Genetic Diseases of the Kidney

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Genetic Diseases of the Kidney

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Contents

Contributors

Preface

PART I: General Background

CHAPTER 1 Genetic Approaches to Human Disease

INTRODUCTION

BRIEF HISTORY OF GENETICS

TRANSMISSION OF SINGLE-GENE DISEASES IN HUMANS

NON-MENDELIAN OR COMPLEX TRAITS

THE HUMAN GENOME

NATURE OF MUTATIONS

CONSEQUENCES OF MUTATIONS

IDENTIFYING DISEASE-CAUSING MUTATIONS

MAPPING MENDELIAN TRAITS IN HUMAN PEDIGREES

IDENTIFICATION OF COMMON ALLELES THAT CONTRIBUTE TO COMPLEX TRAITS

PERSPECTIVES ON THE FUTURE OF HUMAN DISEASE GENETICS

SUMMARY AND PERSPECTIVE

REFERENCES

CHAPTER 2 Clinical Applications of Genetics

BASIC PRINCIPLES OF GENETIC TESTING

SERVICES OFFERED BY GENETIC LABORATORIES

COUNSELING AND INFORMED CONSENT

ETHICAL CONSIDERATIONS IN GENETIC TESTING

CURRENT APPLICATIONS OF GENETIC TESTING

MOLECULAR ANALYSES: CURRENT APPROACHES, NEW INNOVATIONS, FUTURE DIRECTIONS

PHARMOCOGENOMICS

SUMMARY

REFERENCES

PART II

A. Primary Genetic Diseases of Nephron Function

CHAPTER 3 Logic of the Kidney

KIDNEY FUNCTION: A SYSTEMS APPROACH

WALK THROUGH THE NEPHRON

INTEGRATION OF ANATOMY AND PHYSIOLOGY: REGULATION

CONCLUSION

REFERENCES

B. Primary Genetic Diseases of the Glomerulus

CHAPTER 4 Alport’s Disease and Thin Basement Membrane Nephropathy

INTRODUCTION

RENAL GLOMERULUS

GLOMERULAR BASEMENT MEMBRANE

ALPORT’S DISEASE

THIN BASEMENT MEMBRANE NEPHROPATHY

CONCLUSIONS

REFERENCES

CHAPTER 5 Idiopathic Nephrotic Syndrome

INTRODUCTION

GENETIC DEFECTS OF STRUCTURAL PROTEINS

GENETIC DEFECTS OF TRANSCRIPTION FACTORS

SMARCAL1 AND SCHIMKE IMMUNO-OSSEOUS DYSPLASIA

GENETIC DEFECTS OF METABOLIC GENES

GALLOWAY-MOWAT SYNDROME

CONCLUSIONS

REFERENCES

CHAPTER 6 Focal Segmental Glomerulosclerosis

INTRODUCTION

THE PODOCYTE

FOCAL AND SEGMENTAL GLOMERULOSCLEROSIS

MENDELIAN DISEASE

RECESSIVE FSGS: NPHS2

DOMINANT FSGS

SYNDROMIC FSGS

MITOCHONDRIAL PATTERNS OF INHERITANCE

ANIMAL MODELS

SECONDARY FSGS

CLINICAL SPECTRUM OF DISEASE

SPORADIC FSGS

APPROACH TO THERAPY

IMPLICATIONS

REFERENCES

C. Primary Genetic Diseases of the Proximal Renal Tubules

CHAPTER 7 Diseases of Renal Glucose Handling

INTRODUCTION

PHYSIOLOGY OF RENAL GLUCOSE TRANSPORT

INHERITED DISORDERS OF RENAL GLUCOSE TRANSPORT

SUMMARY AND OUTLOOK

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 8 Primary Inherited Aminoacidurias: Genetic Defects in the Renal Handling of Amino Acids

