Pediatric Dialysis [3 ed.] 9783030668617, 3030668614

Table of contents :
Preface
Acknowledgments
Contents
Contributors
Part I: Essential Primers
1: Notes on the History of Dialysis Therapy in Children
Introduction
Peritoneal Dialysis
Hemodialysis
Patient Registries and Multicenter Studies
Conclusion
References
2: The Biology of Dialysis
Introduction
Biology of Uremic Toxicity
Solute Removal Mechanisms in Extracorporeal Dialysis
Diffusion
Solute Removal by Convection
Solute Removal by Internal Filtration
New Membrane Designs for Enhanced Removal of Large Toxins
Solute Removal by Adsorption
Peritoneal Dialysis: Biologic and Mass Transfer Considerations
Factors Affecting Solute Transport
Relationship Between Clearance and Mass Removal Rate Among Various Renal Replacement Therapies
Clearance as a Dialyzer Performance Parameter
Whole-Blood Clearance
Blood Water and Plasma Clearance
Dialysate-Side Clearance
Whole-Body Clearance
References
3: The Demographics of Dialysis in Children
Introduction
Sources of Demographic Data on Pediatric Dialysis Patients
Incidence and Prevalence
Access to Dialysis Around the World
Effect of Era on the Incidence and Prevalence of ESKD in Children
Effect of Age on the Incidence of RRT and Treatment Modality
Primary Kidney Disease Diagnosis
Mortality Risk
Conclusion
References
4: Chronic Dialysis in Developing Countries
Introduction
Economic Indicators
Epidemiology of Renal Replacement Therapy in Developing Countries
Demographics of the ESRD Population in Developing Countries
Challenges Faced by Developing Countries in the Provision of Pediatric RRT
Conclusion
References
5: Organization and Management of a Pediatric Dialysis Program
Introduction
Operational Management
Facility Culture and Organization
Physical Space Needs
Staffing the Unit
Billing and Regulatory Guidelines
Care Implementation
Modality Selection
Patient/Family Education
Patient Care Plans
Patient and Family Support
Transition and Transfer of Care
Quality Improvement and Safety
Oversight and Ongoing Operations
Conclusion
References
6: Role of the Advanced Practice Provider in a Pediatric Dialysis Program
Introduction
History of the Advanced Practice Provider (APP)
Nurse Practitioner
Physician Assistant
Orientation for the APP
The APP in the Dialysis Unit
Role of the APP in Hemodialysis
Role of the APP in Peritoneal Dialysis
Role of the APP in Critical Care Nephrology
Billing Practices for the APP
The Role of the APP in Transitions of Care
CKD-ESKD
Dialysis to Transplant
Pediatric to Adult Care
The Role of the APP in Improving Patient Outcomes
Conclusion
References
7: Quality Improvement Strategies and Outcomes in Pediatric Dialysis
Introduction
Clinical Practice Guidelines and Clinical Performance Measures
Oversight of Centers for Medicaid and Medicare (CMS) and State Regulations
Quality Assessment and Performance Improvement Program
Networks
The ESRD Quality Incentive Program of the USA
Consolidated Renal Operations in a Web-Enabled Network (CROWNWeb)
National Healthcare Safety Network (NHSN)
Dialysis Facility Report (DFR)
Dialysis Facility Compare
Developing a Quality Assessment Performance Improvement (QAPI) Program
Challenges for the Small Pediatric Program
Quality Improvement Design
What Is the Problem?
Quality Improvement Methodology
What Are We Trying to Accomplish?
How Will We Know a Change Is an Improvement?
What Changes Can We Make That Will Result in Improvement?
Plan
Do
Study
Act
Sustainability
Conclusion
References
8: Antibiotic Stewardship in the Pediatric Dialysis Unit
Introduction
Antibiotic-Resistant Bacterial Infections in Children
Common Pathogens in Pediatric Dialysis Patients
Negative Consequences of Antibiotic Use
Antibiotic Use in Children
Antibiotic Use in Dialysis Patients
Antimicrobial Stewardship
Antimicrobial Stewardship Strategies
Inpatient
Outpatient
Dialysis Specific
Diagnostics
Hemodialysis
Peritoneal Dialysis
Infection Prevention
Vaccination
Summary
References
Part II: Considerations Around the Initiation of Dialysis
9: The Decision to Initiate Dialysis in Children and Adolescents
Introduction
Methodology for Measuring Kidney Function
Predialysis Patient Monitoring and Preparation for Dialysis
Indications for Initiating Dialysis
Absolute Indications for Initiating Dialysis
Relative Indications for Initiating Dialysis
Uremic Symptoms
Hyperkalemia
Hyperphosphatemia
Malnutrition
Growth Failure
Timing of Elective Dialysis Initiation
Estimated GFR at Dialysis Initiation
Consensus Statements Regarding Dialysis Initiation
Arguments for Early (“Timely”) Initiation
Arguments for Delayed Initiation
Choice of Mode of Dialysis
References
10: Urological Issues in Pediatric Dialysis
Introduction
Urological Causes of Chronic Kidney Disease
Posterior Urethral Valves
Vesicoureteral Reflux in the Pediatric Dialysis Patient
Neurogenic Voiding Dysfunction
Bladder Augmentation and End-Stage Kidney Disease
Prune Belly Syndrome
Urological Issues in the Pretransplant Workup
Nephrectomy
Inguinal Hernias and Peritoneal Dialysis
Stomas, Catheters, Vascular Access, and Incisions
Summary
References
11: Preservation of Residual Renal Function in Children Reaching End-Stage Renal Disease
Introduction
Measurement of RRF
Clinical Benefits of RRF
General Risk Factors for Loss of Renal Function
Specific Risk Factors for Loss of RRF in Patients on Dialysis
Clinical Management Options to Slow CKD Progression and Preserve RRF on Dialysis
Avoidance of Risk Factors
Blood Pressure Control
RAS Inhibition
Diuretics
Peritoneal Dialysis
Hemodialysis
Emerging Therapies
Special Conditions
References
Part III: Peritoneal Dialysis
12: Peritoneal Access in Children Receiving Dialysis
Peritoneal Dialysis Access
Access Types
Preoperative Evaluation and Preparation
Omentectomy
Fibrin Sealant
Surgical Technique
Laparoscopic Technique
Open Technique
Postimplantation Care
Timing of Catheter Use
Chronic Exit-Site Care
Mechanical Complications
Exit-Site Infection, Tunnel Infection, and Peritonitis
PD Catheter Care Post-Kidney Transplantation
Complications with PD Catheter Removal
Conclusion
References
13: Technical Aspects and Prescription of Peritoneal Dialysis in Children
Introduction
Update on PD Connection Technology
Catheter-to-Transfer Set Connectors
Transfer Set-to-Container Connection
Transfer Sets
Straight Transfer Set (the Standard Oreopoulos System)
The Y-Set
Peritoneal Dialysis Prescription
The Peritoneal Dialysis System
Peritoneal Microcirculation
Peritoneal Membrane
Dialysis Fluid Compartment
Driving Forces of Solute and Water Exchange
Diffusive Transport
Ultrafiltration
Convective Mass Transfer
Peritoneal Membrane Function Tests
Mass Transfer Area Coefficient
Peritoneal Equilibration Test
Standard Permeability Analysis
Personal Dialysis Capacity Test
Prescription of Peritoneal Fill Volume
Prescription of Dwell Time
Peritoneal Dialysis Methods and Regimens
Continuous Ambulatory Peritoneal Dialysis (CAPD)
Automated Peritoneal Dialysis (APD)
Nightly Intermittent Peritoneal Dialysis (NIPD)
Continuous Cyclic Peritoneal Dialysis (CCPD)
Tidal Peritoneal Dialysis (TPD)
Adapted APD
Concluding Remarks
Peritonitis in APD Patients
Evaluation of the Adequacy of Peritoneal Dialysis Treatment
Clearance of Small Solutes
Clearance of Middle-Sized Molecules
Fluid Balance
The Role of Residual Renal Function in Treatment Adequacy
Clinical Evaluation of PD Treatment Adequacy
Monitoring PD Adequacy in the Clinical Setting
Machines for Automated Peritoneal Dialysis
Characteristics of Cyclers for Automated Peritoneal Dialysis
Registration of Treatment Data
Transmission of Treatment Data
Monitoring of Patient Adherence to the Prescribed APD Treatment
Strategies to Enhance Patient Adherence to PD Prescriptions
Conclusions
References
14: Peritoneal Dialysis Solutions
Introduction
Biocompatibility
PD Solution Components
Electrolyte Composition
Calcium
Magnesium
Alternate PD Solutions and Membrane-Sparing Strategies
Conclusion
References
15: Peritoneal Dialysis During Infancy
Introduction
Incidence and Etiology
Ethical Considerations: Should Dialysis Be Initiated?
Peritoneal Dialysis Access
Prescription
Nutrition and Growth
Complications
Hospitalization and Long-Term Outcomes
Conclusions
References
16: Infectious Complications of Peritoneal Dialysis in Children
Introduction
Incidence of PD-Related Infections
Microbiology of PD-Related Infections
Peritonitis
PD Catheter-Related Infections
Risk Factors and Prevention
Patient Age
PD Catheter Design, Insertion, and Postoperative Exit-Site Care
Training
Chronic Exit-Site Care
Touch Contamination
Ostomies
Antibiotic and Antifungal Prophylaxis
Other Factors
Diagnosis and Management of Peritonitis
Diagnosis
Empiric Therapy
Subsequent Treatment of Peritonitis
Gram-Positive Peritonitis
Gram-Negative Peritonitis
Culture-Negative Peritonitis
Fungal Peritonitis
Relapsing Peritonitis
Refractory Peritonitis
Diagnosis and Management of PD Catheter-Related Infections
Diagnosis
Treatment of PD Catheter-Related Infections
Outcome
References
17: Noninfectious Complications of Peritoneal Dialysis in Children
Mechanical Complications of PD
Obstruction of PD Fluid Flow
Prevention Strategies
Treatment Options
Outcome
Dialysate Leakage
Risk Factors and Prevention
Diagnosis
Management
Hernia
Risk Factors
Clinical Features
Diagnosis
Prevention
Treatment
Hydrothorax
Pathogenesis
Clinical Features
Diagnosis
Treatment
Technique-Related Complications
Peritoneal Membrane Failure
Pathogenesis
Differential Diagnosis
Management
Prognosis
Encapsulating Peritoneal Sclerosis
Pathogenesis
Diagnosis
Treatment
Prognosis
Metabolic Complications
Dyslipidemia and Insulin Resistance
Hypokalemia
Hypermagnesemia
Other Complications
Hemoperitoneum
Pathogenesis
Diagnosis
Management
Acute Pancreatitis
Pathogenesis
Diagnosis
Management
Prognosis
References
18: Remote Patient Monitoring in Peritoneal Dialysis
Introduction
Remote Monitoring Techniques
Benefits of RPM
RPM Implementation and Data Handling
Regulatory Issues and Reimbursement
Conclusion
References
Part IV: Hemodialysis
19: Hemodialysis Vascular Access in Children
Background
Vein Preservation in Children with CKD
Hemodialysis Vascular Access Choices and Outcomes
Arteriovenous Fistula
General Remarks, Patient Evaluation, and Preparation
Placement and Perioperative Handling
Monitoring and Complications
Arteriovenous Graft
General Remarks, Evaluation, and Preparation
Placement and Perioperative Handling
Monitoring and Complications
Central Venous Catheters
General Remarks, Evaluation, and Preparation
Placement and Perioperative Handling
Monitoring and Complications
Summary
References
20: Technical Aspects of Hemodialysis in Children
Introduction
The Extracorporeal Blood Circuit (Fig. 20.1)
Hemodialyzer
Hemodialyzer Membranes
Sterilization and Reuse
Blood Tubing
Blood Pump
Heparin Pump
The Dialysate Circuit (Fig. 20.2)
Water Purification
Dialysate
Dialysate Flow Rates
Ultrafiltration Control
Safety and Monitoring Systems
Pressure Monitors
Air Trap
Blood Leak Monitors
Conductivity Monitor
Non-invasive Blood Volume Monitoring
Dialysance and Online Monitoring of Clearance
Maintenance
Disinfection and Sterilization
Descaling
Complications and Troubleshooting
Dialyzer Reactions and Biocompatibility
Hemodialysis Technique Variations
Hemodiafiltration
Single-Needle Dialysis
Summary
References
21: Haemodiafiltration: Principles, Technique, and Advantages over Conventional Haemodialysis
Introduction and Defining a Need for Convective Clearance on Dialysis
Principles of Solute Clearance by HD and HDF
Haemodialysis (HD)
Haemodiafiltration (HDF)
Haemofiltration (HF)
Definition and Types of HDF Therapy
Modes of HDF
Post-dilution HDF
Pre-dilution HDF
Mid-dilution HDF
Mixed Dilution HDF
Choosing the Optimal HDF Modality
Requirements for HDF and Technical Aspects
‘Ultrapure’ Water for HDF
High-Flux Membranes
Dialysis Machines with Accurate Ultrafiltration Control
Calculation of Solute Clearances in HDF
The Concept of ‘Backfiltration’
Writing a HDF Prescription
Practical Guide for the Optimization of the Convective Volume
Clinical Studies and Potential Advantages of HDF over Conventional HD
HDF: Potential Advantages over Conventional HD
Studies in Adults
Studies in Children
Conclusions
References
22: Maintenance Hemodialysis During Infancy
Introduction
Epidemiology/Indications
Technical Issues
Vascular Access
Equipment (Machines/Dialyzers/Blood Lines)
Blood Flow
Connection and Disconnection
Anticoagulation
Ultrafiltration (UF) and Dry Weight Assessment
HD Schedule
Clinical Problems
Growth
Anemia
Hypertension
CKD/MBD
Psychosocial Impact
Outcomes
Conclusions
References
23: Home Haemodialysis in Children
Introduction
Rationale for Augmented Home HD
Home HD Prescriptions
Setting Up a Paediatric Home HD Program
Patient Selection Criteria
Infrastructure
Finances and Business Case
Safety
Vascular Access
Anticoagulation
Family Centric Remote Monitoring and Support
Effective Training and Education Program
Staffing
Dialysis Equipment
Dialysis Systems Requiring Home Water Conversions
Mobile HD System: NxStage™
Adult Home HD Experience
Paediatric Home HD Experience
Summary
References
24: Infectious Complications of Hemodialysis in Children
Hemodialysis Access in Children
HD Catheters and Infection: Greater Risks with Children
Catheter-Related Bloodstream Infections
Incidence and Epidemiology of CRBSI
Pathogenesis and Risk Factors for CRBSI
Microbial Colonization and Biofilm
Clinical Risk Factors for CRBSI
Clinical Presentation of CRBSI
Diagnosis of CRBSI
Initial Clinical Management of Suspected CRBSI
Catheter Replacement
Catheter In Situ Treatment: Antimicrobials for Empiric and Calculated Therapy
Antibiotic Therapy: Specifics of Provision
Antimicrobial Locks in CRBSI
Role of Strategies to Prevent CRBSI
Staphylococcus Colonization
Exit Site Care
HD Catheter Hubs
Innovative HD Catheter Design and Composition
Antimicrobial Locks as Preventative Strategy
Exit Site and Tunnel Infections
AVF and AVG Infections
Transmissible Infections in the Pediatric Hemodialysis Unit
Infection Prevention and Surveillance
Conclusion
References
25: Non-infectious Complications of Hemodialysis in Children
Introduction
Acute Complications
Dialysis Disequilibrium Syndrome (DDS)
Acute Hemodynamic Changes
Intradialytic Hypotension
Intradialytic Hypertension
Blood and Circuit Component Reactions
Allergic Reactions
Air Embolism and Microbubbles
Miscellaneous Complications
Chronic Hemodialysis Complications
Sleep Disorders
Dialysis-Related Amyloidosis
Conclusion
References
Part V: Management of Secondary Complications of Chronic Dialysis
26: Nutritional Assessment and Prescription for Children Receiving Maintenance Dialysis
Introduction and Overview
Nutrition Overview for Hemodialysis
Nutrition Overview for Peritoneal Dialysis
Growth
Nutrition Assessment
Anthropometric Evaluation
Plotting Growth
Other Measures
Dietary Evaluation
Nutrition-Focused Physical Exam
Prescribing Nutrition
Energy and Macronutrient Needs
Protein
Carbohydrate and Fat
Micronutrient Needs
Electrolyte Management
Bone Mineral Management
Vitamins
Minerals
Fluid Management
Age-Based Considerations
Infants and Young Children
Enteral and Oral Formula or Breast Milk Feeding
Transition to Oral Feeding
Childhood
Adolescents and Young Adults
Nutrition Considerations for Preparation of Transfer to Adult-Focused Facilities
Special Considerations
Prematurity
Protein Energy Wasting/Uremic Failure to Thrive
Overweight and Obesity
Parenteral Nutrition/IDPN
Nutrition Counseling Strategies
Nutrition Considerations in Preparation for Transplant
Summary
References
27: Controlled Enteral and Parenteral Nutrition in Children on Dialysis
Introduction
Rationale for Nutritional Supplementation in Pediatric CKD
Indications for Supplemental Nutritional Support
Indications for Tube Feeding
Evidence for Benefits of Tube Feeding: Infants
Evidence for Benefits of Tube Feeding: Older Children
Nasogastric (NG) Versus Gastrostomy Tube Feeding
Practical Aspects of Enteral Tube Feeding
Gastrointestinal Disturbances in Children with CKD
Impaired Oromotor Development
Transition to Oral Feeding
Intradialytic Parenteral Nutrition (IDPN) and Intraperitoneal Nutritional Supplementation
Summary
References
28: Growth and Pubertal Development in Children and Adolescents Receiving Chronic Dialysis
Introduction
Final Height and Height Prediction
Clinical Presentation
Intrauterine Growth
Growth During Infancy
