Challenges in Pediatric Kidney Transplantation: A Practical Guide

Contents
Contributors
Part I: Immunologic Challenges
1: Immunologic Challenges Pre-transplant
Introduction
What Is Human Leukocyte Antigen (HLA)?
Pre-transplant
How Does Sensitization Occur?
Why Is HLA Compatibility Important?
Epitope Mismatch
How Are HLA Antibodies Detected and HLA Matching Performed?
Antibody Detection
Cell-Based Assays
Solid-Phase Assays
Is Median Fluorescent Intensity (MFI) Signal a Surrogate Measure of the Level of HLA Antibody?
Peri-transplant
The Virtual Crossmatch (vXM) in Transplantation
Unexpected Crossmatch Scenarios
Clinical Scenarios and Interpretation of Crossmatch Results in Kidney Transplantation
Conclusion
Questions and Answers with Explanation
References
2: Challenges in Post-transplant Immunologic Monitoring
Challenges in Post-transplant Immunologic Monitoring
Conventional Monitoring Post-Transplant
Serum Creatinine (Graft Function)
Drug Monitoring and Variability
Surveillance Monitoring of Donor-Specific Antibodies
Non-HLA Antibodies
Surveillance Biopsies (SBs)
Innovative Biomarkers for Immunologic Monitoring Post-transplant
Donor-Derived Cell-Free DNA (dd-cfDNA)
Urinary Biomarkers
Molecular Diagnostics
The Future of Post-transplant Immune Monitoring
Q&A
Bibliography
3: Rejection Challenges: Diagnosis and Management
A Brief History of Rejection
An Evolving Paradigm of Rejection: From Discreet Episodic Events to a Fluctuating Continuum of Immune Alloreactivity
Pathophysiology of Alloimmune Activation and Downstream Processes
T Cell Development and Activation
T Cell Migration and Mechanisms of Injury in T Cell-Mediated Rejection with the Allograft
B Cell Development and Activation
Alloantibodies and Antibody-Mediated Rejection
Alloimmune Chronicity
Detecting Rejection and Monitoring Its Course
Clinical Monitoring and Biopsy Indication
Surveillance Biopsies
Follow-Up Biopsies
Biomarkers for Rejection
Gene Expression Signatures
Chemokines
Metabolomics
Cell-Free DNA
Predisposing Risk Factors for Rejection
Recipient-Related Risks
Donor-Recipient Interface
Donor-Related Risks
Silent Sensitization
HLA Mismatch
Post-transplant Factors
Hyperacute Rejection
Acute T Cell-Mediated Rejection (TCMR)
Clinical and Histological Features
Treatment of TCMR
Corticosteroids
Lymphocyte-Depleting Therapies
Late Acute TCMR
B Cell-Rich and Plasma Cell-Rich Acute Rejection
B Cell-Rich Rejection
Plasma Cell-Rich Acute Rejection
Active Antibody-Mediated Rejection (AMR)
Clinical and Histological Features
Treatment of AMR
Plasmapheresis and IVIG
Rituximab
Bortezomib
Emerging Treatments
Response to Treatment
Chronic Active TCMR
Clinical and Histological Features
Management
Chronic Active AMR
Clinical and Histological Features
Management
Emerging Therapies
Post Rejection Infection Prophylaxis
Special Circumstances: Infection and Rejection
AGPN and Rejection
BK Virus and Rejection
Case Studies
References
Part II: Infectious Challenges
4: Pretransplant Donor and Recipient Infectious Challenges
Pretransplant Infectious Disease Evaluation
Evaluation of the Pediatric Kidney Transplant Candidate
HIV and Hepatitis Viruses
Cytomegalovirus/Epstein-Barr Virus Serostatus of Donor and Recipient
Cytomegalovirus
Epstein-Barr Virus
Mycobacterium tuberculosis
Fungal Infections and Endemic Mycoses
Parasitic Infections
COVID-19
Urinary Tract Infections
PHS Increased Risk Donors
Window Period Duration and the Risk of Virus Transmission
Outcomes of PHS Increased Risk Donors in Pediatric Kidney Transplantation
Informed Consent
Posttransplant Testing
Immunizations
Preparing the Dialysis Patient for Transplantation
Vaccine Schedule: Current American Academy of Pediatrics Recommendations