PRIMARY INHERITED AMINOACIDURIAS

DEFECTS ASSOCIATED WITH HETEROMERIC AMINO ACID TRANSPORTERS

HARTNUP DISORDER

THE MOLECULAR BASES OF INTESTINAL ABSORPTION AND RENAL REABSORPTION OF AMINO ACIDS

REFERENCES

CHAPTER 9 Primary Renal Uricosuria

INTRODUCTION

BASICS OF URATE HANDLING IN HUMAN KIDNEY

HEREDITARY RENAL HYPOURICEMIA

REFERENCES

CHAPTER 10 The Fanconi Syndrome

INTRODUCTION

HISTORY OF THE FANCONI SYNDROME

ETIOLOGY

GENETIC CAUSES

SYSTEMIC AND RENAL DISEASES

EXOGENOUS SUBSTANCES

BRIEF OVERVIEW OF PROXIMAL TUBULE TRANSPORT

CLINICAL PATHOPHYSIOLOGY

CELLULAR MECHANISMS OF PROXIMAL TUBULE TRANSPORT DEFECTS

ANIMAL MODELS OF FANCONI SYNDROME

TREATMENT

SUMMARY

REFERENCES

CHAPTER 11 Proximal Renal Tubular Acidosis

INTRODUCTION

CELLULAR AND MOLECULAR MECHANISMS OF ACID–BASE TRANSPORT IN THE PROXIMAL TUBULE

DEFINITION AND CLINICAL FEATURES OF PROXIMAL RTA

SPECIFIC DISORDERS CAUSING PROXIMAL RENAL TUBULAR ACIDOSIS

TREATMENT

REFERENCES

CHAPTER 12 Dent’s Disease

INTRODUCTION

PHYSIOLOGY OF CLC CHLORIDE CHANNELS

GENETICS

CLINICAL PHENOTYPE AND PATHOPHYSIOLOGY OF DENT’S DISEASE

TREATMENT

REFERENCES

D. Primary Genetic Diseases of the Thick Ascending Limb of Henle

CHAPTER 13 Molecular Genetics of Gitelman’s and Bartter’s Syndromes and their Implications for Blood Pressure Variation

INTRODUCTION

HISTORY OF BARTTER’S AND GITELMAN’S SYNDROMES

MUTATIONS IN NCC CAUSE GITELMAN’S SYNDROME

UNIFORMITY OF ELECTROLYTE PHENOTYPES OF PATIENTS WITH GITELMAN’S SYNDROME

PATHOPHYSIOLOGY OF GITELMAN’S SYNDROME

CLINICAL SIGNS AND SYMPTOMS IN GITELMAN’S SYNDROME

GITELMAN’S SYNDROME PATIENTS HAVE REDUCED BLOOD PRESSURE AND INCREASED DIETARY SALT INTAKE

GITELMAN’S SYNDROME PATIENTS DISPLAY INCREASED BONE DENSITY

MUTATIONS IN NKCC2

MUTATIONS IN ROMK

MUTATIONS IN CLCNKB

MUTATIONS IN BARTTIN CAUSE BARTTER’S SYNDROME WITH SENSORINEURAL DEAFNESS

COMBINED MUTATIONS IN CLCNKA AND CLCNKB CAUSE BARTTER’S SYNDROME WITH SENSORINEURAL DEAFNESS

MUTATIONS IN THE CALCIUM-SENSING RECEPTOR (CASR)

OTHER GENETIC DISEASES WITH FEATURES THAT OVERLAP WITH GITELMAN’S AND BARTTER’S SYNDROMES

PATHOPHYSIOLOGY OF BARTTER’S SYNDROME

GENOTYPE–PHENOTYPE CORRELATIONS (TABLE 13.1) AND DIAGNOSIS

TREATMENT OF PATIENTS WITH GITELMAN’S AND BARTTER’S SYNDROMES

EFFECTS OF THE HETEROZYGOUS STATE FOR GITELMAN’S AND BARTTER’S SYNDROMES ON BLOOD PRESSURE IN THE POPULATION

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 14 Molecular Genetics of Magnesium Homeostasis

INTRODUCTION

PHYSIOLOGY OF MAGNESIUM HOMEOSTASIS

FAMILIAL HYPOMAGNESEMIA WITH HYPERCALCIURIA AND NEPHROCALCINOSIS (FHHNC)

