signaling Mediators of EPO......Page 9
Hepcidin and Regulation of Serum Iron levels......Page 10
Iron and Regulation of Hemoglobin Production......Page 11
References......Page 12
Further reading......Page 14
Heart and Vasculature......Page 15
Regulation of EPOR expression......Page 16
Recruitment of EPC......Page 17
Erk1/2......Page 18
References......Page 19
Further reading......Page 21
History of recombinant human erythropoietin......Page 22
Biosimilar EPOs......Page 23
Potential strategies for modifying erythropoietin to create new EPO analogs......Page 24
Darbepoetin alfa......Page 25
Intravenous Administration – Hemodialysis Patients......Page 26
Subcutaneous Administration – Pre-Dialysis CKD Patients......Page 27
Effects of C.E.R.A. In Vitro and in Animal Models......Page 28
Effects of C.E.R.A. in Patients with CKD Anemia......Page 29
Peptide-Based ESAs......Page 30
References......Page 31
Erythropoietin pathophysiology in CKD patients......Page 36
Anemia of chronic kidney disease......Page 38
Target Hemoglobin in CKD Patients......Page 39
Randomized Controlled Trials......Page 40
Erythropoietin Treatment and the Risk of
Hypertension and Graft Thrombosis......Page 41
Hemoglobin Targets in Children......Page 42
References......Page 43
Further reading......Page 47
Vitamin D and the Kidney: Introduction and Historical Perspective......Page 48
Experimental Evidence of the Role of Vitamin’D in Rickets......Page 50
Discovery of the Structure of Vitamin D......Page 51
Cinacalcet......Page 52
References......Page 53
Further reading......Page 54
Introduction......Page 55
Phosphate homeostasis......Page 56
Physiology and Tubular Localization......Page 57
Cellular and Molecular Aspects......Page 58
Parathyroid Hormone (PTH)......Page 59
Fibroblast Growth Factor 23 (FGF-23)......Page 60
Other Hormonal Regulators......Page 61
Role of phosphate in the regulation of renal vitamin D metabolism......Page 62
Autosomal Dominant Hypophosphatemic Rickets (ADHR)......Page 63
Autosomal Recessive Hypophosphatemia (ARHP)......Page 64
Fibrous Dysplasia (FD)......Page 66
Tumoral Calcinosis (TC) with/without Hyperphosphatemia......Page 67
Hypoparathyroidism and Pseudohypoparathyroidism......Page 68
References......Page 69
Further reading......Page 76
The History of the Renin–Angiotensin System......Page 77
The 20th century......Page 79
The Ambiguity of the Renin–Angiotensin–Aldosterone System......Page 81
Conclusion......Page 82
References......Page 83
Further reading......Page 84
The classical circulating renin–
angiotensin system (RAS)......Page 85
Renin biosynthesis and secretion......Page 86
The renin receptor......Page 87
Angiotensin-converting enzyme (ACE)......Page 88
AT1 receptors......Page 89
AT2 receptors......Page 90
Intrarenal renin–angiotensin system......Page 91
Brain renin–angiotensin system......Page 93
Vascular tissue renin–angiotensin system......Page 94
Aldosterone and mineralocorticoid receptors......Page 95
Clinical effects of the renin–angiotensin–aldosterone system (RAAS)......Page 97
References......Page 99
Further reading......Page 103
Historical background......Page 104
Overview of the RAS pathway......Page 105
RAS and Renal Hemodynamics......Page 106
Collecting Duct......Page 107
RAS in Chronic Renal Disease......Page 108
RAS and RAS Blockade in Diabetic Nephropathy......Page 109
RAS in Lupus and Other Autoimmune Disease......Page 110
Renin inhibitors......Page 111
References......Page 112
Further reading......Page 117
Cardiac RAS: local versus endocrine origin......Page 118
RAS actions at the cellular level......Page 119
Pathophysiology of RAS in Cardiac Function......Page 121
References......Page 122
Angiotensin-Converting Enzyme Inhibitors......Page 126
Tissue-binding......Page 127
Application of Pharmacologic Differences......Page 128
Pharmacokinetics......Page 129
Pharmacokinetics......Page 131
Blood Pressure Lowering Effect......Page 132
ACE inhibitors and angiotensin receptor blockers with other agents......Page 133
Select side-effects of ACE inhibitors and angiotensin-receptor blockers......Page 134
References......Page 135
Vasopressin in the Kidney: Historical Aspects......Page 139
Hypothalamus......Page 141
Vasopressin receptors......Page 142
Localization of Vasopressin Receptors in the Kidney......Page 143
