Pediatric Nephrology

Description

Over the course of the previous seven editions, Pediatric Nephrology has become the standard reference text for students, trainees, practicing physicians (pediatricians, nephrologists, internists, and urologists), subspecialists, and allied health professionals seeking information about children’s kidney diseases. It is global in perspective, reflecting the fact that the international group of editors are all acknowledged world experts.  The latest edition of this text is no different, providing a comprehensive, state-of-the-art overview on pediatric nephrology. Much like the previous edition, the latest edition reviews the most critical aspects of the field. Topics covered include developmental physiology and diseases, renal physiology and diagnostic approaches, glomerular disease, kidney involvement in systemic diseases, renal tubular disorders, homeostasis, cystic kidney disease and related disorders, urinary tract disorders, hypertension, acute kidney injury, and chronic kidney failure. Unlike the previous edition, however, the chapters in this edition now combine physiology, clinical management, and pathology for ease of use. The latest edition also includes a new section on the evaluation of different disorders that can have multiple etiologies, setting the stage for the evaluation and management of specific diseases.  This book serves as a superb resource and an invaluable asset for practitioners, health professionals, and trainees seeking out information about children's kidney diseases.  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