Growth During Mid-childhood
The Pubertal Phase
Pubertal Development
Pubertal Growth
Segmental Growth
Etiology of Growth Failure in Chronic Kidney Disease
Underlying Renal Disease
Consequences of Renal Disease
Protein-Calorie Malnutrition
Metabolic Acidosis
CKD-Mineral and Bone Disorder (CKD-MBD)
Anemia
Physical Activity
Endocrine Changes
Gonadotropic Hormone Axis
Gonadal Hormones
Gonadotropins
Somatotropic Hormone Axis
Growth Hormone Secretion and Metabolism
Growth Hormone Receptor and GH Signaling
Insulin-Like Growth Factor Plasma Binding and Tissue Action
Treatment of Growth Failure in Chronic Kidney Disease and on Dialysis
General Measures
Correction of Acid-Base/Electrolyte Abnormalities
Dialysis and Intensified Dialysis
Transplantation
Endocrine Therapies
Active Vitamin D
Calcimimetics
Growth Hormone
Efficacy of rhGH in Prepubertal Children
Effects of rhGH on Pubertal Growth and Final Height
Efficacy of rhGH in Infants
General rhGH Treatment Strategies
Potential Adverse Events Associated with rhGH Therapy
Future Perspectives
References
29: The Management of CKD-MBD in Pediatric Dialysis Patients
Introduction
Changes in Mineral Metabolism with Progressive CKD
Effects of Non-mineral Factors on CKD-MBD
Assessment of CKD-MBD in Children Undergoing Maintenance Dialysis
Which Targets for PTH in Pediatric Dialysis?
Management of CKD-MBD in Children Undergoing Maintenance Dialysis
Effects of Primary Kidney Diseases Inducing a Specific Bone Impairment in Addition to CKD-MBD
Conclusion and Perspectives
References
30: The Cardiovascular Status of Pediatric Dialysis Patients
Epidemiology of CVD in CKD Patients
Cardiovascular Disease Begins Early in the Course of CKD
Risk Factors for the Development of CVD in CKD
“Traditional” Risk Factors
Uremia-Related Risk Factors
Surrogate Measures of Cardiovascular Risk in CKD Patients
Left Ventricular Structure and Function
Vascular Structure, Function, and Coronary Artery Calcification (CAC)
Progression of Vascular Calcification Through Different Stages of CKD
Physiological Inhibitors of Calcification
The Role of Vitamin D in Cardiovascular Health in CKD
The Vascular Biology of Calcification
The Bone-Vascular Link
Evaluation and Management of CV Risks in CKD
The Need for More Frequent Dialysis
Management of Key Modifiable Risk Factors That Contribute to the Development and Progression of CVD in CKD
Prevention and Treatment of Hypertension and LVH
Ca–P–PTH and Vitamin D Management
Prevention and Treatment of Lipid Abnormalities
Supportive Treatment
Conclusion
References
31: Management of Hypertension in Pediatric Dialysis Patients
Introduction
Prevalence of Hypertension in Pediatric Dialysis Patients
Etiology of Hypertension in Pediatric Dialysis Patients
Short- and Long-Term Consequences of Hypertension
Hospitalization
Alterations of Vascular Morphology and Function
Left Ventricular Hypertrophy
Cardiovascular Mortality
Diagnosis of HTN in Dialysis Patients
Role of Ambulatory Blood Pressure Monitoring (ABPM)
ABPM in Hemodialysis Patients
ABPM in Peritoneal Dialysis Patients
Treatment of Hypertension
Adjustment of Dry Weight/Optimization of Dialysis
Dry Weight
Optimization of Dialysis
Dietary Intervention: Fluid and Salt Intake
Pharmacological Treatment
Native Nephrectomy
Summary
References
32: Management of Anemia in Children Receiving Chronic Dialysis
Introduction
Normal Erythropoiesis and Disordered Mechanisms in Kidney Disease
Hypoxia Stimulates New Red Blood Cell Production
Iron Is Required for the Synthesis of Hemoglobin
Hepcidin Regulates the Ferroportin-Based Movement of Iron
Epidemiology of Anemia in Children on Dialysis
Definition of Anemia
Incidence, Prevalence, and Risk Factors
Adverse Associations
Clinical Management of Anemia
Symptoms of Anemia
Initial Diagnostic Evaluation of Anemia
Erythropoietin Levels
Laboratory Assessment of Iron Status
Goal Hemoglobin Levels in Children on Dialysis
Recombinant Human Erythropoietin Therapy
Available Forms of rHuEPO
Epoetin
Darbepoetin Alfa
CERA
ESA Dosing for Children
Children May Require Higher Absolute ESA Doses than Adults
Safety of ESA Therapy
Novel Erythropoiesis-Stimulating Agents
ESA Hyporesponsiveness: Definition and Risk Factors
Bone Disease Secondary to Hyperparathyroidism
Medications
Aluminum Toxicity
Hypervolemia
Anti-rHuEPO Antibodies
Red Blood Cell Transfusion
Iron Therapy
Oral Iron Supplementation
Intravenous Iron Supplementation
Iron Safety
Novel Routes of Iron Supplementation
Future Directions
References
33: Immune Function and Immunizations in Dialyzed Children
Introduction
Immune Dysfunction
White Blood Cell Differentiation and Function
Phagocytic Cells and Receptors
Immunoglobulins
Immunizations
Diphtheria, Tetanus, and Pertussis Vaccine
Haemophilus influenzae Type b (Hib) Conjugate Vaccine
Hepatitis B Vaccine
Inactivated Polio Virus Vaccine
Measles, Mumps, Rubella Vaccine
Varicella Zoster Vaccine
Pneumococcal Vaccine
Hepatitis A, Meningococcal, Human Papillomavirus, and Rotavirus Vaccines
Influenza Vaccine
Bacille Calmette-Guerin (BCG) Vaccine
Summary
References
34: Neurocognitive Functioning in Pediatric Dialysis
Introduction
The Interaction of Brain Development, Kidney Disease, and Dialysis
Brain Development
Kidney-Brain Connections
The Impact of Dialysis on Kidney-Brain Connections
Neurocognitive Functioning and Neuroimaging in Pediatric Dialysis
Neurocognitive Functioning in Pediatric Dialysis
Neuroimaging Findings in Pediatric Dialysis
Management of Cognitive Dysfunction in Children on Dialysis
Early Intervention
School Age
Adolescence and Adult Transition
Conclusions and Directions
References
35: Psychosocial Adjustment and Adherence to Prescribed Medical Care of Children and Adolescents on Dialysis
Psychosocial Adjustment
Child Adjustment
Parent and Family Adjustment
Treatment of Psychosocial Problems
Adherence to Prescribed Medical Regimens
Assessment of Adherence
Factors Associated with Adherence
The Impact of Treatment Adherence on Health and Other Outcomes
Interventions to Promote Adherence
Summary and Directions for Future Research
Implications for Clinical Practice and Psychosocial Care
References
Part VI: Drugs and Dialysis
36: Drug Administration and Pharmacogenomics in Children Receiving Acute or Chronic Renal Replacement Therapy
Introduction
Basic Concepts of Drug Disposition
Absorption
Distribution
Biotransformation/Elimination
Alteration of Drug Disposition in Renal Failure and Dialysis
Hemodialysis
Continuous Renal Replacement Therapies
Peritoneal Dialysis
Dosing Strategies in Children with Renal Failure
Future Considerations: Pediatric Pharmacogenetics
References
37: Role of Radiological Assessment and Intervention in Pediatric Dialysis
Introduction
Classification of Contrast Media
Iodinated Contrast Media
Renal Handling of Contrast Media
Mechanisms for Toxicity of Iodinated Contrast Media
Dialysis in the Removal of Iodinated Contrast Media
Dialysis as a Strategy to Minimize Contrast-Induced Nephropathy
Negative Contrast Media
Ferumoxytol
Gadolinium
Renal Handling of Gadolinium
Mechanisms for Toxicity of Gadolinium
Dialysis in the Removal of Gadolinium
Nephrogenic Systemic Fibrosis
Creation and Maintenance of Venous Access for Hemodialysis
Role of Imaging for Acquired Cystic Kidney Disease
References
38: Extracorporeal Therapy for Drug Overdose and Poisoning
Introduction
Poison Characteristics
Management of the Poisoned Patient
Pharmacokinetic Concepts
Molecular Weight
Volume of Distribution
Protein Binding
Hydro- and Lipophilicity
Ionization
Intercompartmental Transfer
Rebound
Endogenous Clearance
Toxicokinetics
Specific Issues in Neonates and Young Infants
Extracorporeal Clearance
Extracorporeal Modalities
Intermittent Hemodialysis (IHD)
Continuous Renal Replacement Therapy (CRRT)
Sustained Low-Efficiency Dialysis (SLED)
Therapeutic Plasma Exchange (TPE)
Exchange Transfusion
Hemoperfusion
Molecular Adsorbent Recirculating System (MARS)
Single-Pass Albumin Dialysis (SPAD)
Peritoneal Dialysis
Therapeutic Decisions
Acetaminophen
Salicylates
Barbiturates
Carbamazepine
Valproic Acid (VPA)
Phenytoin
Lithium
Methanol
Ethylene Glycol
Metformin
Conclusion
References
Part VII: Outcome of Chronic Dialysis
39: Long-Term Outcome of Chronic Dialysis in Children
Introduction
Epidemiology
Worldwide and Nationwide Registries
Age, Modality, and Primary Kidney Disease at the Start of Dialysis
Long-Term Dialysis in Pediatric Patients
Patient Survival
Mortality Rate
Cause of Death
Mortality Risk
Technique Failure Rate
Complications of Long-Term Dialysis
Cardiovascular Disease
Long-Term Dialysis and CVD in Adults
Long-Term Dialysis and CVD in Children
Chronic Kidney Disease-Mineral and Bone Disorder
Bone Disease
Vascular and Valvular Calcification
Longitudinal Growth
Peritoneal Dysfunction and Encapsulating Peritoneal Sclerosis (EPS)
Peritoneal Dysfunction
Encapsulating Peritoneal Sclerosis
Pathophysiology
Incidence of EPS
EPS Development Can Be Predicted
Risk Factors
PD Duration
Composition of Dialysate
Peritonitis
Discontinuation of PD
Drugs
Diagnosis of EPS
Clinical Diagnosis
Radiological Diagnosis
Pathological Diagnosis
Treatment
Surgery
Nutritional Support
Outcome
Prevention
Cognitive Functioning
Quality of Life
Social Outcome
Conclusion
References
40: Health-Related Quality of Life of Children and Adolescents on Dialysis
Introduction
Assessment of HRQOL
Child Health and Illness Profile (CHIP)
Child Health Questionnaire
PedsQL Generic Core Scales
PedsQL ESRD Module
Early Investigations of the Quality of Life of Youth on Dialysis
Current Findings: Quality of Life of Youth on Dialysis
Comorbidities and HRQOL
Conclusions
References
41: Transition and Transfer to Adult Care for Adolescents and Young Adults with Advanced Chronic Kidney Disease
Introduction
Clinical Vignettes
Overview
Named Healthcare Worker and Transition Champion
Starting Early
Attention to Psychosocial Issues and Needs, Including Educational Challenges
Adherence to Treatment, Despite Asynchronous Brain Development
Acceptance That the Disease Does Not End with Childhood
School and Vocational Training in Difficult Circumstances
Additional Challenges in Special Social Situations
Regular Evaluation of Adherence
Patient and Family Engagement and Empowerment
Regular Assessment of Transition Preparation Using Standardized Tools
Tracking Progress of Individual Patients and of the Clinic’s Transition Process as a Whole
Timing of Transfer
Succinct Relevant Patient Transfer Summaries
A Personalized Health Passport or Summary Document for the Patient
Open Bidirectional Communication Between the Pediatric and Adult Teams
Recognition by the Adult Team of the Young Adult’s Developmental Needs
Continuation of the Transition Process After Transfer to Adult Care, Until the Young Person Is Fully Integrated and Able to Function in the Adult System
Education and Training for Healthcare Professionals
Financial Considerations
Quality Improvement and Research
Public Policy
Summary
References
42: Ethical Decision-Making in Pediatric Dialysis
Introduction
Ethical Considerations in Withholding and Withdrawing Dialysis Treatment
The History of Dialysis Provision and Ethical Implications
Best Interest Standard and Harm Principle in Pediatric Decision-Making
The Technological Imperative
Equivalence of Withholding and Withdrawing Dialysis
Considerations for Forgoing Dialysis
Process of Forgoing Dialysis
Disagreement
Futility
Allocation of Resources
Time-Limited Trials
Special Populations
Suspected ESKD in the Antenatal Period
Suspected ESKD in the Neonatal Period
Developmentally Disabled Children and Those with Significant Comorbidities
Children Who Are Not Transplant Candidates
Undocumented Immigrants/Refugees
Adolescents Who Make a Request to Forgo Dialysis
Conclusions
References
Part VIII: Special Indications, Techniques and Applications
43: Diagnosis and Treatment of Acute Kidney Injury in Children and Adolescents
Introduction
Diagnosis of Acute Kidney Injury
Definition of AKI
Epidemiology and Outcomes of AKI
Incidence and Short-Term Outcomes
Risk Factors
Long-Term Outcomes
Pathophysiology of AKI
Clinical Evaluation of AKI
Classification and Etiology (Table 43.3)
History and Physical Examination (Table 43.4)
Diagnostic Laboratory Evaluation (Table 43.5)
Management of Acute Kidney Injury
AKI Management Prior to Renal Support Therapy
Investigational Strategies to Risk-Stratify AKI
Fluid Management
Electrolyte Management
Pharmacological Therapy
Timing and Modality of Renal Support Therapy
Modality of RST
Performing Acute Peritoneal Dialysis for AKI
Access
Acute Peritoneal Dialysis Prescription (Table 43.6)
Complications
Acute Hemodialysis for AKI
Acute Hemodialysis Prescription
Continuous Renal Replacement Therapy for AKI
Vascular Access (Table 43.8)
CRRT Machine and Modality (Fig. 43.3)
Hemofilter and Blood Prime
Solutions (Table 43.9)
CRRT Prescription: Blood Flow (Table 43.10)
CRRT Prescription: Solute Clearance (Table 43.10)
CRRT Prescription: Ultrafiltration (Table 43.10)
Anticoagulation
CRRT Complications
Nutritional Management for AKI and RST-AKI
Drugs in AKI
Conclusion
References
44: Neonatal Acute Kidney Injury
Introduction
Case Presentation
Defining Neonatal AKI
Consequences and Medical Management of AKI
Fluid Overload
Fluid Management
Dysnatremias
Hyperkalemia
Metabolic Acidosis
Hyperphosphatemia and Hypocalcemia
Nutrition and Other Metabolic Alterations
Limiting Nephrotoxin Exposure
Other Medical Treatments of Neonatal AKI
Indications for Renal Replacement Therapy (RRT)
Renal Replacement Therapy Modalities
Peritoneal Dialysis
Extracorporeal Therapies
Vascular Access
Fluid to Prime Machine
Continuous Versus Intermittent Duration
Hemodialysis
CRRT
Newer RRT Machines for Young Infants
References
45: Acute Kidney Injury in Less Well-Resourced Countries
Introduction
Epidemiology and Etiology
Diagnostic Evaluation (See Also Chaps. 43 and 44)
Clinical Evaluation
Laboratory Evaluation
Management
Therapy of Complications
Management of Fluid and Electrolytes
Pharmacologic Therapy
Nutrition
Fluid Administration
Fluid Boluses
Fluid Overload
Drugs to Remove Fluid
Drug Administration
Renal Replacement Therapy (RRT): Table 45.1
Outcomes
References
46: Extracorporeal Liver Support Therapies for Children
Introduction
Indications for Extracorporeal Liver Support Therapy
Acute and Acute-on-Chronic Liver Failure
Cholestatic Pruritus
Artificial Liver Support Devices
Combined Plasma Exchange and Hemodialysis Therapies
Bioartificial Liver Support Devices
Implementation of ELS
Data for Extracorporeal Liver Support
Outcome of ELS in Patients with Liver Failure
Conclusion
References
47: Dialytic Therapy of Inborn Errors of Metabolism in Case of Acute Decompensation
Introduction
Clinical Manifestations and Laboratory Investigations
Etiologies
Treatment
Nutritional and Pharmacological Management
Metabolite Removal by Dialysis
Hyperammonemic Disorders
Maple Syrup Urine Disease (MSUD)
Other Organic Aciduria
Dialysis Equipment
Catheter
Dialyzer
Dialysis Machines and Tubing
Dialysis Management
Clinical Outcomes
References
48: Therapeutic Apheresis in Children
Introduction
Principles of Separation
Pediatric-Specific Technical Considerations
Vascular Access
Extracorporeal Volume and Blood Priming
Anticoagulation
Volumetric Control
Apheresis Treatment Modalities and Procedures
Plasmapheresis
Erythrocytapheresis
Leukapheresis
Plateletpheresis
Photopheresis
Lipoprotein Apheresis
Immunoadsorption
Indications for Apheresis Techniques
ANCA-Associated Glomerulonephritis
Thrombotic Microangiopathies
Focal Segmental Glomerulosclerosis (Recurrent)
Solid Organ Transplantation
Summary
References
49: Evaluating and Preparing the Pediatric Dialysis Patient for Kidney Transplantation
Introduction
Historical Context
Benefits of Transplant Over Dialysis
Transplant Referral: Timing and Indications
Surgical Considerations
Medical and Immunological Considerations
Psychosocial Considerations
Evaluation to Transplant
Deceased Donation
Living Donation
References
50: The Spectrum of Patient and Caregiver Experiences
Introduction
The Patient Experience
Feeling Different
Loss of Control
Lifestyle Restrictions
Managing Treatment
Coping Strategies
The Caregiver Experience
Emotional Turmoil and Uncertainty
Loss of Control
Change in Family Dynamics
Lifestyle Restrictions
Caregiver Burden
Financial Burden
Personal Growth
Implications for Practice
Conclusion
References
Index