GITELMAN AND BARTTER SYNDROMES

HYPOMAGNESEMIA WITH SECONDARY HYPOCALCEMIA (HSH)

AUTOSOMAL DOMINANT HYPOMAGNESEMIA DUE TO MUTATION IN FXYD2

ISOLATED RECESSIVE RENAL HYPOMAGNESEMIA

CONCLUSIONS AND FUTURE DIRECTIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 15 Inherited Diseases of the Calcium-Sensing Receptor: Impact on Parathyroid and Renal Function

INTRODUCTION

THE CALCIUM-SENSING RECEPTOR

ROLE OF THE CaR IN THE PARATHYROID

ROLE OF THE CaR IN THE KIDNEY

ROLE OF THE CAR IN OTHER TISSUES INVOLVED IN CALCIUM HOMEOSTASIS

FAMILIAL HYPOCALCIURIC HYPERCALCEMIA (FHH) [OMIM 14598]

NEONATAL SEVERE PRIMARY HYPERPARATHYROIDISM (NSHPT) [OMIM 239200]

AUTOSOMAL DOMINANT HYPOPARATHYROIDISM (ADH) (OMIM) [#601298]

BARTTER’S SYNDROME WITH ACTIVATING CAR MUTATIONS

CaR-BASED THERAPEUTICS

SUMMARY AND FUTURE ISSUES

DEDICATION

REFERENCES

E. Primary Genetic Diseases of the Distal Convoluted Tubule and Collecting Duct

CHAPTER 16 Liddle’s Syndrome (Pseudoaldosteronism)

INTRODUCTION

PSEUDOALDOSTERONISM

ENaC AND Na[sup(+)] ABSORPTION IN THE ASDN

GENOTYPE–PHENOTYPE RELATIONSHIP

DIFFERENTIAL DIAGNOSIS

PATHOPHYSIOLOGY

MUTATIONS OF THE PY MOTIF: A DUAL EFFECT ON ENaC FUNCTION

PY MOTIFS AND ALDOSTERONE RESPONSE

MOUSE MODELS OF LIDDLE’S SYNDROME

PATHOGENESIS

REFERENCES

CHAPTER 17 The Syndrome of Apparent Mineralocorticoid Excess

CLINICAL FEATURES OF THE SYNDROME OF APPARENT MINERALOCORTICOID EXCESS (AME)

MOLECULAR STUDIES OF 11β-HYDROXYSTEROID DEHYDROGENASE (11-HSD)

THE HSD11B2 GENE

MOLECULAR GENETIC ANALYSIS OF APPARENT MINERALOCORTICOID EXCESS

REFERENCES

CHAPTER 18 Pseudohypaldosteronism Type 1 and Hypertension Exacerbated in Pregnancy

MINERALOCORTICOID RECEPTOR MUTATIONS IN HUMAN DISEASE

ALDOSTERONE BIOLOGY

PSEUDOHYPOALDOSTERONISM TYPE 1

ANIMAL MODELS OF PHA1

HYPERTENSION EXACERBATED BY PREGNANCY

THE S810L MUTATION ALTERS RECEPTOR SPECIFICITY VIA A NEW INTRAMOLECULAR CONTACT

GENETICS

A SPLICING DEFECT IN MR[sub(L810)] CARRIERS

PERSPECTIVES

REFERENCES

CHAPTER 19 The Syndrome of Hypertension and Hyperkalemia (Pseudohypoaldosteronism Type II): WNK Kinases Regulate the Balance Between Renal Salt Reabsorption and Potassium Secretion

THE ROLE OF THE KIDNEY IN THE REGULATION OF BLOOD PRESSURE AND ELECTROLYTE HOMEOSTASIS

PSEUDOHYPOALDOSTERONISM TYPE II: A HUMAN MODEL TO EXPLORE COORDINATED REGULATION OF BLOOD PRESSURE AND ELECTROLYTE HOMEOSTASIS

HYPOTHESES OF PHAII PATHOPHYSIOLOGY

MOLECULAR GENETICS OF PSEUDOHYPOALDOSTERONISM TYPE II: EVIDENCE FOR GENETIC HETEROGENEITY AND DISCOVERY OF THE WNK PROTEIN KINASES

