Textbook of Nephro-Endocrinology

Front Cover

Textbook of Nephro-Endocrinology

Copyright Page

Contents

List of Contributors

Preface

PART I: THE KIDNEY AS AN ENDOCRINE ORGAN

Section I: Erythropoietin

Chapter 1 Erythropoietin: An Historical Overview of Physiology, Molecular Biology and Gene Regulation

I. Introduction

II. Hormonal regulation of erythropoiesis

III. Identification of the site of erythropoietin production

IV. Assays of erythropoietin

V. Isolation and characterization of erythropoietin

VI. Erythropoietin effector mechanisms

VII. Regulation of erythropoiesis by hypoxia

VIII. Regulatory elements of erythropoietin (EPO) gene

IX. Erythropoietin – the paradigm for gene regulation by hypoxia

X. Hypoxia inducible-factor (HIF)

XI. The elusive nature of the oxygen sensor

XII. Degradation of HIF by the ubiquitin-proteosomal pathway

XIII. Disruption of the oxygen-sensing pathway in cancer

XIV. Disruption of the oxygen-sensing pathway in hereditary polycythemia

XV. Pharmacological manipulation of HIF

XVI. Summary

References

Chapter 2 Erythropoiesis: The Roles of Erythropoietin and Iron

I. Erythropoiesis: an overview

II. Role of erythropoietin in erythropoiesis

III. Role of iron in erythropoiesis

References

Chapter 3 Extra-Hematopoietic Action of Erythropoietin

I. Introduction

II. The EPO receptor (EPOR)

III. Regulation of EPOR expression

IV. Action of EPO

V. Mechanisms of EPO action

VI. Summary

References

Chapter 4 Development of Recombinant Erythropoietin and Erythropoietin Analogs

I. Introduction

II. History of recombinant human erythropoietin

III. Biosimilar EPOs

IV. Potential strategies for modifying erythropoietin to create new EPO analogs

V. Darbepoetin alfa

VI. Continuous erythropoietin receptor activator (C.E.R.A.)

VII. Small molecule ESAs

VIII. Other strategies for stimulating erythropoiesis

IX. Conclusions

References

Chapter 5 Erythropoietin Anemia and Kidney Disease

I. Introduction

II. Erythropoietin pathophysiology in CKD patients

III. Anemia of chronic kidney disease

IV. Anemia and erythropoietin treatment in children with CKD

V. Conclusions

References

Section II: Vitamin D, PTH and Novel Regulators of Phosphate

Chapter 6 Vitamin D and the Kidney: Introduction and Historical Perspective

I. Introduction

II. Vitamin D

III. Cinacalcet

References

Chapter 7 Vitamin D: Molecular Biology and Gene Regulation

I. Vitamin D

II. The 1,25-dihydroxyvitamin D/vitamin D receptor complex

III. Relevance of 1,25-dihydroxyvitamin D/VDR actions in health and in kidney disease

IV. Concluding remarks

References

Chapter 8 Molecular Biology of Parathyroid Hormone

I. Introduction

II. Biosynthesis and metabolism

III. PTH receptors

IV. Isoforms

V. Physiological actions of PTH

References

Chapter 9 Endocrine Regulation of Phosphate Homeostasis

I. Introduction

II. Phosphate homeostasis

III. Renal phosphate transport

IV. Role of phosphate in the regulation of renalvitamin D metabolism

V. Mouse models with renal defects of phosphatetransport

VI. Disorders with an abnormal regulation of renalphosphate transport

References

Section III: Renin–Angiotensin

Chapter 10 The History of the Renin–Angiotensin System

I. Introduction

II. The 20th century

III. The 21st century

IV. The dream to be normotensive and drug free

V. Conclusion

References

Chapter 11 Molecular Biology of Renin and Regulation of its Gene

I. Introduction

II. Production and activation of renin

III. Renin gene structure and regulation

IV. Renin gene mutation and disease

V. Future perspectives

References

Chapter 12 Physiology and Regulation of the Renin–Angiotensin–Aldosterone System

I. Introduction

II. The classical circulating renin–angiotensin system (RAS)

III. Renin biosynthesis and secretion

IV. The renin receptor

V. Angiotensin-converting enzyme (ACE)

VI. The ACE-2/angiotensin (1–7)/mas receptor pathway

VII. AT1 receptors

VIII. AT2 receptors

IX. Angiotensin receptor heterodimerization

X. Tissue renin–angiotensin systems

XI. Intrarenal renin–angiotensin system

XII. Brain renin–angiotensin system

XIII. Vascular tissue renin–angiotensin system

XIV. Cardiac renin–angiotensin system

XV. Aldosterone and mineralocorticoid receptors

XVI. Clinical effects of the renin–angiotensin–aldosterone system (RAAS)

XVII. Summary

References

Chapter 13 The Renin–Angiotensin–Aldosterone System and the Kidney

I. Introduction

II. Historical background

III. Overview of the RAS pathway

IV. Physiologic effects of RAS

V. Renin inhibitors

VI. Conclusion

References

Chapter 14 The Renin–Angiotensin System and the Heart

I. Introduction

II. Cardiac RAS: local versus endocrine origin

III. RAS actions at the cellular level

IV. RAS and the coronary circulation

V. Significance of the RAS on cardiac function

VI. Conclusions

References

Chapter 15 Renin–Angiotensin Blockade: Therapeutic Agents

I. Introduction

II. Therapeutic classes

III. Pharmacology

IV. ACE inhibitors and angiotensin receptor blockers with other agents

V. Select side-effects of ACE inhibitors and angiotensin-receptor blockers

VI. Summary

References

PART II: THE KIDNEY AS A HORMONAL TARGET

Section IV: Antidiuretic Hormone

Chapter 16 Vasopressin in the Kidney: Historical Aspects

I. Introduction

II. Hypothalamus

III. Vasopressin receptors

IV. Vasopressin regulated urea transport

V. Aquaporins