Citation preview

Pediatric Dialysis Bradley A. Warady Steven R. Alexander Franz Schaefer Editors

Third Edition

123

Pediatric Dialysis

Bradley A. Warady Steven R. Alexander  •  Franz Schaefer Editors

Pediatric Dialysis Third Edition

Editors Bradley A. Warady Department of Pediatrics University of Missouri-Kansas City School of Medicine, Division of Pediatric Nephrology, Children’s Mercy Kansas City Kansas City, MO USA

Steven R. Alexander Stanford University School of Medicine Division of Pediatric Nephrology Department of Pediatrics Palo Alto, CA USA

Franz Schaefer Division of Pediatric Nephrology Center for Pediatrics and Adolescent Medicine, University of Heidelberg Heidelberg, Germany

ISBN 978-3-030-66860-0    ISBN 978-3-030-66861-7 (eBook) https://doi.org/10.1007/978-3-030-66861-7 © Springer Nature Switzerland AG 2021 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

We thank our families for the support they provide us. We thank our colleagues for the insight they share with us. We thank our patients for the trust they have in us. The editors

Preface

The provision of optimal dialysis therapy to children requires a thorough understanding of the multidisciplinary way the pediatric patient is affected by kidney failure. It was based on this philosophy that the inaugural edition of Pediatric Dialysis was published in 2004 and the second edition in 2012. Thankfully, the care of pediatric patients requiring dialysis has continued to improve, in large part the result of our ever-increasing understanding of the many factors which play a significant role in defining patient outcomes. We, in turn, believe that enhancement of the content of our text from nearly a decade ago is imperative so that Pediatric Dialysis may continue to serve as a contemporary, comprehensive, and authoritative source of information that can not only help facilitate the provision of superb patient care by seasoned clinicians, but can also help meet the demand of our young trainees for the information that they require as a foundation for the future advances that they will surely initiate. To that end, we have been fortunate once again to successfully enlist the expertise of experts from around the globe to provide superb contributions to the third edition of Pediatric Dialysis. One-hundred authors either updated chapters from the second edition or created all new content designed to reflect essential elements of current clinical management strategies. The inclusion of several new chapters on topics such as Antibiotic Stewardship in the Pediatric Dialysis Unit, Infectious Complications of Hemodialysis in Children, Remote Patient Monitoring in Peritoneal Dialysis, Ethical Decision Making in Children with End-Stage Kidney Disease and The Spectrum of Lived Experience: The Patient Experience has resulted in a text which remains the most comprehensive source of state-of-the-art information on the dialysis of infants, children, and adolescents currently available. To all the authors, we are eternally grateful for their commitment to this project. We have been humbled by the encouragement of our colleagues to publish this third edition. However, as clinicians ourselves who have spent many hours over the past four decades on hospital wards, in the intensive care unit, and in the dialysis unit applying what we have learned from the documented experience of others, we know that this text is a unique source of the knowledge and ingenuity exhibited by the global pediatric nephrology community and, as such, cannot help but to serve as a valuable tool with a singular

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emphasis on successfully caring for our challenging patient population. If that goal can be achieved through the publication of the third edition of Pediatric Dialysis and even one child benefits from our combined efforts, it will all have been worthwhile. Kansas City, MO, USA Stanford, CA, USA Heidelberg, Germany

Bradley A. Warady Steven R. Alexander Franz Schaefer

Acknowledgments

The editors would like to thank Michael Griffin from Springer, who graciously kept this project as a personal priority and whose project management skills and patience contributed greatly to the successful completion of this book.

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Contents

Part I Essential Primers 1 Notes on the History of Dialysis Therapy in Children������������������   3 Steven R. Alexander and Pierre Cochat 2 The Biology of Dialysis��������������������������������������������������������������������  17 William R. Clark and Claudio Ronco 3 The Demographics of Dialysis in Children������������������������������������  35 Jeffrey J. Fadrowski and Lesley Rees 4 Chronic Dialysis in Developing Countries ������������������������������������  47 Hui-Kim Yap and Francisco Cano 5 Organization and Management of a Pediatric Dialysis Program������������������������������������������������������������������������������  55 Amy Nau 6 Role of the Advanced Practice Provider in a Pediatric Dialysis Program��������������������������������������������������������������������������������������������  69 Jessica J. Geer and Kathleen F. Mallett 7 Quality Improvement Strategies and Outcomes in Pediatric Dialysis����������������������������������������������������������������������������������������������  81 Helen Currier, Pamela S. Heise, and Leyat Tal 8 Antibiotic Stewardship in the Pediatric Dialysis Unit������������������ 101 Jason G. Newland and Alicia M. Neu Part II Considerations Around the Initiation of Dialysis 9 The Decision to Initiate Dialysis in Children and Adolescents���� 115 Rima S. Zahr, Larry A. Greenbaum, and Franz Schaefer 10 Urological Issues in Pediatric Dialysis ������������������������������������������ 131 Joshua D. Chamberlin, Angus Alexander, Armando J. Lorenzo, and Antoine E. Khoury

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11 Preservation of Residual Renal Function in Children Reaching End-Stage Renal Disease�������������������������������� 157 Il-Soo Ha and Franz Schaefer Part III Peritoneal Dialysis 12 Peritoneal Access in Children Receiving Dialysis ������������������������ 175 Bradley A. Warady and Walter S. Andrews 13 Technical Aspects and Prescription of Peritoneal Dialysis in Children�������������������������������������������������������������������������� 193 Enrico Eugenio Verrina and Lyndsay A. Harshman 14 Peritoneal Dialysis Solutions ���������������������������������������������������������� 229 Elizabeth Harvey 15 Peritoneal Dialysis During Infancy������������������������������������������������ 249 Enrico Vidal and Joshua Zaritsky 16 Infectious Complications of Peritoneal Dialysis in Children�������������������������������������������������������������������������� 265 Alicia M. Neu, Bradley A. Warady, and Franz Schaefer 17 Noninfectious Complications of Peritoneal Dialysis in Children�������������������������������������������������������������������������� 291 Sevcan A. Bakkaloğlu and Christine B. Sethna 18 Remote Patient Monitoring in Peritoneal Dialysis������������������������ 315 Claus Peter Schmitt and Daljit K. Hothi Part IV Hemodialysis 19 Hemodialysis Vascular Access in Children������������������������������������ 325 Michael Boehm, Deepa H. Chand, and Mary L. Brandt 20 Technical Aspects of Hemodialysis in Children���������������������������� 341 Franz Schaefer and Jordan M. Symons 21 Haemodiafiltration: Principles, Technique, and Advantages over Conventional Haemodialysis����������������������������� 359 Rukshana Shroff, Evgenia Preka, and Bruno Ranchin 22 Maintenance Hemodialysis During Infancy���������������������������������� 379 Sarah J. Swartz and Fabio Paglialonga 23 Home Haemodialysis in Children�������������������������������������������������� 389 Daljit K. Hothi and Claus Peter Schmitt 24 Infectious Complications of Hemodialysis in Children���������������� 401 Ali Mirza Onder and Michael J. G. Somers 25 Non-infectious Complications of Hemodialysis in Children���������������������������������������������������������������������������������������� 437 Dagmara Borzych-Dużałka and Elizabeth Harvey

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Part V Management of Secondary Complications of Chronic Dialysis 26 Nutritional Assessment and Prescription for Children Receiving Maintenance Dialysis ������������������������������������ 463 Christina L. Nelms, Nonnie Polderman, and Rosanne J. Woloschuk 27 Controlled Enteral and Parenteral Nutrition in Children on Dialysis���������������������������������������������������������������������������������������������� 489 Bethany J. Foster and Anne Tsampalieros 28 Growth and Pubertal Development in Children and Adolescents Receiving Chronic Dialysis���������������������������������������� 509 Dieter Haffner and John D. Mahan 29 The Management of CKD-MBD in Pediatric Dialysis Patients���������������������������������������������������������������������������������������������� 541 Justine Bacchetta and Isidro B. Salusky 30 The Cardiovascular Status of Pediatric Dialysis Patients������������ 559 Rukshana Shroff and Mark M. Mitsnefes 31 Management of Hypertension in Pediatric Dialysis Patients������ 589 Elke Wühl and Joseph T. Flynn 32 Management of Anemia in Children Receiving Chronic Dialysis ������������������������������������������������������������������������������ 609 Meredith A. Atkinson and Bradley A. Warady 33 Immune Function and Immunizations in Dialyzed Children������ 633 Annabelle N. Chua and Sevcan A. Bakkaloğlu 34 Neurocognitive Functioning in Pediatric Dialysis������������������������ 649 Stephen R. Hooper and Erum Aftab Hartung 35 Psychosocial Adjustment and Adherence to Prescribed Medical Care of Children and Adolescents on Dialysis���������������� 665 Kristin Loiselle Rich, Rebecca J. Johnson, and Melissa K. Cousino Part VI Drugs and Dialysis 36 Drug Administration and Pharmacogenomics in Children Receiving Acute or Chronic Renal Replacement Therapy���������� 683 Bridget L. Blowey, J. Steven Leeder, and Douglas L. Blowey 37 Role of Radiological Assessment and Intervention in Pediatric Dialysis������������������������������������������������������������������������������ 709 Vikas R. Dharnidharka and Douglas C. Rivard 38 Extracorporeal Therapy for Drug Overdose and Poisoning�������� 725 Vimal Chadha

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Part VII Outcome of Chronic Dialysis 39 Long-Term Outcome of Chronic Dialysis in Children ���������������� 745 Masataka Honda, Chikako Terano, Tomohiro Inoguchi, Kaori Kikunaga, Ryoko Harada, and Jaap W. Groothoff 40 Health-Related Quality of Life of Children and Adolescents on Dialysis�������������������������������������������������������������������� 785 Rebecca J. Johnson and Susan L. Furth 41 Transition and Transfer to Adult Care for Adolescents and Young Adults with Advanced Chronic Kidney Disease�������� 793 Lorraine E. Bell and Dirk Bethe 42 Ethical Decision-Making in Pediatric Dialysis������������������������������ 811 Aaron Wightman, Bruno Ranchin, and Aviva M. Goldberg Part VIII Special Indications, Techniques and Applications 43 Diagnosis and Treatment of Acute Kidney Injury in Children and Adolescents���������������������������������������������������������������� 827 Emma Heydari Ulrich, David Selewski, and Michael Zappitelli 44 Neonatal Acute Kidney Injury�������������������������������������������������������� 861 Cherry Mammen and David Askenazi 45 Acute Kidney Injury in Less Well-­Resourced Countries ������������ 883 Mignon I. McCulloch and Arvind Bagga 46 Extracorporeal Liver Support Therapies for Children���������������� 895 Betti Schaefer, Claus Peter Schmitt, and Rajit K. Basu 47 Dialytic Therapy of Inborn Errors of Metabolism in Case of Acute Decompensation ������������������������������������������������������ 909 Lucile Barcat, Patricia Monnier, Franz Schaefer, and Philippe Jouvet 48 Therapeutic Apheresis in Children������������������������������������������������ 921 Christina Taylan and Scott M. Sutherland 49 Evaluating and Preparing the Pediatric Dialysis Patient for Kidney Transplantation����������������������������������������������� 945 Sandra Amaral and Lars Pape 50 The Spectrum of Patient and Caregiver Experiences������������������ 957 Allison Tong, Ansara H. Piebenga, and Bradley A. Warady Index���������������������������������������������������������������������������������������������������������� 975

