Pediatric Kidney Disease

Preface
Contents
Part I: Investigative Techniques in Pediatric Nephrology
1: Antenatal Assessment of Kidney Morphology and Function
Introduction
Fetal Imaging Methods
The Normal Urinary Tract
Bladder
Kidneys
Evidence of Normally Functioning Urinary Tract
Ultrasound Findings as Evidence of Abnormal Fetal Kidney and Urinary Tract
Abnormal Renal Number
Abnormal Location of Kidney
Abnormal Renal Echogenicity
Abnormal Renal Size
Urinary Tract Dilatation
Renal Cysts
Renal Tumors
Bladder Abnormalities
Assessment of Fetal Renal Function
Amniotic Fluid Volume
Fetal Urine Biochemical Markers
Fetal Blood Sampling
Ultrasound-Guided Renal Biopsies
Specific Renal and Urinary Tract Pathologies
Pre-renal Causes of Fetal Renal Abnormalities
Intrauterine Growth Restriction (IUGR)
Renal Vein Thrombosis
The Twin-To-Twin Transfusion Syndrome
Maternal Alcohol/Drug Intake
Alcohol
Renin-Angiotensin System (RAS) Antagonists
Nonsteroidal Antiinflammatory Drugs (NSAID)
Cocaine
Immunosuppressive Medications During Pregnancy
Primary Congenital Kidney Anomalies
Multicystic Dysplastic Kidney (MCDK)
Autosomal Recessive Polycystic Kidney Disease (ARPKD)
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Renal Hypoplasia and Dysplasia
Congenital Nephrotic Syndrome
Postrenal Causes of Fetal Renal Abnormalities
Pelvicoureteric Junction Stenosis
Vesicoureteric Reflux (VUR)
Uretero-Vesical Junction Obstruction (Megaureter)
Duplex Kidneys
Bladder Outlet Obstruction
Fetal Intervention for Lower Urinary Tract Obstruction
References
2: Laboratory Evaluation of Renal Disease in Childhood
Assessment of the Urine
Urinalysis
Urine Microscopy
Urinary Protein Excretion
Assessment of Renal Function
Glomerular Filtration
Inulin
Serum Creatinine
Creatinine Clearance (Ccr)
Equations to Predict GFR
Cystatin C
Other Methods
Iohexol and Iothalamate
EDTA, DTPA Nuclear GFR
The Slope-Intercept Method
The Distribution Volume Method
Assessment of Tubular Function
Fractional Excretion of Sodium (FeNa)
Tubular Reabsorption of Phosphate (TRP)
Glucosuria
Transtubular Potassium Gradient (TTKG)
Aminoaciduria
Assessment of Acid Base Status
Total Carbon Dioxide (Total CO2) and Bicarbonate (HCO3−)
Serum Anion Gap (SAG)
Urine Anion Gap
Urine Osmolar Gap
Urine-Blood pCO2 (U-B pCO2)
General Biochemistry
Serum Sodium
Serum Potassium
Serum Calcium, Phosphorus, and Calcium-Phosphorus Product
Serum Albumin
Serum Uric Acid
Urinary Calcium
Urinary Sodium
Urinary Magnesium
Urinary Citrate
Urinary Oxalate
Urinary Uric Acid
Assessment of the Renin-Angiotensin-Aldosterone System
Renin
Aldosterone
Plasma Aldosterone Concentration (PAC) to Plasma Renin Activity Ratio
Endocrine Testing Relevant to Nephrology
ADH/Copeptin
Biochemical Testing for the Diagnosis of Pheochromocytoma
Complement Pathway Assessment
Laboratory Assessment of Various Glomerulopathies
Antineutrophil Cytoplasmic Antibodies (ANCA)
Antinuclear Antibodies (ANA) and Anti-doubled Stranded DNA (Anti-dsDNA)
References
3: Imaging and Radiological Interventions in the Pediatric Urinary Tract
Introduction
Imaging-Associated Risks
Ionizing Radiation
Intravenous Contrast Agents
Sedation and Anesthesia
Ultrasonography
Greyscale US
Color Doppler
Contrast-Enhanced Ultrasonography
Contrast-Enhanced Voiding Urosonography (ceVUS)
US Contrast Safety
Voiding Cystourethrography
Nuclear Medicine
Overview of Radiopharmaceuticals
Direct Radionuclide Cystogram (DRC)
Indirect Radionuclide Cystogram
Direct vs. Indirect Radionuclide Cystogram
Kidney Cortical Scan
Functional Kidney Imaging and Renography
Diuretic Renogram
Computed Tomography
Magnetic Resonance Imaging
Magnetic Resonance Urography
Radiography
Excretory Urography
Retrograde Urethrography
Interventional Radiology
Patient Evaluation and Preparation
Facilities and Equipment
Types of Interventions
Applications of Diagnostic and Interventional Radiology Techniques
Neonatal Diseases
Urinary Tract Dilation Classification System
Other Congenital Abnormalities of the Kidneys and Urinary Tract
Neonatal Renovascular Conditions
Interventional Radiology in the Neonate
Urinary Tract Infections and Vesicoureteral Reflux
Interventional Radiology Techniques in UTI
Neoplasm
Interventional Radiology in Pediatric Kidney Tumors
Trauma
Interventional Radiology in Kidney Trauma
Renovascular Hypertension
Cystic Kidney Diseases
Kidney Stones and Nephrocalcinosis
Kidney Stone Imaging
Nephrocalcinosis
Conclusion
References
4: Molecular Diagnosis of Genetic Diseases of the Kidney: Primer for Pediatric Nephrologists
Introduction
General Genetic/Genomic Concepts
Deoxyribonucleic Acid (DNA)
Gene
Genome
Genetic vs. Genomic
Other Omics
Online Resources
Variations in the Genome
How to Assess Genomic Variations
Is the Allele Common or Rare?
Coding vs. Non-coding Variants
Mutation Types
Degree of Conservation
Single Nucleotide Polymorphisms
Single Nucleotide Variants
Structural Variations
Insertions and Deletions (Indels)
Copy-Number Variations
Copy-Neutral Variations
Chromothripsis
Haploinsufficiency
Online Resources
Modes of Inheritance
Dominant Genotypes
Recessive Genotypes
X-Linked Inheritance
Mitochondrial
Genetic/Genomic Methods
SNPs Genotyping
Linkage Analysis
Homozygosity Mapping
Genome-Wide Association Studies
Polymerase Chain Reaction
DNA Sequencing Technologies
Sanger Method
Next-Generation Sequencing Methods
Third Generation Sequencing Methods
Whole-Exome Sequencing
Whole-Genome Sequencing
Online Resources
Clinical Implementation in Nephrology
Finding Pathogenic Mutations for Mendelian Disease
Clinical Vignette
Genetic Heterogeneity
Finding Risk Alleles for Complex Diseases
Complex Diseases: Associated with Common and/or Rare Variants?
Clinical Implications of Genome-Wide Association Studies
Source of Missing Heritability: Rare Variants?
Pharmacogenetics/Pharmacogenomics
Online Resources
Barriers to Implementation in the Clinic
Patients’ Health Literacy and Numeracy
Online Resources for Patients
Physicians’ Health Literacy and Numeracy
Online Resources for Physicians
Test Costs and Gene Patents
Demonstration of Efficacy and Cost-Effectiveness
Ethical and Legal Issues
Mis-attributed Paternity
Medically Actionable Variants
Privacy
Genetic Discrimination
Direct-to-Consumer Testing of Presymptomatic Minors
Online Resources
References
Glossary
5: Tools for Kidney Tissue Analysis
Introduction
Kidney Biopsy
Indication
Procedure
Processing of Biopsy Specimens
Histopathological Assessment
Protein Analysis
RNA Analysis
DNA Analysis
Indirect Measurements
References
Part II: Disorders of Kidney Development
6: Functional Development of the Nephron
General Overview of Antenatal, Perinatal, and Postnatal Fluid and Electrolyte Homeostasis
Glomerular Function in the Fetal, Perinatal, and Postnatal Period
Fetal GFR
Neonatal GFR
Vasoregulatory Mechanisms of the Neonatal Kidney
Renal Vasoconstrictors in the Developing Nephron
The Renin-Angiotensin System (RAS)
Renal Nerves and Catecholamines
Endothelin
Renal Vasodilators in the Developing Nephron
Prostaglandins
Nitric Oxide
The Kallikrein-Kinin System
Disordered Vasoregulatory Mechanisms
Vasomotor Nephropathy (VMNP)
Water Transport in the Developing Kidney
Antidiuretic Hormone in the Development of Water Transport
Normal ADH Physiology
Development of Water Transport in the Collecting Duct
Tonicity of the Developing Medullary Interstitium
Postnatal Urine Flow
Sodium Transport in the Developing Kidney
Early Postnatal Natriuresis
Neonatal Transition to Positive Sodium Balance
Maturation of Sodium Transport Mechanisms in the Developing Nephron
Proximal Tubule
Loop of Henle
Distal Tubule
Cortical Collecting Duct
Developmental Paracrine Regulation of Renal Sodium Excretion
Renin: Angiotensin: Aldosterone System (RAS)
Catecholamines
Glucocorticoids and Thyroid Hormone
Fractional Excretion of Sodium
Potassium Transport in the Developing Kidney
Maturation of Potassium Transport Mechanisms in the Developing Nephron
Proximal Tubule and Loop of Henle
Cortical Collecting Duct
Regulation of Potassium Balance in the Neonate
Acid-Base Regulation in the Developing Kidney
Proximal Tubule Handling of Bicarbonate in the Neonate
Thick Ascending Limb of Henle’s Loop
Cortical Collecting Duct
Regulation of Maturational Acid-Base Homeostatic Mechanisms
Glucocorticoids
Renal Calcium Handling in the Developing Kidney
Renal Calcium Handling in Postnatal Period
Renal Phosphate Handling in the Developing Kidney
Regulation of Renal Phosphate Handling in the Developing Kidney
Magnesium Handling in the Developing Kidney
Renal Glucose Handling in the Developing Kidney
Renal Amino Acid Handling in the Developing Kidney
Assessment of Renal Functional Maturation
References
7: Structural Development of the Kidney
Overview of Human Kidney Development
Origin of the Mammalian Kidney
Induction of Nephrons from the Metanephric Mesenchyme
Specification of the Metanephric Mesenchyme
Nephron Induction
