Pediatric Nephrology

Preface
Contents
Contributors
Part I: Developmental Physiology and Diseases
1 Pre-natal Development of the Kidneys and Urinary Tract
Introduction
Studying Kidney and Urinary Tract Development
Origin of the Mammalian Kidney
Nephron Formation
Specification of Nephron Progenitors/Cap Mesenchyme
Nephron Induction
Nephron Segmentation
Glomerulogenesis
Nephron and Podocyte Endowment
Podocyte Terminal Differentiation
Glomerular Capillary Tuft Development
Renal Stroma
Vascular Development of the Kidney
Angiogenesis Versus Vasculogenesis
Origins of the Peritubular Capillary Endothelia
Molecular Control of Renal Vascular Development
Collecting System Development
Ureteric Bud Induction and Outgrowth
Ureteric Branching Morphogenesis
Cortical and Medullary Collecting Duct Patterning
Lower Urinary Tract Development
Anatomic and Functional Development
Molecular Control of Ureter and Bladder Development
Ureter
Bladder
Ureter-Bladder Anastomosis
Summary
References
2 Postnatal Renal Maturation
Maturation of GFR
Measuring GFR in the Neonate
Preterm Neonate Nephron Development and GFR
Organization of the Tubular Nephron
Principals of Membrane Transport
Maturation of Na+,K+-ATPase Along the Nephron
Proximal Tubule Transport
Glucose Transport
Amino Acid Transport
Organic Anion and Cation Transport
Phosphate Transport
Proximal Tubule Acidification
Proximal Tubule NaCl Transport
Proximal Tubule Water Transport
Thick Ascending Limb
Distal Convoluted Tubule
Urinary Concentration and Dilution
Distal Tubule Acidification
Cortical Collecting Tubule Sodium Transport
Potassium Transport
References
3 Congenital Anomalies of the Kidneys
Synonyms
Clinical Presentation of Congenital Anomalies of the Kidneys
Antenatal Presentation of CAKUT
Renal Agenesis
Renal Hyperechogenicity and Parenchymal Cysts
Renal Ectopia and Fusion Anomalies
Diagnosis and Imaging of Congenital Anomalies of the Kidneys
Amniotic Fluid Index (AFI) and Maximal Vertical Pocket (MFP)
Kidney Size
Antenatal Imaging
Oligo/anhydramnios and Consequences
Treatment of Congenital Anomalies of the Kidney with Oligohydramnios
Genetics of Congenital Kidney Anomalies
Complex Phenotypes from Variable Genetic Backgrounds
Genetic Perspective on Congenital Kidney Anomalies
Monogenic Disorders
Copy-Number Variation
Common Variants
Syndromes Associated with CAKUT
Trisomies and CAKUT
Environmental Factors that Predispose to Congenital Anomalies of the Kidney
Cross-References
References
4 Stem Cells and Kidney Regeneration
Introduction
Embryonic Renal Stem/Progenitor Cells
Kidney Development
Identification of Embryonic Renal Stem/Progenitor Cells
Generation of Kidney Lineage Cells from PSCs
PSCs
Directed Differentiation of PSCs into Kidney Lineage Cells
Kidney Reconstruction
Cell Therapies Using Human PSC-Derived Kidney Progenitors
Embryonic Renal Stem/Progenitor Cells Reprogrammed from Adult Renal Cells
Adult Renal Stem/Progenitor Cells
Stem Cells of Extrarenal Sources
Sources of Adult Renal Cells Responsible for In Vivo Regeneration
Adult Renal Stem/Progenitor Cells Expanded Ex Vivo
Stem Cell Niche in Adult Kidney
CSCs in Kidney
CSCs in Adult Renal Cell Carcinoma (RCC)
CSCs in WT
Towards Clinical Applications and Practical Use
Conclusions
References
Part II: Renal Physiology and Diagnostic Approaches
5 Assessment of Kidney Function in Children, Adolescents, and Young Adults
Summary and Key Points
Background
The Importance of Measuring Kidney Function
Current Gold Standard/Exogenous Methods
Comparison of Exogenous GFR Methods, Technical Aspects
Fluorescent GFR Markers
Impractical Aspects of Exogenous GFR Measurement
Endogenous Markers of Kidney Function
Serum Creatinine
Small Molecular Weight Proteins as Markers of GFR
Cystatin C (CysC)
Serum Cystatin C to Creatinine Ratio
Beta Trace Protein (BTP)
Beta-2 Microglobulin
Ferrocyanide
N,N,N-trimethyl-L-alanyl-L-proline betaine (TMAP)
Formulae for the Estimation of GFR
Kidney Function Measurement and Interpretation in Special Health Conditions
Age-Related Issues of Kidney Function Measurement
Race-Related Correction in Kidney Function
Sex-Related Correction in Kidney Function and Disparities in Disease Progression
Imaging for the Measurement of Kidney Function
Conclusions
Cross-References
References
6 Imaging Kidneys and the Urinary Tract
Synonyms
Diagnostic Procedures
Ultrasound
Technique
Application
Voiding Cystourethrography
Technique
Intravenous Pyelography
Technique
Application
Retrograde Urethrography
Technique
Application
Computed Tomography
Technique
Application
Nuclear Medicine
Technique
Dynamic Renal Scintigraphy
Cortical Scintigraphy
Adrenal Gland Scintigraphy
Radionuclide Cystography
Applications
Magnetic Resonance Imaging
Technique
Application
Congenital Kidney and Urological Disorders
Fetal Imaging
Megaureter
Ureterocele
Ureteropelvic Junction Obstruction
Abnormal Kidney Number or Location
Horseshoe Kidney and Crossed Fused Ectopia
Renal Dysplasia
Duplex Collecting System
Ectopic Ureters
Bladder Abnormalities
Urethral Abnormalities
Vesicoureteral Reflux
Hereditary Disorders
Cystic Kidney Diseases
Tuberous Sclerosis
Infections of the Urinary Tract
Renal Failure
Renal Transplant
Urolithiasis and Nephrocalcinosis
Urolithiasis
Nephrocalcinosis
Trauma to the Urinary Tract
Renal and Urinary Tract Tumors
Role of Imaging
Imaging of Specific Renal Tumors
Wilms´ Tumor
Lymphoma
Vascular Disease and Hypertension
Renal Artery Stenosis
Renal Vein Thrombosis
Pheochromocytoma
Cross-References
References
7 Technical Aspects of Renal Pathology
Introduction
Obtaining Tissue
General Considerations
Percutaneous Renal Biopsy
Other Biopsy Techniques
Assessment of the Renal Biopsy
Adequacy of Sample
Allotment of Tissue
Light Microscopy
Immunofluorescence Microscopy
Electron Microscopy
Normal Kidney Morphology
Patterns of Injury
Overall Pattern
Selected Specific Patterns of Injury
Mesangial Hypercellularity
Endocapillary Hypercellularity/Proliferative Lesions
Membranoproliferative Pattern
Exudative Pattern
Crescents
Segmental Sclerosis
Thrombosis
Acute Tubular Injury
Interstitial Fibrosis/Tubular Atrophy (IFTA)
Acute Interstitial Nephritis
Prognostic Implications of Biopsy Findings
New Methods for the Future
References
8 Approach to the Child with Hematuria and/or Proteinuria
Synonyms
Approach to the Child with Hematuria
Introduction
Epidemiology
Etiology
Clinical Approach (Figs. 1 and 2)
Approach to the Child with Proteinuria
Introduction
Albuminuria Versus Proteinuria
How to Measure Urine Protein
Spot Urine Sample Versus 24-h Collection
Clinical Approach
Nonpathological Proteinuria
Pathological Proteinuria
Indications for Kidney Biopsy in a Child with Proteinuria (Fig. 3)
Cross-References
References
Part III: Glomerular Diseases
9 Nephrotic Syndrome: Classification and Evaluation
Definition
Pathogenesis
Clinical Evaluation at Onset
Indications for Genetic Testing
Indications for Kidney Biopsy
Cross-References
References
10 Genetic Basis of Nephrotic Syndrome
Introduction
Molecular Mechanisms of Monogenic Nephrotic Syndrome
Slit Diaphragm Genes
Nephrin (NPHS1)
Podocin (NPHS2)
CD2-Associated Protein (CD2AP)
Transient Receptor Potential Channel 6 (TRPC6)
Phospholipase C Epsilon 1 (PLCE1)
Actin Cytoskeleton Genes
Alpha Actinin 4 (ACTN4)
Inverted Formin Type 2 (INF2)
Actin-Regulating Protein Rho-GAP 24 (ARHGAP24)
Rho GDP Dissociation Inhibitor α (ARHGDIA)
Myosin 1E (MYO1E)
WDR73
WT1
LMX1B
SMARCAL1
Nucleoporin Genes
Mitochondria Genes
LAMB2
Genes Associated with Other Renal Phenotypes
Complex Inheritance
FSGS in African Americans
Childhood Steroid Sensitive Nephrotic Syndrome (SSNS)
Implications on Disease Stratification and Diagnosis
Current Classification
Stratification Based on Diagnosis of Single Gene Mutations
Immune-Based Nephrotic Syndrome
Circulating Factor Disease
Other Means of Stratification Based on Molecular Signatures
Diagnostic Implications
Future Directions
Cross-References
References
11 Congenital Nephrotic Syndrome
Synonyms
Primary Nephrotic Syndrome
Nephrin (NPHS1) and CNS of the Finnish Type (CNF)
Podocin (NPHS2)
Wilms Tumor Suppressor 1 (WT1)
Laminin β2 (LAMB2)
Phospholipase C Epsilon 1 (PLCε1)
Other Genes
Secondary Nephrotic Syndromes
Infections
Immune Disorders