VI. Nephrogenic diabetes insipidus

VII. Vaptans

References

Chapter 17 Molecular Biology and Gene Regulation of Vasopressin

I. Introduction

II. The antidiuretic hormone, vasopressin

III. Vasopressin receptors

IV. Cellular regulation of water, electrolyte and mineral reabsorption

V. Vasopressin, renal hemodynamics and blood pressure

References

Chapter 18 Vasopressin Antagonists in Physiology and Disease

I. Introduction

II. Physiologic antagonists

III. Vasopressin antagonists and their role in the treatment of water-retaining disorders

IV. Are vasopressin antagonists safe?

V. Summary and unanswered questions

References

Chapter 19 Diabetes Insipidus and SIADH

I. Introduction

II. Diabetes insipidus and SIADH

III. Hyponatremic encephalopathy

References

Section V: The Atrial Natriuretic Peptides

Chapter 20 ANP, BNP and CNP: Physiology and Pharmacology of the Cardiorenal Axis

I. Introduction

II. The natriuretic peptides production, processing and release

III. Natriuretic peptide particulate guanylyl cyclase receptors and physiological actions

IV. Natriuretic peptide receptor and enzymatic pathways for clearance and metabolism

V. Pathophysiologic implications in cardiorenal regulation

VI. Pharmacology and therapeutics of native peptides

VII. Novel delivery systems

VIII. Novel chimeric and synthetic natriuretic peptides

IX. Future directions

References

Section VI: Aldosterone

Chapter 21 Aldosterone: History and Introduction

I. Early history of aldosterone

II. Post-discovery progress to approximately 1970

III. Blockers of aldosterone action

References

Chapter 22 Aldosterone Receptors and Their Renal Effects: Molecular Biology and Gene Regulation

I. Introduction

II. Aldosterone-binding sites and the mineralocorticoid receptor (MR)

III. Molecular biology of the MR

IV. Distribution of the mineralocorticoid receptor in the nephron

V. Proteins induced by aldosterone in transport epithelia

VI. Non-genomic effects of aldosterone in the kidney

References

Chapter 23 Aldosterone and its Cardiovascular Effects

I. Introduction

II. Aldosterone and the heart

III. Aldosterone and stroke

IV. Aldosterone and renal disease

V. Potential mechanisms mediating the adverse cardiovascular effects of aldosterone (Figure 23.1)

VI. Therapeutic considerations

VII. Conclusions

References

Chapter 24 Regulation of Aldosterone Production

I. Introduction

II. Aldosterone biosynthesis

III. Factors regulating aldosterone production

IV. Diseases of aldosterone production

V. Summary

References

Section VII: Endocrine Disorders in Renal Failure

Chapter 25 Insulin Resistance and Diabetes in Chronic Renal Disease

I. Introduction

II. Historical perspective

III. Cellular mechanisms of insulin secretion and action

IV. Clinical physiology of insulin resistance

V. Measurement of insulin resistance

VI. Metabolic syndrome

VII. Pathogenesis of insulin resistance in chronic kidney disease

VIII. Regulation of renal glucose production

IX. Syndromes of severe insulin resistance

X. Treatment

XI. Management of diabetes in chronic kidney disease

XII. Hyperglycemia associated with renal transplantation

XIII. Conclusions

References

Chapter 26 Growth Hormone

I. Growth hormone and insulin-like growth factor-1 in renal failure

II. Pediatric implications: growth failure and the GH/IGF-I axis

III. Adult Implications: myriad effects of disturbed GH/IGF-I axis in CKD

IV. Effects of recombinant growth hormone treatment in renal failure

V. The horizon for improving growth and anabolism in renal failure

VI. Summary

References

Chapter 27 Sexual Dysfunction in Men and Women with Chronic Kidney Disease

I. Introduction

II. Sexual dysfunction in uremic men

III. Evaluation of sexual dysfunction in the uremic man

IV. Treatment of sexual dysfunction in the uremic man

V. Outcomes associated with hypogonadism and treatment

VI. Sexual dysfunction in uremic women

VII. Treatment

References

Chapter 28 Thyroid Status in Chronic Renal Failure Patients – a Non-Thyroidal Illness Syndrome

I. Introduction

II. Circulating thyroid hormone profile

III. Thyroid hormone kinetics

IV. Tissue T3 content and T4 uptake

V. The hypothalamo-pituitary thyroid axis

VI. Iodide retention, goiter, hypo- and hyperthyroidism

VII. Effects of dialysis and transplantation

VIII. Thyroid biology in chronic renal failure and other non-thyroidal illnesses

IX. Should thyroid hormone be replaced in CRF and other non-thyroidal illness patients?

X. Summary

References

Chapter 29 Metabolic Acidosis of Chronic Kidney Disease

I. Introduction

II. Regulation of acid–base balance with normal renal function and chronic kidney disease

III. Acid–base production

IV. Renal bicarbonate generation

V. Cellular buffering

VI. Renal tubular bicarbonate reabsorption

VII. Hormonal regulation of acid–base balance with normal renal function and with CKD

VIII. Clinical characteristics of the metabolic acidosis of chronic kidney disease

IX. Clinical characteristics of acid–base parameters in dialysis patients

X. Effects of metabolic acidosis of CKD on cellular function

XI. Treatment of the metabolic acidosis of CKD

References

Chapter 30 Pregnancy and the Kidney

I. Introduction

II. Normal pregnancy

III. Pre-eclampsia and HELLP syndrome

IV. Other hypertensive disorders of pregnancy

V. Renal failure in pregnancy

References

INDEX