Ureteric Bud Induction and Branching
Ureteric Bud Induction and Outgrowth
Positive Regulation of GDNF-RET Signaling
Negative Regulation of GDNF-RET Signaling
Renal Branching Morphogenesis
Proliferation and Apoptosis in Branching Morphogenesis
Signaling Molecules in Branching Morphogenesis
Formation of Nephrons
Nephron Segmentation
Glomerulogenesis
Podocyte Terminal Differentiation
Glomerular Capillary Tuft Development
Formation of the Collecting System
Medullary Patterning and Formation of the Pelvicaliceal System
Development of the Ureteral Smooth Muscle
Renal Stroma
References
8: Disorders of Kidney Formation
Introduction
Classification and Definition of Renal Malformations
Epidemiology and Longterm Outcomes of Renal Malformations
Abnormal Molecular Signaling in the Malformed Kidney
Human Renal Malformations with a Defined Genetic Etiology
The GDNF/RET Signaling Pathway
Branchio-Oto-Renal Syndrome
Townes-Brocks Syndrome and VATER/VACTERL Associations
Renal-Coloboma Syndrome
Renal Cyst and Diabetes Syndrome
Kallmann Syndrome
Renal Tubular Dysgenesis and Mutations of RAS System Elements
CHD1L, CHD7 and CHARGE Syndrome
DSTYK and CAKUT
Copy Number Variants, CAKUT and Neuropsychiatric Disorders
Environmental Factors and Renal Malformations
Clinical Approach to Renal Malformation
Clinical Approach to Specific Malformations
Unilateral Renal Agenesis
Renal Hypoplasia
Renal Dysplasia
Multicystic Dysplastic Kidney
Renal Ectopia
Renal Fusion
References
Part III: Ciliopathies
9: Ciliopathies: Their Role in Pediatric Kidney Disease
Cilia in the Historic Context
Ciliary Ultrastructure
Ciliary Assembly
Cilia and Cell Cycle
Intraflagellar Transport (IFT)
Ciliary Signalling Pathways
Hedgehog Signalling
Wnt Signalling and Planar Cell Polarity (PCP)
Flow Hypothesis, Ca-Signalling/Mechanosensation and mTOR
Yap-Hippo Signalling
Other Cilia Associated Cell Signalling Pathways
Cilia in Renal Disease
Polycystic Kidney Disease (ADPKD and ARPKD)
Syndromal Nephronophthisis (NPHP)
Bardet-Biedl-Syndrome (LMBBS, BBS)
Alström Syndrome
Joubert-Syndrome Related Disorders (JSRD)
Ciliary Chondrodysplasias
Summary and Conclusion
References
10: Polycystic Kidney Disease: ADPKD and ARPKD
Introduction
Classification and Differential Diagnosis of Cystic Kidney Diseases
Clinical Aspects Guiding Diagnosis in Patients with Kidney Cysts
General Considerations on Genetic Diagnostics for Polycystic Kidney Disease
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Epidemiology and Morphology
Clinical Course
Kidney Function
Diagnosis by Imaging and Emerging Imaging Markers Predicting Clinical Courses
Early-Onset ADPKD and Clinical Spectrum of Kidney Disease in Pediatric ADPKD
Arterial Hypertension
Extra-Renal Manifestations
ADPKD Genetics
PKD1 and PKD2 Genes and Their Encoded Polycystin-1 and -2 Proteins
PKD1/PKD2 Variant Spectrum and Routine Diagnostic Testing
Genotype-Phenotype Correlations
Autosomal Recessive Polycystic Kidney Disease (ARPKD)
Epidemiology and Morphology
Clinical Course and Prenatal Diagnosis
Diagnosis by Imaging
Perinatal Disease and Mortality
Kidney Disease
Liver Disease
Additional Extra-Renal Manifestations
Genetics
PKHD1 Gene and Polyductin/Fibrocystin Protein
Genotype-Phenotype Correlations
Phenotypic Variability Among Affected Siblings
Prenatal Diagnosis
Therapeutic Management
Lifestyle Measures, Pediatric Treatment of CKD and Treatment of Co-morbidities
Blood Pressure Control
Management of CKD and ESKD in Pediatric PKD Patients
Management of Liver Disease
Management of Perinatal Disease in ARPKD
Emerging Targeted Therapies
Vasopressin V2 Receptor Antagonists
Somatostatin Analogues
mTOR Inhibition and Other Targeted Therapy of Cellular Metabolism
Dietary Intervention
References
11: Nephronophthisis and Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD)
The Nephronophthisis complex
Nephronophthisis
Genetics
Genotype-Phenotype Correlation
Extra-renal Disease Manifestations
Senior-Løken Syndrome
Joubert Syndrome
COACH Syndrome
Meckel Gruber Syndrome
Congenital Oculomotor Apraxia Type Cogan II
RHYNS Syndrome
Skeletal Ciliopathies
Respiratory Phenotype
Future Challenges: Genetic and Phenotypic Heterogeneity
Therapy
Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD)
Terminology and Classification
Pathophysiology
Clinical Presentation
Clinical Presentation of ADTKD-UMOD
Clinical Presentation of ADTKD-MUC1
Clinical Presentation of ADTKD-Ren
Clinical Presentation of ADTKD-HNF1B
Clinical Presentation of ADTKD-SEC61A1
Diagnostic Work-Up and Genetic Testing
Therapy
References
Part IV: Glomerular Disorders
12: Hematuria and Proteinuria
Introduction
Hematuria
Definition
Urine Dipstick
Urine Microscopy
Etiology
Child with Red or Dark-Colored Urine
Child with Associated Lower Urinary Tract Symptoms
Child with Clinical Features of Acute Glomerulonephritis
Asymptomatic Child with Incidental Finding of Microscopic Hematuria on Urine Dipstick
Clinical Approach
History
Physical Examination
Investigations
Indications for Kidney Biopsy
Proteinuria
Renal Handling of Proteins
Albuminuria
Definition of Abnormal Urinary Protein Excretion in Children
Urine Dipstick
Sulfosalicylic Acid Test
Quantification of Proteinuria: 24-h Urine Specimen Versus Spot Urine Specimen
Clinical Scenarios
Child with Edema
Child with Intermittent Proteinuria
Child with Persistent Proteinuria
Clinical Approach to Proteinuria
History
Physical Examination
Investigations
Urine Examination
Blood Examination
Kidney Imaging
Audiometry
Indications for Kidney Biopsy
Potential Role of Genetic Testing in Evaluation of Proteinuria in Children
Treatment Options for Significant Proteinuria in the Non-nephrotic Range
Dietary Protein Recommendations
Drugs with Anti-proteinuric Effects
Conclusion
References
13: Steroid Sensitive Nephrotic Syndrome
Introduction
Epidemiology
Aetiology and Pathogenesis
A T Cell Disease but New Thoughts on B Cells
A Circulating Factor
Phenotypes of Cytokine Secreting T Cells: Th1, Th2, Treg, Th17
Genetic Influence in the Aetiology of SSNS
Role of the Thymus
Role of Infection
Summary
Histopathology
Minimal Change Disease (MCD)
Mesangial Proliferative Glomerulopathy (MesPGN)
IgM Nephropathy
IgA Nephropathy with Nephrotic Syndrome
C1q Nephropathy
Focal Segmental Glomerulosclerosis
Clinico-pathological Correlations at Presentation of Nephrotic Syndrome
Clinical and Laboratory Features at Onset of Nephrotic Syndrome
Outcome of Children with SSNS
Relapse
Kidney Function and the Development of Late Steroid Resistance
Other Complications of Steroid Sensitive Nephrotic Syndrome
Indications for Kidney Biopsy
Management of Steroid Sensitive Nephrotic Syndrome
Treatment of the First Episode of Nephrotic Syndrome with Corticosteroids
Treatment of Relapsing SSNS with Corticosteroids
Adverse Effects of Corticosteroids
Corticosteroid Sparing Agents in Frequently Relapsing and Steroid Dependent SSNS
Alkylating Agents
Calcineurin Inhibitors
Levamisole
Mycophenolate Mofetil/Mycophenolate Sodium
Rituximab
Choice of First Corticosteroid Sparing Agent for Children with FRNS or SDNS
Other Agents
Vaccinations in Children with SSNS
Conclusions
References
14: Steroid Resistant Nephrotic Syndrome
Introduction
Definitions
Epidemiology
Histopathological Findings
Focal Segmental Glomerulosclerosis (FSGS)
Clinical and Pathologic Classification of FSGS
Pathogenesis
Hereditary and Monogenic Forms of SRNS
Common Gene Variants Associated with SRNS/FSGS
Circulating Factors
Podocyte Endowment, Loss, Regeneration and Glomerulosclerosis
Diagnostic Evaluation
Patient and Family History
Clinical Assessment
Laboratory Workup
Genetic Testing
Kidney Biopsy
Management
Confirmation Period
Therapeutic Pathway
Pharmacotherapies
RAS Blockade
Calcineurin Inhibition
Mycophenolate-Mofetil (MMF)
B-Cell Depleting Agents
Newer Therapies and Ongoing Clinical Trials
Treatment of Monogenic SRNS
Long-Term Prognosis of SRNS
Complications of Nephrotic Syndrome
Hyperlipidemia
Thrombosis
Nutrition
Immunization
Kidney Transplantation
References
15: Hereditary Nephrotic Syndrome
Introduction
Hereditary Disorders of Early Glomerular Development
WT1 Gene Mutations
NPHS1 Gene Mutations Associated with Autosomal Recessive CNS of the Finnish Type (CNF)
NPHS2 Gene Mutations Associated with Autosomal Recessive Steroid-Resistant Nephrotic Syndrome
LAMB2 Gene Mutations Associated with Pierson Syndrome
LMX1b Gene Mutations Associated with Autosomal Dominant Nail-Patella Syndrome
PLCE1 Gene Mutations Associated with Autosomal Recessive Nephrotic Syndrome
PTPRO Gene Mutations Associated with Autosomal Recessive Nephrotic Syndrome
ARHGDIA Gene Mutations in Autosomal Recessive DMS
EMP2 Gene Mutations Associated with Autosomal Recessive Childhood-Onset Nephrotic Syndrome
NUP Nephropathy
Hereditary Disorders with Late-Onset Nephrotic Syndrome
ACTN4 Gene Mutations Associated with Adulthood FSGS (FSGS1)