Diagnosis
Clinical Findings
Kidney Biopsy
Genetic Testing
Management
Albumin Substitution
Antiproteinuric Medications
Nutrition
Additional Medications
Nephrectomy and Dialysis
Kidney Transplantation
Cross-References
References
12 Clinical Aspects of Genetic Forms of Nephrotic Syndrome
Introduction
Isolated SRNS
Autosomal Recessive Forms
NPHS2
NPHS1
PLCE1
Less Common Gene Defects Causing AR-SRNS
MYO1E
PTPRO
CRB2
CD2AP
Autosomal Dominant Forms
INF2
TRPC6
WT1
ACTN4
Less Common Gene Defects Causing AD-SRNS
ARHGAP24
ANLN
X-Linked Forms
TBC1D8B
Syndromic SRNS
SRNS and Urogenital Abnormalities
Denys-Drash syndrome (DDS)
Frasier Syndrome
SRNS and Ocular Abnormalities
Pierson Syndrome
SRNS and Central Nervous System Abnormalities
Galloway-Mowat Syndrome
Less Common Early-Onset SRNS with Intellectual Disability
ARHGDIA Nephropathy
KANK4 Nephropathy
SRNS and Peripheral Neuropathy
Charcot-Marie-Tooth Disease
SRNS and Skeletal Dysplasia
Schimke Immuno-Osseous Dysplasia
Nail Patella Syndrome
SRNS and Skin Disorders
ILNEB Syndrome
SRNS and Storage Disorders
Disorders of Sphingolipid Disorders
Lysosomal Storage Disorder
Reverse Phenotyping and SRNS Phenocopies
Complex Inheritance
Familial Forms of Steroid Sensitive Nephrotic Syndrome
Phenotyping
Principles of Treatment
Supportive Therapy
Immunomodulators
Targeted Therapy
Principles of Transplantation
Selection of Organ Donors
Recurrence of Genetic Forms of SRNS
Perspectives
References
13 Inherited Diseases of the Glomerular Basement Membrane
The Glomerular Basement Membrane
Function of the Glomerular Basement Membrane
Basement Membrane Pathology
Alport Syndrome
Genetics and Impact on the GBM
Clinical Features
Kidney
Hearing
Eye
Others
Pathology
Kidney
Diagnostic Considerations
Treatment
Transplantation
Pierson Syndrome
Genetics
Clinical Features
Pathology
MYH9-Related Disorders
Genetics
Clinical Features
Pathology
Treatment
Nail-Patella Syndrome
Genetics
Clinical Features
Pathology
Treatment
Cross-References
References
14 Steroid-Sensitive Nephrotic Syndrome
Introduction
Historical Background
Etiology
Mechanisms of Proteinuria
Mechanisms of Glomerular Injury
Genetic Basis
Immune Mechanism
Podocyte-Specific Pathways
Clinical Features
Evaluation
Urinalysis
Biochemistry
Hematology
Renal Biopsy
Minimal Change Disease (MCD)
Diffuse Mesangial Proliferation
Focal Segmental Glomerulosclerosis (FSGS)
Immunofluorescence Patterns
IgM-Associated Nephropathy
C1q Nephropathy
IgA Deposits and MCD
Therapy
Management of Initial Episode
Disease Course and Therapy of Relapses
Management of Frequent Relapses
Choice of Therapy
Long-Term Alternate Day Steroids
Cyclophosphamide
Levamisole
Cyclosporine
Tacrolimus
Mycophenolate Mofetil (MMF)
Mizoribine
Rituximab
Late Steroid Resistance
Supportive Care
Nutrition
Edema, Hypovolemia, and Fluid Overload
Complications
Infections
Immunizations
Thromboembolism
Dyslipidemia
Osteoporosis
Long-Term Outcome
References
15 Nongenetic Forms of Steroid-Resistant Nephrotic Syndrome
Pathophysiology
Idiopathic FSGS
Maladaptive Injury Response
Obesity-Related Glomerulopathy
Low Nephron Mass
Infection-Associated FSGS
Toxic Exposures
Drug-Induced Podocytopathy
Pathology
Histopathology (Fig. 2)
Immunofluorescence
Electron microscopy
The Columbia Classification of FSGS and Clinical Relevance
Research Directions of Histopathology
Management
Immunosuppressive Regimens
Pulse Corticosteroids
Calcineurin Inhibitors (CNI)
Mycophenolate Mofetil (MMF)
Rituximab
Ofatumumab
Cyclophosphamide
Combination of Immunosuppressive Agents
Novel Therapeutic Strategies
Anti-IL 2 Antibodies
Abatacept
Adalimumab
Fresolimumab
Adrenocorticotropic Hormone (ACTH)
Non-immunosuppressive Strategies
Low-Density Lipoprotein (LDL) Apheresis
Galactose
Sparsentan
Adjunctive Therapies
Supportive Care and Management of Complications
Outcomes
Transplantation
References
16 Membranous Nephropathy
Introduction
Incidence, Prevalence, and Etiology
Pathophysiology
General Mechanisms
Intrinsic Podocyte Antigens
Extrinsic Podocyte Antigens
Complement Activation and Podocyte Injury
Gene Polymorphisms and Risk of Primary MN
Clinical Features and Laboratory Investigations
Histopathology
Diagnosis, Serology, and Kidney Biopsy Staining
Prognostic Indicators and Treatment
Cross-References
References
Part IV: Kidney Involvement in Systemic Diseases
17 Immunoglobulin A Nephropathy in Children
Introduction
Pathophysiology
Genetic Factors
Circulating IgA Molecules
Complement Activation
Innate Immunity, Mucosal Immunity
Pathology
Immunohistologic Findings
Electron Microscopy
Light Microscopic Findings
Repeat Renal Biopsy
Differences Between Childhood and Adult Patients
Oxford Classification
Clinical Features
Laboratory Investigations
Biomarkers
Differential Diagnosis
Relationship Between IgAN and IgA Vasculitis (Henoch-Schoenlein) Nephritis
Chronic Liver Disease
Idiopathic Nephrotic Syndrome
Natural History and Prognosis
Long-Term Outcome After Renal Transplantation
Management
Therapeutic Agents for Treatment
Renin-Angiotensin System Blockers
Glucocorticoids
Combined Corticosteroids and Immunosuppressive Medications
Mycophenolate Mofetil
Cyclophosphamide
Rituximab
Calcineurin Inhibitors
Tonsillectomy
Fish Oil/Omega 3 Fatty Acids
Coagulation Modifying Agents
Future Therapies for IgAN
Management of IgAN in Children
Selection of Patients
References
18 Henoch Schönlein Purpura Nephropathy
Introduction
Epidemiology
Mechanisms of Disease
Role of Genetic Conditioning
Pathogenesis and Mechanisms of Disease Progression
Clinical Features
Pathology
Light Microscopy
Immunofluorescence
Electron Microscopy
Comparison of IgA Vasculitis with Nephritis with IgA Nephropathy
Timing of Biopsy and Histology Findings
Histological Classifications and Their Significance
ISKDC
MEST
Other Classifications
Laboratory Investigations
Clinicopathologic Correlation
Differential Diagnosis
Relationship Between IgA Nephropathy and IgA Vasculitis
Treatment
Prevention of Nephritis
Treatment Options
Immunosuppressive Agents
Long-Term Course
Hypertension
Complications During Pregnancy
Chronic Kidney Disease
End Stage Kidney Disease
Recurrence in Renal Allograft
Conclusions
References
19 Renal Vasculitis
Synonyms
Introduction
ANCA Associated Vasculitides
Microscopic Polyangiitis
Granulomatous Polyangiitis (GPA) (Wegener Granulomatosis)
Eosinophilic Granulomatosis with Polyangiitis (EGPA) (Churg-Strauss Syndrome)
Kawasaki Disease
Childhood Polyarteritis Nodosa (PAN)
Deficiency of Adenosine Deaminase 2 (ADA2)
Takayasu Arteritis
Behçet Disease
References
20 Lupus Nephritis
Synonyms
Introduction
Pathogenesis
Animal Models
Genetics
Environment
Hormonal Factors
Immune Complexes (Antibody-Mediated Immunity)
Innate Immunity
Lymphocytes (Cell-Mediated Immunity)
Pathogenesis of Nephritis
Clinical Manifestations
Kidney Involvement
Extrarenal Manifestations
Mucocutaneous
Musculoskeletal
Nervous System
Cardiovascular
Pulmonary
Gastrointestinal
Hematologic and Reticuloendothelial System
Endocrine
Ocular
Drug-Induced Lupus
Neonatal Lupus
Antiphospholipid Syndrome (aPLS)
Kidney Biopsy, Pathology
Histological Classification
Activity and Chronicity
Non-classifiable Kidney Manifestations
Indications for Repeat Biopsy
Laboratory Investigations
Urinalysis
Immunologic Studies
Extrarenal Manifestations
Prognostic Factors
Management
Initial Therapy for Proliferative Lupus Nephritis
Initial Therapy for Membranous Nephropathy
Maintenance Therapy
Conservative Management
Refractory Lupus Nephritis
Relapses of Lupus Nephritis
Extrarenal Disease
Geographic, Race, and Ethnic Considerations
Outcomes
Activity and Damage
SLE on Dialysis
SLE Following Transplantation
References
21 Autoantibodies and Kidney Diseases
Synonyms
Introduction
Antiphospholipid Syndrome
Pathogenesis
Clinical Manifestations
Renal Involvement
Antiphospholipid Syndrome-Associated Nephropathy
Lupus Nephritis (LN) and aPLs
Catastrophic APS and Kidneys
Antiphospholipid Syndrome and End-Stage Renal Disease (ESRD)
Treatment
Treatment of CAPS
Treatment of APSN
Anti-glomerular Basement Membrane Disease
Definition
Epidemiology
Etiology
Clinical Presentation
Diagnosis
Differential Diagnosis
Treatment
Outcome
IgG4-Related Disease
Introduction
Is IgG4-RD an Autoimmune Disease?