THE WNKs ARE A NOVEL FAMILY OF SALT-SENSITIVE SERINE-THREONINE KINASES WITH A UNIQUE CATALYTIC STRUCTURE

WNK1 AND WNK4 LOCALIZE TO THE ALDOSTERONE-SENSITIVE DISTAL NEPHRON AND EXTRARENAL CHLORIDE-TRANSPORTING EXTRARENAL EPITHELIA

WNK1 AND WNK4 REGULATE DIVERSE ALDOSTERONE-SENSITIVE MEDIATORS OF ION TRANSPORT VIA DISTINCT MECHANISMS

IN VIVO MOUSE MODELS OF WNK1 AND WNK4 FUNCTION

PATHOPHYSIOLOGICAL MECHANISMS OF PHAII

POSSIBLE ROLE OF WNK1 AND WNK4 IN ESSENTIAL HYPERTENSION AND WNKs AS POTENTIAL TARGETS OF NOVEL THERAPEUTICS

THE ROLE OF THE WNK KINASES IN THE REGULATION OF CELL VOLUME AND INTRACELLULAR CHLORIDE HOMEOSTASIS

VOLUME SENSITIVITY OF CATION/CHLORIDE COTRANSPORTERS IS REGULATED BY AN INTERACTION BETWEEN THE WNK AND STE20-TYPE KINASES SPAK/OSR1

THE WNK KINASE/STE20-TYPE KINASE/NKCC PHOSPHORYLATION CASCADE

WNK3: A BRAIN-ENRICHED KINASE WITH RECIPROCAL ACTIONS ON THE NKCCs AND KCCs

CONCLUSIONS AND FUTURE DIRECTIONS

ACKNOWLEDGMENTS

DEDICATION

REFERENCES

CHAPTER 20 Distal Renal Tubular Acidosis

INTRODUCTION

DEFINITION AND CLINICAL FEATURES

α-INTERCALATED CELL FUNCTION

AUTOSOMAL DOMINANT DISTAL RENAL TUBULAR ACIDOSIS

AUTOSOMAL RECESSIVE TYPE 1 RTA

GENOTYPE–PHENOTYPE CORRELATIONS IN PRIMARY DISTAL RTA

OTHER FORMS OF dRTA

ACKNOWLEDGMENT

REFERENCES

CHAPTER 21 Nephrogenic Diabetes Insipidus: Vasopressin Receptor Defect

CELLULAR ACTIONS OF VASOPRESSIN

RARENESS AND DIVERSITY OF AVPR2 MUTATIONS

BENEFITS OF GENETIC TESTING

MOST MUTANT V[sub(2)] RECEPTORS ARE NOT TRANSPORTED TO THE CELL MEMBRANE AND ARE RETAINED IN THE INTRACELLULAR COMPARTMENTS

NONPEPTIDE VASORESSIN RECEPTOR ANTAGONISTS ACT AS PHARMACOLOGICAL CHAPERONES TO FUNCTIONALLY RESCUE MISFOLDED MUTANT V[sub(2)] RECEPTORS RESPONSIBLE FOR X-LINKED NDI

TESTING PATIENTS WITH NDI; PLEASE AVOID DEHYDRATION

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 22 Nephrogenic Diabetes Insipidus: Aquaporin-2 Defect