TRPC6 Gene Mutations Associated with Late-Onset FSGS (FSGS2)
CD2AP Gene Mutations Associated with Adulthood FSGS (FSGS3)
Susceptibility to Genetic Locus 22q12.3 (FSGS4), Including the Genes MYH9 and APOE1
INF2 Gene Mutations Associated with Autosomal Dominant FSGS (FSGS5) and Charcot-Marie-Tooth Disease
Mutations in MYO1E in Autosomal Recessive FSGS (FSGS6)
Mitochondrial Disorders Associated with Nephrotic Syndrome
Syndromal Disorders Associated with Nephrotic Syndrome
Schimke Syndrome
Galloway-Mowat Syndrome
Clinical Aspects
Long-Term Outcome and Renal Prognosis
Therapeutic Implications
Living Related Donor Transplantation
Recurrence of Nephrotic Syndrome After Renal Transplantation
Genetic Testing
Genetic Counseling
References
16: Alport Syndrome and Other Type IV Collagen Disorders
Introduction
Alport Syndrome
Introduction
Etiology and Pathogenesis
Type IV Collagen Proteins, Tissue Distribution and Genes
Genetics
Clinical Manifestations
Kidney Phenotype
Hearing
Ocular Anomalies
Leiomyomatosis
Other Findings
Kidney Pathology
Diagnosis and Differential Diagnosis
Treatment
Kidney Transplantation
Hereditary Angiopathy with Nephropathy, Aneurysms and Cramps (HANAC Syndrome)
Pathology
Genetics
References
17: IgA Nephropathy
Introduction
Epidemiology
Genetic Background
Pathogenesis
The Mucosal Immunity in IgAN
Complement Activation in IgAN
Renal Pathology of Children with IgAN
Light Microscopy
Immunofluorescence
Electron Microscopy
Clinical Features
Natural History
Risk Prediction
Treatment
Tonsillectomy
Inhibition of the Renin-Angiotensin System
Glucocorticoids
New Formulations of Corticosteroids
Mycophenolate Mofetil
Cyclophosphamide
Rituximab
Calcineurin Inhibitors
Future Therapies for IgAN
A Practical Approach to Treatment of Children with IgAN
References
18: Membranous Nephropathy
Incidence
Etiology
Pathophysiology
Heymann Nephritis, the First Experimental Model of MN
Alloimmune Neonatal MN: Neutral Endopeptidase as the Target Antigen
M-Type Phospholipase A2 Receptor-Associated MN
Role of PLA2R-ab-Related MN in Childhood
Pregnancy and Exposure to Maternal PLA2R-ab
Additional Target Antigens Since PLA2R
Thrombospondin Type-1 Domain-Containing 7A (THSD7A)
Additional Antigens with Potential Secondary MN Associations
Semaphorin 3B
Food Antigen-Related MN
Enzyme Replacement Therapy as a Cause of Alloimmune MN
The Case of Secondary MN
Genetic Factors
Clinical Presentation
Laboratory Investigations
Histopathology
Specific Diagnostic Approaches
Prognosis and Predictors
Treatment
Safety
Class V (Membranous) Lupus Nephritis
Conclusions
References
19: Postinfectious and Infectious Glomerulopathies
Introduction
Post-streptococcal Glomerulonephritis
Epidemiology
Pathogenesis
Pathology
Clinical Features
Complications
Clinical Variants
Laboratory Findings
Kidney Biopsy and Differential Diagnosis
Treatment
Prognosis
Shunt Nephritis
Endocarditis-Associated Glomerulonephritis
HIV Related Kidney Disease
Conclusion
References
20: Rapidly Progressive Glomerulonephritis
Definition
Pathophysiology
Underlying Triggers for Crescent Formation
Pathogenesis of Crescent Formation
Initiation of Crescent Formation
Formation
Resolution of Crescents
Causes and Immunopathologic Categories
Immune Complex Crescentic GN
Pauci-immune Crescentic GN
Anti-GBM Crescentic GN
Idiopathic RPGN
Epidemiology
Clinical Features
Investigations
Serology
Renal Histology
Light Microscopy
Immunohistology and Electron Microscopy
Evaluation and Diagnosis
Treatment
Medications
Newer Agents
Plasmapheresis
Immune Complex Crescentic GN
Postinfectious RPGN
Pauci-immune Crescentic GN
Anti-GBM Crescentic GN
Outcome
Post-transplant Recurrence
References
Part V: Complement Disorders
21: The Role of Complement in Kidney Disease
The Emerging Concept of Complement-Mediated Diseases
The Complement System
Diagnosing Complement-Mediated Nephropathies
Detecting Complement Activation
Detecting Autoantibodies
Collecting Blood and Urine Samples
Immunohistological Diagnosis
Targeting Complement in the Treatment of Kidney Disease
Summary and Perspectives
References
22: Atypical Hemolytic Uremic Syndrome
Introduction
Definition of Atypical HUS
Incidence and Prevalence of Atypical HUS
The Alternative Pathway of Complement
Clinical Presentation
Age and Gender
Family History
Triggering Events
Histology of Atypical HUS
Manifestations Outside the Kidneys
Making the Diagnosis of Atypical Hemolytic Uremic Syndrome
Biological Assays to Support the Clinical Diagnosis of Atypical HUS
Complement Investigations in Patients Suspected to Have aHUS
Genetic Screening in Patients with Atypical HUS
Rare Coding Variants in the CFH Gene
Rare Coding Variants in the CFI Gene
Rare Coding Variants in the MCP Gene
Rare Coding Variants in the C3 Gene
Rare Coding Variants in the CFB Gene
Combined Complement Gene Mutations
Mode of Inheritance and Penetrance
Complement Alternative Pathway: From Gene Change to TMA Lesion
Variants of Unknown Significance in Complement Genes: Disease Relevant or Benign?
Genetic Abnormalities in Genes Not Related to Complement
Diacylglycerol Kinase ε Mutations
Cobalamin C Metabolism Defect Related HUS
Rare Variants in Genes with Debatable Clinical Relevance
Acquired Complement Abnormalities in Atypical HUS
Anti-factor H Autoantibodies
Anti-factor I Antibodies
Outcome of Atypical HUS Prior to the Availability of C5 Inhibition Therapy
Treatment of Atypical HUS Prior to the Availability of C5 Inhibition Therapy
Plasma Therapy
Kidney Transplantation
Treatment Recommendations
Eculizumab
Ravulizumab
Risk of Meningococcal Infection on C5 Inhibition Therapy and Its Prevention
Treatment of Anti-factor H Antibody Associated HUS
Global Variations in Atypical HUS Treatment Recommendations
C5 Inhibition Therapy Monitoring
Duration of C5 Inhibition Therapy in Children with aHUS in Their Native Kidneys
Kidney Transplantation for aHUS Patients Today
Potential Future Therapies
Conclusion
References
23: C3 Glomerulopathies
Introduction
Histopathology of C3 Glomerulopathy
Light Microscopy (LM)
Immunofluorescence Microscopy (IF)
Electron Microscopy (EM)
Transition from Acute Proliferative and Exudative Glomerulonephritis to C3G
Histopathology of Immune Complex Mediated Membranoproliferative Glomerulonephritis
Classification of C3G
Pathogenesis
Autoimmune Forms of C3G
Genetic Forms
Clinical Presentation
Presentation at Onset of Disease
Extra-Renal Manifestations
Diagnosis
Differential Diagnosis
Laboratory Evaluation
Outcome
Treatment
Immunosuppressive Agents
Other Immunosuppressive Agents
Plasma Infusion or Plasma Exchange
Complement Inhibitors
Renoprotective Agents
Treatment of Recurrence Post-Renal Transplantation
Summary
References
Part VI: The Kidney and Systemic Disease
24: Postinfectious Hemolytic Uremic Syndrome
Introduction
Shiga Toxin-Producing Escherichia coli HUS
History of HUS and Definitions
Epidemiology of STEC Infections and STEC-HUS
Pathogenesis of STEC Disease and HUS
Shiga Toxin and Its Glycolipid Receptor
Laboratory Diagnosis of STEC Infections
From Colitis to HUS
Hematologic Manifestations of STEC-HUS
AKI in STEC-HUS
Extrarenal Manifestations
Histopathology of STEC-HUS
Prevention and Treatment of STEC Disease
Vaccines
Therapeutic Interventions During STEC Colitis
Fluid Therapy
Analgesia
Anti-Motility Drugs and Antibiotics
Therapeutic Intervention During STEC-HUS
AKI Management in STEC-HUS
Antihypertensive Therapy
Kidney Replacement Therapy
Anticomplement Therapy in STEC-HUS
Complications and Long-Term Outcome
Long-Term Outcome and Monitoring
STEC-HUS and Kidney Transplantation
Shigella dysenteriae HUS
Pneumococcal (Streptococcus pneumoniae) HUS
Epidemiology
Pathogenesis
Presentation of pnHUS and Clinical Course
Laboratory Studies and Biomarkers
Complement and pnHUS
Treatment of pnHUS
Outcome of pnHUS
Clostridium HUS
Influenza HUS
COVID-19 and HUS
HIV HUS
References
25: Renal Vasculitis in Children
Introduction
Classification of Vasculitides
Classification of Childhood Vasculitis
Large Vessel Vasculitis
Takayasu Arteritis
Medium-Vessel Vasculitis
Polyarteritis Nodosa
Kawasaki Disease
Small-Vessel Vasculitis
Anti-Glomerular Basement Membrane Disease
Cryoglobulinemic Vasculitis
ANCA-Associated Vasculitis
Renal Pathology
Light Microscopy
Immunofluorescence
Electron Microscopy
Pathogenesis
Genetic Factors
Environmental Factors
The Pathogenicity of ANCA
Pathogenesis of Vascular Inflammation
Pathogenesis of Granulomatosis
The Role of the Alternative Complement Pathway
The Role of B and T Cells
Clinical Features
Granulomatosis with Polyangiitis (GPA)
Microscopic Polyangiitis (MPA)
Eosinophilic Granulomatosis with Polyangiitis
Laboratory Results
Disease Activity Assessment
Disease Damage Assessment
Renal Transplantation
Monogenic Forms of Renal Vasculitis
Type I Interferonopathies
Coatomer Associated Protein Subunit Alpha Gene Syndrome
Deficiency of Adenosine Deaminase 2
Hypocomplementemic Urticarial Vasculitis Syndrome