IgG4-Related Kidney Disease
Clinical Features
Radiological Findings
Kidney Pathology
Diagnostic Criteria
Treatment
Cryoglobulinemic Vasculitis
Definition and Classification
Epidemiology
Etiopathogenesis
Clinical Manifestations
Diagnosis
Treatment and Outcome
Conclusion
References
22 Membranoproliferative Glomerulonephritis and C3 Glomerulopathy in Children
Introduction
From a Morphology to a Pathogenesis-Based Disease Classification
Histopathology
C3 Glomerulopathy
Differentiating C3 Glomerulonephritis from Dense Deposit Disease
Immunoglobulin-Associated Membranoproliferative GN
Membranoproliferative Glomerulonephritis Without Immunoreactants
Transition Between IC-MPGN and C3G
Lessons Learned from Animal Models
Lessons Learned from Patients
Autoimmune Forms of C3G
Genetic Forms of C3 Glomerulopathy
Clinical Features
Diagnosis
Differential Diagnosis
Therapy
Supportive Therapy
Immunosuppressive Therapy
Complement Targeting Therapy
Clinical Outcomes
Future Perspectives
References
23 Thrombotic Thrombocytopenic Purpura, Atypical Hemolytic Uremic Syndrome, and Spectrum of Thrombotic Microangiopathy
Introduction
Thrombotic Thrombocytopenic Purpura
Introduction
Pathophysiology
Diagnosis
Management
Complement and the Link to Disease
Atypical HUS
Epidemiology
Clinical Features
Pathophysiology
Genetics
Genetics Forms of Complement-Mediated aHUS
CFH-Associated aHUS
MCP-Associated aHUS
CFI-Associated aHUS
C3-Associated aHUS
CFB-Associated aHUS
Thrombomodulin-Associated aHUS
Genetic Forms of aHUS Unrelated to Complement
Cobalamin C Deficiency-Associated aHUS
DGKE-Associated aHUS
Plasminogen-Associated aHUS
Autoimmune Forms of aHUS
Diagnosis
Management of aHUS
Long-Term Complications
Transplantation
Spectrum of Thrombotic Microangiopathy (TMA)
Introduction and Nomenclature
Pathophysiology and Biomarkers
Clinical Presentation and Outcome
Treatment
TMA Associated with Pregnancy
Incidence and Pathophysiology
Clinical Presentation and Diagnostic Approach
Treatment and Outcome
Special Considerations
TMA Associated with Solid Organ Transplantation
Incidence and Pathophysiology
Clinical Presentation and Diagnostic Approach
Treatment and Outcome
TMA Associated with Hematopoietic Stem Cell Transplantation
Incidence and Pathophysiology
Clinical Presentation and Diagnostic Approach
Treatment and Outcome
TMA Associated with Autoimmune Diseases
Systemic Lupus Erythematosus
Incidence and Pathophysiology
Clinical Presentation and Diagnostic Approach
Treatment and Outcome
Antiphospholipid Syndrome (APS)
Antineutrophil Cytoplasmic Antibodies (ANCA) Associated Vasculitis
TMA Associated with Cobalamin C Deficiency
TMA Associated with Drug Exposure
Quinine
Chemotherapy
VEGF Inhibitors
TMA Associated with Infection
Streptococcus pneumoniae HUS
TMA Associated with Malignant Hypertension
Conclusion
Cross-References
References
24 Infection-Related Hemolytic Uremic Syndrome (HUS)
Introduction and Classification
Epidemiology
Incidence of STEC Infection and STEC-HUS
Incidence of Streptococcus pneumoniae-Associated HUS
STEC-Associated HUS
Pathogenesis and Pathophysiology
Microbiology of Escherichia coli
Source of Infection
Diagnosis of STEC Infection
Characteristics of Stx
Mechanisms of Stx-Mediated Cell Injury (Fig. 3 [26])
Involvement of Inflammatory Components
Polymorphonuclear Neutrophils
Complement System
Clinical Course (Fig. 4 [12])
Long-Term Complications (Prognosis)
Acute Management of HUS
General Management of Patient with STEC-HUS
Fluid Management
Hematological Symptoms Management and Treatment with Blood Products
Antibiotics in STEC-HUS
Preventive Measures to Decrease Chance of Developing STEC-HUS and Additional Treatments and Therapies in Development
Streptococcus pneumoniae-Associated HUS
Pathophysiology
Clinical Course
Management
HUS Associated with Shigella dysenteriae Type 1, Influenza Virus, and Other Infections
HUS Associated with Shigella dysenteriae Type 1
Influenza Associated HUS and HUS Associated with Other Viral Infections
Reference
25 Acute Post-Streptococcal Glomerulonephritis
Introduction
Epidemiology
Pathogenesis
Clinical Characteristics
Diagnosis
Treatment
Prognosis
References
26 Infections That Affect the Kidney (Nonviral)
Introduction
Bacterial Infections
Tropical Infections
Tuberculosis (TB)
Leptospirosis
Diagnosis
Treatment
Rickettsia
Infection-Related Glomerulonephritis
Glomerulonephritis Associated with Bacterial Infections: Endocarditis/Shunt Nephritis
Bacterial Endocarditis
Shunt Nephritis
Parasitic Infections
Malaria
Epidemiology
Clinical Features of Malaria
Uncomplicated Malaria
Renal Involvement in Malaria
Malarial AKI
Clinical Features of Malarial AKI
Treatment of Malarial AKI
Malarial Glomerular Disease
Diagnosis and Treatment of Malaria
Filaria
Epidemiology
Clinical Presentation and Genitourinary Involvement in Filariasis
Diagnosis
Treatment
Onchocerca volvulus and Loa loa
Schistosomiasis
Epidemiology
Clinical Features
Pediatric Schistosomiasis
Renal Involvement
Diagnosis
Prevention and Treatment
Leishmaniasis
Epidemiology
Kidney Involvement
Diagnosis
Treatment
Trypanosomiasis
Trichenella
Echinococcosis (Hydatid Disease)
Fungal Infections
Others
Serious Forms of Urinary Tract Infection
Acute Focal Bacterial Nephritis
Renal Abscess
Xanthogranulomatous Pyelonephritis (XPN)
References
27 Viral Infections and the Kidney
Viruses
Viral Infections and Kidney Diseases
Specific Viral Kidney Diseases
Parvovirus B19 (PVB19)
Epidemiology
Pathology
Pathogenesis
Presentation
Management
Herpes Viruses
Cytomegalovirus (CMV)
Epidemiology
Pathology
Pathogenesis
Presentation
Management
Adenovirus
Epidemiology
Pathology
Presentation
Management
BK-Virus (BKV)
Epidemiology
Pathology
Presentation
Management
Coronavirus
COVID-19
Epidemiology
Pathology
Pathogenesis
Presentation
Management
Hepatitis B Virus (HBV)
Epidemiology
Pathology
Pathogenesis
Presentation
Management
Outcome
Hepatitis C Virus (HCV)
Epidemiology
Pathology
Pathogenesis
Presentation
Evaluation
Management
Outcomes
Viral Hemorrhagic Fevers
Dengue Virus
Yellow Fever
Ebola Virus
Hantavirus
Congo-Crimean Hemorrhagic Fever (CCHF)
Rift Valley Fever Virus (RVFV)
Marburg Virus
Argentine Hemorrhagic Fever (AHF)
HIV-Associated Nephropathies
Pathology
Pathogenesis
Presentation and Outcomes
References
28 Sickle Cell Nephropathy in Children
Introduction
Pathogenesis and Pathology of Sickle Cell Nephropathy
Glomerular Disease
Glomerular Disease Pathogenesis
Glomerular Pathology in SCD
Tubulointerstitial Disease
Defective Urinary Concentrating Mechanisms
Alterations in Potassium and Acid-Base Homeostasis
Papillary Necrosis
Clinical Features and Treatment of SCN
Glomerular Disease
Hyperfiltration
Albuminuria
Hypertension
Tubulointerstitial Disease
Hyposthenuria, Enuresis, and Nocturia
Hematuria and Papillary Necrosis
Medullary Carcinoma
Acute Kidney Injury (AKI)
Chronic Kidney Disease (CKD)
Renal Function Measurements and Imaging Findings
Anemia in SCD Patients with CKD
Renal Replacement Therapy
Prognosis
Risk Factors for CKD Progression
Albuminuria
AKI
Hemolysis
Genetic Factors
Dialysis and Renal Transplantation Outcomes
Sickle Cell Trait
Conclusions
References
29 The Kidney in Type I Diabetes
Introduction
Natural History of Diabetic Kidney Disease
DKD Manifestations in Youth with T1D
Pathogenesis
Risk Factors
Glycemic Control
Other Risk Factors
Screening and Diagnosis
New Biomarkers
Prevention and Treatment
Glycemic Control
Additional Treatment Strategies
Other Interventions
Conclusions
References
30 The Kidney in Metabolic Syndrome
Introduction
Definitions of MS in Children
Effect of Cardiometabolic Parameters on the Kidney
Mechanisms of Kidney Damage
Obesity-Induced Glomerulopathy
Epidemiological Evidence Linking Childhood MS to Kidney Outcomes
MS-Related Kidney Outcomes in Special Populations
Children with Low Birth Weight and/or Prematurity
Preexisting-CKD and Kidney Transplantation
Glomerular Disease
Renal Complications of Type 2 Diabetes Mellitus in Children and Adolescents
The Effect of Nontraditional Cardiometabolic Factors on Kidney Outcomes
Nonalcoholic Fatty Liver Disease (NAFLD)
Uric Acid
Early Biomarkers of Kidney Injury
Evaluation of Children with MS for Kidney Outcomes
Treatment of MS-Induced Kidney Injury
References
31 Renal Manifestations of Metabolic Disorders in Children
Introduction
Congenital Diseases of Glycosylation
Diseases of Purine and Pyrimidine Metabolism and Urate Transport
Diseases of the Purine Savage Pathway
Diseases of De Novo Purine Biosynthesis
Diseases of Purine Breakdown
Diseases of De Novo Pyrimidine Synthesis
Inherited Defects of Uric Acid Transport
Lecithin-Cholesterol Acyl Transferase Deficiency
Lysinuric Protein Intolerance
References
32 The Kidney in Methylmalonic Acidaemia
Synonyms
Introduction
Clinical Symptoms and Biochemical Markers of Kidney Disease in MMA
Pathophysiology of Kidney Disease in MMA
Renal-Related Complications in MMA
Treatment Options
Other Defects in the Cobalamin Metabolism
References
33 The Kidney in Mitochondrial Diseases
Introduction
Mitochondrial DNA Defects Associated with Kidney Disorders
Nuclear-Encoded Mitochondrial Kidney Disorders
Coenzyme Q10 Deficiencies and Related Nephropathies
COQ2 Nephropathy
COQ6 Nephropathy
PDSS1 and PDSS2 Nephropathies