INTRODUCTION

MOLECULAR STRUCTURE OF AQUAPORINS

AQUAPORIN 2

HISTORY OF NDI

THE AQP2 GENE

TREATMENT FOR NDI

REFERENCES

PART III: Genetic Abnormalities of Renal Development and Morphogenesis

CHAPTER 23 An Overview of Renal Development

INTRODUCTION

ANATOMIC DESCRIPTION OF KIDNEY DEVELOPMENT

SPECIFICATION OF THE NEPHRIC (WOLFFIAN) DUCT AND NEPHROGENIC CORD

METANEPHRIC KIDNEY DEVELOPMENT

CONCLUSION

REFERENCES

CHAPTER 24 Polycystic Kidney Disease

INTRODUCTION

DIAGNOSIS AND CLINICAL FEATURES

GENETICS OF POLYCYSTIC KIDNEY DISEASE

POLYCYSTIN-1

POLYCYSTIN-2

POLYDUCTIN/FIBROCYSTIN

CILIA

POLYCYSTIC KIDNEY DISEASES AND CELLULAR PATHWAYS

THERAPY IN PKD

REFERENCES

CHAPTER 25 Nephronophthisis

OVERVIEW ON NEPHRONOPHTHISIS AND RELATED DISORDERS

MODE OF INHERITANCE

EPIDEMIOLOGY

CLINICAL FEATURES OF NPHP

PATHOLOGY

MOLECULAR GENETICS OF NPHP: AN ETIOLOGICAL CLASSIFICATION OF NPHP

FUNCTION OF NEPHROCYSTINS AND PATHOGENESIS OF NPHP

DIAGNOSTICS: MOLECULAR GENETICS, IMAGING, AND LABORATORY STUDIES

THERAPY, PROGNOSIS, AND GENETIC COUNSELING

REFERENCES

CHAPTER 26 Medullary Cystic Disease

INTRODUCTION

HISTORY

EPIDEMIOLOGY

GENETICS

PATHOPHYSIOLOGY

CLINICAL MANIFESTATIONS

PATHOLOGY

DIAGNOSIS

TREATMENT

FUTURE HORIZONS

REFERENCES

CHAPTER 27 Renal Dysgenesis

INTRODUCTION

RENAL DEVELOPMENTAL DEFECTS

KIDNEY DEVELOPMENT

HUMAN SYNDROMES ASSOCIATED WITH RENAL DYSGENESIS

ACKNOWLEDGMENTS

REFERENCES

PART IV: Inherited Neoplastic Diseases Affecting the Kidney

CHAPTER 28 The Genetic Basis of Cancer of the Kidney

INTRODUCTION

VON HIPPEL-LINDAU DISEASE

OTHER MANIFESTATIONS

MANAGEMENT OF PATIENTS WITH VHL

HEREDITARY PAPILLARY RENAL CELL CANCER

BIRT-HOGG-DUBÉ SYNDROME

HEREDITARY LEIOMYOMATOSIS AND RENAL CELL CARCINOMA

CONCLUSIONS

REFERENCES

CHAPTER 29 Wilms’ Tumor

INTRODUCTION

WILMS’ TUMOR: HISTOLOGY, GENETICS, AND ASSOCIATED SYNDROMES

THE WT1 GENE, mRNAS, AND PROTEINS

THE ROLE OF WT1(–KTS) VS. WT1(+KTS) ISOFORMS

WT1 FUNCTION DURING KIDNEY DEVELOPMENT

WT1 IN HUMAN UROGENITAL SYNDROMES

(–KTS) AND (+KTS) EXPRESSING MOUSE MODELS OF KIDNEY DISEASE

CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 30 Tuberous Sclerosis

INTRODUCTION

CLINICAL FEATURES OF TSC

CLINICAL AND MOLECULAR GENETICS OF TSC

GENOTYPE–PHENOTYPE CORRELATIONS

GENETIC COUNSELING IN TSC

MOLECULAR PATHOGENESIS OF TUBEROUS SCLEROSIS

THERAPIES FOR TSC

ACKNOWLEDGMENTS

REFERENCES

PART V: Systemic Diseases with Renal Involvement: Monogenic Disorders

CHAPTER 31 Nail-Patella Syndrome

CLINICAL FEATURES AND NATURAL HISTORY

ESTABLISHING THE DIAGNOSIS

MANAGEMENT, TREATMENT, AND COUNSELING

LMX1B: GENE STRUCTURE, MUTATIONS IN NPS AND THEIR PREDICTED EFFECT

HISTORY OF THE LMX1B GENE AND ANIMAL MODELS OF NPS AND LMX1B FUNCTION

ROLE OF LMX1B DURING KIDNEY DEVELOPMENT

PATHOGENESIS OF NPS AND IMPORTANT QUESTIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 32 Mitochondrial Diseases of the Kidney

