Renal Transplantation in Pediatric Age

Topic Name Introduction Indications Pre-Transplant Evaluation Donor Selection Surgical Technique Post-Operative Care Immunosuppression Complications Long-Term Outcomes

Introduction to Pediatric Renal Transplantation

Renal transplantation is the preferred treatment for end-stage renal disease (ESRD) in children, offering better quality of life and long-term survival compared to dialysis. Pediatric renal transplantation presents unique challenges due to size considerations, immune system differences, and growth and developmental factors.

Key points:

• First successful pediatric kidney transplant: 1954
• Accounts for about 5% of all kidney transplants worldwide
• Graft survival rates have significantly improved over the past decades
• Requires a multidisciplinary approach involving pediatric nephrologists, urologists, transplant surgeons, and specialized support staff

Indications for Pediatric Renal Transplantation

The most common indications for renal transplantation in children include:

1. Congenital anomalies of the kidney and urinary tract (CAKUT) - about 30-50% of cases
   • Renal dysplasia
   • Obstructive uropathy
   • Reflux nephropathy
2. Focal segmental glomerulosclerosis (FSGS) - about 10-15% of cases
3. Hereditary nephropathies
   • Alport syndrome
   • Cystinosis
   • Primary hyperoxaluria
4. Hemolytic uremic syndrome (HUS)
5. Chronic glomerulonephritis

Timing of transplantation is crucial and should be considered when GFR falls below 30 mL/min/1.73m² or earlier in cases of growth failure or other complications of chronic kidney disease.

Pre-Transplant Evaluation

A comprehensive pre-transplant evaluation is essential to ensure the best possible outcomes. This includes:

1. Medical assessment
   • Complete history and physical examination
   • Assessment of cardiovascular status
   • Evaluation of nutritional status and growth
   • Screening for infections (CMV, EBV, HIV, hepatitis B and C)
2. Urological evaluation
   • Voiding cystourethrogram (VCUG)
   • Assessment of bladder function
3. Immunological testing
   • ABO blood typing
   • HLA typing
   • Panel reactive antibody (PRA) screening
4. Psychosocial evaluation
   • Assessment of family support and adherence potential
   • Evaluation of cognitive and developmental status
5. Vaccination status review and update

Special considerations in pediatric patients include assessment of growth potential, neurodevelopmental status, and family dynamics that may impact post-transplant care.

Donor Selection in Pediatric Renal Transplantation

Donor selection is a critical factor in pediatric renal transplantation. The two main types of donors are:

1. Living donors
   • Usually a parent or close relative
   • Advantages: better HLA matching, scheduled surgery, shorter cold ischemia time
   • Considerations: ethical concerns, donor safety
2. Deceased donors
   • Standard criteria donors (SCD)
   • Expanded criteria donors (ECD) - less commonly used in pediatric recipients
   • Considerations: organ size matching, cold ischemia time

Key factors in donor selection:

• ABO compatibility
• HLA matching
• Donor size (ideally within 20% of recipient's size)
• Donor age (younger donors preferred for better long-term outcomes)
• Viral status (CMV, EBV)

In pediatric transplantation, there's often a preference for living donors due to better outcomes, especially in younger recipients.

Surgical Technique in Pediatric Renal Transplantation

The surgical approach in pediatric renal transplantation requires special considerations due to the smaller size of recipients. Key aspects include:

1. Recipient preparation
   • Optimization of nutritional status
   • Management of anemia and electrolyte imbalances
   • Consideration of pre-operative dialysis
2. Surgical approach
   • Typically extraperitoneal approach through a modified Gibson incision
   • Intraperitoneal approach may be used in very small children (<15 kg)
3. Vascular anastomosis
   • Usually to the aorta and inferior vena cava in small children
   • To iliac vessels in larger children and adolescents
   • Use of microscope or loupes for precision in small vessels
4. Urinary tract reconstruction
   • Extravesical ureteroneocystostomy (Lich-Gregoir technique) most common
   • Consideration of native ureter use in cases of bladder dysfunction
5. Closure and drainage
   • Careful closure to prevent wound complications
   • Use of drains based on surgeon preference and individual case

Special considerations:

• Management of size mismatch between adult-sized kidney and small recipient
• Thrombosis prevention in small vessels
• Attention to fluid balance and blood pressure control during surgery

Post-Operative Care in Pediatric Renal Transplantation

Post-operative care is crucial for the success of pediatric renal transplantation. Key aspects include:

1. Immediate post-operative management
   • Close monitoring in pediatric ICU
   • Fluid and electrolyte management
   • Pain control
   • Monitoring for surgical complications
2. Immunosuppression
   • Induction therapy (e.g., basiliximab, anti-thymocyte globulin)
   • Maintenance immunosuppression (typically tacrolimus, mycophenolate, and steroids)
   • Drug level monitoring and dose adjustment
3. Graft function monitoring
   • Regular assessment of urine output
   • Serum creatinine and electrolytes
   • Doppler ultrasound to assess graft perfusion
4. Infection prevention and monitoring
   • Prophylactic antibiotics
   • CMV and PCP prophylaxis
   • Monitoring for opportunistic infections
5. Nutrition and growth
   • Early resumption of enteral feeding
   • Monitoring of growth parameters
   • Consideration of growth hormone therapy if indicated

Long-term follow-up:

• Regular clinic visits for graft function assessment
• Monitoring for long-term complications (e.g., hypertension, metabolic disorders)
• Psychosocial support and education for patient and family
• Transition planning for adolescents moving to adult care

Immunosuppression in Pediatric Renal Transplantation

Immunosuppression is a cornerstone of successful renal transplantation. The regimen in pediatric patients requires careful consideration of efficacy, side effects, and long-term outcomes.

1. Induction therapy
   • Interleukin-2 receptor antagonists (e.g., basiliximab)
   • T-cell depleting agents (e.g., anti-thymocyte globulin) for high-risk patients
2. Maintenance immunosuppression
   • Calcineurin inhibitors (CNIs)
     • Tacrolimus (preferred over cyclosporine due to better outcomes)
     • Close monitoring of drug levels
   • Antiproliferative agents
     • Mycophenolate mofetil (MMF) or mycophenolic acid (MPA)
   • Corticosteroids
     • Trend towards early steroid withdrawal or avoidance in selected patients
3. mTOR inhibitors
   • Sirolimus or everolimus
   • Used in selected cases (e.g., CNI toxicity, malignancy)

Special considerations in pediatric immunosuppression:

• Impact on growth and development
• Higher metabolic rates requiring weight-based dosing
• Adherence challenges, especially in adolescents
• Long-term effects on fertility and future pregnancies
• Risk of post-transplant lymphoproliferative disorder (PTLD), especially in EBV-negative recipients

Monitoring and adjustment:

• Regular therapeutic drug monitoring
• Protocol biopsies to detect subclinical rejection
• Individualization of regimen based on immunological risk, comorbidities, and side effects

Complications in Pediatric Renal Transplantation

Despite advances in surgical techniques and immunosuppression, complications can occur. These can be categorized into early and late complications:

Early Complications (within first month)

1. Surgical complications
   • Vascular thrombosis (higher risk in small children)
   • Urine leak
   • Lymphocele
   • Wound infection
2. Delayed graft function
3. Acute rejection
4. Infections (bacterial, viral)

Late Complications

1. Chronic allograft nephropathy
2. Recurrence of primary disease (e.g., FSGS)
3. Post-transplant lymphoproliferative disorder (PTLD)
4. Cardiovascular complications
   • Hypertension
   • Left ventricular hypertrophy
5. Metabolic complications
   • New-onset diabetes after transplantation (NODAT)
   • Dyslipidemia
   • Obesity
6. Growth retardation
7. Bone disease (e.g., osteoporosis)
8. Malignancies

Management strategies:

• Regular monitoring and screening protocols
• Prompt intervention for acute complications
• Tailoring immunosuppression to minimize side effects
• Multidisciplinary approach involving pediatric specialists
• Patient and family education for early recognition of complications

Long-Term Outcomes in Pediatric Renal Transplantation

Long-term outcomes in pediatric renal transplantation have significantly improved over the past decades. Key aspects include:

Graft Survival

• 1-year graft survival rates: >95% for living donor and >90% for deceased donor transplants
• 5-year graft survival rates: ~85% for living donor and ~75% for deceased donor transplants
• Factors affecting long-term graft survival:
  • HLA matching
  • Donor source (living vs. deceased)
  • Recipient age (adolescents at higher risk of graft loss)
  • Episodes of acute rejection
  • Medication adherence

Patient Survival

• 5-year patient survival rates: >95%
• 20-year patient survival rates: ~85%
• Significantly better than patients maintained on dialysis

Quality of Life

• Improved physical functioning and energy levels
• Better cognitive development and academic performance
• Enhanced social integration
• Challenges remain in areas of medication adherence and transition to adult care

Growth and Development

• Catch-up growth often observed post-transplant, especially in younger children
• Final adult height may still be compromised in some patients
• Pubertal development generally proceeds normally, but delays can occur

Psychosocial Outcomes

• Improved overall quality of life compared to dialysis
• Challenges in medication adherence, especially during adolescence
• Impact on family dynamics and sibling relationships
• Educational and vocational achievements generally comparable to healthy peers

Long-term Complications

• Cardiovascular disease remains a leading cause of morbidity and mortality
• Risk of malignancy, particularly post-transplant lymphoproliferative disorder (PTLD)
• Metabolic complications (diabetes, dyslipidemia)
• Bone disease and growth issues

Transition to Adult Care

• Critical period with increased risk of graft loss
• Structured transition programs can improve outcomes
• Focus on self-management skills and medical knowledge

Continuous improvements in immunosuppression regimens, surgical techniques, and long-term care strategies are expected to further enhance outcomes in pediatric renal transplantation.