Treatment and Management of Renal Vasculitis
Induction Treatment
Cyclophosphamide and Glucocorticoids
Rituximab
Plasma Exchange
Mycophenolate Mofetil
Anti-TNF Therapy
Avacopan
Adjunctive Measures
Maintenance Treatment
Treatment of Relapses
References
26: Lupus Nephritis
Introduction
Epidemiology
Etiopathogenesis
Clinical Presentation
Lupus Nephritis
Other Organ Systems
Dermatological
Cerebral
Haematological
Rheumatological
Other Organs
Antiphospholipid Syndrome
Classification Criteria
Disease Activity Scoring Systems
Investigations
Blood Investigations
Immunology Testing
Urine Investigations
Other Investigations
Follow-Up
Histological Classification of Lupus Nephritis
Treatment
Drug Treatment
Severe Multisystem Disease with or Without Nephritis (ISN/RPG Class III–V)
Induction Therapy
Corticosteroids
Mycophenolate Mofetil
Cyclophosphamide
Rituximab
Plasma Exchange
Intravenous Immunoglobulin
Maintenance Therapy
Corticosteroids
Mycophenolate Mofetil
Azathioprine
Hydroxychloroquine
Emerging Therapeutic Options
Treatment of Antiphospholipid Syndrome (APS)
General Renal Management
General Management
Sun Protection
Immunisations
Management of Infection
Prognosis
Treatment Related Complications and Mortality
Thrombosis
Cardiovascular Disease
Adherence to Treatment
Renal Replacement Therapy
Conclusion
References
27: IgA Vasculitis Nephritis (Henoch-Schönlein Purpura Nephritis)
Introduction
Diagnostic Criteria
Epidemiology
Clinical Findings
Skin
Joints
Gastrointestinal Tract
Other Nonrenal Organ Involvement
Kidney
Risk Factors for Renal Involvement
Atypical Presentation
Laboratory and Radiologic Investigations
Renal Histopathologic Findings
Light Microscopy Findings
Immunofluorescence Findings
Electron Microscopy Findings
Clinicopathologic Correlations
Risk Factors for Poor Prognosis
Pathogenesis
Genetic Predisposition
Abnormalities of IgA
Activation of Complement
Activation of Eosinophils
Cytokines and Coagulation Abnormalities
Mesangial Proliferation and Crescent Formation
Treatment
Prevention of Nephritis in IgA Vasculitis
Treatment of IgAVN
The KDIGO Guidelines and Therapeutic Considerations in Pediatric IgAVN
Indications for Renal Biopsy
Treatment of Mild or Moderately Severe IgAVN
Treatment of Severe IgAVN
Special Conditions
Renal Transplantation
Pregnancy
References
28: Metabolic Disorders Affecting the Kidney
Introduction
Methylmalonic Acidemia and Propionic Acidemia
Clinical Picture of Isolated Methylmalonic Acidemias
Clinical Picture of Combined Methylmalonic Acidurias
Kidney Involvement
Conservative Treatment
Isolated Methylmalonic Acidemias
Combined Methylmalonic Acidurias
Kidney and Liver Transplantation
Lysinuric Protein Intolerance
Kidney Involvement
Treatment
Kidney Transplantation
Fabry Disease
Fabry Disease in Children and Adolescents
Renal Biopsy
Long Term Follow-Up: Renal and Extra-Renal Complications
Therapy
Glycogen Storage Disease (GSD) Type 1a and 1b
References
29: Primary Hyperoxaluria
Introduction
Epidemiology of Primary Hyperoxaluria
Primary Hyperoxaluria Type 1
Biology and Molecular Basis
Clinical Spectrum
Primary Hyperoxaluria Type 2
Biology and Molecular Basis
Clinical Spectrum
Primary Hyperoxaluria Type 3
Biology and Molecular Basis
Clinical Spectrum
Diagnosis and Differential Diagnosis
General Remarks and Clinical Diagnosis
Biochemical Screening and Diagnosis
Confirmation of Diagnosis by Genetic Testing
Differential Diagnosis and Secondary Hyperoxaluria
Genetic Counselling in PH
Treatment
Current Treatment Options
Conservative Treatment
Fluid Intake
Dietary Considerations
Vitamin B6
RNA Interference Therapeutics
Oxalate Degrading Bacteria
Other Medication
Dialysis
Transplantation Strategies
Conclusions and Outlook
References
30: Cystinosis
Introduction
Historical Aspects
Epidemiology
Genetics
Mutation Spectrum
Genotype: Phenotype Correlations
Pathogenesis
ATP Depletion
Increased Apoptosis
Altered Redox Homeostasis and Increased Oxidative Stress
Altered Vesicle Trafficking and Cell Signaling
Mechanism of Chronic Interstitial Damage
Clinical Presentation
Kidney Disease
Renal Pathology
Kidney Transplantation
Extra-renal Involvement
Ocular Impairment
Growth Impairment
Endocrine Impairment
Central Nervous System and Muscle Impairment
Intelligence and School Performance
Gastro-intestinal Disease
Bone Disease
Other Clinical Features
Cystinosis in Adults
Late Onset and Ocular Forms of Cystinosis
Diagnosis
Treatment
Feeding Recommendations
Symptomatic Therapy of Renal Fanconi Syndrome
Hormone Replacement Therapy
Specific Treatment with Cysteamine
Cysteamine Eye Drops
Prognosis and Future Treatments
References
31: The Kidney in Sickle Cell Disease
Hyposthenuria, Renal Papillary Necrosis, and Nocturnal Enuresis
Hyposthenuria
Renal Papillary Necrosis
Nocturnal Enuresis
Albuminuria
Glomerular Filtration Rate
Progressive CKD, End-Stage Kidney Disease, and Mortality
Acute Kidney Injury
Tubular Abnormalities and Acidification Defects
Hypertension
References
32: Diabetic Kidney Disease
Introduction to Diabetic Kidney Disease
Epidemiology of Diabetes in Children
Clinical Risk Factors for Diabetic Kidney Disease
Natural History
Pathophysiology
Biomarkers
Pathology
Screening and Monitoring
Albuminuria
Glomerular Filtration Rate
Blood Pressure
Lipids
Treatment
Blood Sugar Control
Smoking Cessation
Lipid Management
Hypertension Management
Novel Therapies
References
33: Disordered Hemostasis and Renal Disorders
Hemostasis
Primary Hemostasis
Vessel Wall
Endothelium
Platelets
Secondary Hemostasis
Anticoagulation System
Fibrinolytic System
Other Components
Age-Appropriate Development of Hemostasis (Developmental Hemostasis)
Primary Hemostasis
Secondary Hemostasis
Anticoagulation System
Thrombolytic System
Bleeding in Renal Disease
Uremic Coagulopathy
Clinical Manifestations
Pathogenesis
Intrinsic Platelet Abnormalities
Platelet: Vessel Wall Abnormalities
Treatment
Clotting in Renal Disease
Thrombotic Manifestations of Nephrotic Syndrome
Epidemiology
Pathogenesis
Prevention and Treatment
Renal Vein Thrombosis
Renal Artery Thrombosis
Renal Vascular Thrombosis in Renal Transplantation
Hemolytic Uremic Syndrome and Coagulation
Diagnosis of Thromboembolism
Thrombophilia Work Up
Treatment
Conclusion
References
Part VII: Renal Tubular Disorders
34: Differential Diagnosis and Management of Fluid, Electrolyte and Acid-Base Disorders
Introduction
Water and Salt
Introduction
Body Fluid Compartments
Effective Circulating Volume
Blood Osmolality: Measurement of Sodium
Dehydration and Extracellular Fluid Volume Depletion
Degree of Dehydration
Laboratory Testing and the Type of Fluid Lost
Dysnatremia
Consequences, Symptoms and Diagnostic Work Up
Hyponatremia
Introduction
Evaluating the Cause
Hypernatremia
Introduction
Evaluating the Cause
Management
Maintenance and Perioperative Fluids
Dehydration
Hydration in Infectious Diseases Associated with a Tendency Towards Hyponatremia
Hyponatremia
Potassium
Balance
Regulation of Circulating Potassium
External (≈ Renal) Potassium Homeostasis
Internal Potassium Homeostasis
Prenatal and Neonatal Potassium Balance
Symptoms, Signs, and Consequences of Hypokalemia and Hyperkalemia
Evaluating the Causes of Hypokalemia and Hyperkalemia (“Diagnostic Tests”)
Hypokalemia
Clinical Work Up
Management
Hyperkalemia
Clinical Work Up
Management
Acid-Base Balance
Introduction
Systemic Effects of Metabolic Acid-Base Abnormalities
Respiratory System
Potassium Balance
Ca++ (and Mg++) Balance
Hemoglobin Oxygen Affinity
Cardiovascular System
Central Nervous System
Metabolism
Metabolic Acidosis
High Anion Gap Metabolic Acidosis
Normal Anion Gap Metabolic Acidosis (= “Hyperchloremic”)
Urine Net Charge
Metabolic Acidosis During the First Months of Life
Symptoms, Signs, Consequences
Clinical Work Up
Management
Metabolic Alkalosis
Symptoms, Signs, Consequences
Management
Respiratory Acid-Base Disturbances
Calcium
Balance
Hypocalcemia
Non-neonatal Hypocalcemia
Symptoms and Signs
Causes
Diagnostic Work Up
Neonatal Hypocalcemia
Symptoms and Signs
Causes
Early Neonatal Hypocalcemia
Late Neonatal Hypocalcemia
Hypercalcemia
Signs and Symptoms
Causes
Diagnostic Work Up
Management
Magnesium
Balance
Hypomagnesemia
Decreased Intake, Poor Intestinal Absorption or Intestinal Loss
Renal Losses
Further Causes
Neonatal Hypomagnesemia
Symptoms, Signs, Consequences
Hypokalemia
Hypocalcemia
Repletion
Inorganic Phosphate
Balance
Hypophosphatemia
Low Dietary Intake or Poor Intestinal Absorption
Internal Redistribution
Urinary Loss
Symptoms, Signs, Consequences
Management
Hyperphosphatemia
References
35: Renal Fanconi Syndromes and Other Proximal Tubular Disorders
Introduction
Clinical Features
Biochemical Abnormalities
Proteinuria
Aminoaciduria
Organic Aciduria
Glycosuria
Renal Tubular Acidosis
Phosphaturia
Hypercalciuria
Hypokalemia
Other Substances
Pathogenesis
Disruption of Energy Production
Glutathione Depletion