Contents

Contributors

Angus  Alexander, MBBCh, FCS, FRACS Department of Paediatric Surgery, The Children’s Hospital at Westmead, Sydney, NSW, Australia Steven  R.  Alexander, MD Department of Pediatrics, Lucile Packard Children’s Hospital at Stanford, Stanford, CA, USA Sandra  Amaral, MD, MHS The Children’s Hospital of Philadelphia, Pediatrics, Division of Nephrology, Philadelphia, PA, USA Walter S. Andrews, MD  Department of General Surgery, Children’s Mercy Kansas City, Kansas City, MO, USA David Askenazi, MD, MSPH, FASN  University of Alabama at Birmingham, Pediatric and Infant Center for Acute Nephrology, Children’s of Alabama, Birmingham, AL, USA Meredith A. Atkinson, MD, MHS  Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA Justine  Bacchetta, MD, PhD Pediatric Nephrology, Rheumatology and Dermatology Unit, Reference Center for Rare Renal Diseases and Rare Diseases of Calcium and Phosphate Metabolism, Hôpital Femme Mère Enfant, Bron, France Arvind  Bagga, MD, FAMS All India Institute of Medical Sciences, Department of Pediatrics, New Delhi, India Sevcan  A.  Bakkaloğlu, MD Department of Pediatric Nephrology, Gazi University School of Medicine, Ankara, Turkey Lucile  Barcat, MD Sainte-Justine Hospital, Department of Pediatrics, Montreal, QC, Canada Rajit K. Basu, MD, MS  Children’s Healthcare of Atlanta, Emory University, Department of Pediatrics, Critical Care Medicine, Atlanta, GA, USA Lorraine E. Bell, MDCM, FRCPC  Department of Pediatrics, Division of Nephrology, McGill University Health Centre, Montreal Children’s Hospital, Montreal, Québec, Canada Dirk  Bethe, Dipl.-Psych Pediatric Nephrology Division, University Hospital Heidelberg, Heidelberg, Germany

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Bridget L. Blowey, PharmD  Department of Pharmacy, Children’s Hospital of Philadelphia, Philadelphia, PA, USA Douglas  L.  Blowey, MD  Department of Pediatrics, CMH Integrated Care Solutions, Children’s Mercy, Kansas City, MO, USA Michael Boehm, MD  Division of Pediatric Nephrology and Gastroenterology, Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria Dagmara Borzych-Dużałka, MD, PhD  Division of Pediatric Nephrology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA Mary  L.  Brandt, MD Pediatric Surgery Department, Tulane University School of Medicine and Children’s Hospital of New Orleans, New Orleans, LA, USA Francisco Cano, MD  Luis Calvo Mackenna Children’s Hospital, University of Chile, Pediatric Nephrology, Santiago, Chile Vimal  Chadha, MD Department of Pediatrics, University of MissouriKansas City School of Medicine, Acute Kidney Injury Program, Children’s Mercy Kansas City, Kansas City, MO, USA Joshua  D.  Chamberlin, MD Department of Urology, Loma Linda University, Loma Linda, CA, USA Department of Urology, Loma Linda University Children’s Hospital, Loma Linda, CA, USA Deepa  H.  Chand, MD, MHSA Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA Annabelle  N.  Chua, MD Department of Pediatrics, Duke Children’s Hospital, Durham, NC, USA William  R.  Clark, MD Department of Chemical Engineering, Purdue University, West Lafayette, IN, USA Pierre Cochat, MD, PhD  Service de néphrologie rhumatologie dermatologie pédiatriques, Centre de référence des maladies rénales rares, Hospices Civils de Lyon & Université Claude-Bernard Lyon 1, Lyon, France Melissa K. Cousino, PhD  Department of Pediatrics, C.S. Mott Children’s Hospital, Ann Arbor, MI, USA Helen  Currier, MA, BSN, CENP, CNN  Department of Medical Affairs, Medical Science Liaison, Rockwell Medical, Wixom, MI, USA Vikas  R.  Dharnidharka, MD, MPH Division of Pediatric Nephrology, Hypertension and Pheresis, Department of Pediatrics, Washington University School of Medicine and St. Louis Children’s Hospital, St. Louis, MO, USA Jeffrey  J.  Fadrowski, MD, MHS Division of Pediatric Nephrology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Contributors

Contributors

xvii

Joseph T. Flynn, MD, MS  University of Washington School of Medicine, Division of Nephrology, Seattle Children’s Hospital, Seattle, WA, USA Bethany  J.  Foster, MD, MSCE Department of Pediatrics, Montreal Children’s Hospital of the McGill University Health Centre, Montreal, QC, Canada Susan L. Furth, MD, PhD  Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA Jessica  J.  Geer, MSN, C-PNP, CNN-NP  Department of Renal Services, Texas Children’s Hospital, Houston, TX, USA Aviva M. Goldberg, MD, MA, FRCPC  Department of Pediatrics and Child Health, Max Rady College of Medicine, Section of Pediatric Nephrology, Winnipeg, MB, Canada Larry  A.  Greenbaum, MD, PhD Emory University and Children’s Healthcare of Atlanta, Division of Pediatric Nephrology, Atlanta, GA, USA Jaap  W.  Groothoff, MD, PhD Pediatric Nephrology Department, Amsterdam UMC/Emma Children’s Hospital, Amsterdam, Netherlands Il-Soo Ha, MD, PhD  Department of Pediatrics, Seoul National University Children’s Hospital, Seoul, Republic of Korea Dieter  Haffner, MD Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Lower Saxony, Germany Ryoko  Harada, MD Department of Nephrology, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan Lyndsay  A.  Harshman, MD, MS University of Iowa Stead Family Children’s Hospital, Pediatric Nephrology, Dialysis, and Transplantation, Iowa City, IA, USA Erum  Aftab  Hartung, MD, MTR Division of Nephrology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA Elizabeth Harvey, MD, FRCPC  Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, ON, Canada Pamela S. Heise, MSN, BBA, RN, CPN, CNN  Renal & Pheresis Services, Assistant Director of Clinical Practice, Texas Children’s Hospital, Houston, TX, USA Masataka  Honda, MD, PhD Department of Clinical Research Support Center, Metropolitan Children’s Medical Center, Tokyo, Japan Stephen R. Hooper, PhD  Department of Allied Health Sciences, School of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA Daljit K. Hothi, MBBS, MRCPCH, MD  Department of Nephrology, Great Ormond Street Hospital for Children Foundation Trust, London, UK

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Tomohiro Inoguchi, MD  Department of Nephrology, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan Rebecca  J.  Johnson, PhD, ABPP Division of Developmental and Behavioral Health, University of Missouri-Kansas City School of Medicine, Children’s Mercy Kansas City, Kansas City, MO, USA Philippe  Jouvet, MD, PhD Sainte-Justine Hospital, Department of Pediatrics, Montreal, QC, Canada Antoine  E.  Khoury, MD, FRCSC, FAAP Department of Urology, University of California, Irvine, Orange, CA, USA Department of Urology, Children’s Hospital of Orange County, Orange, CA, USA Kaori  Kikunaga, MD Department of Nephrology, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan J.  Steven  Leeder, PharmD, PhD Department of Pediatrics, Children’s Mercy Research Institute, Children’s Mercy Hospital, Kansas City, MO, USA Armando J. Lorenzo, MD, MSc  Department of Surgery, Hospital for Sick Children, Toronto, ON, Canada John  D.  Mahan, MD Department of Pediatric Nephrology, Nationwide Children’s Hospital, The Ohio State University College of Medicine, Columbus, OH, USA Kathleen  F.  Mallett, MSN, FNP-C, CNN-NP Division of Nephrology, Children’s Mercy Kansas City, Kansas City, MO, USA Cherry  Mammen, MD, MHSc Department of Pediatrics, Division of Nephrology, BC Children’s Hospital, Vancouver, BC, Canada Mignon  I.  McCulloch, FCP Paeds, FRCPCH  Red Cross War Memorial Children’s Hospital, Paediatric Nephrology and Solid Organ Transplant, Rondebosch, Cape Town, South Africa Mark M. Mitsnefes, MD, MS  Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA Patricia Monnier, MD, PhD  Department of Obstetrics Gynecology, Royal Victoria Hospital, Montreal, QC, Canada Amy Nau, MBA, MSN, RN, CNN  Children’s Mercy Hospital, Division of Nephrology, Kansas City, MO, USA Christina L. Nelms, MS, RD, LMNT  PedsFeeds, University of Nebraska, Kearney, NE, USA Alicia  M.  Neu, MD Division of Pediatric Nephrology, Department of Pediatrics, Pediatric Dialysis and Kidney Transplantation, The Johns Hopkins University School of Medicine, Baltimore, MD, USA Jason  G.  Newland, MD, Med Department of Pediatrics, Washington University in St. Louis, St. Louis Children’s Hospital, St. Louis, MO, USA

Contributors

Contributors

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Ali Mirza Onder, MD  Department of Pediatrics, Batson Children’s Hospital of Mississippi, Jackson, MS, USA Fabio  Paglialonga, MD Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy Lars Pape, MD, PhD  University Hospital of Essen, Department of Pediatrics II, Essen, Northrhine-Westfalia, Germany Ansara  H.  Piebenga Parent of Child with Chronic Kidney Disease, Mt. Pleasant, SC, USA Nonnie  Polderman, BS Division of Nephrology, British Columbia Children’s Hospital, Vancouver, BC, Canada Evgenia  Preka, MD  Paediatric Nephrology, University Southampton NHS Foundation Trust, Southampton, UK

Hospital

Bruno  Ranchin, MD Pediatric Nephrology Department, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France Lesley Rees, MD, FRCPCH  Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK Kristin Loiselle Rich, PhD  Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA Douglas  C.  Rivard, DO Department of Radiology, Children’s Mercy, Kansas City, MO, USA Claudio  Ronco, MD Department of Medicine, University of Padova, Padova, Italy Department of Nephrology Dialysis and Transplantation, International Renal Research Institute (IRRIV), San Bortolo Hospital, Vicenza, Italy Isidro B. Salusky, MD  Division of Pediatrics Nephrology, Department of Pediatrics, UCLA Mattel Children’s Hospital, Los Angeles, CA, USA Betti  Schaefer, MD Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany Franz Schaefer, MD  Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany Claus  Peter  Schmitt, MD  Center for Pediatric and Adolescent Medicine, Univercity Hospital Heidelberg, Heidelberg, Germany David Selewski, MD, MS  Department of Pediatrics, Division of Pediatric Nephrology, Medical University of South Carolina, Charleston, SC, USA Christine  B.  Sethna, MD, EdM  Pediatric Nephrology, Cohen Children’s Medical Center of New  York, Zucker School of Medicine at Hofstra/ Northwell, Feinstein for Medical Research, New Hyde Park, NY, USA

xx

Rukshana  Shroff, MD, FRCPCH, PhD Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK Michael  J.  G.  Somers, MD Division of Nephrology, Boston Children’s Hospital, Boston, MA, USA Scott M. Sutherland, MD  Department of Pediatrics, Division of Nephrology, Stanford Children’s Health and Lucille Packard Children’s Hospital, Stanford, CA, USA Sarah  J.  Swartz, MD Department of Pediatrics, Renal Services, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, USA Jordan M. Symons, MD  Department of Pediatrics, University of Washington School of Medicine, Seattle Children’s Hospital, Seattle, WA, USA Leyat Tal, MD  Department of Pediatrics, Renal Section, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, USA Christina Taylan, MD  Department of Pediatric Nephrology, Children’s and Adolescents’ Hospital, University Hospital of Cologne, Cologne, Germany Chikako  Terano, MD Department of Nephrology, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan Allison Tong, PhD, MM, MPH (hons) BMedSc  The Children’s Hospital at Westmead, Centre for Kidney Research, Sydney, NSW, Australia Anne  Tsampalieros, MD, PhD Children’s Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada Emma  Heydari  Ulrich, BSc, MD, FRCPC Division of Nephrology, Department of Pediatrics, Stollery Children’s Hospital, University of Alberta, Edmonton, AB, Canada Enrico  Eugenio  Verrina, MD Dialysis Unit, IRCCS Istituto Giannina Gaslini, Department of Pediatrics, Genoa, Italy Enrico  Vidal, MD, PhD Department of Woman’s and Child’s Health, Pediatric Nephrology, Dialysis and Transplant Unit, University-Hospital of Padova, Padua, Italy Bradley  A.  Warady, MD  Department of Pediatrics, Division of Pediatric Nephrology, Children’s Mercy Kansas City, Kansas City, MO, USA Aaron  Wightman, MD, MA  Divisions of Nephrology and Bioethics and Palliative Care, Department of Pediatrics, Seattle Children’s Hospital, University of Washington School of Medicine, Seattle, WA, USA Rosanne  J.  Woloschuk, BSc Nutr RD  Jim Pattison Children’s Hospital, Royal University Hospital, Saskatoon, SK, Canada Elke Wühl, MD  Center for Pediatrics and Adolescent Medicine, University Hospital Heidelberg, Division of Pediatric Nephrology, Heidelberg, Germany

Contributors

Contributors

xxi

Hui-Kim  Yap, MD Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Rima  S.  Zahr, DO Pediatric Nephrology and Hypertension, Le Bonheur Children’s Hospital, University of Tennessee Health Science Center, Memphis, TN, USA Michael  Zappitelli, MD, MSc Division of Nephrology, Department of Pediatrics, Toronto Hospital for Sick Children, University of Toronto, Toronto, ON, Canada Joshua Zaritsky, MD, PhD  Department of Pediatrics, Nemours/A.I. duPont Hospital for Children, Wilmington, DE, USA

Part I Essential Primers

1

Notes on the History of Dialysis Therapy in Children Steven R. Alexander and Pierre Cochat

Introduction Prior to the 1950s and 1960s, the study and management of disorders of the kidney was the province of general physicians. As described by Stuart Cameron, along with the introduction of the renal biopsy and its interpretation, the introduction of dialysis was “…an important motor which accelerated the emergence of nephrology as a specialty. Suddenly there was a need for specialist knowledge to apply the complex data from the increasing number of critically ill patients who survived their primary disease only to go into acute renal failure…” [1, 2]. When long-term dialysis became possible in the 1960s, hundreds of adult dialysis units sprang up in North America and Europe, and by the 1970s, nephrology had become “…an autonomous specialty with an uneasy relationship to general internal medicine. There is no doubt that those physicians who chose to make dialysis their principal interest were to some extent a breed apart…” [1]. In contrast, the discipline of pediatric nephrology emerged in response to different drivers. S. R. Alexander (*) Department of Pediatrics, Lucile Packard Children’s Hospital at Stanford, Stanford, CA, USA e-mail: [email protected] P. Cochat Service de néphrologie rhumatologie dermatologie pédiatriques, Centre de référence des maladies rénales rares, Hospices Civils de Lyon & Université Claude-Bernard Lyon 1, Lyon, France