Action of Vasopressin in the Toad Bladder, Collecting Tubules and Inner Medulla......Page 144
Vasopressin Effect in the Other Renal Tubules......Page 145
Red Blood Cells......Page 146
Acute Regulation of Urea Transport by Vasopressin......Page 147
Aquaporins......Page 148
Acute Regulation of Aquaporin Transport by Vasopressin......Page 150
Nephrogenic diabetes insipidus......Page 151
Vaptans......Page 152
References......Page 153
Structure, Synthesis and Secretion......Page 160
Similarity to Oxytocin......Page 161
Pathology Associated with Dysregulation of AVP Secretion and Actions......Page 162
V1a, V1b and V2 Cloning......Page 163
Tissue/Cellular Localization......Page 164
Molecular Structure......Page 165
Signaling of Vasopressin Receptors......Page 167
Actions and Interactions of AVP Receptors......Page 168
Regulation of CD ENaC by AVP......Page 169
AVP Increases the Activity of NKCC2......Page 171
AVP increases chloride reabsorption in the TAL......Page 172
Urea Reabsorption is Stimulated by AVP......Page 173
UT-A2 is Increased by AVP......Page 174
AVP and Renal Blood Flow......Page 175
Hypertension may Correlate With Urinary Concentrating Ability......Page 176
References......Page 177
Inhibition of Vasopressin Release......Page 184
Inhibition of Vasopressin Action......Page 185
Vasopressin antagonists and their role in the treatment of water-retaining disorders......Page 186
Hypothyroidism......Page 187
Syndrome of Inappropriate ADH secretion......Page 188
Cardiac Failure......Page 189
Cirrhosis......Page 190
Are vasopressin antagonists safe?......Page 191
References......Page 192
Further reading......Page 195
Diabetes Insipidus......Page 196
Congenital Nephrogenic Diabetes Insipidus......Page 197
Acquired Nephrogenic Diabetes Insipidus......Page 199
Central Diabetes Insipidus......Page 201
Diagnosis of DI......Page 203
Treatment of Hypernatremia Due to Diabetes Insipidus......Page 204
Pathogenesis of Hyponatremia......Page 205
Pathogenesis of SIADH......Page 206
Epidemiology of SIADH......Page 207
Exercise-Associated Hyponatremia......Page 208
Cerebral Salt Wasting (CSW)......Page 209
Diagnosis of SIADH and Evaluation of Hyponatremia......Page 210
Treatment of SIADH......Page 211
Clinical Symptoms......Page 212
Gender......Page 213
Treatment of Hyponatremic Encephalopathy......Page 214
References......Page 215
Further reading......Page 221
Aldosterone: History and Introduction......Page 222
Activity of the Amorphous Fraction......Page 224
Loss of Faith in Significance of the Amorphous Fraction......Page 225
Discovery of Electrocortin (Aldosterone) as a Hormone......Page 226
Isolation in Crystalline Form......Page 227
Identification and Synthesis of Aldosterone (Electrocortin)......Page 228
Adrenal Site of Production of Steroids......Page 229
Metabolism of Aldosterone......Page 230
Diagnostic Criteria and Approaches......Page 231
Na Fluorescence......Page 232
Isotopic Methods......Page 233
Enduring Concepts and Findings......Page 234
Spironolactone......Page 235
Eplerenone......Page 236
References......Page 237
Further reading......Page 240
Aldosterone-binding sites and the mineralocorticoid receptor (MR)......Page 241
Molecular biology of the MR......Page 242
Post-Translational Modifications of the MR......Page 244
Oligomeric Structure of Steroid Receptors......Page 245
MR Trafficking......Page 246
Mineralocorticoid Receptor Selectivity......Page 248
Proteins induced by aldosterone in transport epithelia......Page 249
Non-genomic effects of aldosterone in the kidney......Page 252
References......Page 254
Clinical Studies Supporting a Role for Aldosterone in the Pathophysiology of Cardiac Disease......Page 261
Aldosterone and Animal Models of Heart Disease......Page 262
Aldosterone and Animal Models of Diabetic and Non-Diabetic Renal Injury......Page 263
Effect of Aldosterone on Intracellular Signaling Pathways......Page 264
Aldosterone and Inflammation......Page 265
Dietary Sodium and Aldosterone-Mediated Cardiovascular Injury......Page 266
Conclusions......Page 267
References......Page 268
Further reading......Page 271
Aldosterone biosynthesis......Page 272
Physiology of the RAAS (see Chapter 12 for Detailed Discussion)......Page 273
Ang II-Regulated Intracellular Glomerulosa Cell Signaling Pathways......Page 275
Chronic Effects of Ang II......Page 277
Potassium-Regulated Intracellular Signaling Pathways......Page 278