COQ8B Nephropathy
COQ9 Nephropathy
Other Nuclear-Encoded Mitochondrial Disorders Associated with Renal Involvement
Disorders of OXPHOS Subunits and Assembly Factors
Mitochondrial DNA Maintenance Defects
Disorders of Mitochondrial Translation
Defects of Mitochondrial Lipid Membranes and Dynamics
Disorder of Iron-Sulfur Cluster Biosynthesis
Other Disease Mechanisms
Approach to Diagnosis of Mitochondrial Kidney Disease
Management and Treatment
Cross-References
References
34 Fabry Disease
Pathophysiology and Genetics
Clinical Manifestations
Neuropathic Pain and Gastrointestinal Symptoms
Angiokeratomas
Eyes and Ears
Kidney
Heart
Central Nervous System (CNS)
Diagnosis
Treatment
General Remarks
Pain and Gastrointestinal Symptoms
Skin
Eyes and Ears
Kidney
Heart
CNS
Enzyme Replacement Therapy
Chaperone Therapy
References
35 Hyperoxaluria
Introduction
Definition
Primary Hyperoxalurias
Metabolic Defects
Genetic Analysis
Primary Hyperoxaluria Type 1
Pathophysiology
Epidemiology
Diagnosis and Outcomes
Diagnosis
Outcome
Treatment: Supportive Measures
Dialysis
Transplantation
Treatment: RNA Interfering Agents
Treatment: Future Developments
Primary Hyperoxaluria Type 2
Pathophysiology
Genetics
Clinical Presentation
Diagnosis
Treatment and Outcomes
Primary Hyperoxaluria Type 3
Pathophysiology
Genetics
Clinical Presentation
Diagnosis
Treatment and Outcomes
Secondary Hyperoxalurias
Enteric Hyperoxaluria
Abuse Intake of Oxalate Precursors
Patients with ESKD
Food-Induced Secondary Hyperoxaluria
Management
Conclusion
References
Part V: Renal Tubular Disorders
36 Pediatric Fanconi Syndrome
Pathophysiology
Receptor-Mediated Endocytosis
Sodium-Dependent Reabsorption
Signs and Symptoms
Growth Faltering
Polyuria, Polydipsia, and Dehydration
Generalized Aminoaciduria
Glucosuria
Hypophosphatemia
Metabolic Acidosis
Sodium and Potassium Losses
Hypercalciuria
Hyperuricosuria
Low-Molecular-Weight Proteinuria
Decreased Urinary Excretion of Osteopontin and Uromodulin
Causes of FS
Hereditary Causes of Fanconi Syndrome
Cystinosis
Dent Disease
Lowe Syndrome
Mitochondrial Diseases
Enoyl-Coenzyme A Hydratase/L-3-Hydroxyacyl-Coenzyme A Dehydrogenase (EHHADH) Deficiency
Galactosemia
Hereditary Fructose Intolerance
Glycogen Storage Disease Type I
Fanconi-Bickel Syndrome
Tyrosinemia Type I
Wilson Disease
Lysinuric Protein Intolerance [100-102]
Microvillous Inclusion Disease
Maturity-Onset Diabetes of the Young (MODY)
Type IIa Sodium/Phosphate Cotransporter (NaPi-IIa) Deficiency
Arthrogryposis-Renal Dysfunction-Cholestasis (ARC) Syndrome
Idiopathic Fanconi Syndrome
Acquired Forms of Fanconi Syndrome
Endogenous Causes
Exogenous Causes
Drugs
Other Chemical Compounds
Heavy Metals
Therapy
References
37 Cystinosis
Introduction
Overview
History
The Basic Defect
Pathology
Genetics
The CTNS Gene
Clinical Aspects
Cystinosis Variants
Early Clinical Manifestations
Renal Tubular Fanconi Syndrome with Rickets
Glomerular Damage
Growth Impairment
Ocular Involvement
Hypothyroidism
Cognition and Psychological Aspects
Other Clinical Findings
Diagnosis
Postnatal Diagnosis
Prenatal Diagnosis
Heterozygote Detection
Differential Diagnosis
Therapy
Replacement of Renal Losses
Other Symptomatic Treatments
Renal Replacement Therapy and Kidney Transplantation
Oral Cysteamine Therapy
Cysteamine Eyedrops
Other Therapeutic Considerations
Hematopoietic Stem Cell Transplantation
Cystinosis in Adults
Growth and Appearance
Myopathy
Pancreatic Involvement
Hypogonadism
Central Nervous System Involvement
Ocular Findings
Other Complications
Death
Cross-References
References
38 Renal Tubular Acidosis
Introduction
Historical Development of the Classification of RTA
Physiology of Acid Secretion
HCO3- Reabsorption
Ammonia Generation and Recycling
Distal Tubular H+ Secretion
Proximal Renal Tubular Acidosis
Pathophysiology
Renal Fanconi Syndrome
Etiology
Hereditary Isolated pRTA
Diagnosis
Treatment
Distal Renal Tubular Acidosis (Type I)
Pathophysiology
Pathophysiological Consequences
Bone Disease
Hypercalciuria and Nephrocalcinosis
Hypokalemia
Salt Wasting
Impaired Ammonia Excretion
Etiology/Genetics
Genotype-Phenotype Correlation
Sensorineural Deafness
Hemoglobinopathy
Amelogenesis Imperfecta
Molecular Aspects of Distal Renal Tubular Acidosis
SLC4A1
ATP6V1B1 and ATP6V0A4
FOXI1
WDR72
Other Genes
Secondary dRTA
Incomplete Distal Renal Tubular Acidosis
Diagnosis
History and Examination
Biochemistry: Blood
Biochemistry: Urine
Urine pH
Urinary Anion Gap
Urinary pCO2
Stimulation Tests of Urinary Acidification
The Short Ammonium Chloride Test
The Prolonged Ammonium Chloride Test
Furosemide Testing
Furosemide + Fludrocortisone Testing
Other Urine Abnormalities
Imaging
Genetic Testing
Treatment
Mixed Proximal and Distal Renal Tubular Acidosis (Type III)
Hyperkalemic Renal Tubular Acidosis (Type IV)
Pathophysiology
Aldosterone Deficiency
Aldosterone Resistance
Pseudohypoaldosteronism Type 1 (PHA1)
Pseudohypoaldosteronism Type 2 (PHA2 or Gordon Syndrome)
Acquired Type IV RTA
Treatment
References
39 Aminoaciduria and Glycosuria in Children
Synonyms
Introduction
Aminoaciduria
General Characteristics of Tubular Amino Acid Transport
Specificity and Classification of Amino Acid Transport Systems
Classification of Amino Acid Transport Systems by Chemical Properties/Substrate Specificity
Classification of Amino Acid Transport Systems by Sequence Homology/Structural Features
Hereditary Aminoacidurias
Cationic Aminoaciduria
Neutral Aminoaciduria
Iminoaciduria and Glycinuria
Dicarboxylic Aminoaciduria
β-Aminoaciduria
Glycosuria
General Characteristics of Renal Glucose Transport
Molecular Biology of Na+-Glucose Cotransporters
Molecular Biology of Facilitative Glucose Transporters
Hereditary Glycosuria
Familial Renal Glycosuria
Fanconi-Bickel Syndrome
Cross-References
References
40 Renal Hypophosphatemia
Introduction
Phosphate Homeostasis
Regulators of Phosphate Homeostasis
Hypophosphatemic Disorders
Clinical, Biochemical, and Radiographic Manifestations Including Differential Diagnosis
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), McCune-Albright Syndrome (MAS), and Epidermal Neavi
Hypophosphatemic Disorders with Normal or Suppressed FGF23 Activity
HHRH (SLC34A3 Mutation)
Hypophosphatemia and Nephrocalcinosis (SLC34A1 Mutation, OMIM#612286)
Osteoglophonic Dysplasia (OMIM#166250)
Nephrolithiasis and Osteoporosis Associated with Hypophosphatemia
Fanconi Syndrome
Iatrogenic Phosphate Wasting
Treatment of XLH
Phosphate and Active Vitamin D Metabolites (Children and Adults)
In Children
In Adults
Burosumab (Children and Adults)
Burosumab in Children with XLH
Burosumab in Adults with XLH
Adjunctive Therapies
Growth Hormone
Calcimimetics
Surgical Care and Dental Care
Expected Outcomes
Treatment of Other Forms of Hypophosphatemic Rickets
References
41 Inherited Disorders of Sodium and Potassium Handling
Bartter Syndromes
Introduction
Antenatal Bartter Syndrome
Genetics
Clinical Manifestations
Differential Diagnosis
Pathophysiology
Treatment
Transient Antenatal Bartter Syndrome (tBS)
Genetics
Clinical Manifestations
Pathophysiology
Treatment
Antenatal Bartter Syndrome with Sensorineural Deafness
Genetics
Clinical Manifestations
Pathophysiology
Treatment
Classic Bartter Syndrome
Genetics
Pathophysiology
Clinical Manifestations
Differential Diagnosis, Unusual Associations, and Pseudo-Bartter Syndromes
Treatment
Gitelman Syndrome
Genetics
Pathophysiology
Clinical Manifestations
Phenotype Variability and Potential Severity of GS
Blood Pressure in GS: Effect of the Carrier State
Differential Diagnosis
Treatment
Pseudohypoaldosteronism Type I
Clinical and Biochemical Features
Pathophysiology and Genetics
Treatment and Prognosis
References
42 Inherited Disorders of Renal Magnesium Handling
Introduction/Physiology
Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis
Gitelman Syndrome
EAST/SeSAME Syndrome
Isolated Dominant Hypomagnesemia 1
Isolated Dominant Hypomagnesemia 2
Isolated Recessive Hypomagnesemia
Hypomagnesemia with Secondary Hypocalcemia
Hypomagnesemia, Refractory Seizures, and Mental Retardation 1
Hypomagnesemia, Refractory Seizures, and Mental Retardation 2
HNF1B Nephropathy
Transient Neonatal Hyperphenylalaninemia
Mitochondrial Hypomagnesemia
Management of Hypomagnesemia/Magnesium Deficiency
References
43 Inherited Disorders of Renal Calcium Handling
Calcium Physiology
Disturbances of Calcium Homeostasis
Hypercalciuria
Hypocalcemia
Autosomal Dominant Hypocalcemia
Hypercalcemia
Hypercalcemia with Inappropriately High PTH
Hypercalcemia with Suppressed PTH and Inappropriately High 1,25-(OH)2-Vitamin D3
References
44 Inherited Disorders of Water Handling
Introduction
Physiology of Urine Concentration, Including Vasopressin-Regulated Water Permeability
Short-Term Regulation of Water Reabsorption in Collecting Duct
Long-Term Regulation of Water Reabsorption in Collecting Duct
Alternative Signaling Pathways
Congenital Nephrogenic Diabetes Insipidus
Clinical Presentation
Diagnostic Procedures
Secondary Nephrogenic Diabetes Insipidus
Acquired Nephrogenic Diabetes Insipidus
Nephrogenic Diabetes Insipidus: Genetics
X-Linked Nephrogenic Diabetes Insipidus: Mutations in AVPR2
Nephrogenic Syndrome of Inappropriate Antidiuresis
Genotype-Phenotype Correlations in X-Linked NDI?