Based in the classic work of pediatric physiologists on fluid and electrolyte metabolism, regulation of intracellular and extracellular fluid, acid-base homeostasis, and parenteral fluid therapy, the first generation of pediatric nephrologists who arose in the 1950s and 1960s were rarely exposed to the care of children with acute or chronic renal failure [3, 4]. It is emblematic that the early starting point of pediatric nephrology as a specialty is traced by many to the organization of the International Study of Kidney Disease in Children (ISKDC) in the 1960s, which was a study of childhood nephrotic syndrome [1]. Early pediatric nephrologists rarely cared for children suffering what is now called acute kidney injury (AKI), a role more often played by pediatric surgeons. Those who cared for children with what is now known as chronic kidney disease (CKD) focused on dietary restrictions and diuretic, antibiotic, and electrolyte therapy, attempting to ease the progression to end-stage kidney disease (ESKD). When ESKD was reached, older children and adolescents often had to look to adult ESKD programs for access to chronic dialysis and transplantation; infants and younger children were frequently offered only palliative care [5]. During the past six decades, the landscape has changed dramatically. Acute and chronic dialysis is now routinely available for children throughout the world, and the study of dialysis therapy and the disordered physiology of the pediatric patient with AKI or ESKD has come to occupy a prominent if not dominant place in pediatric

© Springer Nature Switzerland AG 2021 B. A. Warady et al. (eds.), Pediatric Dialysis, https://doi.org/10.1007/978-3-030-66861-7_1

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nephrology research [4]. Pediatric nephrology training programs worldwide are expected to teach trainees how to dialyze children of all ages, and modern pediatric nephrology training program graduates come equipped with technical skills unimagined by the founders of the specialty. With increasing acceptance of universal access to dialysis therapy for children has come a concomitant growth in the demand for pediatric nephrologists, leading to a steady increase in the size of pediatric nephrology programs. Unlike adult dialysis programs, many of which long ago separated from their academic roots, pediatric dialysis programs remain firmly grounded in university medical centers and medical school-­ affiliated children’s hospitals, a fortunate association that has promoted a culture of scientific inquiry in what easily could have become a purely technical and derivative discipline. In this chapter we have attempted to briefly review selected high points in the development of dialysis therapy for children, focusing on the ingenuity and resourcefulness of some of these early pioneers. It is an exciting story. We have left a detailed description of these innovations to the chapters that follow. Our goal is to place these advances in historical context, acknowledging the debt owed those pioneering pediatric nephrologists, nurses, engineers, dieticians, and social workers and their young patients and their families. All have helped make a complex and life-­ sustaining therapy a part of routine medical management for children throughout the world.

Peritoneal Dialysis The roots of the use of peritoneal dialysis (PD) in children can be traced to the use of the peritoneal cavity to treat dehydration in infants. In 1918, two Johns Hopkins pediatricians, Kenneth Blackfan and Kenneth Maxcy, first described the successful fluid resuscitation of dehydrated infants using intraperitoneal injections of saline solution [6]. At that time, dehydrated infants too small or dehydrated to permit intravenous access were treated by “clysis,” injecting fluids into the subcutaneous tissues. Blackfan and Maxcy noted

S. R. Alexander and P. Cochat

that clysis was often disappointing, because “… absorption from the subcutaneous tissues is often very slow and after repeated injections is almost nil….” Injection of physiologic sodium chloride solution directly into the peritoneal cavity was “…simple…practicable and accompanied by a minimum of risk to the patient…” [6]. These same characteristic features, simplicity, practicality, and safety, have made peritoneal dialysis particularly well suited for use in children for the past 100 years. The 1949 experience of Henry Swan and Harry H. Gordon should be credited as the first conclusive demonstration of the lifesaving potential of PD when used to treat acute renal failure in children [7]. These pioneering Denver pediatric surgeons employed continuous peritoneal lavage to treat three acutely anuric children, 9 months, 3 years, and 8 years of age. Rigid surgical suction tips covered by metal sheaths with multiple perforations were implanted into the upper abdomen and pelvis allowing large volumes (~33  liters/ day) of sterile, physiologic Tyrode’s solution to flow by gravity from 20-liter carboys continuously into and out of the abdomen. Ultrafiltration was controlled by adjusting the dextrose concentration between 2% and 4%, while dialysate temperature was regulated by changing the number of illuminated incandescent 60-W light bulbs in a box placed over the inflow tubing. The two older children regained normal renal function and survived after 9 and 12 days of peritoneal lavage; the infant was sustained for 28  days, but did not regain renal function and succumbed to obscure complications. Peritonitis occurred only once and responded to intraperitoneal antibiotics. Removal of urea and maintenance of fluid balance were successful in all three children, although obviously herculean efforts were required to deliver this therapy [7]. Although impractical and technically difficult to deliver, the continuous peritoneal lavage of Swan and Gordon should be credited as the first conclusive demonstration of the lifesaving potential of PD when used to treat acute kidney injury (AKI) in children. It was more than a decade before the use of PD in children was again reported. During the

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1950s and early 1960s, the development of disposable nylon catheters [16] and commercially prepared dialysis solutions led to the replacement of continuous peritoneal lavage techniques with intermittent forms of PD, allowing the routine use of peritoneal dialysis as a treatment for AKI and some intoxications in adults [8–11]. These methods were adapted for use in children in the early 1960s by teams in Indianapolis and Memphis [12, 13] who also showed how PD could be effective in the treatment of the boric acid and salicylate intoxications commonly seen in small children at that time [14, 15]. Subsequent reports established PD as the most frequently employed renal replacement therapy (RRT) for AKI in pediatric patients [16–22]. Compared to hemodialysis (HD), PD appeared ideally suited for use in children. It was intrinsically simple, practical, safe, and easily adapted for use in patients of all ages and sizes, from premature newborn infants to fully grown adolescents. In contrast, HD at this early stage of development required large extracorporeal blood circuits and vascular access that was difficult to achieve and maintain in pediatric patients (see later in this chapter). Although successful as a treatment for AKI, early PD techniques were poorly suited for the child with ESKD. The need to re-insert the dialysis catheter for each treatment made prolonged use of PD in small patients problematic. In the largest published pediatric series from the disposable catheter period, Feldman, Baliah and Drummond maintained seven children, ages 6–14  years on intermittent peritoneal dialysis (IPD) for 3.5–8 months while awaiting transplantation [23]. Treatments were infrequent, ranging from every 7–12 days to every 4–12  weeks. Although complications were few, at the time of the report, two children had died, two had been transferred to HD, and three remained on PD; no child had been successfully transplanted [23]. More than any other advance, it was the development of a permanent peritoneal catheter that made long-term PD an acceptable form of treatment for pediatric patients. First proposed by Palmer, Quinton, and Gray in 1964 [24] and later refined by Tenckhoff and Schechter in 1968 [25],

the permanent PD catheter revolutionized chronic PD for adults and children in the same way the Scribner shunt transformed chronic HD, both making long-term renal support therapy possible. In Seattle, the new permanent peritoneal catheters were combined with an existing automated dialysate delivery system that had been designed by Boen, Mion, Curtis, and Shilipetar for use in the home [26, 27]. In the early 1970s, this work culminated in the establishment in Seattle of the first pediatric chronic home PD program [28]. The success of the Seattle program throughout the 1970s showed that chronic IPD could be a practical option for some children with ESKD [29]. Additional limited experience with chronic IPD was reported from several other pediatric centers [30–33], but enthusiasm for the technique was limited. Chronic IPD seemed to involve many of the least desirable features of chronic HD, including substantial fluid and dietary restrictions, immobility during treatments that lasted many hours, and the need for complex machinery requiring parental or nursing supervision, without providing the efficiency of HD.  Moreover, it became clear from efforts to maintain adult ESKD patients on chronic IPD that long-term technique survival was not often achieved [34]. Inadequate dialysis resulting in severe undernutrition and frequent peritonitis were cited as the most common causes of IPD failure in the 1970s, leading to widespread reliance on HD among adult dialysis programs and limited access to chronic dialysis for children, especially infants. Pediatric dialysis and transplant programs at the time routinely excluded infants and small children, reasoning with Hurley that “…although it is technically possible to perform hemodialysis and transplantation in these children, the myriad of well-known problems… should contraindicate such therapy…” [35], and with Reinhart, “…we may find the price the child pays for life too great…” [36]. During a period in which advances in ESKD therapy pushed the upper age limits for successful therapy well into the seventh and eighth decades, the youngest ESKD patients remained therapeutic orphans, considered by many to have severely limited chances for survival [36, 37].

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The description of what became known as continuous ambulatory peritoneal dialysis (CAPD) by Robert Popovich and Jack Moncrief and associates in 1976 heralded a new era in the treatment of ESKD in children [38]. As originally described, 2  liters of dialysate were infused into an adult’s peritoneal cavity and retained for 4–5 hours, then drained, and repeated a total of five times per day while the patient went about regular daily activities [39]. As early experience with CAPD in adults was analyzed by pediatric nephrologists, it became clear that this new modality offered theoretical advantages to children when compared to HD and IPD that included near steady-state biochemical control, no disequilibrium syndrome, greatly reduced fluid and dietary restrictions, and freedom from repeated dialysis needle punctures. CAPD allowed children of all ages to receive dialysis at home, which offered a more normal childhood. And for the first time, CAPD made it possible to routinely provide chronic dialysis for infants and small children, which meant that this population could now be safely maintained on CAPD until they reached a transplantable age and size. The first child to receive CAPD was a 3-year-­ old girl in Toronto in 1978 [40, 41]. Although a number of pediatric dialysis programs in North America [42–45] and Europe [46, 47] quickly followed suit, enthusiasm in many areas was tempered by the availability of dialysis fluid only in 2000-mL containers. In Canada, small-volume plastic dialysis fluid containers were provided by Baxter, Inc. soon after the first pediatric CAPD patients were trained there in 1978, but it would be another 2 years before small-volume containers became available in the United States and the rest of the world [48]. During the 1980s, the popularity of CAPD for children spread worldwide [49]. In Japan, where transplantation was less common due to religious prohibitions on organ donation, Masataka Honda and other pioneers established large CAPD programs that demonstrated the long-term capabilities of the modality in children [50]. Pediatric nephrologists in developing countries soon realized that CAPD was relatively affordable, which meant that ESKD was no longer an inexorably

S. R. Alexander and P. Cochat

lethal condition for children from families with limited resources [51–53], and throughout the world, the survival of so many more children with ESKD increased demand for the multidisciplinary pediatric specialists required to care for them. The next big step in the evolution of PD for children was the resurgence of automated cycling machinery. As we have seen, during the 1960s and 1970s, automated PD machinery was used to deliver chronic IPD, but treatments were infrequent, with patients often receiving three PD treatments per week, usually for 12 hours overnight. Following the success of CAPD, in the early 1980s, quality of life issues made a revival of interest in automated PD inevitable in those countries where it could be afforded. The CAPD technique required interruption of daily activities several times each day for dialysis exchanges; how much easier and less intrusive it would be to relegate dialysis to nightly exchanges performed by automated cyclers while the patient and family slept. The first reports of an automated dialysis fluid cycling device adapted to provide “continuous” cycler PD (CCPD) were published in 1981 by groups in Charlotte, North Carolina, and Houston, Texas [54, 55]. The technique maintained the principle of continuous PD by cycling dialysate exchanges through the night and leaving an exchange in place during the day. CCPD was first shown to work in a pediatric patient by the Houston group in 1981 [55]. Soon, CCPD became extremely popular among pediatric dialysis programs in developed countries worldwide [56–61]. During the late 1980s, improvements in renal transplantation increased renal allograft and patient survival rates so dramatically in children that all forms of dialysis were viewed even more as a bridge to get children safely to or between kidney transplants [56]. The ready availability of potent vitamin D analogues, ESKD-friendly phosphate binders and nutritional supplements and formulas, controlled enteral nutrition via gastrostomy or nasogastric tubes, recombinant human erythropoietin, and recombinant human growth hormone (see Chaps. 26, 27, 28, 29, 30, 31, and 32) gave pediatric nephrologists a power-

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ful armamentarium with which to bring the child on chronic dialysis safely to transplantation in relatively good condition. Attention could then be turned to quality of life issues, scholastic and emotional development, and child and family psychosocial adjustment to the rigors of ESKD and chronic dialysis (see Chaps. 34 and 35). Before 1982, fewer than 100 pediatric patients had been treated with CAPD worldwide, and CCPD for children was virtually unknown. During the ensuing three decades, continuous forms of PD became available in pediatric dialysis centers throughout the world. Regional, national, and international multicenter study groups and registries developed during this period have since added much to our knowledge of peritoneal dialysis in children [57–62]. These efforts have spawned an extensive series of clinical guidelines and treatment options that will be discussed in many of the chapters that follow.

sheets of cellulose acetate used in the packing industry; in addition, it had the necessary qualities of a good dialysis membrane: it could be easily sterilized without injury to the material and had a long shelf life. When cellophane tubes became widely available as sausage casings in the 1920s, studies in animals showed the casings also made excellent diffusion membranes [66]. Clinical application of cellophane and heparin in the construction of a dialysis device awaited Kolff’s invention of the rotating drum kidney in 1944. Pediatric application of the Kolff artificial kidney was first reported in 1950 by John Merrill and his colleagues in Boston who included a 3 1/2-year-old boy with nephrotic syndrome in their initial series of 42 adult patients dialyzed using a rotating drum machine essentially the same as Kolff’s original design [67].

Hemodialysis The clinical use of an “artificial kidney” was pioneered in 1944  in adult patients suffering from acute renal failure by Willem J. (“Pim”) Kolff [63], a Dutch physician in Nazi-occupied Holland during the Second World War. Kolff’s interest in dialysis grew from his experiences caring for young patients with renal failure for whom treatment options were essentially nonexistent at that time [64]. Prior to Kolff’s remarkable invention, the stage had been set for the introduction of an extracorporeal dialysis device by the availability of two key elements: heparin and cellophane. Heparin was first purified from an extract of liver tissue in 1916 by a second year medical student at Johns Hopkins, Jay MacLean, working in the laboratory of a prominent hematologist, William H. Howell [65]. Heparin rapidly replaced hirudin, a naturally occurring, but often toxic, anticoagulant extracted from the heads and gullets of leeches. The basis for cellophane is cellulose, a substance first purified from wood in 1885. Cellophane had been available since 1910 as

As described by Merrill: “…blood is led from the radial artery by means of an inlying glass cannula through a rotating coupling to the surface of a revolving metal drum. Here it passes through a length of cellophane tubing (~20 meters) wound spirally around the drum, and is carried by the motion of the drum to the distal end. During its course, the blood-filled tubing is passed through a rinsing fluid maintained at a constant temperature of 101 degrees F in a 100 liter container. Into this medium, diffusion from the blood takes place through the cellophane membrane. Distally, the blood is passed through a second rotating coupling, and pumped to inflow flasks, whence it is fed by gravity to a vein in the forearm through another inlying cannula….” [67] Merrill’s pediatric patient received a single 4-hour dialysis treatment and was said to have had “…modest improvement, but of short duration…” [67]. In 1955, FM Mateer, L Greenman, and TS Danowski described their experience at the Children’s Hospital of Pittsburgh with eight hemodialysis treatments in five severely uremic children, 7–15  years of age, all of whom were “…either stuporous or confused... overbreathing present in three of the five… (one child) had developed pulmonary edema, and convulsions

8

had appeared in (two children)…” [68]. Their equipment was built by the Westinghouse Company based on an Alwall coil kidney design [69]. Alwall’s coil kidney in effect turned Kolff’s rotating drum on its end submerging the coils of cellophane tubing completely in the dialysate bath. Mateer’s version of the coil kidney was more compact than the Kolff machine, consisting of ~15 meters of 1 1/8-inch cellophane tubing wound on stainless steel screens submerged in a warmed 32-liter bath of dialysate. An in-line roller pump propelled heparinized blood through the tubing from the radial artery through the cellophane coils to return via the saphenous vein. Dialysate consisted of Pittsburgh tap water to which was added sodium, calcium, chloride, bicarbonate, glucose, and variable amounts of potassium; a fresh batch was mixed every 200  minutes, and with every bath change, an antibiotic (usually oxytetracycline) was injected into the tubing leading to the artificial kidney [68]. For these severely uremic children, hemodialysis was clearly a heroic treatment that was surprisingly effective, if only temporarily. After treatments lasting 2–13 hours, all patients became more alert, pulmonary edema and overbreathing improved, phosphorus levels fell, and blood non-­ protein nitrogen levels decreased from an average of 231 to 113 mg/dL. Two of the five children survived, one recovering normal renal function after an episode of what may have been hemolytic uremic syndrome (“...previously well... bloody diarrhea...oliguria, albuminuria, profound anemia...”). Mateer concluded that, while dialysis had been successful in supporting this child’s reversible ATN, “...in view of the difficulty in assessing elements of reversibility of renal failure in chronic states, more frequent use of dialysis is indicated in these situations...” [68]. In 1957, Frank H Carter and a team at the Cleveland Clinic that included Willem Kolff, who had emigrated to the United States in 1950, next described eight HD treatments in five children (2–14 years of age) using an improved and disposable Alwall twin coil kidney that could be modified for children 90 days whose hemoglobin is within the defined target range 10–12 g/dL by 15% by May 2020.

 ow Will We Know a Change Is H an Improvement? In order to determine whether an intervention that has been implemented has actually led to an improvement, the team will need to have a balanced set of measurements [24]. These measures can be divided into outcome measures, process measures, and balancing measures [19, 20, 25] (Table 7.4). Setting global measures can act as a reminder of the overall goal of the QI project and what the team is ultimately trying to achieve. Cycle measures can vary from PDSA cycle to PDSA cycle, depending on what was learned in the previous cycle and what new intervention is being tested [20].