Chronic Effects of Potassium......Page 279
Chronic Action of ACTH on Aldosterone Production......Page 280
Inhibitors of Aldosterone Biosynthesis......Page 281
CYP21......Page 282
Primary Hyperaldosteronism......Page 283
Secondary Hyperaldosteronism (see Chapter 23 for Additional Details)......Page 285
References......Page 286
Insulin Resistance and Diabetes in Chronic Renal Disease......Page 293
Historical perspective......Page 295
Cellular mechanisms of insulin secretion and action......Page 296
Clinical physiology of insulin resistance......Page 297
Measurement of insulin resistance......Page 298
Overview......Page 299
Definition......Page 300
Obesity......Page 302
Hyperglycemia......Page 303
Hypertension......Page 304
Dyslipidemia......Page 306
Proteinuria......Page 307
Pathogenesis of insulin resistance in chronic kidney disease......Page 308
Syndromes of severe insulin resistance......Page 309
Dietary Management......Page 310
Insulin Sensitizers......Page 311
Management of diabetes in chronic kidney disease......Page 312
Conclusions......Page 313
Normal GH/IGF-I Axis......Page 320
Growth Hormone and Growth Hormone Resistance in CKD......Page 322
Insulin-Like Growth Factor-I and Insulin-Like Growth Factor-I Abnormalities in CKD......Page 324
Impact of Growth Failure in Children
with CKD......Page 325
Modifiable Factors......Page 326
Adult Implications: myriad effects of disturbed GH/IGF-I axis in CKD......Page 327
Growth and the Pediatric Response to
GH Therapy......Page 328
Dosing Recommendations......Page 329
Effects in Adults with Chronic Renal Failure Treated with rGH......Page 330
The horizon for improving growth and anabolism in
renal failure......Page 332
References......Page 333
Further reading......Page 336
Vascular System......Page 337
Testicular Function......Page 338
Hypothalamic–Pituitary Function......Page 339
Evaluation of sexual dysfunction in the uremic man......Page 340
Treatment of sexual dysfunction in the uremic man......Page 341
Outcomes associated with hypogonadism and treatment......Page 343
Treatment......Page 345
References......Page 347
Further reading......Page 348
Circulating thyroid hormone profile......Page 349
Thyroid hormone kinetics......Page 351
Tissue T3 content and T4 uptake......Page 353
The hypothalamo-pituitary thyroid axis......Page 356
Effects of dialysis and transplantation......Page 358
Thyroid biology in chronic renal failure and other non-thyroidal illnesses......Page 360
Should thyroid hormone be replaced in CRF and other non-thyroidal illness patients?......Page 361
References......Page 362
Further reading......Page 364
Acid–base production......Page 365
Renal bicarbonate generation......Page 367
Renal tubular bicarbonate reabsorption......Page 368
Hormonal regulation of acid–base balance with normal renal function and with CKD......Page 369
Aldosterone......Page 370
Glucocorticoids......Page 371
Growth Hormone and IGF-1......Page 372
Onset, Prevalence and Magnitude......Page 373
Serum Electrolyte Pattern......Page 374
Renal Tubular Bicarbonate Generation and Urinary Acidification......Page 375
Clinical characteristics of acid–base parameters in dialysis patients......Page 376
Effects of metabolic acidosis of CKD on cellular function......Page 378
Muscle Wasting......Page 379
Exacerbation or Development of Cardiac Disease......Page 380
Growth Hormone and Thyroid Function......Page 381
Treatment of the metabolic acidosis of CKD......Page 382
References......Page 383
Renal Adaptation......Page 390
Cardiac and Vascular Adaptation in Pregnancy......Page 391
Epidemiology and Risk Factors......Page 392
Hypertension......Page 393
Uric Acid......Page 394
Renal Changes and Pathology......Page 395
HELLP Syndrome and Hematological Abnormalities......Page 396
Abnormal Placentation......Page 397
Maternal Endothelial Function......Page 398
Oxidative Stress......Page 399
Angiogenic Factors......Page 400
Screening......Page 401
Management of the HELLP Syndrome......Page 402
Secondary Causes of Hypertension in Pregnancy......Page 403
Management of Chronic Hypertension in Pregnancy......Page 404
Thrombotic Microangiopathy......Page 405
Diabetic Nephropathy......Page 406
End-Stage Renal Disease and Dialysis......Page 407
Immunosuppressive therapy......Page 408
References......Page 409
Further reading......Page 419