Summary of recommendations with end stage kidney disease, including transplant candidates [62–64]
Hepatitis B
Influenza Vaccine
Pneumococcal Vaccine [68, 69]
Special Situations [70, 71]
Household/Live Donor Vaccination
Live Vaccines
Varicella Vaccine
Measles-Mumps-Rubella Vaccine
Recombinant and Inactivated (“Killed”) Vaccines
DTaP/Tdap/dT Vaccine
Poliovirus Vaccine
Haemophilus Influenzae Type B Vaccine
Hepatitis A Vaccine
Hepatitis B Vaccine
Meningococcal Vaccine
Human Papillomavirus
Updating Immunizations for the Dialysis Patient Awaiting Transplant
Questions
References
5: Post-transplant Recipient Infectious Challenges
Introduction
Opportunistic Post-Kidney Transplant Infections (CMV, EBV, and BK Virus and PJP)
Cytomegalovirus (CMV)
Risk Factors
Clinical Presentation
Screening
Prophylaxis and Preemptive Therapy
Treatment
BK Virus
Risk Factors
Clinical Presentation
Screening
Treatment
Epstein-Barr Virus
Risk Factors
Clinical Presentation
Screening
Treatment
Pneumocystis jirovecii pneumonia (PJP)
Resurgent Viral Infection Outbreaks: Measles and Mumps
Cancer Risks
Cancer Incidence
Cancer Risk Factors
Immunosuppression Burden
EBV Recipient-Donor Sero-Mismatch
Time Since Transplant
HLA Haplotypes
Pre-transplant Malignancy
Age
Gender
Race
Donor Source
Recombinant Growth Hormone (rGH) Use
Cancer Prevention Strategies
Cancer Treatment
Cancer Outcomes
Urinary Tract Infections (UTI)
Prevalence
Risk Factors
Prevention
Treatment
Asymptomatic Bacteriuria
Outcomes
MOC Questions
References
Part III: Disease Challenges
6: Urological Considerations for Pediatric Renal Transplantation: CAKUT Challenges
Urological Complications Post-transplant
References
7: Rheumatologic Challenges
Systemic Lupus Erythematosus
Introduction
Clinical Course of Renal Involvement and Outcomes
Renal Transplantation in Lupus Nephritis
Recurrence of Lupus Nephritis Post-transplantation
Health Disparities in Systemic Lupus Erythematosus and Lupus Nephritis
Conclusion
IgA Vasculitis
Introduction
Clinical Course of Renal Involvement and Outcomes
Renal Transplantation in IgAV Nephritis and Outcomes
ANCA-Associated Vasculitis
Introduction
Clinical Course of Renal Involvement and Outcomes
Renal Transplantation in Childhood AAV and Outcomes
Conclusion
References
8: Recurrent Disease Challenges in Pediatric Kidney Transplantation
Introduction
Atypical Hemolytic Uremic Syndrome (aHUS)
Nature and Frequency of Primary Disease
Considerations for Transplant Planning
Risk Factors for Recurrence and Treatment of Recurrence
Risk of Disease Recurrence in the Era of Eculizumab
Additional Post-transplant Considerations
C3 Glomerulopathy (C3G)
Nature and Frequency of C3G
Considerations for Transplant Planning
Risk Factors for Recurrence and Treatment of C3G Recurrence
IgA Nephropathy
Nature and Frequency of IgA Nephropathy (IgAN)
Risk Factors for Recurrence
Considerations for Transplant Planning
Treatment of IgAN Recurrence
Impact of IgAN on Graft Function and Survival
IgA Vasculitis (Henoch-Schonlein Purpura)
Lupus Nephritis
Nature and Frequency of Disease
Risk for Disease Recurrence
Considerations for Transplant Planning
Impact of RLN on Graft Function and Survival
Other Diseases
Primary Hyperoxaluria Type 1 (Oxalosis)
Membranous Nephropathy
Conclusion
References
9: Nephrotic Syndrome Challenges: An Old Recurring Problem
APOL1
Mechanism of Renal Injury
Second Hit Modifiers
Clinical Implications
Pre-transplant Nephrectomy
Proteinuria
WT1 Mutation
Disease Recurrence
Genetic Mutations
Living vs Deceased Donation
Clinical Features Predictive of DR
Circulating Factor and DR
Treatment of Disease Recurrence
Plasmapheresis
Immunoadsorption
Rituximab
Cyclosporine
Lipid Apheresis
Questions
Bibliography