Outcome measure Process measure Balancing measure

How does the system affect your patient? Is the system/intervention performing as planned? Are there unintended consequences?

Once the problem and measures are defined, the next step is to plan for change and test for improvement. The Model for Improvement framework of Plan-Do-Study-Act (PDSA) cycle is a process where teams can test a change, gather data, and, based on the results, determine the next PDSA cycle, leading to a series of PDSA cycles until the final aim is reached (Fig.  7.5). Unlike research, testing change on a small scale allows the team to test multiple interventions without disrupting the system as a whole and makes it less likely to create resistance to the final change.

Plan During the plan stage, the team needs to set the goals and objectives for the PDSA cycle. Determine what your outcome, process, and balancing measures are for this PDSA cycle and over what time period its success will be assessed. These measures may be different from the global measures. Describe in detail how the test will be carried out, and determine who is going to be responsible for each task, including the plan for data collection. Here, predictions on what is expected to happen when the test is implemented should be stated. Predictions are helpful to compare to actual practice as a way to examine why a change did or did not make the anticipated improvement [25]. The PDSA worksheet (Fig.  7.6), by the Institute for Healthcare Improvement, is a helpful guide on how to methodologically approach a PDSA cycle. After extensive review to understand why dialysis dependent patients were not meeting

H. Currier et al.

96 Fig. 7.5 Plan-Do-­ Study-Act (PDSA) cycle

Chenges That Result in Improvement

TA DA

D P

A P

S D

Hunches Theories Ideas

A

P

S

D

A

P

S

D

S A

Implementation of Change

Wide-Scale Tests of Change

Follow-up Tests

Very Small Scale Tests

the target hemoglobin goal, the team identified that provider variability as it relates to dose adjustment of ESA was one of the top areas for improvement. To minimize variability, an anemia management protocol was developed, and one dialysis nurse was designated as the anemia manager to adjust all ESA and iron dosing. The outcome measure is the number of HD patients whose Hgb was in target range between 10 and 12 g/dL. The process measure is the number of HD patients whose ESA and iron were adjusted by the anemia manager according to the anemia management protocol, and the balancing measure is whether or not ESA and/or iron dose adjustments were delayed if the anemia manager was not available.

Do The “Do” stage is where the intervention that was described in the planning stage is implemented into the clinical setting [19, 20, 25]. Data are collected on the predefined measures.

Study The study stage looks at how the results from the intervention compare with the initial predictions. Since multiple cycles can be done in a short amount

of time, the data can be analyzed over time [19, 25]. A simple, yet powerful, way to determine whether or not the implementation is resulting in change is to use a run chart (also termed time series chart) [20]. A run chart is a visual display of data plotted over time. It illustrates whether a change has led to an improvement, and whether the change shows nonrandom variations or patterns [20, 25]. The use of a run chart in improvement work includes [20, 26]: • Displaying data to make process performance visible • Determine whether a change tested resulted in improvement • Determine whether gains made through improvement are being sustained over time To construct a run chart, the horizontal axis is usually a unit of time, and the vertical axis is the quality measure being studied. In order to interpret a run chart, the median will need to be calculated and drawn as the centerline. Using the following probability-based rules allows for objective analysis of the run chart to determine whether the improvement happened by chance or not [26]. • Shift –– Shift is when six or more data points fall above or below the median line. If the data point falls on the median line, then it does not count.

7  Quality Improvement Strategies and Outcomes in Pediatric Dialysis Fig. 7.6 PDSA worksheet

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Template: PDSA Worksheet Objective:

Act

Plan

Study Do

1. Plan: Plan the test, including a plan for collecting data.

Questions and predictions:

Who, what, where, when:

Plan for collecting data

Act

Plan

Study Do

2. DO: Run the test on a small scale.

Describe what happened. What data did you collect? What observations did you make?

Act

Plan

Study Do

3. Study: Analyze the results and compare them to your predictions.

Summarize and reflect on what you leared:

Act

Plan

Study Do

4. Act: Based on what you leared from the test, make a plan for your next step.

Determine what modifications you should make – adapt, adopt, or abandon:

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• Trend –– If five or more data points are going in the same direction (all up or all down). If two data points are the same, only one is counted. • Runs –– A run is a series of data points on one side of the median. If the process is occurring in a random pattern, the data points should go above and below the median with regularity. If the process is occurring in a nonrandom pattern, then the run chart will show “too few” or “too many” runs. The way to determine how many runs there are is to count the number of times the line connecting the data points crosses the median and add one. To determine if there are “too few” or “too many” runs, one can reference the published charts based on a 36.3 kg

Recommended volume of blood culture (ml)a 2 4 6

% of total blood volumea 4 4 3

20

2.5

40–60

1.8–2.7

Assumes two sets of blood cultures are obtained This table is adapted from Miller et al. [62]

a

Diagnostics Identifying the specific bacterial pathogen causing an infection in a patient receiving dialysis is paramount in performing effective antimicrobial stewardship. Data have demonstrated that the rate of culture-negative peritoneal dialysis-associated peritonitis can be as high as 30% [28]. Without pathogen identification and antibiotic susceptibilities, unnecessary broad-spectrum antibiotics with prolonged durations will occur. Therefore, specific strategies are essential to maximize the ability to identify bacterial pathogens in patients receiving hemodialysis and peritoneal dialysis.

for non-specific symptoms, then blood cultures must be obtained. One study demonstrated that a majority of CRBSIs had already received antimicrobials prior to obtaining a blood culture, which can significantly decrease the positivity rate of these important cultures [61]. Blood cultures should still be obtained if a patient has already received antibiotics when suspicion for CRBSI is present. After obtaining blood cultures, the most important factor in recovering bacteria in adults and children is the volume of blood collected [62]. Studies have shown, even in children, that blood Hemodialysis culture positivity rate is significantly improved when the appropriate amount of blood is obtained In patients receiving hemodialysis, non-specific [63]. For adults, 20–30  ml is recommended for signs and symptoms could signify a catheter-­ each blood culture set. In children, the blood volrelated bloodstream infection (CRBSI). For this ume collected can be based on weight by kiloreason, if antibiotics are to be empirically started gram or age of the child (Table 8.1). Due to the

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logistical difficulty in using weight, some institutions have recommended that for every 1 year of life, 1 milliliter of blood should be obtained. The minimum blood volume obtained is 1 ml for preterm and term infants. Every institution that obtains blood cultures should have standard processes and recommendations on blood culture volumes and a method to evaluate the reliability of this collection. Another important factor in maximizing the sensitivity of blood cultures is the number of sets obtained. When a blood culture is obtained, ideally the blood volume is placed into an aerobic and anaerobic bottle, one set. Additionally, two sets of blood cultures should be obtained from different sites (e.g., hemodialysis catheter hub, hemodialysis circuit, peripheral) [64, 65]. Not only does this help in better identifying pathogens, but it also allows clinicians to better determine if a bacterium identified from a blood culture is possibly a contaminant. Data have demonstrated that blood culture contamination is higher when obtained from catheter hubs versus peripheral cultures [62]. However, in patients on chronic dialysis, peripheral venipuncture is often avoided to preserve vessels for future access. For this reason, guidelines have recommended in hemodialysis patients with suspected CRBSI that two sets of blood cultures may be obtained from the hemodialysis circuit and the catheter hub. If dialysis is ongoing and obtaining blood cultures is not feasible or desirable from the catheter hub, then two sets of blood cultures collected from the hemodialysis circuit, separated in time (minutes), may be a practical approach, although no data are available assessing the sensitivity and specificity of this approach [64, 65].

may either be centrifuged or 20–30  ml placed into three or four blood culture bottles. If the fluid is centrifuged, the sediment is resuspended with approximately 10 ml of saline, and then this fluid is plated on solid microbiology media that identify aerobic and anaerobic bacteria. Importantly, the fluid should be processed within 6  hours of being collected. In some instances, families in rural communities will need to collect the fluid on their own and then bring it to a facility that has the microbiology capabilities needed to perform the required cultures [28].

Peritoneal Dialysis As previously mentioned, culture-negative peritoneal cultures occur in almost one-third of peritoneal dialysis-associated peritonitis. As in hemodialysis, peritoneal cultures should be obtained prior to the start of antibiotics, and a large volume of peritoneal fluid is recommended. After obtaining up to 50 ml of peritoneal fluid, the fluid

Infection Prevention Essential to reducing the use of antibiotics is preventing infections. In hemodialysis and peritoneal dialysis, extra attention is needed to prevent healthcare-associated infections due to the increased risk of infection associated with the presence of a foreign body. The development of required procedures for both the placement and maintenance of hemodialysis and peritoneal catheters has led to significant reductions in bloodstream infections, exit site infections, and peritonitis [34, 66]. The CDC has developed a guideline on the prevention of catheter-related bloodstream infections with key areas to address (Table 8.2). While Table 8.2  Key areas for the prevention of intravascular catheter infections Education, staffing, and training Selection of catheter and site Hand hygiene and aseptic technique Maximal sterile barrier precautions Skin preparation Catheter site dressing regimens Catheter securement devices Antimicrobial and antiseptic impregnated catheters

Antibiotic lock prophylaxis Replacement of catheters Replacement of administration sets Patient cleansing Systemic antibiotic prophylaxis Performance improvement Anticoagulants Needleless intravascular catheter systems

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this guideline addresses prevention of all catheter-­ related bloodstream infection, it lists important procedures specific to dialysis patients and hemodialysis catheters. For example, povidone iodine antiseptic ointment or bacitracin/gramicidin/polymyxin B ointment is recommended at the exit site after insertion of the catheter and after each dialysis session [67]. A comprehensive peritoneal dialysis infection prevention bundle specifically for children has been developed and shown to significantly reduce peritoneal dialysis-associated peritonitis by over 30%. Important to this prevention bundle was the development of a performance improvement collaborative, SCOPE (Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease), that provided the infrastructure for ­ dialysis facilities to collaborate and learn together the best methods for implementation of the prevention bundle elements [34, 68]. Similar to hemodialysis catheters, prevention strategies are targeted to both the insertion of the peritoneal catheter and the ongoing maintenance of assuring that the catheter does not become infected. Three bundles were developed which included (1) peritoneal dialysis catheter insertion bundle, (2) peritoneal dialysis catheter/exit site follow-up care bundle, and (3) peritoneal dialysis patient and caregiver training bundle. The specific elements in each bundle can be found in Chap. 16.

Vaccination Vaccination is a key component in efforts to reduce the use of antibiotics by preventing unnecessary infections. Children with chronic kidney disease are at increased risk of infection due to their impaired immune system. While concerns have existed about a child’s response to vaccines while on dialysis, data suggest that their immune response to many vaccines is not significantly different from children with normal renal function. Children on dialysis should follow the recommended schedule published annually by the CDC’s Advisory Committee on Immunization Practices (ACIP). Children receiving corticosteroids at a daily dose greater than

2 mg/kg or 20 mg for more than 14 days should not receive the measles, mumps, rubella, and varicella zoster vaccines, as they are comprised of attenuated live viruses. In addition to the routine schedule, dialysis patients are at increased risk of severe disease due to influenza and Streptococcus pneumoniae. Annually, all children on dialysis should receive the inactivated influenza vaccine. For children less than 8 years of age who have not received the vaccine, two doses are required in the first year separated by 1 month. For S. pneumoniae, children should receive the ACIP-required 13-valent conjugate vaccine plus the 23-valent polysaccharide vaccine once they are 2 years of age or older. For older children or teenager who received the 7-valent conjugate, a single dose of the 13-valent vaccine should be given, followed 4 weeks later by the 23-valent vaccine. The 23-valent polysaccharide vaccine should be administered 5 years after the original dose [69].

Summary The increasing incidence of antibiotic-resistant bacterial infections threatens the ability of clinicians to be able to provide important care such as dialysis to our pediatric patients. Children requiring dialysis are at increased risk of these types of infections. Antimicrobial stewardship is imperative in this population to aid in limiting the potential antibiotic-resistant infections as well as adverse drug events that can be associated with the use of antibiotics (e.g., CDI). Numerous strategies have been effective in improving antibiotic use in both the inpatient and outpatient setting including prospective audit with feedback and peer comparison. Furthermore, the most effective antimicrobial stewardship relies on diagnosing the infection by obtaining the correct cultures, with the correct blood or peritoneal fluid volumes prior to the use of antibiotics. Finally, the best way to decrease antimicrobial use and perform the best stewardship is to prevent infections through the use of evidenced-based care bundles and vaccination.