Reduced Activity of Cotransporters
Disruption of the Endocytic Pathway (Megalin/Cubilin)
Primary Renal Fanconi Syndromes
Secondary Forms of Inherited Renal Fanconi Syndromes
Cystinosis
Tyrosinemia
Mitochondrial Cytopathies
Fanconi-Bickel-Syndrome
Fructose Intolerance
Galactosemia
ARC-Syndrome
Membranous Nephropathy with Anti-proximal Tubule Basement Membrane Antibodies
Dent Disease
Clinical Features
Genetics
Pathophysiology
Treatment
Lowe Syndrome
Clinical Features
Genetics
Pathophysiology
Treatment
Acquired RFS
Chemotherapeutic Agents
Antibiotics and Antiretrovirals
Treatment
References
36: Bartter-, Gitelman-, and Related Syndromes
Basic Principles of Ion Transport in the TAL and the Early DCT
Hypokalemic Salt-Wasting Tubular Disorders
Renal Salt-Wasting with Hypokalemia and Hypochloremic Metabolic Alkalosis
Historical Overview and Nomenclature
Genetic Disorders with Hypokalemic Salt-Wasting
Bartter Syndrome Type 1 (BS1)
Bartter Syndrome Type 2 (BS2)
Bartter Syndrome Type 3 (BS3)
Bartter Syndrome Type 4a (BS4a)
A Digenic Disorder: Bartter Syndrome Type 4b (BS4b)
X-Linked Transient Bartter Syndrome (BS5)
Gitelman Syndrome (GS)
EAST/SeSAME Syndrome
Treatment
References
37: Disorders of Calcium and Magnesium Metabolism
Calcium Physiology
Disturbances of Calcium Homeostasis
Hypercalciuria
Hypocalcemia
Autosomal Dominant Hypocalcemia
Hypercalcemia
Clinical Findings
Diagnostic Workup
Treatment
Hypercalcemia with Inappropriately High PTH
Familial Hypocalciuric Hypercalcemia/Neonatal Severe Hyperparathyroidism
Hypercalcemia with Suppressed PTH and Inappropriately High 1,25-(OH)2-Vitamin D3
Idiopathic Infantile Hypercalcemia
Magnesium Physiology
Magnesium Depletion
Manifestations of Hypomagnesemia
Hypokalemia
Hypocalcemia
Neuromuscular Manifestations
Cardiovascular Manifestations
Clinical Assessment of Magnesium Deficiency
Hereditary Disorders of Mg2+ Handling
Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis
Gitelman Syndrome
EAST/SeSAME Syndrome
Hypomagnesemia with Secondary Hypocalcemia
Hypomagnesemia, Refractory Seizures and Mental Retardation Type 2
Isolated Dominant Hypomagnesemia
Hypomagnesemia, Episodic Ataxia/Myokymia Syndrome
Isolated Recessive Hypomagnesemia
Hypomagnesemia, Refractory Seizures, and Mental Retardation 1
HNF1B Nephropathy
Transient Neonatal Hyperphenylalaninemia
Mitochondrial Hypomagnesemia
Acquired Hypomagnesemia
Cisplatin and Carboplatin
Aminoglycosides
Calcineurin Inhibitors
EGF Receptor Antibodies
Proton-Pump Inhibitors (PPIs)
Miscellaneous Agents
Therapy of Hypomagnesemia
References
38: Disorders of Phosphorus Metabolism
Introduction
Phosphate Homeostasis
Regulators of Phosphate Homeostasis
Hypophosphatemic Disorders
Clinical, Biochemical, and Radiological Manifestations
Clinical Findings
Radiological Findings
Biochemical Findings
Hypophosphatemic Disorders with Increased FGF23 Activity
X-Linked Hypophosphatemia (PHEX Mutation)
ADHR (FGF23 Mutation)
ARHR (1, DMP1 Mutation; 2, ENPP1 Mutation)
Raine Syndrome Associated (FAM20C Mutation)
Tumor-Induced Osteomalacia and Tumor-Induced Rickets (TIO)
Hypophosphatemic Rickets and Hyperparathyroidism
Fibrous Dysplasia (FD) and McCune-Albright Syndrome (MAS)
Hypophosphatemic Disorders with Normal or Suppressed FGF23 Activity
HHRH (SLC34A3 Mutation)
Hypophosphatemia and Nephrocalcinosis (SLC34A1 Mutation)
Nephrolithiasis and Osteoporosis Associated with Hypophosphatemia
Fanconi Syndrome
Treatment of XLH
Phosphate Supplementation and Active Vitamin D Metabolites
Monitoring and Dose Adjustments During Conventional Treatment
Burosumab
Efficacy and Safety
Monitoring and Dose Adjustments During Burosumab Treatment
Adjunctive Therapies
Growth Hormone
Calcimimetics
Surgical Management
Dental Care
Expected Outcomes
Treatment of Other Forms of Hypophosphatemic Rickets
References
39: Renal Tubular Acidosis
Introduction
Physiology of Renal Acid-Base Handling
Bicarbonate Reabsorption
Proximal Tubule
Thick Ascending Limb of Henle’s Loop
Collecting Duct
Acid Secretion
Ammonia Genesis and Recycling
Ammonia Genesis
Ammonia Recycling
Pathophysiology of Renal-Acid Base Handling
Definitions
Proximal Renal Tubular Acidosis (Type II RTA)
Clinical Presentations
Diagnosis
Treatment
Prognosis
Distal Renal Tubular Acidosis (Type I RTA)
Clinical Presentation
Distal RTA with Mutations in AE1 (SLC4A1)
Distal RTA with Mutations in Proton Pump Subunits a4 (ATP6V0A4) and B1 (ATP6V1B1)
Distal RTA with Mutations in FOXI1
Distal RTA with Mutations in WDR72
Candidate Genes
Diagnosis
Treatment
Prognosis
Mixed Proximal and Distal Renal Tubular Acidosis (Type III RTA)
Hyperkalemic Renal Tubular Acidosis (Type IV RTA)
Clinical Presentation
Diagnosis
Treatment
References
40: Diabetes Insipidus
History
Clinic
Presentation in Infancy
Clinical Features and Long-Term Prognosis
Physiologic Principles
Tubular Concentration/Dilution Mechanism (Countercurrent Mechanism with Figure)
AVP Effects in the Kidney
Extrarenal Effects of AVP
Diagnosis
Diagnostic Procedures
Water Deprivation Test
DDAVP Test
Differential Diagnosis
Central DI
X-Linked and Autosomal NDI
Partial NDI
Secondary NDI
Secondary Inherited NDI
Obstructive Uropathy
Interstitial Renal Disease
Lithium
Hypercalcaemia and Hypercalciuria
Hypokalaemia
Disorders Impairing the Generation of a Medullary Concentration Gradient
Bartter Syndrome
Urea Transporter
Genetics
AVPR2
AQP2
Treatment
General Aspects of Treatment
Osmotic Load Reduction
Diuretics
Non-steroidal Anti-inflammatory Drugs (NSAID)
Future Perspectives
Molecular Chaperones
Prostaglandin Receptor Agonists
References
Part VIII: Renal Neoplasia and Tubulointerstitial Disease
41: Pediatric Renal Tumors
Introduction
Wilms Tumor
Epidemiology
Predisposition Syndromes
Pathology
Nephrogenic Rests and Nephroblastomatosis
Presentation
Evaluation and Staging
Treatment
Prognosis and Outcomes
Late Effects
Clear Cell Sarcoma of the Kidney
Epidemiology
Pathology
Presentation and Evaluation
Treatment
Prognosis and Outcomes
Late Effects
Malignant Rhabdoid Tumor
Pediatric Renal Cell Carcinoma
Renal Medullary Carcinoma
Renal Angiomyolipoma and Epithelioid Angiomyolipoma
Ewing Sarcoma of the kidney
Congenital Mesoblastic Nephroma
Cystic Tumors
Ossifying Renal Tumor of Infancy
Metanephric Tumors
Summary
References
42: Tubulointerstitial Nephritis in Children
Introduction and Historical Perspective
Epidemiology
Histology and Pathogenesis
Clinical Findings
Diagnosis
Urinary Sediment
Low Molecular Weight Proteinuria
Blood Work
Urinary TIN Biomarkers
Radiology
Biopsy
Causes, Treatment and Outcomes
Drugs
Tubulointerstitial Nephritis with Uveitis
Infections
Granulomatous Interstitial Nephritis
Sarcoidosis
Sjögren’s Syndrome
Other Systemic Autoimmune Diseases
Xanthogranulomatous TIN
Idiopathic TIN
Chronic Interstitial Nephritis
Epidemiology
Pathology
Clinical Findings
Etiology
Treatment and Prognosis
Outcomes
References
Part IX: Urinary Tract Disorders
43: Diagnosis and Management of Urinary Tract Infections
Introduction
Background
Clinical Presentation
Diagnosis of Urinary Tract Infection
Differentiating Upper from Lower Urinary Tract Infections
Pathogenesis
Bacterial Virulence
Organisms Causing Infection
Treatment of the Acute Episode
Imaging After a Febrile Urinary Tract Infection
Ultrasonography
Voiding Cystourethrography
Renal Scintigraphy
Other Imaging Modalities
Impact of Reduced Imaging
Antibiotic Prophylaxis
Antibiotic Prophylaxis in Children with Major Urologic Malformation, Spina Bifida, Neurogenic Bladder and Intermittent Catheterisation
Surgical Correction of VUR
Additional Therapies
Circumcision
Cranberry Juice
Probiotics
Long-Term Clinical Consequences
Summary
References
44: Vesicoureteral Reflux
Introduction
Embryology
Anatomic Factors
Extra-anatomic Factors
Associated Conditions
Multicystic Dysplastic Kidney (MCDK)
Renal Agenesis
Ectopia and Duplication
Syndromes
Incidence
Age
Gender and Race
Presentation
Antenatal Diagnosis
Urinary Tract Infections
Siblings with VUR
Genetics of Reflux
Association of Urinary Tract Infections
Diagnosis
Renal Bladder Ultrasound
Voiding Cystourethrogram
Dimercaptosuccinic Acid Scan
Experimental Diagnosis Modalities
Voiding Ultrasonography
Magnetic Resonance Imaging
Grading of VUR
Bladder and Bowel Dysfunction
Potential for Reflux Resolution
Potential for Renal Injury
Reflux Nephropathy
Management of VUR
Antibiotic Prophylaxis
Treatment of Bladder and Bowel Dysfunction
Surgical Management
Minimally Invasive Treatment Options
Endoscopic Treatment
Laparoscopic and Robotic Treatment
Open Surgical Techniques
Intravesical (Cohen) Cross-trigonal Reimplantation
Extravesical (Lich-Gregoir) Reimplantation
Controversies and Conclusions
References
45: Obstructive Uropathies
Introduction
Common Obstructive Uropathies
Ureteropelvic Junction Obstruction
Megaureter
Duplex Kidney
Posterior Urethral Valves
References
46: Renal Calculi
Introduction
Epidemiology
Gender
Age
Race/Ethnicity