10: Challenges of Maintaining Adequate Health and Well-Being, Growth, Nutrition, and Development in Pediatric Transplant Recipients
Vaccinations
Pre-transplant
Post-transplant
Vaccines and Travel
Nutritional Challenges
Pre-transplant
CKD 2–5 Pre-dialysis
Hemodialysis
Peritoneal Dialysis
Nutritional Management in CKD and Dialysis
Enteral Nutrition Support
Post-transplant
Appetite and Weight
Transition from Enteral to Oral Feeding
Medication Effects
Nutritional Management Post-transplant
Food Safety
Growth Challenges
Growth Hormone Physiology
Growth and CKD
Growth After Kidney Transplant
Outcomes
Growth Hormone Utilization
Indications and Contraindications for Growth Hormone
Work-Up, Treatment, and Monitoring
Work-Up
Treatment
Monitoring
Safety of Growth Hormone in Transplant Recipients
Metabolic Bone Disease
Pathophysiology of CKD-BMD
Bone Mineral Monitoring
Post-transplant Bone Metabolism
PTH, FGF-23, and Hypophosphatemia
Hypomagnesemia
Vitamin D
Immunosuppression
Role of Sex Hormones
Prevention Strategies
Steroid Minimization
Diet and Physical Activity
Treatment
Pharmacologic Therapies
Developmental and Psychosocial Impairments
Questions
References
Part IV: Medication Challenges
11: Challenges Surrounding Induction Protocols in Children
Immunologic Basis of Current Induction Protocols
T-Cell Activation and the Immune Response
Overview of Induction Therapy in Pediatric Renal Transplantation
Anti-inflammatory Steroids
IL-2 Cell Surface Receptor Blockade
Basiliximab and Daclizumab
Abatacept and Belatacept
Leukocyte Depletion Agents
Antithymocyte Globulin
Induction Therapies Targeted at B Cells
Selecting the Most Appropriate Induction Agent
Conclusions and Future Challenges
Questions
References
12: Post-transplant Medication Challenges
Introduction
Section I: Post-transplant Immunosuppression Strategies
Maintenance Immunosuppression
Antiproliferative Agents
Azathioprine
Mycophenolic Acid Derivatives
Efficacy
Steroids
Efficacy
Calcineurin Inhibitors
Cyclosporine
Tacrolimus
Efficacy
Target of Rapamycin Inhibitors
Sirolimus
Everolimus
Efficacy
Costimulatory Blockade
Belatacept
Efficacy
Section II: Post-transplant Immunosuppression Challenges
Adverse Effects
Antiproliferative Agents
Steroids
Calcineurin Inhibitors
Target of Rapamycin Inhibitors
Costimulatory Blockade (Belatacept)
Drug Interactions
Antiproliferative Agents
Calcineurin Inhibitors and Target of Rapamycin Inhibitors
Interactions Between Immunosuppressants
Role of Pharmacogenetics
Infections
Malignancy
Pregnancy and Fertility
Medication Nonadherence
Conclusion
Self-Assessment Questions
References
Part V: Surgical Challenges
13: Challenges in Surgical Approach and Complications in Pediatric Renal Transplant
Introduction
Recipient Preoperative Evaluation
Donor Selection
Surgical Operation Overview
Postsurgical Complications
Wound Infections
Vascular Thrombosis
Vascular Stenosis
Urologic Complications
Perinephric Lymphoceles, Hematomas, and Abscesses
Surgical Approach and Complications in Pediatric Renal Transplant
(Questions)
Surgical Approach and Complications in Pediatric Renal Transplant
(Answers)
References
14: Multiorgan Transplantation Challenges
Multiorgan Allocation
Pediatric Heart-Kidney Transplantation
Pediatric Liver-Kidney Transplantation
Primary Hyperoxaluria
Pediatric Kidney-Pancreas Transplantation
Liver-Kidney-Pancreas Transplant
Kidney-Intestinal and Multivisceral Transplants
Future Directions
Questions
References
Part VI: Ethical Challenges
15: Ethical Challenges in Pediatric Kidney Transplantation
Introduction
Children with Intellectual Disability and Other Co-morbidities
Undocumented Children
Non-adherent Children
Under-Vaccinated Children
Conclusions
Multiple Choice Questions
References
Index