The Autosomal Recessive and Autosomal Dominant Forms of Nephrogenic Diabetes Insipidus: Mutations in the Aquaporin-2 Water Cha...
Differential Diagnosis between the X-Linked and the Autosomal Forms of NDI
Nephrogenic Diabetes Insipidus in Females
Nephrogenic Diabetes Insipidus: Treatment
Conventional Treatment
Therapeutic Strategies for Treatment of X-Linked NDI
Therapeutic Strategies for Treatment of Autosomal NDI
Therapeutic Strategies for NSIAD
References
45 Pediatric Tubulointerstitial Nephritis
Introduction
Structure and Function of the Tubulointerstitial Compartment
Pathophysiology of TIN
Pathogenesis
Proteinuria-Induced Tubular Cell Injury
Tubulointerstitial Fibrosis Development
Chronic Hypoxia in Fibrosis
Epidemiology
Pathology
Etiology
Drug-Induced TIN
DRESS Syndrome
Secondary Immune Acute TIN
Systemic Lupus Erythematosus (SLE)
Sjogren Syndrome
TINU
Inflammatory Bowel Disease (IBD)
Kawasaki Disease (KD)
Allograft Nephropathy
IgG4-Related Kidney Disease
Toxic Nephropathy
Aristolochic Acids
Old and Novel Anti-Cancer Drugs
Infection Associated TIN
Leptospira
Group A Streptococcus
TIN of Unknown Etiology
Mesoamerican Nephropathy
Genetic Causes of Tubulointerstitial Diseases
Clinical Presentation
Urinary Biomarkers
Diagnostic Approach
Treatment
Prognosis
Cross-References
References
Part VI: Omeostasis
46 Sodium and Water Disorders: Evaluation and Management
Water Homeostasis
Hyponatremia
Pathogenesis
Diagnosis
SIAD
Cerebral Salt Wasting Syndrome (CSW)
Hospital-Acquired Hyponatremia
Consequences of Hyponatremia and Hyponatremic Encephalopathy
Treatment of Hyponatremic Encephalopathy
Cerebral Demyelination Complicating the Correction of Hyponatremia
Therapies for Hyponatremia
Hypernatremia
Pathogenesis
Diagnosis
Diabetes Insipidus
Clinical Manifestations
Treatment
References
47 Potassium Disorders: Evaluation and Management
Potassium Homeostasis
Regulation of Internal Potassium Balance
Plasma Potassium Concentration
Hormones
Acid-Base Balance
Other Factors
Regulation of External Potassium Balance
Renal Handling of Potassium
Glomerular Filtration
Proximal Tubule
Thick Ascending Limb of the Loop of Henle (TALH)
Distal Nephron
Potassium Secretion
Potassium Absorption
Developmental Regulation of Distal Potassium Transport
Renal Response to Dietary Potassium
Hormones
Circadian Control of Renal Potassium Excretion
Contribution of the Gastrointestinal Tract
Disorders in Potassium Balance
Hyperkalemia
Altered Internal Balance
Altered External Balance
Causes of Hyperkalemia
Evaluation of Hyperkalemia
Treatment of Hyperkalemia
Hypokalemia
Altered Internal Balance
Altered External Balance
Causes of Hypokalemia
Evaluation of Hypokalemia
Treatment of Hypokalemia
References
48 Clinical Use of Diuretics
Introduction
Diuretic Sites Along the Nephron
Proximal Tubule
Thick Ascending Limb of the Loop of Henle
Early Distal Convoluted Tubule
Late Distal Nephron (DCT2, CNT, CCD, MCD)
Aquaporin-Containing Segments: Collecting Duct and Proximal Tubule/Thin Descending Limb of the Loop of Henle.
Clinical Use of Loop Diuretics in States of Acute Volume Overload
Diuretics in Specific Clinical Settings
Acute Post-Infectious Glomerulonephritis (APSGN)
Nephrotic Syndrome
Chronic Congestive Heart Failure
Treatment of Shock in the PICU
Congenital Heart Surgery
Acute Lung Injury
Traumatic Brain Injury/Cerebral Edema
Ascites
Neonates
Chemotherapy Protocols
Kidney Transplantation
Prolongation of Urine Output in End-Stage Renal Disease
Nonrenal Applications of Acetazolamide
Diuretic Use in Calcium Nephrolithiasis
SGLT2 Inhibitors in Diabetic Nephropathy
Dosing and Pharmacokinetic Properties of Commonly Used Diuretics in Pediatrics (Table 2)
References
Part VII: Cystic Kidney Diseases and Related Disorders
49 Autosomal Dominant Polycystic Kidney Disease
Synonyms
Introduction
Genetics, Structure, and Function of Mutated Proteins
Pathophysiology of Kidney Cyst Formation
Structural Kidney Disease: Implications for Symptoms and Disease Progression
Renal Manifestations
Extrarenal Manifestations
Prenatal, Very Early Onset (VEO), and Severe ADPKD
Diagnostic Considerations
Prognosis
Treatment
Conclusion
Cross-References
References
50 Autosomal Recessive Polycystic Kidney Disease
Introduction
Epidemiology, Diagnosis, and Pathology
Genetics
Molecular Basis of Disease
Genotype-Phenotype Correlations
Atypical ARPKD and Phenocopy Disorders
Genetic Testing
Preimplantation Genetic Diagnosis (PGD)
Protein Function and Pathophysiology
Clinical Disease Course and Clinical Management
Perinatal Period
Kidney Disease
Biliary Tract Disease
Transplantation
Additional Features
Future Horizon
References
51 Renal Involvement in Tuberous Sclerosis Complex
Introduction
Genetics
Clinical Aspects and Treatment of TSC Renal Disease
General Clinical Aspects
Multidisciplinary Care
Chronic Kidney Disease
Hypertension
Specific Aspects Including Diagnosis, Surveillance, and Treatment of TSC Associated Renal Disease
Angiomyolipomata
Cystic Disease
TSC Polycystic Kidney Disease
TSC Microcystic Kidney Disease
TSC Focal Cystic Kidney Disease
TSC Cortical Cystic Kidney Disease
TSC Multicystic Kidney Disease
Practical Approach to Surveillance and Treatment
Cell Biology of TSC Renal Disease
Angiomyolipomata
Cystic Disease
Oncocytoma and Renal Cell Carcinoma
References
52 Nephronophthisis and Related Ciliopathies
Synonyms
Natural History of Nephronophthisis and Related Ciliopathies
Pathology and Histopathology
Molecular Genetics and Disease Mechanisms
NPHP1
NPHP2/Inversin
NPHP3
NPHP4
NPHP5
NPHP6/CEP290
NPHP7/GLIS2
NPHP8/RPGRIP1L
NPHP9/NEK8
ZNF423 and CEP164
WDR19/NPHP13, IFT172/NPHP17, and Other Genes Encoding Intraflagellar Transport (IFT) Proteins
ANKS6/NPHP16
CEP83/NPHP18
DCDC2/NPHP19
MAPKBP1/NPHP20
Animal Models
Extrarenal Manifestations of NPHP
Retinal Involvement (Senior-Loken Syndrome)
Cerebellar Vermis Hypoplasia (Joubert Syndrome)
Liver Fibrosis
Multi-organ Cystic Dysplasia with Severe Brain Malformations (Meckel Syndrome)
Cardiac Defects and Situs Inversus
Skeletal Defects
Bardet-Biedl Syndrome
Diagnosis
Laboratory Studies
Imaging
Molecular Genetic Diagnostics
Genetic Counseling
Differential Diagnosis
Prognosis and Therapy
Cross-References
References
53 Autosomal Dominant Tubulointerstitial Kidney Disease
Synonyms
Introduction
Epidemiology of ADTKD
Presentation of ADTKD
Clinical Characteristics
Chronic Kidney Disease
Urinary Concentration Defect and Enuresis
Hyperuricemia and Gout
Hypomagnesemia
Hypertension
Anemia
Imaging
Laboratory Studies
Genetic Testing
Pathology Findings
Differential Diagnosis
Specific Forms of ADTKD
ADTKD-UMOD Is Caused by Mutations in Uromodulin
Protein Function
Clinical Presentation
Pathophysiology
Diagnostic Testing
Therapeutic Approaches
ADTKD-MUC1 Is Caused by Mutations in Mucin-1
Protein Function
Clinical Presentation
Pathophysiology
Diagnostic Testing
Therapeutic Approaches
ADTKD-HNF1B Is Caused by Mutations in Hepatocyte Nuclear Factor 1β
Protein Function
Clinical Presentation
Pathophysiology
Diagnostic Testing
Therapeutic Approaches
ADTKD-REN Is Caused by Mutations in the Gene Encoding Renin
Protein Function
Clinical Presentation
Pathophysiology
Diagnostic Testing
Therapeutic Approaches
ADTKD-SEC61A Is Caused by Mutations in SEC61A
Protein Function
Clinical Presentation
Pathophysiology
Diagnostic Testing
Therapeutic Approaches
Treatment of ADTKD
Conclusion
Cross-References
References
Part VIII: Urinary Tract Disorders
54 Urinary Stone Disease and Nephrocalcinosis
Synonyms
Epidemiology of Childhood Urinary Stone Disease
Nephrocalcinosis
Risk Factors for Urinary Stone Disease
Idiopathic Hypercalciuria
Hyperoxaluria
Hypocitraturia
Hyperuricosuria
Structural Malformations of the Urinary Tract and Urinary Tract Infections
Drug- and Toxin-Induced Urinary Stones
Clinical Conditions Associated with Urinary Stone Disease
Mechanism of Stone Formation
Genetics of Urinary Stone Disease
Family Studies
Twin Studies
Genealogy Studies
Genome-Wide Association Studies
Rare Monogenic Causes of Urinary Stone Disease
Clinical Features
Diagnostic Evaluation
Management of Acute Urinary Stone Events
Prevention of Urinary Stone Recurrence
Fluid Intake
Dietary Considerations
Pharmacological Treatment
Cross-References
References
55 Urinary Tract Infections in Children
Introduction and Background
Clinical Presentation
UTI Etiology
Cystitis Pathogenesis
Pyelonephritis Pathogenesis
Host Immune Response
Mechanisms of Kidney Scarring
Diagnosis of Urinary Tract Infection
Differentiating Upper from Lower Urinary Tract Infections
Treatment of an Acute UTI