Regional Differences
Pathogenesis
Initial Presentation, Evaluation and Management
Diagnostic Imaging
Stone Analysis
Differential Diagnosis
Acute Management
Evaluation for Risk of Recurrent Nephrolithiasis
Surveillance
Types of Kidney Stones
Calcium-Based Stones
Uric Acid Stones
Monogenic Forms of Nephrolithiasis
Stones and Structural Abnormalities of the Urinary Tract
Stones and Urinary Tract Infection
Drug-Induced Nephrolithiasis
Specific Pediatric Populations at Risk for Nephrolithiasis
Management
Dietary Considerations
Surgical Treatment
Extracorporeal Shock Wave Lithotripsy
References
47: Voiding Disorders in Children
Introduction
Nocturnal Enuresis
Definition and Epidemiology
Pathophysiology
Nocturnal Urine Production
Bladder Function
Comorbidities
Constipation
Psychological/Behavioural Problems: Attention Deficit, Neurocognitive Dysfunction
Sleep
Hypertension
Renal Diseases
Drug Induced Changes in Circadian Rhythm
Genetics
Evaluation
Treatment
Treatment [8–11]
Desmopressin (DDAVP) [78, 153–156]
Anti-muscarinic Therapy
Cognitive Training and Psychotherapy
Alternative Treatments
Treatment Refractory MNE (Fig. 47.3)
Other Forms of Urinary Incontinence (Fig. 47.5)
Epidemiology
Definitions and Characteristics
Assessment
Overactive Bladder
Voiding Postponement
Underactive Bladder
Dysfunctional Voiding
Bladder Outlet Obstruction
Stress Incontinence
Vaginal Reflux
Giggle Incontinence
Extraordinary Daytime Urinary Frequency
Bladder Neck Dysfunction
Evaluation
Treatment
Overactive Bladder (Formerly Urge Incontinence)
Dysfunctional Voiding (Staccato Voiding)
Underactive Bladder
Neuropathic Incontinence
Structural Incontinence
Other Types of Incontinence
Giggle Incontinence
Vaginal Voiding
Summary
References
Part X: Hypertension
48: Hypertension: Epidemiology, Evaluation, and Blood Pressure Monitoring
Introduction and Importance
Morbidity and Mortality During Childhood
Cardiac Complications
Neuropathy/Retinopathy
Cognitive Dysfunction
Kidney Disease
Risk Across Life Course
Definition and Epidemiology
Definition and Classification
Children and Adolescents Aged 1–17 Years of Age
Infants Under a Year of Age
Hypertensive Emergency
Incidence and Prevalence
Screening Recommendations
Emerging At-Risk Populations
Blood Pressure Measurement
Technical Considerations
Lower Extremity Measurement
Measurement in Infants
Importance of Repeated Measurements
Blood Pressure Follow-Up and Diagnosis Protocol
Elevated Blood Pressure
Stage 1 Hypertension
Stage 2 Hypertension
Ambulatory Blood Pressure Monitoring
Technical Considerations
Classifications Incorporating Ambulatory Blood Pressure Monitoring
White Coat Hypertension
Masked Hypertension
Indications for Ambulatory Blood Pressure Monitoring
Evaluation
History
Physical Exam
Secondary Causes and Target Organ Damage
Laboratory Workup
Albuminuria
Renin-Angiotensin-Aldosterone System
Uric Acid
Kidney Imaging
Renovascular Imaging
Cardiac Imaging
Additional Considerations
Co-morbidities
Cardiovascular Phenotyping
Follow Up for Patients with Hypertension
Out-of-Office Measurement
Home
School
Transition of Care
Conclusions and Future Directions
References
49: Renovascular Hypertension in Children
Introduction
Clinical Presentation
Clinical Symptoms
Laboratory Evaluation
Vascular Involvement
Causes of Renovascular Disease in Childhood
Epidemiology
Fibromuscular Dysplasia (FMD)
Takayasu Arteritis (TA)
Differentiation Between Fibromuscular Dysplasia (FMD) and Takayasu’s Arteritis (TA)
Genetic and Syndromic Causes
Neurofibromatosis Type 1 (NF Type 1)
Williams Syndrome
Extrinsic Compression of Renal Artery
Other Rare Causes
Transplant Renal Artery Stenosis
Imaging
Non-invasive Imaging
Kidney Ultrasound and Doppler Studies
CTA and MRA
Renal Scintigraphy
Invasive Imaging
Digital Subtraction Angiography (DSA)
Renal Vein Renin Sampling
Further Imaging
Cranial MR with Angiography
Echocardiography
Treatment
Pharmacological Treatment
Angioplasty
Surgery
Outcome
Technical Results
Blood Pressure
Kidney Function
Summary
References
50: Renal Hypertension: Etiology and Management
Introduction
The Role of the Kidney in Hypertension
Mechanisms of Blood Pressure Regulation by the Kidneys
Hypertension and the Kidneys
Pathomechanisms of Hypertension in Chronic Kidney Disease
Hypertension in Specific Renal Conditions
Hypertension in Acute Kidney Injury
Hypertension in Chronic Kidney Disease
Hypertension in Pediatric Dialysis Patients
Hypertension in Pediatric Renal Transplant Recipients
Hypertension Associated with Disorders of Renal Tubular Sodium Handling
Antihypertensive Treatment Strategies in Acute and Chronic Kidney Disease
Blood Pressure Target
Choice of Antihypertensive Drugs
Treatment of Hypertension in Children with Acute Kidney Injury
Treatment of Hypertension in Children with CKD
Treatment of Hypertension in Dialysis Patients
Treatment of Hypertension in Transplant Patients
Treatment of Patients with Monogenic ‘Low-Renin’ Hypertension
Monitoring of Patients with Renal Hypertension
Conclusions
References
Part XI: Acute Kidney Injury and Neonatal Nephrology
51: Acute Kidney Injury: Pathophysiology, Diagnosis and Prevention
Introduction
Definitions, Staging, Risk Stratification
Epidemiology
Clinical Classification
Functional AKI (Prerenal AKI, Volume-Responsive AKI)
Pathophysiology of Prerenal AKI
Structural AKI (Intrinsic AKI)
Morphology of Intrinsic AKI
Alterations in Hemodynamics and Microcirculation
Alterations in Tubule Dynamics
Alterations in Tubule Cell Metabolism
Alterations in Tubule, Endothelial, and Glomerular Cell Structure
Alterations in Tubule Cell Death
Alterations in Tubule Cell Proliferation and Differentiation
Alterations in the Microvasculature
Alterations in the Inflammatory Response
Alterations in Gene Expression
Alterations in Metabolomics
Unique Aspects of Septic AKI
AKI and Distant Organ Dysfunction
Clinicopathologic Correlations and Therapeutic Implications
Mechanisms Underlying Long-Term Sequelae of AKI
Postrenal AKI
Clinical Presentation
Identifying the Underlying Cause
Distinguishing Between Functional and Structural AKI
Distinguishing Between AKI and CKD
Determining the Severity of AKI
Considering a Diagnostic Fluid Challenge
Considering a Kidney Biopsy
Problems with Serum Creatinine Measurements in AKI
Serum Cystatin C as a Functional Biomarker
Novel Early Biomarkers of Kidney Damage in AKI
Prevention of AKI
Hydration
Fluid Resuscitation
Nephrotoxin Management
Unproven Pharmacologic Agents for Prevention of AKI
Mannitol
Loop Diuretics
Dopamine
Fenoldopam
Natriuretic Peptides
N-Acetylcysteine
Methylxanthines
Prognosis and Outcome
Concluding Remarks
References
52: Management of Pediatric Acute Kidney Injury
Introduction
Medical Management of AKI
Renal Perfusion
Volume Status
Electrolyte Abnormalities
Acid-Base Disturbances
Nutritional Interventions
Delivery
Protein
Calories and Lipid
Nutrients
Glycemic Control
Avoidance of Nephrotoxins
Other Medical Therapies
Growth Factors
Adenosine Receptor Antagonists
Renal Replacement Therapies in AKI
Modality Choice
Acute Peritoneal Dialysis
Initiation
Prescription and Technique
Complications
Acute Intermittent Hemodialysis
Initiation
Complications
Continuous Renal Replacement Therapies
Initiation
Blood Flow Rates
Solutions
Prescription
Anticoagulation
CRRT Use in Combination Therapies
Extra-corporeal Membrane Oxygenation
Plasma Therapy
Complications
Outcome
Extended Hemodialysis Techniques
Conclusion
References
53: Neonatal Kidney Dysfunction
Kidney Function in Neonates
Renal Blood Flow in Newborns
Glomerulogenesis
Glomerular Function Rate (GFR)
Water, Electrolyte and Acid-Base Disorders in Neonates
Metabolic Acidosis
Metabolic Alkalosis
Hyperkalemia
Hypokalemia
Hypernatremia
Hyponatremia
Hypocalcemia
Hypercalcemia
Acute Kidney Injury (AKI) in Neonates
Definition and Epidemiology
Risk Factors and Etiology
Conservative Management of Neonatal AKI
Dialysis in Newborns
Peritoneal Dialysis
Hemodialysis
Continuous Kidney Replacement Therapy (CKRT)
CKST Prescription for Neonates
Management of Hyperammonemia with Kidney Support Therapy
Outcomes of Neonatal AKI
Critically Ill Neonates
Outcomes of Neonates Treated with Kidney Support Therapy (KST) for AKI
Long-term Effects of Prematurity and Neonatal AKI on Chronic Kidney Disease
Future Directions in Neonatal AKI
References
Part XII: Chronic Kidney Disease
54: Demographics of CKD and ESRD in Children
Introduction
Part I: CKD (Stages I–4)
Definition of CKD
Screening for CKD
Demographics of CKD
Europe
North America
Latin America and the Caribbean
Asia
Middle East
Africa
Causes of CKD
Part II: KRT (CKD Stage 5D and 5 T)
Incidence
Prevalence
Causes of ESKD
Conclusion
References
55: Progression of Chronic Kidney Disease and Nephroprotective Therapy
Natural Course of Chronic Kidney Disease Progression in Children
Mechanisms of Kidney Failure Progression
Factors Modifying the Risk of Kidney Disease Progression