8  Antibiotic Stewardship in the Pediatric Dialysis Unit

References

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Clostridium difficile infection resistant Staphylococcus aureus in children with no idenis associated with increased risk of death and protified predisposing risk. JAMA. 1998;279(8):593–8. longed hospitalization in children. Clin Infect Dis. 8. Herigon JC, et  al. Antibiotic management of 2013;57(1):1–8. Staphylococcus aureus infections in US chil 24. Pant C, et al. Clostridium difficile infection is associdren's hospitals, 1999–2008. Pediatrics. ated with poor outcomes in end-stage renal disease. J 2010;125(6):e1294–300. Investig Med. 2012;60(2):529–32. 9. Creech CB 2nd, et  al. Increasing rates of nasal 25. Redpath Mahon AC, et  al. Factors associated with carriage of methicillin-resistant Staphylococcus high-cost hospitalization for peritonitis in children aureus in healthy children. Pediatr Infect Dis J. receiving chronic peritoneal dialysis in the United 2005;24(7):617–21. States. Pediatr Nephrol. 2019;34(6):1049–55. 10. Fritz SA, et al. Prevalence of and risk factors for com 26. Raaijmakers R, et al. Fungal peritonitis in children on munity-acquired methicillin-resistant and methicillin-­ peritoneal dialysis. Pediatr Nephrol. 2007;22(2):288–93. sensitive staphylococcus aureus colonization in 27. Warady BA, Bashir M, Donaldson LA. Fungal peritochildren seen in a practice-based research network. nitis in children receiving peritoneal dialysis: a report Pediatrics. 2008;121(6):1090–8. of the NAPRTCS. Kidney Int. 2000;58(1):384–9. 11. Price A, et  al. Methicillin-resistant Staphylococcus 28. Warady BA, et al. Consensus guidelines for the preaureus and methicillin-susceptible Staphylococcus vention and treatment of catheter-related infections aureus screening in a cohort of haemodialysis patients: and peritonitis in pediatric patients receiving pericarriage, demographics and outcomes. J Hosp Infect. toneal dialysis: 2012 update. Perit Dial Int. 2012;32 2015;90(1):22–7. Suppl 2:S32–86. 12. Blowey DL, Warady BA, McFarland KS.  The treat 29. Gerber JS, et al. Variability in antibiotic use at chilment of Staphylococcus aureus nasal carriage in dren's hospitals. Pediatrics. 2010;126(6):1067–73. pediatric peritoneal dialysis patients. Adv Perit Dial. 30. Lee BR, et al. The burden of inappropriate antibiotic 1994;10:297–9. surgical prophylaxis in pediatric patients: a national 13. Szeto CC, et  al. ISPD catheter-related infection point prevalence study. in Pediatric Academic Society; recommendations: 2017 update. Perit Dial Int. 2018. Toronto, Canada. 2017;37(2):141–54.

110 31. Hersh AL, et  al. Antibiotic prescribing in ambu latory pediatrics in the United States. Pediatrics. 2011;128(6):1053–61. 32. Kronman MP, Zhou C, Mangione-Smith R. Bacterial prevalence and antimicrobial prescribing trends for acute respiratory tract infections. Pediatrics. 2014;134(4):e956–65. 33. Snyder GM, et  al. Antimicrobial use in outpatient hemodialysis units. Infect Control Hosp Epidemiol. 2013;34(4):349–57. 34. Neu AM, et  al. Implementation of standardized follow-up care significantly reduces peritonitis in children on chronic peritoneal dialysis. Kidney Int. 2016;89(6):1346–54. 35. Sharma A, et al. Survival and complications of cuffed catheters in children on chronic hemodialysis. Pediatr Nephrol. 1999;13(3):245–8. 36. Stefanidis CJ.  Prevention of catheter-related bacteremia in children on hemodialysis: time for action. Pediatr Nephrol. 2009;24(11):2087–95. 37. Sucupira C, et al. Surveillance system of hemodialysis-­ associated infections in a pediatric unit. Infect Control Hosp Epidemiol. 2012;33(5):521–3. 38. Wang K, et  al. Cuffed-tunneled hemodialysis catheter survival and complications in pediatric patients: a single-center data analysis in China. Int J Clin Exp Med. 2015;8(6):9765–71. 39. Gerding DN. The search for good antimicrobial stewardship. Jt Comm J Qual Improv. 2001;27(8):403–4. 40. CDC.  Core Elements of Hospital Antibiotic Stewardship Programs. Atlanta, GA: US Department of Health and Human Services; 2014. 41. CDC.  National Healthcare Safety Network (NHSN) Patient Safety Component Manual; 2018. Atlanta, GA. 42. Barlam TF, et  al. Implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016;62(10):e51–77. 43. Hecker MT, et al. Impact of syndrome-specific antimicrobial stewardship interventions on use of and resistance to fluoroquinolones: an interrupted time series analysis. Am J Infect Control. 2019; 44. Sammons JS, Toltzis P, Zaoutis TE.  Clostridium difficile infection in children. JAMA Pediatr. 2013;167(6):567–73. 45. Tamma PD, et al. Association of adverse events with antibiotic use in hospitalized patients. JAMA Intern Med. 2017;177(9):1308–15. 46. Parker SK, et al. Anti-infective acquisition costs for a stewardship program: getting to the bottom line. Clin Infect Dis. 2017;65(10):1632–7. 47. Gerber JS, et al. Effect of an outpatient antimicrobial stewardship intervention on broad-spectrum antibiotic prescribing by primary care pediatricians: a randomized trial. JAMA. 2013;309(22):2345–52.

J. G. Newland and A. M. Neu 48. Hurst AL, et  al. Handshake stewardship: a highly effective rounding-based antimicrobial optimization service. Pediatr Infect Dis J. 2016;35(10): 1104–10. 49. Metjian TA, et  al. Evaluation of an antimicrobial stewardship program at a pediatric teaching hospital. Pediatr Infect Dis J. 2008;27(2):106–11. 50. Newland JG, et  al. Impact of a prospective-audit-­ with-feedback antimicrobial stewardship program at a children's hospital. J Pediatric Infect Dis Soc. 2012;1(3):179–86. 51. D'Agata EMC, et al. The positive effects of an antimicrobial stewardship program targeting outpatient hemodialysis facilities. Infect Control Hosp Epidemiol. 2018;39(12):1400–5. 52. D'Agata EMC, et al. Clinical and economic benefits of antimicrobial stewardship programs in hemodialysis facilities: a decision analytic model. Clin J Am Soc Nephrol. 2018;13(9):1389–97. 53. McPherson C, et  al. Characteristics of pediatric antimicrobial stewardship programs: current status of the Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS) Collaborative. Antibiotics (Basel). 2018:7(1). 54. Neuman MI, et al. Influence of hospital guidelines on management of children hospitalized with pneumonia. Pediatrics. 2012;130(5):e823–30. 55. Newman RE, et  al. Impact of a guideline on management of children hospitalized with community-acquired pneumonia. Pediatrics. 2012;129(3):e597–604. 56. Hamdy RF, et al. Pediatric ASP toolkit; 2019. 57. Partners NQ.  National quality partners playbook: antibiotic stewardship in acute care; 2016. 58. Gerber JS, et  al. Durability of benefits of an outpatient antimicrobial stewardship intervention after discontinuation of audit and feedback. JAMA. 2014;312(23):2569–70. 59. Meeker D, et al. Nudging guideline-concordant antibiotic prescribing: a randomized clinical trial. JAMA Intern Med. 2014;174(3):425–31. 60. Meeker D, et al. Effect of behavioral interventions on inappropriate antibiotic prescribing among primary care practices: a randomized clinical trial. JAMA. 2016;315(6):562–70. 61. Tokars JI, et al. A prospective study of vascular access infections at seven outpatient hemodialysis centers. Am J Kidney Dis. 2001;37(6):1232–40. 62. Miller JM, et al. A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2018 update by the Infectious Diseases Society of America and the American Society for Microbiology. Clin Infect Dis. 2018;67(6):813–6. 63. Connell TG, et  al. How reliable is a negative blood culture result? Volume of blood submitted for culture in routine practice in a children's hospital. Pediatrics. 2007;119(5):891–6.

8  Antibiotic Stewardship in the Pediatric Dialysis Unit 64. Kallen AJ.  Identifying and classifying bloodstream infections among hemodialysis patients. Semin Dial. 2013;26(4):407–15. 65. Mermel LA, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-­ related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;49(1):1–45. 66. Yi SH, et al. Sustained infection reduction in outpatient hemodialysis centers participating in a collaborative bloodstream infection prevention effort. Infect Control Hosp Epidemiol. 2016;37(7):863–6.

111 67. O'Grady NP, et  al. Guidelines for the prevention of intravascular catheter-related infections. Clin Infect Dis. 2011;52(9):e162–93. 68. Neu AM, et  al. Design of the standardizing care to improve outcomes in pediatric end stage renal disease collaborative. Pediatr Nephrol. 2014;29(9):1477–84. 69. Esposito S, et  al. Vaccine administration in chil dren with chronic kidney disease. Vaccine. 2014;32(49):6601–6.

Part II Considerations Around the Initiation of Dialysis

9

The Decision to Initiate Dialysis in Children and Adolescents Rima S. Zahr, Larry A. Greenbaum, and Franz Schaefer

Introduction The initiation of chronic dialysis in a child is a dramatic event for the patient and family. There are absolute indications for initiating dialysis in some patients (e.g., bilateral nephrectomy, uremic pericarditis). In other patients, the reasons behind the timing of dialysis initiation are less clear. The pediatric nephrologist integrates a great deal of information—laboratory data, clinical impressions, and psychosocial issues—in order to reach a decision regarding the timing of dialysis initiation. An assessment of kidney function is usually a critical part of this process. There is considerable debate regarding the merits of “early” initiation of dialysis in adults. The data needed to address this issue in children is sparse, and the debate is complicated in children by issues such as growth, psychosocial factors, an

R. S. Zahr (*) Pediatric Nephrology and Hypertension, Le Bonheur Children’s Hospital, University of Tennessee Health Science Center, Memphis, TN, USA e-mail: [email protected] L. A. Greenbaum Emory University and Children’s Healthcare of Atlanta, Division of Pediatric Nephrology, Atlanta, GA, USA F. Schaefer Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany

impending kidney transplant, and the need for a lifetime of renal replacement therapy.

 ethodology for Measuring Kidney M Function Assessment of a patient’s kidney function, usually defined as the patient’s glomerular filtration rate (GFR), is useful for determining when to initiate dialysis. This purposely ignores other aspects of kidney function, such as erythropoietin production and synthesis of calcitriol, because dialysis does not replace these functions. However, GFR may be transiently affected by a variety of factors other than the intrinsic kidney disease. For example, intravascular volume depletion, nonsteroidal anti-inflammatory drugs, and antihypertensive therapy, especially angiotensin-­converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), may decrease GFR.  In such instances, a fall in GFR should be interpreted cautiously. A potentially reversible process warrants a repeat measurement of kidney function after eliminating the possible underlying cause of the decrease in the GFR. The gold standard for measuring GFR is inulin clearance, but this technique is usually only available in a research setting. Alternative exogenous substances for measuring GFR include chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA), diethylenetriaminepentaacetic acid (DTPA), iohexol, and iothalamate [1, 2].

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There is evidence for a good correlation between inulin clearance and some of these alternatives [3], although the accuracy may decrease in the setting of a low GFR [4, 5] and in patients with edema [6]. These techniques are expensive and require multiple blood draws over 3 to 4 hours, making them impractical for frequent monitoring. Single-sample methods, while more convenient, are especially problematic when the GFR is low [7]. Creatinine clearance (CrCl) is a widely used approach for estimating GFR. Like inulin, creatinine is freely filtered at the glomerulus, but unlike inulin, there is secretion of creatinine by the proximal tubule. This causes the CrCl to overestimate GFR. The effect of creatinine secretion is small at a normal GFR, causing a 5–10% overestimation of GFR.  The relative impact of creatinine secretion increases as GFR decreases, leading to a more significant overestimation of GFR. In one study of adults with a mean GFR of 22 ml/min, the CrCl was close to double the inulin clearance [8]. Further, a variety of factors influence creatinine secretion. Creatinine secretion is lower in patients with polycystic kidney disease and higher in patients with glomerular disease [9]. Some medications, such as cimetidine, trimethoprim, and some fibrates, decrease creatinine secretion. Advanced liver disease may increase creatinine secretion. Finally, a valid calculation of CrCl requires an accurately timed urine collection. All of these factors limit the accuracy of CrCl, especially at the low levels of GFR when decisions regarding dialysis initiation are necessary. Despite its limitations, CrCl is an easy and inexpensive surrogate for GFR.  CrCl is calculated via the following equation: CrCl =

U vol ´ U Cr ´ 1.73 min´ SCr ´ BSA

(9.1) where CrCl is the creatinine clearance (ml/ min/1.73 m2); Uvol, urine volume (mL); UCr, urine creatinine concentration (mg/dL); Min, collection period in minutes (1440 for 24  hours); SCr, serum creatinine (mg/dL); and BSA, body surface area in m2. A CrCl requires a timed urine collection, usually 12 or 24 hours, necessitating bladder cathe-

terization in the absence of urinary continence. This is a significant impediment to repeat measurements in young children. At low levels of GFR, the percentage of filtered urea that is reabsorbed is approximately equal to the percentage of filtered creatinine that is secreted. Therefore, the mean of CrCl and urea clearance is another way of estimating GFR; it is quite accurate at low levels of GFR in adults [10, 11]. In children, an estimated GFR (eGFR) may be calculated from the serum creatinine using an equation that uses patient height and a constant of 0.413 irrespective of age and gender [12]. The equation is referred to as the “CKiD creatinine equation” or the “modified Schwartz equation.” eGFR =

Height ( cm ) ´ 0.413

(9.2) Scr This equation and subsequent referenced equations in this chapter are based on measuring creatinine using the enzymatic method traceable to isotope dilution mass spectrometry (IDMS traceable). A different constant was used for estimating GFR with an equation using the Jaffe method for determination of creatinine [13]. Hence, it is critical to be aware of the laboratory methodology that is being utilized when applying these formulas. The accuracy of these formulas has been questioned by a number of studies [14, 15]. The formulas appear especially problematic in malnourished children and at the low levels of kidney function where decisions regarding dialysis initiation need to be made [15]. There are multiple factors that decrease the accuracy of formulas that depend on the serum creatinine concentration to estimate GFR. The serum creatinine concentration depends on the balance between creatinine generation and excretion. Creatinine is largely derived from breakdown of muscle creatine. Thus, creatinine generation is proportional to muscle mass, which varies greatly in children and is mostly related to size, but also varies due to gender, age, and individual differences. In adults, there are racial differences in creatinine generation [16]. Children with uremia may lose muscle mass due to malnutrition, possibly reducing the rise in



9  The Decision to Initiate Dialysis in Children and Adolescents

serum creatinine concentration. Spinal cord injury and amputation are other potential causes of a misleadingly low serum creatinine. During cooking, creatine in meat is converted to creatinine. Therefore, serum creatinine is partially influenced by the amount of dietary meat, which often decreases in kidney insufficiency due to phosphorus restriction and anorexia. Extrarenal creatinine excretion increases in patients with chronic kidney disease (CKD) [17]. Moreover, tubular creatinine secretion increases as the GFR decreases [8]. Extrarenal excretion and tubular secretion blunt the increase in serum creatinine concentration that should occur as GFR decreases. As stressed above, medications and the specific disease causing CKD can affect creatinine secretion as well [9]. The serum protein cystatin C, an endogenous protein produced by all nucleated cells, is an alternative to creatinine for estimating GFR [18] and is preferred in children with decreased GFR [15, 19] and obese children [20]. There are also equations that use a combination of cystatin C and creatinine to determine eGFR [12, 18, 21]. A more complex formula, derived from the CKiD study, utilizes creatinine, cystatin C, blood urea nitrogen (BUN), height, and sex for estimating GFR [22]. For adult patients, the CKD-EPI creatinine equation [23] has generally replaced older equations such as the Cockcroft-Gault [24] and the Modification of Diet in Renal Disease (MDRD) equation [25]. There are also CKD-EPI equations that utilize cystatin C alone or cystatin C and serum creatinine [26]. In young adults, there are clearly limitations of the creatinine-derived equations. For an 18-year-old, the CKD-EPI creatinine equation provides a higher eGFR than the CKiD creatinine equation [27, 28]. Neither equation is accurate in young adults when compared to iohexol GFR [28]. The CKD-EPI equations using either cystatin C alone or cystatin C with creatinine are the best options, though an average of the CKD-EPI creatinine equation and the CKiD creatinine equation is also a reasonable option [28].