INTRODUCTION

MITOCHONDRIAL GENOME AND GENETICS

FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS)

INTERSTITIAL NEPHRITIS

FANCONI’S SYNDROME

RHABDOMYOLYSIS

ONCOCYTOMA

ELECTROLYTE ABNORMALITIES

HYPERTENSION

TREATMENT

GENETIC COUNSELING

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 33 Primary Hyperoxaluria

INTRODUCTION

BIOCHEMISTRY

GENETICS

DIAGNOSIS/SCREENING

TREATMENT/MANAGEMENT

UNCLASSIFIED HYPEROXALURIA

CONCLUSION

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 34 The Oculocerebrorenal Syndrome of Lowe

INTRODUCTION

GENETICS

FUNCTION OF OCRL1 GENE PRODUCT (ocrl1)

PHYSICAL FEATURES

OPHTHALMOLOGIC ABNORMALITIES

NEUROLOGIC MANIFESTATIONS

MUSCULOSKELETAL MANIFESTATIONS

RENAL MANIFESTATIONS

RENAL PATHOLOGY

DIAGNOSIS

CARRIER DETECTION

PRENATAL DIAGNOSIS

TREATMENT

REFERENCES

CHAPTER 35 Fabry’s Disease (α-Galactosidase A Deficiency): An X-linked Nephropathy

INTRODUCTION

THE CLASSIC PHENOTYPE

HETEROZYGOTES FOR THE CLASSIC PHENOTYPE

THE LATER-ONSET VARIANTS

PATHOLOGY

THE METABOLIC AND MOLECULAR DEFECTS IN FABRY DISEASE

DIAGNOSIS

TREATMENT

ENZYME REPLACEMENT THERAPY

FUTURE THERAPIES

FUTURE PROSPECTS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 36 Hereditary Fructose Intolerance

INTRODUCTION

HISTORY

CLINICAL FEATURES AND PRESENTATION (TABLE 36.1)

PERILS OF FRUCTOSE POISONING IN THE CLINICAL ENVIRONMENT

THE SYNDROME OF CHRONIC FRUCTOSE INTOXICATION

EFFECTS OF HEREDITARY FRUCTOSE INTOLERANCE ON THE KIDNEY

INHERITANCE OF HEREDITARY FRUCTOSE INTOLERANCE

PATHOLOGICAL INJURY IN HEREDITARY FRUCTOSE INTOLERANCE

METABOLISM OF FRUCTOSE

PRIMARY BIOCHEMICAL DEFECT IN FRUCTOSE INTOLERANCE

THE ENZYMATIC DEFECT

THE ENVIRONMENTAL FACTOR: FRUCTOSE, A UBIQUITOUS NUTRIENT

MOLECULAR PATHOLOGY OF ALDOLASE B DEFICIENCY

DIAGNOSIS OF HEREDITARY FRUCTOSE INTOLERANCE

TREATMENT AND PROGNOSIS

PREVENTION OF FRUCTOSE INTOLERANCE BY GENETIC SCREENING

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 37 The Branchio-oto-renal Syndrome