Age at Attainment of Kidney Mass Deficit
Gender
Underlying Kidney Disease and Genetic Pathology
Epigenetics and Fetal Programming
Hypertension
Proteinuria
Metabolic Acidosis
Dyslipidemia and Insulin Resistance
Hyperuricemia
Bone Metabolism
Environmental Factors
Treatment Strategies in Kidney Disease Progression
Blood Pressure Control
Proteinuria Control
Pharmacological Treatment Options
Antihypertensive and Antiproteinuric Pharmacotherapy
Antihypertensive Combination Therapies
Antihypertensive Chronotherapy
SGLT-2 Inhibition
Anti-inflammatory Drugs
Other Supportive Treatment Strategies
Conclusions
References
56: Growth and Puberty in Chronic Kidney Disease
Introduction
Normal Growth
Effect of CKD on the Phases of Growth
The Fetal Phase
The Infantile Phase
The Childhood Phase
The Pubertal Phase
Pubertal Development
Pubertal Growth
Segmental Growth
Adult Height and Height Prediction
Causes of Growth Failure in CKD
Cause of Renal Disease
Congenital Abnormalities of the Kidneys and Urinary Tract (CAKUT)
Glomerulopathies
Tubular and Interstitial Nephropathies
Stage of CKD and Dialysis
Protein-Calorie Malnutrition
Protein-Energy Wasting
Obesity
Metabolic Acidosis
Disturbances of Water and Electrolyte Balance
CKD-Mineral and Bone Disorder (CKD-MBD)
Anemia
Endocrine Changes
Gonadotropic Hormone Axis
Gonadal Hormones
Gonadotropins
Somatotropic Hormone Axis
Growth Hormone Secretion and Metabolism
Growth Hormone Receptor and GH Signaling
Insulin-Like Growth Factor Plasma Binding and Tissue Action
Corticosteroid Treatment
Treatment of Growth Failure in Chronic Kidney Disease
General Measures
Dialysis and Intensified Dialysis
Transplantation
Endocrine Therapies
Vitamin D
Calcimimetics
Growth Hormone
Efficacy of rhGH in Prepubertal Children
Effects of rhGH on Pubertal Growth and Adult Height
Efficacy of rhGH in Infants
General rhGH Treatment Strategies
Potential Adverse Events Associated with rhGH Therapy
Future Perspectives
References
57: Neurodevelopment in Chronic Kidney Disease
Introduction
Early Development
Intellectual Function (IQ)
ESKD Onset in Infancy and Early Childhood
Mixed Age Groups Including Mild to Moderate CKD
Executive Function
Academic Achievement and Educational/Vocational Outcomes
Cognitive Outcomes and Kidney Transplantation
Genetics of Neurodevelopment and Kidney Development
Neuroimaging
More Frequent Hemodialysis and Neurocognitive Functioning
Conclusion
References
58: Nutritional Challenges in Pediatric Kidney Disease
Introduction
Nutrition Assessment
Anthropometric Measures
Dietary Assessment
Assessing Protein Status: Normalized Protein Catabolic Rate vs. Serum Albumin
Nutrition Management
Energy
Energy Requirements
Appetite Stimulants
Nutritional Supplementation
Infant, Pediatric and Adult Renal Formula Options
Enteral Feeding
Parenteral Nutrition
Intradialytic Parenteral Nutrition (IDPN)
Limiting Energy Intake
Protein
Protein Requirements
Modifying Dietary Protein Intake
Carbohydrates
Fiber
Fat
Potassium
Sodium
Salt and Sugar in Hypertension
Fluid Intake
Calcium and Phosphorous
Calcium and Phosphorous Intake
Calcium
Phosphorous
Acid Load
Vitamins, Minerals and Trace Elements
Trace Elements
Vitamin D
Other Fat-Soluble Vitamins
Transplantation
References
59: Anemia in Chronic Renal Disease
Introduction
Pathophysiology of Anemia
Erythropoietin Deficiency
Blood Loss
Decreased Red Blood Cell Survival
Bone Marrow Suppression
Iron Deficiency
Inadequate Dialysis
Malnutrition
Inflammation
Hyperparathyroidism
B12 or Folate Deficiency
Aluminum Toxicity
Carnitine Deficiency
Medications
Summary
Epidemiology of Anemia in Pediatric CKD
Clinical Effects of Anemia
Clinical Evaluation of Anemia
Initial Evaluation
Chronic Monitoring
Treatment of Anemia
Target Hemoglobin
Hemoglobin Monitoring
Erythropoiesis Stimulating Agents
Recombinant Human Erythropoietin
Pharmacokinetics
Dosing
Complications
Darbepoetin Alpha
Efficacy
Pharmacokinetics
Dosing
Complications
Methoxy Polyethylene Glycol-Epoetin Beta
Efficacy
Pharmacokinetics
Dosing
Complications
Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors
Monitoring Iron Stores
Diagnosis of Iron Deficiency
Iron Therapy
Oral Iron
Intravenous Iron
Preparations
Acute Dosing
Chronic Dosing
Complications
References
60: Disorders of Bone Mineral Metabolism in Chronic Kidney Disease
Introduction
Epidemiology
Pathogenesis
Disorders of Calcium Homeostasis
Abnormalities of 1,25(OH)2D Metabolism in CKD
25-Hydroxy Vitamin D Deficiency
Abnormalities of Phosphate Metabolism and Phosphaturic Hormone FGF23
Secondary Hyperparathyroidism
The Impact of Metabolic Acidosis
Further Mediators of CKD Bone Disease
Bone Histology in CKD-MBD
Bone Mineral Accrual and Peak Bone Mass
Linear Growth
Clinical Manifestations
Bone Pain
Myopathy
Skeletal Deformities
Slipped Epiphyses
Fractures
Growth Retardation
Cardiovascular Calcifications
Post-transplant Bone Disease
Assessment of Renal Bone Disease
Biochemistry
Serum Calcium
Serum Phosphate
Parathyroid Hormone
Alkaline Phosphatase
25(OH)D and 1,25(OH)2D
Additional Serum Markers of Bone Turn Over
Aluminum
Imaging
Radiography of the Skeleton
Measurements of Bone Mineral Density
Peripheral Quantitative Computer Tomography (pQCT)
Bone Biopsy
Imaging of the Parathyroid Glands
Imaging of Vascular Alterations
Treatment
Diet
Dialysis
Phosphate Binders
Magnesium Salts
Calcium Free Phosphate Binders
Aluminum Containing Phosphate Binders
Iron-Based Phosphate Binders
Newer P-Binders
Long-term Safety of Phosphate Binder Therapy
Vitamin D
Active Vitamin D Sterols
The Mode of Calcitriol Administration
Synthetic Vitamin D Analogues
Calcimimetic Agents
Parathyroidectomy
Treatment After Renal Transplantation
Future Therapeutic Perspectives
Prognosis
References
61: Cardiovascular Disease in Pediatric Chronic Kidney Disease
Epidemiology
Cardiovascular Mortality: Leading Cause of Death in Children with CKD
Specific Causes of Cardiac Death
Risk Factors
Traditional Risk Factors
CKD-Related Risk Factors
Vascular Disease in Pediatric CKD
Non-invasive Studies of Vascular Abnormalities
Coronary Artery Calcification
Carotid Intima-Media Thickness
Pulse Wave Velocity
ABPM and Ambulatory Arterial Stiffness Index (AASI)
Flow-Mediated Dilation, Postischemic Reactive Hyperemia
Mechanisms of Vascular Calcification in CKD
The Kidney-Vascular-Bone Axis
Calcification Inhibitors
Promoters of Calcification and Premature Aging in CKD
Uremic Toxins and Endothelial Dysfunction
The Heart in Pediatric CKD
Cardiac Remodeling
Early Markers of Cardiomyopathy
Evaluation of LVM in Children
Studies of LVH in Children with CKD
Left Ventricular Function and Pediatric CKD
Clinical Approach to CVD in Children with CKD
Hypertension
Dyslipidemia
Obesity and Physical Inactivity
Left Ventricular Hypertrophy
Mineral and Bone Disorder
Future
References
62: Ethical Issues in End Stage Kidney Disease
Introduction
Contemporary Bioethics and the Limits of Parental Decision-Making
Ethical Issues in Dialysis and ESRD
Withholding, Withdrawal, and Forgoing Dialysis Treatment
Withholding, Withdrawal, Equivalence
Technological Imperative
Futility
Time-Limited Trial of Therapy
Palliative Care
Ethical Issues in Kidney Transplantation
Consideration of Quality of Life in Transplant Decisions
Assessment of Adherence
Assessments of Alcohol and Other Substance Use
Justice and Broader Social Concerns in Pediatric Kidney Care
Caregiver Burden
Racism, Disparities and Structural Injustices
Ethical Care in the Setting of Resource Limitations
References
63: Psychosocial Issues in Children with Chronic Kidney Disease
Introduction
Psychiatric and Psychosocial Challenges
Psychiatric Disorders and Symptoms
Social Functioning
Quality of Life
Long-Term Functional Outcomes
Identification and Measurement of Psychosocial Issues in the Clinical Setting
Management of Psychosocial Issues in the Clinical Setting
Gaps in the Literature and Future Directions
Conclusions
References
Part XIII: Kidney Replacement Therapy
64: Initiation of Kidney Replacement Therapy: Strategic Choices and Preparation
Introduction
Current Distribution of Initial KRT Modalities Among Pediatric Patients Worldwide
Main Outcomes According to KRT Modality
Optimal Timing of KRT Initiation
Current Recommendations and Guidelines
Pre-ESKD Care and Referral for KRT Initiation
Urgent Versus Non-urgent and Planned Versus Unplanned Start of KRT
Outcome According to the Timing of KRT Initiation
KRT Initiation
Dialysis Availability and Choice of Modality
Dialysis Preparation and Transplant Workup
Dialysis Preparation
Kidney Transplant Workup
Summary: Lifetime Perspectives
References
65: Management of Peritoneal Dialysis in Children
Introduction
The Peritoneal Dialysis Prescription
The Peritoneal Membrane
The Physiology of Dialysis
Determination of Fill Volume
Choice of PD Fluid
Conventional PD Solutions
Alternate Osmotic Agents
Biocompatible Solutions