Imaging
Ultrasonography
Voiding Cystourethrography
Renal Scintigraphy
Other Imaging Modalities
Antibiotic Prophylaxis
Antibiotic Prophylaxis and Risk of UTIs in Different Urological Disorders
Additional Strategies to Prevent UTI
Circumcision
Cranberry
Probiotics
Constipation
Surgical Correction of Vesicoureteral Reflux
Future Clinical UTI Sequelae
Conclusions
Cross-References
References
56 Vesicoureteral Reflux in Children
Synonyms
Introduction
Incidence and Prevalence
Embryology and Anatomy
Grading of VUR
Natural History of VUR
Clinical Presentation of Primary VUR
UTI and VUR
CAKUT/Antenatal Hydronephrosis and VUR
Siblings and VUR
Bladder Bowel Dysfunction
VUR and Renal Scarring
Mechanism of Renal Injury
Risk Factors for Renal Scarring
Recurrent UTI
Vesicoureteral Reflux
Delay in Treatment
Patient Age
Complications of Renal Scarring
Proteinuria
Hypertension
Chronic Kidney Disease (CKD)
Complications in Adults with VUR Diagnosed in Childhood
Genetics of VUR, UTI, and Renal Scarring
Diagnosis of VUR and Renal Injury
Ultrasonography
Voiding Cystourethrogram
Technetium 99 m Dimercaptosuccinic Acid Renal Scan (DMSA renal scan)
Magnetic Resonance Imaging (MRI)
Biomarkers of Renal Injury
Medical Management of VUR
Antimicrobial Prophylaxis
Bladder Bowel Dysfunction
Hypertension and/or Proteinuria
Surgical Management of VUR
Endoscopic Management
Laparoscopic Ureteral Reimplantation
Open Surgical Techniques
Published Guidelines on UTI/VUR
Conclusion
Cross-References
References
57 Pediatric Obstructive Uropathy
Synonyms
Introduction
Epidemiology
Definition of Obstruction
Pathophysiology
Animal Models
Tubular Injury After Ureteral Obstruction
Interstitial Inflammation After Ureteral Obstruction
Interstitial Fibrosis After Ureteral Obstruction
Glomerular, Vascular and Hemodynamic Changes After Ureteral Obstruction
Renal Injury in Neonatal Ureteral Obstruction
Genetics
Genes and Signaling Pathways in Human and Mice
Genetics and the Renin-Angiotensin System
Classification
Diagnosis
Prenatal Diagnosis
Fetal Urine Analysis
Postnatal Diagnosis
Imaging and Nuclear Medicine Studies
Ultrasonography
Voiding Cystourethrogram
Magnetic Resonance Imaging
Diuretic Renography
Other tracers, outside of 99mTc-MAG-3 can also be used
Excretory Urography and Pressure Perfusion Studies
Ureteropelvic Junction Obstruction
Development of the Ureter and the Ureteral Peristaltic Machinery
Genetics of Ureteropelvic Junction Obstruction (UPJO)
Clinical Presentation in UPJO
Management of UPJO
Biomarkers in UPJO
Long-Term Follow-Up in UPJO
Ureterovesical Junction Obstruction
Pathogenesis of UVJO
Clinical Presentation in UVJO
Diagnosis and Management of UVJO
Megacystis Microcolon Intestinal Hypoperistalsis Syndrome
Prune Belly Syndrome (Eagle-Barratt Syndrome)
Posterior Urethral Valves (PUV)
Development of the Bladder and Urethra
Pathophysiology of PUV
Genetics of PUV
Clinical Presentation and Diagnosis
Management of PUV
Prenatal Management of PUV
Postnatal Management of PUV
References
58 Bladder Disorders
Background
Definitions and Terminology
Tools of Investigation
Development of LUT Function
Bladder-Bowel Interaction
Conditions
Detrusor Overactivity
Dysfunctional Voiding
Severe Bladder-Bowel Dysfunction
Neurogenic Bladder
Special Conditions
Evaluation
The Incontinent Child
The Child with Abnormal Voiding Frequency, Voiding Difficulties or Urine Retention
Other Children Needing Evaluation of Bladder Function
Treatment
Overactive Bladder
Dysfunctional Voiding
Neurogenic Bladder or Severe Bladder-Bowel Dysfunction
Special Conditions
References
59 Enuresis
Introduction
Definitions
Enuresis Subtypes
Reduced Bladder Capacity
Nocturnal Polyuria
Epidemiology
Prevalence
Comorbidities and Consequences
Constipation, Fecal Incontinence, and Urinary Tract Infection (BBD)
Behavioral Disorders
Sleep-Disordered Breathing
Consequences
Pathogenesis
Sleep/Circadian Rhythm Disturbances
Circadian Rhythms
Reduced Bladder Reservoir Function
Nocturnal Polyuria
Genetic Factors
Evaluation
History Taking
Physical Examination and Other Diagnostic Procedures
Diaries
Frequency-Volume Charts
Home Recording of Nocturnal Urine Volume
Other Tools
Treatment
First-Line Treatment
Treatment Resistance
References
60 Pediatric Renal Tumors
Introduction
Epidemiology
Radiology
Abdominal Radiography
Ultrasonography
Computed Tomography
Magnetic Resonance Imaging
Nuclear Medicine
Imaging Features of Specific Tumor Types
Wilms Tumor
Nephrogenic Rests
Mesoblastic Nephroma
Clear Cell Sarcoma
Rhabdoid Tumor
Multilocular Cystic Renal Tumor
Renal Cell Carcinoma
Renal Medullary Carcinoma
Screening and High-Risk Populations
Staging Pediatric Renal Tumors
Pathology
Wilms´ Tumor (Nephroblastoma)
Nephrogenic Rests/Nephroblastomatosis
Genetics of Wilms Tumor/Nephrogenic Rests/Nephroblastomatosis and Syndromic Associations
Congenital Mesoblastic Nephroma
Clear Cell Sarcoma of the Kidney
Malignant Rhabdoid Tumor of the Kidney
Treatment
Surgery
Medical Therapy
Targeted Therapy
Radiation
Survivorship
References
61 Onconephrology
Introduction
Nephrology Evaluation of the Oncologic Patient
Acute Kidney Injury
AKI Due to Hypoperfusion
Intrinsic AKI
Obstruction-Induced AKI
Medication-Induced AKI
Glomerular Injury from Chemotherapy
Tubular Injury from Chemotherapy
Tumor Burden and Resection
Radiation-Induced Injury
Tumor Lysis Syndrome
AKI Associated with HSCT
Sinusoidal Obstruction Syndrome
Thrombotic Microangiopathy
Graft-Versus-Host Disease
Proteinuria and Nephrotic Syndrome
Dialysis in AKI
Drug Dosing in CKD and ESKD
Electrolyte and Volume Disturbances
Hyponatremia
Hyperkalemia
Hypokalemia
Hypomagnesemia
Hypercalcemia
Hyperphosphatemia and Hypophosphatemia
Volume Status
Infection
Chronic Kidney Disease
Growth
Nutrition
Bone and Mineral Disease
Anemia
Maintenance Dialysis
Kidney Transplantation
Conclusion
Cross-References
References
Part IX: Hypertension
62 Pathophysiology and Epidemiology of Hypertension in Children
Introduction
Mechanisms of Blood Pressure Regulation
Cardiac Output and Systemic Vascular Resistance
Changes in Systemic Vascular Resistance and Vascular Walls
Sympathetic Nervous System and Central Nervous System
Renin-Angiotensin-Aldosterone System
Aldosterone
Dopamine
Natriuretic Peptides
Endothelin-1
Other Vasoactive Molecules
Circadian Rhythm
The Gut Microbiome
Renal Mechanisms
Primary Hypertension
Genetic and Epigenetic Influences
Influence of Birth Weight and Perinatal Factors
Sympathetic Nervous System Activation
Obesity
Dietary Influences
Uric Acid
Physical Activity and Sleep
Breastfeeding
Environment
Secondary Hypertension
Mendelian Forms of Hypertension
Other Genetic Forms of Hypertension
Hypertension in Renovascular Disease
Hypertension in Acute Kidney Injury and Chronic Kidney Disease
Hypertension in Dialysis Patients
Hypertension After Renal Transplantation
Hypertension in Coarctation of the Aorta
Hypertension in Vasculitis
Hypertension in Endocrine Diseases
Hypertension in Pulmonary Diseases (BPD, Sleep Apnea)
Hypertension in Neurologic Disorders
Pregnancy-Induced Hypertension and Preeclampsia
Drug-Induced Hypertension
Normative Blood Pressure Values in Children and Adolescents
Casual Blood Pressure Measurement
Ambulatory Blood Pressure Monitoring
Home Blood Pressure Measurement
Definition of Hypertension in Children
Casual Blood Pressure Measurement
Ambulatory Blood Pressure
Epidemiology of Hypertension
Prevalence of Hypertension in General Population
Prevalence of Hypertension in Special Population
Prevalence of White Coat Hypertension
Prevalence of Masked Hypertension
Conclusion
Cross-References
References
63 Evaluation and Management of Hypertension in Children
Introduction
Definitions and Classification
Blood Pressure Measurement
Ambulatory Blood Pressure Monitoring
Other Approaches to Blood Pressure Assessment
Blood Pressure During Exercise
Diagnostic Evaluation
Evaluation for Secondary Causes
Renal and Monogenic Causes of Hypertension
Cardiac Causes of Hypertension
Pheochromocytoma and Paraganglioma
Endocrine Disorders
Other Causes of Secondary Hypertension in Children
End-Organ Damage and Stratifying the Risk of Downstream Sequelae
Therapy of Hypertension
Non-pharmacologic
Pharmacologic Therapy
Acute Severe Hypertension
Pheochromocytoma and Paraganglioma
Unanswered Questions/Research Needs
Cross-References
References
64 Renovascular Hypertension in Children: Evaluation and Management
Introduction
Clinical Presentation
Etiology
Fibromuscular Dysplasia
Syndromic RAS
Takayasu Arteritis
Is It Fibromuscular Dysplasia or Takayasu Arteritis?