INTRODUCTION

THE BOR PHENOTYPE

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

THE GENETICS OF BOR SYNDROME

REFERENCES

CHAPTER 38 Primary Metabolic and Renal Hyperuricemia

INTRODUCTION

CLASSIFICATION OF HYPERURICEMIA

PURINE METABOLISM

SINGLE GENE DISORDER FOR OVERPRODUCTION TYPE HYPERURICEMIA

SINGLE GENE DISORDER FOR DECREASED EXCRETION TYPE HYPERURICEMIA

REFERENCES

CHAPTER 39 Hereditary Cystinosis

INTRODUCTION

CLINICAL COURSE

METABOLIC DEFECT

DIAGNOSIS AND TREATMENT

CAUSATIVE GENE AND ENCODED PROTEIN

FUNCTION OF CYSTINOSIN

CTNS MUTATIONS

CYSTINOSIN-DEFICIENT MOUSE MODEL

CONCLUSIONS

REFERENCES

CHAPTER 40 Hepatorenal Tyrosinemia

INTRODUCTION

HTI: A SEVERE LIVER AND KIDNEY DISEASE

DIAGNOSTIC AND DETECTION OF HEREDITARY TYROSINEMIA

TREATMENT FOR HTI

MOLECULAR GENETICS OF HTI

SITE-SPECIFIC REVERSION OF MUTATIONS IN HTI AND RESTORATION OF ENZYME ACTIVITY

ANIMAL MODELS OF HTI

GENE AND CELLULAR THERAPY AS POTENTIAL TREATMENTS IN HTI

PERSPECTIVES

REFERENCES

CHAPTER 41 Renal Disease in Type I Glycogen Storage Disease

HISTORICAL BACKGROUND

CLINICAL PRESENTATION

THE G6Pase COMPLEX AND PATHOPHYSIOLOGY OF GSD-I

THE MOLECULAR BASIS OF GSD-Ia

THE MOLECULAR BASIS OF GSD-Ib

ANIMAL MODELS OF GSD-I

KIDNEY DISEASE ASSOCIATED WITH GSD-I

RENAL DISEASE IN GSD-I AND DIABETES MELLITUS

TREATMENT OF GSD-I

CONCLUSIONS

REFERENCES

CHAPTER 42 Wilson Disease and the Kidney

INTRODUCTION

MOLECULAR PATHOPHYSIOLOGY OF WILSON DISEASE

RENAL COPPER EXCRETION AND TRANSPORT

RENAL TUBULAR INJURY AND OTHER FINDINGS

HEPATORENAL SYNDROME

INTERVENTIONS FOR WILSON DISEASE

DRUG-INDUCED RENAL INJURY

CONCLUSION

REFERENCES

CHAPTER 43 Genetic Defects in Renal Phosphate Handling

INTRODUCTION

GENERAL ASPECTS OF RENAL PHOSPHATE HANDLING

A MOLECULAR VIEW OF RENAL PHOSPHATE TRANSPORT

PRIMARY INHERITED DEFECTS IN RENAL PHOSPHATE HANDING

DEFECTS IN RENAL PHOSPHATE HANDLING SECONDARY TO EXTRARENAL INHERITED DEFECTS

CONCLUSION AND OUTLOOK

ACKNOWLEDGMENTS

REFERENCES

PART VI: Systemic Hereditary Diseases with Renal Involvement: Multifactorial Diseases

CHAPTER 44 Genetic Susceptibility to Kidney Disease a Consequence of Systemic Autoimmunity

INTRODUCTION

CLINICAL OVERVIEW OF LUPUS NEPHRITIS

GENETIC PREDISPOSITION TO SLE

PATHOGENESIS OF LUPUS NEPHRITIS

NEPHRITIC SUSCEPTIBILITY LOCI MAPPED IN MURINE LUPUS MODELS

LUPUS NEPHRITIS LOCI IDENTIFIED IN HUMAN LUPUS

CONCLUSION

REFERENCES

CHAPTER 45 IgA Nephropathy

DEFINITION AND CLINICAL FEATURES

PATHOGENESIS

GENETIC EPIDEMIOLOGY

MOLECULAR GENETICS

CONCLUSIONS

REFERENCES

CHAPTER 46 Susceptibility to Diabetic Nephropathy

OVERVIEW

ANIMAL MODELS OF DIABETIC NEPHROPATHY

FAMILIAL FACTORS IN DIABETIC NEPHROPATHY

CANDIDATE PATHWAYS OF DIABETIC NEPHROPATHY

THE SEARCH FOR GENETIC FACTORS IN TYPE 1 DIABETIC NEPHROPATHY

THE SEARCH FOR TYPE 2 DIABETIC NEPHROPATHY GENES

REFERENCES

CHAPTER 47 HIV-associated Nephropathy

INTRODUCTION

HISTOLOGY

CLINICAL PRESENTATION AND EPIDEMIOLOGY

PATHOGENESIS

TREATMENT

CONCLUSION

REFERENCES

Index

A

B

C

D

E

F

G

H

I

J

K

L

M

N

O

P

R

S

T

U

V

W

X

Z

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