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