Vascular Involvement
Aneurysmal Disease
Diagnostic Imaging
Ultrasound Imaging (Fig. 3)
Renal Scintigraphy
Magnetic Resonance Angiography (MRA) and Computed Tomography Angiography (CTA)
Digital Subtraction Angiography (DSA (Figs. 5 and 6)
Renal Vein Renin Sampling
Treatment
Medical Treatment
Angioplasty
Embolization
Surgery
Sympathetic Renal Denervation (SRD)
Outcome
References
Part X: Acute Kidney Injury
65 Pathogenesis of Acute Kidney Injury
Introduction
Phases of Acute Kidney Injury
Renal Hemodynamics
Renin-Angiotensin System
Arachidonic Acid
Adenosine
Endothelin
Nitric Oxide
Alterations in Microvasculature
Nephronal Factors
Tubule Segment Susceptibility to Injury
Intratubular Obstruction and Backleak
Cellular and Metabolic Alterations
Adenine Nucleotide Metabolism
Reactive Oxygen Molecules
Intracellular Calcium
Phospholipids and Lipases
Disruption of Tubule Cell Architecture
Cell Death
Necrosis and Apoptosis
Autophagy
Inflammatory Response
Sepsis-Induced AKI
Genetic Susceptibility
Biomarkers
Repair Mechanisms
Heat Shock Proteins
Regeneration: Growth Factors
Regeneration: Stem Cells
Long-Term Sequelae
Conclusion
References
66 Evaluation and Management of Acute Kidney Injury in Neonates
Synonyms
Introduction
Acute Kidney Injury in the NICU: Scope of the Problem
AKI Definitions and Biomarkers
High Risk Conditions
Prematurity and Low Birth Weight (LBW)
Term Infants
Perinatal Asphyxia and Hypoxic-Ischemic Encephalopathy (HIE)
Necrotizing Enterocolitis (NEC)
Patent Ductus Arteriosus (PDA)
Congenital Heart Disease and Cardiac Surgery-Associated AKI (cs-AKI)
Congenital Diaphragmatic Hernia (CDH)
Extracorporeal Membrane Oxygenation (ECMO)
Surgical Procedures
Mechanisms
Medication-Induced AKI
Vascular/Ischemic Injury
Renal Vascular Thrombosis
Twin-to-Twin Transfusion Injury
Renal Cortical Necrosis
Evaluation
History
Physical Examination
Fluid Balance
Other Innovations in Neonatal Intensive Care
Management
AKI Identification, Mitigation, and Prevention
Medical Management of AKI Complications
Electrolyte and Mineral Homeostasis
Acid-Base Balance
Therapeutics
Methylxanthines (Theophylline, Aminophylline, and Caffeine)
Theophylline and Aminophylline in Babies with Perinatal Asphyxia
Caffeine Use in Preterm Infants
Diuretics
Kidney Replacement Therapies (KRT)
Peritoneal Dialysis
Hemodialysis
Continuous Kidney Replacement Therapy
Specialized Equipment
Kidney Replacement Therapies in Inborn Errors of Metabolism
Distant Organ Effects
Long-Term Outcomes and Future Directions
Cross-References
References
67 Evaluation and Management of Acute Kidney Injury in Children
Introduction
Definition
The Kidney Disease: Improving Global Outcomes (KDIGO) AKI Definition
Challenges with AKI Definition
Epidemiology
Incidence, Disease Patterns, and Risk Factors
Short-Term Outcomes
Long-Term Outcomes
Etiology and Approach to Evaluation
General Concepts and History-Taking
Physical Examination
Laboratory Investigations
Importance of Considering Clinical Setting During AKI Evaluation
Evaluating Serum Creatinine Rise: Distinguishing Adaptive Renal Response from True Tubular Injury
AKI Injury Biomarkers
Management
Prevention
Fluid Management
Electrolyte Management
Pharmacological Therapy
Kidney Replacement Therapy
Modality Choice
Intermittent Hemodialysis
Peritoneal Dialysis
Continuous Kidney Replacement Therapy
Vascular Access
Machines and Hemofilters
Dialysis and Replacement Fluid Solutions
Blood Flow, Solute Clearance, and Ultrafiltration
Anticoagulation
Complications
Nutrition
Drug Dosing
AKI Follow-Up
Conclusions
References
68 Nephrotoxins
Introduction
Types of Nephrotoxins
Pharmaceuticals
Naturally Occurring Nephrotoxins
Environmental Nephrotoxins
Mechanisms of Nephrotoxicity
Pseudo-nephrotoxicity
Indirect Nephrotoxicity
Vascular Complications
Glomerular Disease
Direct Tubular Toxicity
Acute Interstitial Nephritis
Osmotic Nephrosis
Crystalluria/Nephrolithiasis
Altered Electrolyte Handling
Specific Nephrotoxic Medications
Vancomycin
Aminoglycosides
Intravenous Contrast
Nonsteroidal Anti-inflammatory Drugs
Renin-Angiotensin-Aldosterone System Inhibitors
Prevention and Management
Conclusion
Cross-References
References
Part XI: Chronic Kidney Failure
69 Progression of Chronic Kidney Disease and Nephroprotection in Children
Introduction
Pattern and Timing of CKD Progression
Renal Physiology of Progressive CKD
Risk Factors for CKD Progression
Nonmodifiable Risk Factors
Underlying Kidney Disease and Genetic Disposition
Age at Attainment of Renal Mass Deficit
Fetal Programming
Growth
Major Modifiable Risk Factors in CKD
Hypertension
Proteinuria
Additional Contributing Factor
Nephroprotective Treatment Strategies
Treatment of the Underlying Disease
BP Control
Proteinuria Control
Additional Nephroprotective Treatment Options
Prevention of CKD Progression by Optimized CKD Treatment
Other Potential Treatment Options
Conclusions
References
70 Epidemiology and Management of Chronic Kidney Disease in Children
Introduction
Definition of CKD in Children and Measurement of Kidney Function
Incidence and Prevalence of CKD
Incidence and Prevalence of ESKD in Children
Etiology of CKD and ESKD in Children
Kidney Replacement Therapy Modalities
Epidemiology Surrounding Risk Factors for the Progression of CKD and CKD Management
Non-modifiable Risk Factors for the Progression of CKD to ESKD
Modifiable Risk Factors for the Progression of CKD to ESKD
Predicting the Risk of Progression of CKD
Complications of CKD
Cardiovascular Disease
Growth
Mineral Bone Disease
Neuro-Cognition
Quality of Life
Transition of Children with CKD or ESKD into Adulthood
Mortality in Children with ESKD
Conclusion
References
71 Nutrition, Growth, and Development
Introduction
Normal Growth and Development
Growth and Development in Chronic Kidney Disease
Evaluation of Growth, Development, and Nutritional Status in CKD
Assessing Linear Growth
Assessing Body Weight
Other Measures
Protein Energy Wasting (PEW)
Nutritional Requirements
Energy Requirements
Protein Requirements
Lipid Requirements
Bone Mineral Metabolism
Acid-Base and Electrolytes
Vitamins and Micronutrients
Nutrition Management
Oral Supplementation
Enteral Nutritional Support
Growth Hormone-Insulin Growth Factor (IGF)-I in CKD
Growth Hormone Therapy in Pediatric CKD
Neurocognitive Development
References
72 Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD)
Introduction: CKD-MBD in Pediatrics
Epidemiology
Pathophysiology of CKD-MBD
Normal Bone Development
Bone Structure
Role of Different Cell Types in Bone Structure and Function
Paracrine and Endocrine Functions of Bone Cells
Renal Bone Disease
The Bone Biopsy Procedure
Turnover
Mineralization
Volume
Linear Growth
Interaction Between Primary Kidney Disease and Renal Bone Disease
Autosomal Dominant Polycystic Kidney Disease
Primary Hyperoxaluria
Cystinosis
Other Genetic Syndromes
Bone Disease After Successful Kidney Transplantation
Evaluation of Renal Bone Disease in Children
Biomarkers
Bone Imaging
Cardiovascular Disease in CKD
Epidemiology of Cardiovascular Disease
Risk Factors for CVD
Assessment
Clinical Studies in Children
Pathophysiology of Vascular Calcification
CKD-MBD Management
Goals of Treatment:
Dietary Management of CKD-MBD
Phosphate Binders
Ca-Based P-binders
Ca-Free P-binders
Vitamin D Treatment
Native (Nutritional) Vitamin D Supplementation
Active Vitamin D Sterols
Calcimimetic Agents
Surgical Parathyroidectomy
Antiresorptive Therapies
Growth Hormone Therapy
Dialysis
References
73 Anemia in Chronic Kidney Disease
Synonyms
Introduction
Pathogenesis of Anemia in CKD
Normal Erythropoiesis
Hypoxia Stimulates Red Blood Cell Production
Dysregulated Erythropoiesis in CKD
Iron Is Required for the Synthesis of Hemoglobin
Hepcidin Regulates the Ferroportin-Based Movement of Iron
Definition of Anemia in Children with CKD
Evaluation and Treatment of Anemia
Symptoms of Anemia
Initial Diagnostic Evaluation of Anemia
Erythropoietin Levels
Laboratory Assessment of Iron Status
Recombinant Human Erythropoietin Therapy
Available Forms of rHuEPO
Epoetin
Darbepoetin Alfa
Continuous Erythropoietin Receptor Activator
ESA Dosing for Children
Dosing ESA in Children Compared to Adults
HIF Stabilizers
ESA Hyporesponsiveness
Anti-rHuEPO Antibodies
Red Blood Cell Transfusion
Iron Supplementation
Targets for Biomarkers of Iron Stores
Oral Iron Supplementation
Intravenous Iron Supplementation
Safety of Intravenous Iron
Emerging Routes of Iron Supplementation
Anemia after Successful Renal Transplantation
Clinical Outcomes
Evaluation and Prevention of PTA
Treatment of PTA
References
74 Assessment of Volume Status in Chronic Kidney Disease
Introduction
Consequences of Volume Overload
Consequences of Excessive Volume Depletion
Clinical Assessment of Volume Status
History and Physical Examination