Renal Transplantation in Pediatric Age

1. What are the most common indications for renal transplantation in children?
   Congenital anomalies of the kidney and urinary tract (CAKUT), focal segmental glomerulosclerosis (FSGS), and genetic disorders
2. What is the preferred type of renal transplant for children?
   Living donor transplant
3. What is the minimum weight typically required for a child to receive an adult kidney?
   Approximately 10 kg
4. What is the role of pre-emptive transplantation in pediatric patients?
   To avoid complications of dialysis and improve long-term outcomes
5. How does the immune system of children affect transplant outcomes compared to adults?
   Generally more robust, potentially leading to higher rejection rates but also better long-term graft survival
6. What is the most common surgical approach for pediatric kidney transplantation?
   Extraperitoneal placement in the iliac fossa
7. What are the main immunosuppressive medications used in pediatric renal transplantation?
   Tacrolimus, mycophenolate mofetil, and corticosteroids
8. What is the significance of Epstein-Barr virus (EBV) in pediatric renal transplant recipients?
   Increased risk of post-transplant lymphoproliferative disorder (PTLD)
9. How does growth hormone therapy affect transplanted children?
   Can improve growth without increasing rejection risk in carefully selected patients
10. What is the impact of renal transplantation on cognitive development in children?
    Generally improves cognitive function compared to dialysis
11. What is the role of protocol biopsies in pediatric renal transplant management?
    To detect subclinical rejection and guide immunosuppression
12. How does non-adherence to immunosuppressive medications affect adolescent transplant recipients?
    Major cause of graft loss in this age group
13. What is the significance of recurrent focal segmental glomerulosclerosis (FSGS) after transplantation?
    Can lead to early graft loss, may require plasmapheresis or rituximab
14. How does cytomegalovirus (CMV) infection affect pediatric renal transplant recipients?
    Can cause direct organ damage and increase risk of rejection
15. What is the role of ABO-incompatible transplantation in pediatric patients?
    Expanding the donor pool, especially for young children
16. How does urological reconstruction (e.g., bladder augmentation) affect transplant outcomes in children with lower urinary tract dysfunction?
    May be necessary to create a low-pressure urinary reservoir and protect the graft
17. What is the significance of donor-specific antibodies (DSA) in pediatric renal transplantation?
    Associated with increased risk of antibody-mediated rejection and graft loss
18. How does delayed graft function affect long-term outcomes in pediatric renal transplantation?
    Associated with increased risk of acute rejection and poorer long-term graft survival
19. What is the role of steroid withdrawal in pediatric renal transplant recipients?
    May improve growth and reduce metabolic complications in selected patients
20. How does obesity affect pediatric renal transplant outcomes?
    Associated with increased surgical complications and cardiovascular risk
21. What is the significance of BK virus infection in pediatric renal transplant recipients?
    Can cause nephropathy and graft loss, requires careful monitoring and immunosuppression adjustment
22. How does renal transplantation affect fertility and pregnancy outcomes in female recipients?
    Fertility often improves post-transplant, but pregnancies are high-risk and require careful management
23. What is the role of transition clinics in managing adolescent transplant recipients?
    To prepare patients for transfer to adult care and improve long-term outcomes
24. How does sensitization (presence of anti-HLA antibodies) affect pediatric renal transplant candidates?
    Reduces donor options and increases waiting time for transplantation
25. What is the impact of renal transplantation on quality of life in children?
    Generally improves physical, social, and emotional well-being compared to dialysis
26. How does the use of hepatitis C virus (HCV) positive donors affect pediatric renal transplantation?
    Expanding donor pool, but requires careful consideration and post-transplant antiviral therapy
27. What is the role of machine perfusion in pediatric deceased donor kidney transplantation?
    May improve graft outcomes, especially for marginal donors
28. How does post-transplant diabetes mellitus affect pediatric renal transplant recipients?
    Increases cardiovascular risk and affects long-term graft survival
29. What is the significance of donor age in pediatric renal transplantation?
    Young donors generally provide better long-term graft function, but matching to recipient size is crucial
30. How does the development of de novo donor-specific antibodies affect long-term graft survival in children?
    Associated with chronic antibody-mediated rejection and reduced graft survival

Further Reading

• NIDDK: Pediatric Kidney Disease
• National Kidney Foundation: Kidney Transplant in Children
• UpToDate: Kidney transplantation in children: Overview of care pre- and post-transplant
• NCBI: Pediatric Kidney Transplantation: A Review
• AJKD: Pediatric Kidney Transplantation: Opportunities to Improve Outcomes