Determination of PD Modality/Dwell Time
CAPD vs. APD
Empiric Dialysis Prescriptions
Measures of Peritoneal Membrane Function
Goal-Directed Approach to Prescribing PD
Solute Clearance
Fluid Removal
Peritoneal Dialysis Access
Catheter Configuration
Preoperative Evaluation and Preparation
Catheter Placement Technique
Infectious Complications
Risk Factors and Prevention
Patient Age
PD Catheter Design, Insertion and Post-operative Exit-Site Care
Training
Chronic Exit-Site Care
Touch Contamination
Ostomies
Antibiotic and Antifungal Prophylaxis
Other Factors
Catheter-Related Infections
Peritonitis
Non-Infectious Complications
Catheter-Related Complications
Complications Related to the Dialysis Procedure
Complications Related to Increased Intraperitoneal Pressure
Complications Related to Transfer of Solutes During the Dialysis Procedure
Complications Related to Exposure of Peritoneal Membrane to Dialysis Fluid
References
66: Management of Hemodialysis in Children
Introduction
Prescribing Hemodialysis
Adequacy
Estimation of Dry Weight
Blood Flow Rate
Choice of Dialyser
Extracoporeal Circuit
Dialysate Water
Water Purification Systems
Testing Water Quality
Dialysate Composition
Sodium
Potassium
Bicarbonate
Calcium
Phosphate
Magnesium
Glucose
Dialysis Flow Rate
Dialysate Temperature
Anticoagulation
Commonly Encountered Hemodialysis Complications Dialysis Disequilibrium Syndrome (DDS)
Intradialytic Hypotension
Myocardial Stunning
Intradialytic or Paradoxical Hypertension
Left Ventricular Hypertrophy
Endothelial Dysfunction
Sudden Cardiac Death
Atherosclerosis, Arteriosclerosis, and Calcification
Inflammation
Malnutrition
Dialysis-Related Carnitine Disorder
Hyperhomocysteinaemia
Future Directions
Hemodiafiltration
Definition of HDF Therapy
Importance of Convective Volume
Essential Requirements for Performing HDF
High Flux Membranes
Ultrapure Water for HDF
Dialysis Machines with Accurate Ultrafiltration Control
Writing a HDF Prescription
Potential Advantages of HDF Over Conventional HD
Clinical Studies
Intensified Hemodialysis Options
References
67: Immunosuppression in Pediatric Kidney Transplantation
Introduction
The Immune Response
Classification of Immunosuppressive Agents
Induction Immunosuppressive Therapy
Lymphocyte Depleting Antibodies
Polyclonal Antibodies
Dosage of Thymoglobulin
Efficacy and Safety
IL-2 Receptor Antibodies
Dosage of Basiliximab
Efficacy and Safety
Comparison of Basiliximab with Thymoglobulin
Alemtuzumab
Recommendations
Maintenance Immunosuppressive Therapy
Glucocorticoids
Mechanism of Action
Pharmacokinetics and Drug Interactions
Administration
Side Effects
Steroid Withdrawal or Avoidance
Recurrent Kidney Disease
Calcineurin Inhibitors
Mechanism of Action
Pharmacokinetics and Drug Interactions
Efficacy: Comparison of Ciclosporin and Tacrolimus
Side Effects
Therapeutic Drug Monitoring
Antimetabolic Agents: Azathioprine
Mechanism of Action
Pharmacokinetics and Drug Interactions
Side Effects
Antimetabolic Agents: Mycophenolate Mofetil
Mechanism of Action
Dosage and Pharmacokinetics
Efficacy
Side Effects
Therapeutic Drug Monitoring
Target of Rapamycin (TOR) Inhibitors
Mechanism of Action
Dosage and Pharmacokinetics
Efficacy
Side Effects
Generic Immunosuppressive Drugs
Adherence to Immunosuppressive Medication
Conclusions
References
68: Non-Infectious Post-Transplant Complications: Disease Recurrence and Rejection
Introduction
Recurrence of Primary Kidney Disease in the Allograft
Focal and Segmental Glomerulosclerosis
Nature and Frequency of Primary Disease
Considerations for Transplant Planning: Predicting Risk for Recurrence
Treatment of FSGS Recurrence
Atypical Hemolytic Uremic Syndrome
Nature and Frequency of Primary Disease
Considerations for Transplant Planning
Risk Factors for Recurrence and Treatment of Recurrence
Risk of Disease Recurrence in the Era of Eculizumab
Additional Post-Transplant Considerations
C3 Glomerulopathy
Nature and Frequency of C3G
Considerations for Transplant Planning
Risk Factors for Recurrence and Treatment of C3G Recurrence
IgA-Mediated Kidney Disease
IgA Vasculitis
IgA Nephropathy
Nature and Frequency of IgA Nephropathy
Risk Factors for Recurrence
Considerations for Transplant Planning
Treatment of IgAN Recurrence
Impact of IgAN on Graft Function and Survival
Lupus Nephritis
Nature and Frequency of Disease
Risk for Disease Recurrence
Considerations for Transplant Planning
Impact of RLN on Graft Function and Survival
Acute Graft Dysfunction in the Early Post-Operative Period
Graft Thrombosis
Obstruction
Urine Leak
Investigation of Delayed Graft Function and Peri-Operative Allograft Dysfunction
Treatment of Delayed Graft Function
Acute Rejection and Chronic Allograft Dysfunction
Predictors of Pediatric Renal Allograft Survival
Chronic Allograft Dysfunction
Pre-Implantation Injury
Implantation Injury
Post Implantation Injury
Acute Allograft Dysfunction and Rejection
Allograft Rejection
Chronic Allograft (Late) Rejection
Antibody Mediated Rejection
Donor Specific Antibody
Prevention and Treatment of Rejection
Adequate Immunosuppression
Conclusion
References
69: Prevention and Treatment of Infectious Complications in Pediatric Renal Transplant Recipients
Introduction
Special Considerations in Pediatric Transplantation
Viral Infections
Cytomegalovirus
Epstein-Barr Virus
BK Virus and BKVAN
Varicella
COVID-19
Transplant Candidate Considerations
Post-Transplant Vaccination
COVID-19 and Donor Considerations
Bacterial Infections
Urinary Tract Infection
Other Bacterial Infections
Other Infections
Pneumocystis Jiroveci Pneumonia
Parasitic Infections
Fungal Infections
Immunizations
References
70: Long-Term Outcome of Kidney Failure in Children
Introduction
Chronic Pediatric Renal Replacement Therapy in Developing Countries
Course of Treatment Over Time
Impact of RRT Modality Over Time: Transplantation vs. Dialysis
Mortality
Factors Associated with Mortality
Causes of Death
Trends Over Time in Causes of Death: From Cardiovascular Disease to Infections?
Co-morbidity
Cardiovascular Disease
Infections
Malignancies
Incidence
Type of Cancer
Post-Transplant Lymphoproliferative Disease (PTLD)
Pathophysiology of EBV Associated PTLD
Risk Factors for PTLD
Epstein-Barr Virus (EBV)
CMV/Hepatitis C
Immunosuppressive Therapy
Other
Skin Tumors
Melanoma
Kaposi’s Sarcoma
Other Tumors
Other Somatic Co-morbidities
Psychosocial Consequences
Cognitive Functioning
Quality of Life
Transplant Patients
Dialysis Patients
Effect of Age at Assessment
Trend Over Time
Social Outcome
Employment
Partnership and Independency
Conclusions
References
Part XIV: Drugs and Toxins
71: Drug Use, Dosing, and Toxicity in Kidney Disease
Introduction
Drug Handling by the Kidneys: Principles of Pharmacokinetics/Drug Disposition
Glomerular Filtration of Drugs
Tubular Secretion of Drugs
Tubular Reabsorption of Drugs
Kidney Failure Induced Alterations in Drug Disposition
Age-Related Development of Kidney Function
Dialysis
Guidelines for Drug Dosing in Children with Kidney Failure
Therapeutic Drug Monitoring
Drug Injury to the Kidney: Nephrotoxicity
Pathophysiologic Mechanisms of Drug Nephrotoxicity
Direct Tubular Cell Toxicity
Acute Interstitial Nephritis and Immunologically Mediated Kidney Toxicity
Arteriolar Vasoconstriction
Crystal Accumulation
Proteinuric Glomerular Dysfunction
Vascular Injury/Thrombotic Microangiopathy
Alterations of Fluids and Electrolytes
Other Mechanisms
Ten Rules for Prevention of Drug-Induced Kidney Damage
References
72: Complementary Therapies for Renal Diseases
Introduction
Natural Health Products, TCM, and Massage Therapy
Epidemiology of Complementary Therapy Use
Natural Health Product Quality and Regulation
Legal and Ethical Considerations
Nephrotic Syndrome
TCM
Immunoglobulin A (IgA) Nephropathy
Omega-3 Fatty Acids
TCM
Vitamin E
Urolithiasis
Acupuncture
Massage
Probiotics
Urinary Tract Infections
Cranberry
Probiotics
Vitamin A
Vitamin D
Chronic Kidney Disease
Folic Acid
Oral L-Arginine
Rhubarb
TCM Herbs
Protein Restriction
Rheum Officinale
Topical Herbal Medicine
Bicarbonate
Traditional Chinese Medicine (TCM)
Uremic Pruritus
Acupuncture
Acupressure
Thermal Therapy
Homeopathy
Aromatherapy
Chinese Herbal Bath Therapy
End Stage-Renal Disease (ESKD)
O3FA
Acupressure
Summary
References
73: Environmental Nephrotoxins
Cadmium
Clinical Effects
Acute and Short-Term Effects
Chronic Toxicity
Diagnosis
Prevention of Exposure
Lead
Diagnosis
Management
Mercury
Diagnosis
Management
Prognosis
Uranium
Diagnosis
Management
Pesticides
Diagnosis
Management
Arsenic
Diagnosis
Management
Ochratoxin A
Diagnosis
Management
Aristolochic Acid
Diagnosis
Management
Melamine
The Chinese Epidemic
Non-epidemic Exposures
Pathogenesis of Renal Injury Induced By Melamine-Related Urinary Stones
Clinical Manifestations
Diagnosis
Management
Per- and Polyfluoroalkylated Substances
Chronic Kidney Disease of Unknown Etiology
Diagnosis
References
Index