Blood Pressure
Techniques to Assess Fluid Status
Bioimpedance Analysis (BIA)
Blood Volume Monitoring (HD Only)
Inferior Vena Cava Echography
Lung Ultrasound
N-Terminal Pro-brain Natriuretic Peptide (NT-proBNP)
Conclusions
Cross-References
References
75 Peritoneal Dialysis
Introduction
Principles of Peritoneal Solute and Water Transport
Choice of PD
Initiation of Peritoneal Dialysis and Dialysis Equipment
Initiation of Dialysis
Catheter Placement
Starting PD, Cyclers, and Equipment
Choice of PD Solutions
Prescription of Peritoneal Dialysis
Clinical Approach to the Peritoneal Transport
The Dialysis Dose, Kt/V Urea
The Peritoneal Equilibrium Test
Standardization of PET: Pre-PET Long Dwell
Standardization of Dwell Volume
Free Water Transport: Mini PET
Optimizing PD Prescription
Complications of PD
Infectious Complications
Noninfectious Complications
PD Membrane Transformation/EPS
Remote Patient Monitoring (RPM)
Outcomes
Outlook
References
76 Chronic Hemodialysis in Children
Introduction
Epidemiology of Pediatric Hemodialysis
Dialysis Initiation
Dialysis Modality Selection
Physiology of Hemodialysis
Technical Aspects of Hemodialysis
The Blood Circuit
Hemodialyzers
The Dialysis Fluid Circuit
Ultrafiltration Control
Vascular Access
Prevalence of Different Access Types Used Globally
CVL Types and Sites of Placement
AVF Formation
AVF Cannulation
Outcomes of AVFs and CVLs
Prescribing Hemodialysis and Special Considerations for Children
Anticoagulation for Hemodialysis
Hemodiafiltration
Definition of HDF
Modes of HDF
Requirements for HDF
The Concept of Back-Filtration
Potential Advantages of HDF over Conventional HD
HDF Studies in Adults
HDF Studies in Children
Optimization of the Convective Volume
Home Hemodialysis
HHD Definitions and Prescriptions
Patient Selection Criteria
Requirements for a HHD Program
Potential Advantages of HHD over Conventional HD
Risks and Complications Related to the Hemodialysis Procedure
Intradialytic Hypotension
Dialysis Disequilibrium Syndrome
Fever and Infection
Vascular Access Related Infection
Elevated Blood Pressure
Hemorrhage
Air Embolism
Water-Related Complications
Intradialytic Cramping
Long-Term Outcomes of Chronic Hemodialysis in Children
Cardiovascular Disease and Survival
Nutrition, Growth, and Development
Impaired Health-Related Quality of Life (QoL)
Other Long-Term Complications
Conclusion
References
77 Infant Dialysis
Introduction
Epidemiology
Number of Infants Initiating Chronic Dialysis
Primary Diagnoses and Comorbidities
The Ethics of Infant Dialysis
When to Start Dialysis
Choice of PD/HD
Peritoneal Dialysis
PD Catheters: Choice and Placement
PD Prescription
PD-Related Complications
Hemodialysis
HD Catheters
HD Prescription
HD-Related Complications
Growth and Nutrition
Protein and Energy and Requirements
Salt and Water
CKD-MBD
Long-Term Outcomes
Patient Survival and Causes of Death
Kidney Transplantation
Neurocognitive Outcomes
Conclusion
References
78 Adequacy of Dialysis
Introduction
Hemodialysis Adequacy
Overview
Urea Removal Indices
Urea Reduction Ratio (URR)
Single-Pool Kt/V (spKt/V)
Equilibrated Kt/V (eKt/V)
Standard Kt/V (stdKt/V)
Issues of Scaling Dialysis Dose to ``V´´
Normalized Protein Catabolic Rate (nPCR)
Residual Kidney Clearance
Is More HD Better?
Peritoneal Dialysis Adequacy
Overview
Small Solute Clearance
Clearance of Middle-Sized Molecules and Phosphate
Fluid Balance and Ultrafiltration
Clinical Correlates of PD Adequacy
The Role of Residual Renal Function
References
79 Renal Transplantation: Evaluation of Children and Donors
Introduction
Recipients
Primary Disease and Renal Transplantation
Evaluation of Native Kidneys and Urinary Tract Before Transplantation
Vascular Evaluation
CKD-Related Comorbidities and Risk Factors
Retransplantation
Living Donors
Genetics
ABO Incompatible
Posttransplant Monitoring of the Donor
The Deceased Donor
Pediatric Placement on a Deceased Donor List
Blood Group Issues
Immune Matching
Quality of the Kidney from the Deceased Donor Pool
Infectious Risk
Marginal Donors
Equity Versus Utility
Looking After Children
Determining the Suitability of a Deceased Donor Kidney for a Particular Recipient
Multiorgan Transplants
Summary
References
80 Renal Transplantation: Surgical and Perioperative Management
Introduction
Surgical Management
Back-Table Preparation of the Donor Kidney
Operative Technique in Older Children and Adolescents
Surgical Considerations in Young Children and Small Infants
Urologic Management
Posttransplant Management
Early Postoperative Management (Table 1)
Hemodynamics
Fluid and Electrolyte Management
Urine Output
Infection Surveillance and Prevention [18-20]
Anticoagulation
Posttransplant Complications
Acute Kidney Injury
Surgical Complications
Graft Thrombosis
Renal Artery Stenosis
Hemorrhage
Lymphocele
Urologic Complications
Urinary Leakage
Urinary Tract Obstruction
Peritoneal Fluid Accumulation
References
81 Renal Transplantation: Immunosuppression and Managing Allograft Rejection
Introduction
Classification of Immunosuppressive Agents
Induction Immunosuppressive Therapy
The Polyclonal Lymphocyte-Depleting Antibody Thymoglobulin
The Monoclonal IL-2 Receptor Antibody Basiliximab
Maintenance Immunosuppressive Therapy
The Calcineurin Inhibitors Ciclosporin and Tacrolimus
Therapeutic Drug Monitoring
Antiproliferative Agents
Mycophenolate Mofetil
Azathioprine
The Target of Rapamycin (TOR) Inhibitors Everolimus and Sirolimus
Glucocorticoids
Generic Immunosuppressive Drugs
Adherence to Immunosuppressive Medication
Diagnosis and Management of Allograft Rejection
Hyperacute Rejection
Acute Rejection
Acute Cellular Rejection
Acute Antibody-Mediated Rejection
Noninvasive Biomarkers of Acute Rejection
Therapy
Chronic Rejection or Chronic Allograft Dysfunction
Conclusions and Outlook
References
82 Recurrent Disease After Pediatric Kidney Transplantation
Diseases that Affect the Glomerular Microvasculature
Atypical Hemolytic Uremic Syndrome (aHUS)
Glomerular Diseases with Potential to Recur
FSGS
C3 Glomerulopathy (45%)
Membranous Nephropathy
MPGN Type 1
IgA Nephropathy
Other Glomerulonephritis (GN)
Non-glomerular Causes
Primary Oxalurias
Summary
References
83 Renal Transplantation: Infectious Complications
Introduction
Special Considerations in Pediatric Transplantation
Bacterial Infections
Urinary Tract Infection
Other Bacterial Infections
Viral Infections
Cytomegalovirus
Epstein-Barr Virus and PTLD
Varicella Zoster-Virus
BK Virus
Adenovirus
Common Respiratory Viruses
SARS-CoV-2
Fungal Infections
Candida spp
Aspergillus spp
Pneumocystis
Parasitic Infections
References
84 Renal Transplantation: Non-infectious Complications and Long-Term Outcome
Introduction
Short- and Medium-Term Complications
Hypertension
Dyslipidemia
Post-Transplantation Lymphoproliferative Disorder (PTLD)
Post-Transplant Diabetes Mellitus
Bone Disease Following Transplantation and Growth
Bone Health
Growth
Urologic Complications
Ureteral Obstruction
Dysfunctional Lower Urinary Tract
Urinary Tract Infections
Gastrointestinal Complications
Cosmetic Complications
Thrombotic Microangiopathy
Neurological Complications
Quality of Life
Peer and Family
Education and Employment
Cognitive Functioning
Late Outcome of Pediatric Transplantation
Late Graft Survival and Number of Transplants Over Time
Late Overall and Cardiovascular Mortality
Other Comorbidity
Cardiovascular Disease
Infections
Malignancies
Bone Disease and Motor Disabilities
Cognitive Functioning
Quality of Life
Social Outcomes
References
85 Ethical Issues in Pediatric Nephrology
Introduction
Overview of Principlism
Pediatric Surrogate Decision-Making: The Interface of the Principles of Respect for Autonomy, Beneficence, and Nonmaleficence
Best Interest Standard
The Harm Principle
Seeking State Intervention
Decision-Making in Special Populations in Pediatric Nephrology
Infants
Adolescents
Considerations of Justice
Justice and Resource Constraints
Caregiver Burden
Systemic Injustice
Health Practitioner Bias
Example: A Nonadherent Adolescent with Hypertension and Proteinuria
References
86 Drug Dosing in Abnormal Kidney Function in Children
Background
Renal Clearance
Drug Properties and Dosing in Abnormal Kidney Function in Children
Drug Clearance in Dialysis
Drug Removal During Intermittent Hemodialysis
Drug Removal and Dosing During Continuous Renal Replacement Therapies
Drug Clearance of CRRT Modalities : CVVHF > CVVHDF > CVVHD
Drug Removal by Peritoneal Dialysis
Nephrotoxicity
Conclusions
References
Part XII: Addendum
87 Normal Reference Values
Biochemistry*
Hematology*
Hormones and Nutritional Parameters*
Markers of Kidney Function*
Neonatology*
Renal Ultrasound Values
Rheumatology*
Serum Electrolytes and Blood Gases*
Urine Studies and Tubular Function*
References
Index