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 redialysis Patient Monitoring P and Preparation for Dialysis Systematic patient monitoring is necessary in children with CKD to minimize complications such as malnutrition, hypertension, renal osteodystrophy, and poor growth. In addition, regular monitoring identifies children who have relative or absolute indications for starting dialysis. Anticipation of the need for dialysis permits non-­ emergent placement of a peritoneal dialysis catheter, creation of a vascular access for hemodialysis, or performance of a preemptive kidney transplant. Table  9.1 outlines the necessary components for monitoring children with an eGFR < 30 ml/min/1.73 m2. In addition to medical monitoring, it is important that children and families are psychologically prepared for dialysis. This includes reviewing treatment options and exploring accommodations that will be needed at home and for the child’s education.

Indications for Initiating Dialysis  bsolute Indications for Initiating A Dialysis A variety of signs and symptoms are absolute indications for dialysis initiation. These are manifestations of kidney failure that cause significant morbidity and mortality. There is usually a draTable 9.1  Evaluation schedule for children with stage IV–V chronic kidney disease Timing At least every 3 months

Every 6–12 months

Evaluation Length/height, weight gain, head circumference in infants, blood pressure, acid-base status, electrolytes, creatinine, BUN, CBC, albumin, PTH, estimation of GFR Echocardiography, ABPM, neurodevelopmental assessment in infants

Abbreviations: BUN blood urea nitrogen, CBC complete blood count, PTH parathyroid hormone, ABPM ambulatory blood pressure monitoring

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matic or marked improvement with the initiation of dialysis. An alternative explanation for the clinical finding should be considered, especially if the GFR is unexpectedly high or if dialysis does not result in improvement. Neurologic consequences of uremia that are absolute indications for dialysis include encephalopathy, confusion, asterixis, seizures, myoclonus, and wrist or foot drop. Children should begin dialysis if there is hypertension that does not respond to antihypertensive therapy or pulmonary edema due to volume overload unresponsive to diuretics. Other absolute indications for starting dialysis are pericarditis, bleeding diathesis, and refractory nausea and emesis, especially if associated with weight loss. Bilateral nephrectomy, as may be necessary in some children with congenital nephrotic syndrome or autosomal recessive polycystic kidney disease, is an absolute indication for dialysis. Beyond anuria, there is debate regarding whether there is a level of GFR that is an absolute indication for dialysis. There are recommendations that the presence of malnutrition is an indication for dialysis initiation. Again, there is no consensus regarding the measurement of malnutrition, the degree of malnutrition that must be present, or the role of alternative strategies to alleviate malnutrition prior to the institution of dialysis.

 elative Indications for Initiating R Dialysis Uremic Symptoms While severe uremic symptoms are absolute indications for dialysis, less dramatic symptoms are relative indications. These include fatigue and weakness, cognitive dysfunction, decreased school performance, pruritus, depression, nausea, emesis, anorexia, restless leg syndrome, and poor sleep patterns. The persistence and severity of these symptoms are important criteria. This is especially true when evaluating gastrointestinal symptoms. Intractable emesis is an absolute indication for dialysis, while occasional emesis,

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especially if there are no signs of malnutrition, may not require dialysis initiation. Many of the symptoms that can be associated with uremia have alternative explanations. Medications may cause fatigue, depression, or nausea. Anemia, a correctable problem, may contribute to fatigue. Depression and poor school performance may be related to psychosocial issues. Comorbid conditions may also cause significant symptoms. Conversely, many patients with uremic symptoms may minimize or deny symptoms in an effort to avoid dialysis or because they perceive these symptoms, which may have developed quite gradually, as normal.

Hyperkalemia Hyperkalemia is a potentially life-threatening complication of CKD [29, 30]. As GFR decreases, the remaining nephrons compensate by increasing potassium excretion, but there is a linear relationship between GFR and the ability to excrete a potassium load [31]. Hyperkalemia usually does not become problematic until the GFR is less than 10–20 ml/min/1.73m2, unless the potassium intake is excessive or excretion is reduced [31]. Hyperkalemia develops at a higher GFR in adults and children with hyporeninemic hypoaldosteronism, which may also cause a type IV renal tubular acidosis [31]. Similarly, other patients have a decreased tubular responsiveness to aldosterone, and this pseudohypoaldosteronism may cause hyperkalemia at higher levels of GFR [31]. These patients may also have type IV renal tubular acidosis. Medications, especially ACE inhibitors, calcineurin inhibitors, and potassium-sparing diuretics, are another important cause of reduced urinary potassium excretion. Treatment of hyperkalemia in association with CKD relies on decreasing dietary potassium intake and increasing potassium excretion. In older children, avoidance of foods with high potassium content can have a dramatic effect on potassium intake. Whereas in older children who are receiving liquid formula supplementation it is possible to select a formula with a low potassium content, the potassium content of infant formula does not vary greatly, limiting the effectiveness of formula selection. It should be noted, however,

9  The Decision to Initiate Dialysis in Children and Adolescents

that soy-based and elemental formulas are especially high in potassium. Human milk has a lower potassium content than most formulas, while cow’s milk has about twice the potassium content of most infant formulas. A reduction in the potassium delivery from infant formula is possible by fortifying the formula with sugar (e.g., Polycose) and/or fat. With a higher caloric content, less formula, and hence less potassium, is needed to provide adequate calories. Alternatively, Renastart™, a formula with a very low potassium concentration, is used as a dietary supplement or is combined with another formula; it is not meant to be given as the sole source of nutrition [32]. Increasing potassium excretion can help ameliorate the hyperkalemia of CKD. Loop diuretics increase urinary potassium excretion. Discontinuation of medications that decrease urinary potassium excretion, such as ACE inhibitors, ARBs, nonsteroidal anti-inflammatory drugs, or potassium-sparing diuretics, can have a significant effect on the serum potassium level [33, 34]. Although not usually a significant mechanism of potassium excretion, stool potassium losses become more important as kidney function declines [35]. Constipation should be treated since it may decrease stool potassium losses [36]. Sodium polystyrene sulfonate (Kayexalate®), an exchange resin, binds potassium in the gastrointestinal tract, significantly increasing stool potassium losses. Pretreatment of formula with sodium polystyrene sulfonate is effective, but may cause constipation and problems with other electrolytes, including hypernatremia due to increased formula sodium content [37–39]. Newer oral potassium exchange resins include patiromer [40] and sodium zirconium cyclosilicate [41, 42]. There is some experience pre-treating formula with patiromer [43]. Because of the effectiveness of dietary and medical interventions, the initiation of chronic dialysis is seldom necessary solely to manage hyperkalemia. Nevertheless, repeated episodes of severe hyperkalemia may be considered an absolute indication for dialysis. Poor adherence to dietary restriction or medications usually contributes to refractory hyperkalemia. Hemodialysis and peritoneal dialysis are quite effective at cor-

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recting hyperkalemia, although dietary restriction, and occasionally medical management, is usually still necessary.

Hyperphosphatemia A decrease in filtered phosphate parallels the decrease in GFR characteristic of CKD.  With mild to moderate kidney insufficiency, an increase in the fractional excretion of phosphate by the remaining nephrons initially compensates for the loss of functioning nephrons, permitting the serum phosphorus to remain normal [44]. As the GFR falls, compensation is inadequate, and hyperphosphatemia ensues, typically at CKD stage III [45, 46]. Hyperphosphatemia causes secondary hyperparathyroidism by suppressing 1,25-dihydroxyvitamin D production and calcium levels and through direct stimulation of PTH secretion [47]. Correction of hyperphosphatemia is essential for controlling secondary hyperparathyroidism. In addition, hyperphosphatemia may elevate the serum calcium-phosphorus product and contribute to vascular calcifications [48, 49]. In adult patients with CKD, serum phosphate levels predict mortality and progression of CKD [49–51], while fibroblast growth factor 23 (FGF23) levels, which increase in response to hyperphosphatemia, are a predictor of CKD progression in children [52]. The successful management of hyperphosphatemia in CKD depends on a reduction in phosphate intake by a combination of dietary phosphate restriction and the use of phosphate binders [53]. Early in kidney failure, before hyperphosphatemia develops, a reduction in phosphate intake helps to control secondary hyperparathyroidism [47]. As kidney function declines, dietary restriction alone, because of nutritional constraints and limitations of food palatability, is often inadequate to control hyperphosphatemia, necessitating the use of phosphate binders. Calcium carbonate and calcium acetate are effective phosphate binders in children with CKD, although excessive use may cause hypercalcemia and contribute to systemic calcifications [54]. Sevelamer, a calcium-free phosphate-binding agent, has been effectively utilized to control hyperphosphatemia in children

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[55]. Additional calcium-free phosphate binders include lanthanum carbonate, sucroferric oxyhydroxide, and ferric citrate [56–59]. A majority of the available phosphate binders must be administered in large doses (several grams per day) to be effective; unfortunately, the need to swallow large numbers of largesized tablets or capsules limits the acceptability of medical therapy in children. Hence, poor adherence to dietary and medical therapy is the most important obstacle to the successful control of hyperphosphatemia. While dialysis therapy removes phosphate, it is almost never adequate to control hyperphosphatemia by itself. There is a continued need for dietary restriction and phosphate binders. The initiation of dialysis because of refractory hyperphosphatemia is seldom effective at controlling hyperphosphatemia since the underlying problem, non-adherence to therapy, is still present. Hence, isolated hyperphosphatemia is seldom the only indication for dialysis, unless there is a belief that the combination of dialytic phosphate removal and improved adherence, perhaps due to the more regimented medical care required by dialysis, will facilitate control of hyperphosphatemia. The presence of refractory hyperparathyroidism further lowers the threshold for dialysis initiation.

Malnutrition Uremia causes symptoms such as emesis and anorexia that may prevent adequate caloric intake. In adults and children, dietary protein and energy intake declines as the GFR decreases [60– 64]. In children, this may adversely affect growth [65]. Infants during the first 6  months of life, when growth is rapid, are particularly vulnerable to the negative effects of poor nutrition. Studies in adult patients show an association between malnutrition when starting dialysis and decreased patient survival [62, 63, 66–75]. Nutritional parameters improve in adult patients after the initiation of dialysis [60, 63, 76–81]. When looking at body fat as an index of nutritional status, poor nutritional status at the start of dialysis was associated with a greater increase in

R. S. Zahr et al.

body fat [78]. In other studies, there was a positive correlation between the nutritional status at the start of dialysis and the follow-up nutritional status, suggesting that dialysis may not completely compensate for poor nutrition at dialysis initiation [77, 79]. The improved survival with an increased dialysis dose, the mortality risk associated with malnutrition, and the improvement in nutritional status associated with dialysis are the basis for recommendations to initiate dialysis therapy when a patient has advanced CKD and malnutrition [82–84]. Yet, there are no prospective studies demonstrating that the early initiation of dialysis improves outcome. Aggressive nutritional supplementation, possibly using an enteral feeding gastrostomy tube, may reverse malnutrition in some children without the need for dialysis [85, 86]. There is no one ideal marker of malnutrition. Signs of poor nutrition in children with CKD may include inadequate weight gain, poor linear growth, and loss of muscle mass. If malnutrition is not improved via conservative interventions, then the child with advanced CKD should begin dialysis.

Growth Failure Growth retardation is a common complication of CKD in children [87]. The causes of “uremic” growth failure include malnutrition (most markedly in infants), electrolyte and fluid losses (in children with hypo-/dysplastic kidney disorders), metabolic acidosis, osteodystrophy, and, most importantly beyond infancy, impaired function of the somatotropic hormone axis. Electrolyte and bicarbonate losses can usually be managed conservatively, with favorable effects on growth rates. Forced feeding usually improves the nutritional status, but linear growth may not respond to nutritional recovery once growth failure is established [88]. In children with stable pre-­ dialytic CKD, recombinant growth hormone therapy is indicated. The efficacy of this therapy strongly depends on residual kidney function, mandating a timely start of treatment [89, 90]. Unresponsiveness to recombinant growth hor-

9  The Decision to Initiate Dialysis in Children and Adolescents

mone may be considered as an argument to start dialysis, although improved growth rates are not consistently observed after initiation of standard peritoneal or hemodialysis [91]. However, a subsequent study demonstrated that short daily hemodiafiltration improved responsiveness to growth hormone, leading to remarkable, complete catch-up growth [92]. Hence, the availability of an intense hemodialysis program may be an argument to start dialysis in a child with growth hormone-resistant growth failure.

Timing of Elective Dialysis Initiation The level of kidney function that is an absolute indication for initiating dialysis in children is uncertain. The adult literature is fraught with conflicting conclusions and opinions [93–95]. The debate is complicated by uncertainty regarding the best methodology for evaluating residual kidney function (see Section “Predialysis Patient Monitoring and Preparation for Dialysis”). The IDEAL study directly addressed this question in adults [96]. Patients were randomized to dialysis initiation at an eGFR of 10–15 ml/min/1.73 m2 (early-start) or at an eGFR of 5–7  ml per minute (late-start). The late-start group began dialysis close to 6  months later than the early-start group, but there was no difference in mortality or other adverse events between the two groups. Hence, planned, early initiation of dialysis was not associated with a clinical benefit [96]. In children, there are limited published studies. In a study of children in the United States Renal Data System (USRDS), higher eGFR at dialysis initiation was associated with a higher mortality, especially among patients who initiated hemodialysis [97]. In another study of children in the USRDS, mortality also increased as eGFR at dialysis initiation increased, especially among patients 6  years and older [98]. In a European study, there was no difference in mortality based on level of eGFR at dialysis initiation [99]. There are no randomized studies in children.

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Estimated GFR at Dialysis Initiation In adults, prior to the publication of the IDEAL trial, the eGFR at dialysis initiation was gradually increasing in many countries. However, this trend has either stabilized or reversed since the publication of the IDEAL trial [100, 101]. In a large cohort of European pediatric patients, the median eGFR at initiation of renal replacement therapy (RRT) was 10.4  ml/ min/1.73 m2, with the small percentage of patients who received a preemptive transplant having a significantly higher eGFR at the time of transplant (13.5  ml/min/1.73  m2) [102]. Variables associated with a lower eGFR at onset of RRT included younger age, female gender, and a short interval between the first visit to a pediatric nephrologist and commencement of RRT. In a study of Canadian children, the median eGFR at dialysis initiation was 8.1  ml/ min/1.73  m2 [103]. Canadian children with a genetic cause of end-stage kidney disease (ESKD), living further from a treatment facility, and females were more likely to initiate dialysis at a higher eGFR. In a study of children in the USRDS, a higher eGFR at dialysis initiation was more common in whites, females, underweight or obese patients, and patients with glomerulonephritis as the underlying etiology of ESKD [97].

 onsensus Statements Regarding C Dialysis Initiation The results of the IDEAL study have influenced guidelines on the timing of dialysis initiation; prior guidelines were more likely to reference a GFR threshold for initiating dialysis. The 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend dialysis initiation for specific indications, including symptoms or signs of kidney failure, refractory volume overload, hypertension or nutritional deterioration, and cognitive impairment [104]. Per these guidelines, this “often but not invariably” ensues at a GFR between 5 and 10 ml/min/1.73m2.

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The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines recommend similar clinical criteria to KDIGO for initiating dialysis [105]. The KDOQI guidelines do not provide a GFR criterion, citing the challenges of estimating GFR and the lack of evidence that decision-making based on GFR is beneficial. The European Best Practice Board (EBPB) guidelines on when to start dialysis were specifically updated in response to the IDEAL study [106]. These guidelines recommend consideration of initiation of dialysis when the GFR is