1. Kidney Transplantation in Infants and Small Children
The Good, The Bad, and the Ugly
Blanche Chavers, M.D.
Professor of Pediatrics
University of Minnesota Amplatz Children’s Hospital

2. Disclosure Information Blanche Chavers, MD
I have no financial relationship to disclose
I will not discuss off label use and/or investigational use of drugs in my presentation

3. How is ESRD Defined and How Common is it in US Children?
End stage renal disease - GFR < 15 mL/min/1.73 m2
1% of new US ESRD patients
1.5% of prevalent US ESRD patients
On average, 7000 US children receive ESRD treatment each year

4. Incident ESRD rates, by age figure 6
Incident ESRD rates, by age figure 6.1, per million population, adjusted for gender & race (2001 USRDS ADR)

5. Incidence of Pediatric End-Stage Renal Disease by Race (per million age adjusted population per year, 2008 USRDS ADR)
Black 24
Native American 19
Asian/Pacific Islander 15
White 13

6. Renal dysplasia/hypoplasia

7. Prune-belly syndrome
Intrauterine bladder outlet obstruction associated with
renal dysplasia
hypoplasia of abdominal musculature

8. Posterior Urethral Valves

10. FINNISH-TYPE CONGENITAL NEPHROTIC SYNDROME
(NPHS1)
Onset of proteinuria occurs in utero
Massive proteinuria edema
malnutrition
hypothyroidism
hypercoagulability
infection
With supportive care only: ESRD by 2-3 yrs, high
morbidity/mortality from infection, thrombosis
Excellent survival, QOL with 4-6 mos, aggressive
nutrition, 8-10 kgs

11. Etiology of Kidney Disease in 207 Infants

12. Treatment Options for ESRD
Dialysis
Peritoneal
Hemodialysis
Kidney transplantation

13. Benefits of transplantation
Special issues in 0-5 year olds
Benefits of transplantation
Improved patient survival
Improved growth and development
Improved quality of life
Avoidance of dialysis complications

14. Indications for Kidney Transplantation in Children
ESRD unresponsive to medical management
Progressive growth failure
Developmental delay
Progressive renal osteodystrophy
Failure to thrive

15. Contraindications for Kidney Transplantation in Children
Active malignancy or less than 12 months post treatment for malignancy
Human immunodeficiency viral infection
Positive current T cell crossmatch
Nonadherence with medical management

16. Timing of the Transplant
Optimal age for kidney transplant in the infant with ESRD remains controversial
University of Minnesota minimum requirements are 6 months of age and
kg in body size

17. Transplant Surgeon is key Transplant Nephrologist is key

18. Pediatric Transplant Team
Pediatric Nephrologist
Surgeon
Anesthesiologist
Urologist
Pediatric Intensivist
Neurologist
Psychiatrist / Psychologist
Dialysis and Transplant Ward Nurses
Transplant Nurse Coordinator
Dietitian
Social Worker
Transplant Pharmacist
Child Family Life Specialist
Occupational/Physical and Speech Therapists

19. Transplant the patient under the best possible conditions
Optimize medical management pretransplant

22. Optimize medical management pre transplant
Early referral and evaluation at transplant center
Screen for infections
Ensure up-to-date immunizations including influenza
Correct urological abnormalities pretransplant
Optimize dialysis treatment and encourage compliance with treatment regimen
Correct malnutrition, anemia, acidosis, renal osteodystrophy, growth failure

23. Optimize medical management pre transplant
Correct hypercoagulable state
Pretransplant nephrectomy of native kidneys as indicated
Document patency of the aorta and inferior vena cava
Identify potential living donors or list for deceased donor transplantation
Screen for antileukocyte antibodies in potential deceased donor recipients
Provide psychosocial support to child and family

26. Technically Challenging

27. Very Big Kidney-->Infant & Small Child
Special issues in 0-5 year olds: Risks -Graft thrombosis
Very Big Kidney-->Infant & Small Child
Adult-sized kidney
Big Kidney:
Hemodynamics
Blood flow
Blood pressure
Blood volume
Note: The kidney will shrink to size and GROW with child

28. Consequences of Hypovolemia
Hypotension
Renal hypoperfusion
Acute tubular necrosis
Graft thrombosis/infarction

29. Protecting intravascular volume following kidney transplantation
Vigorous volume-expansion prior to establishing circulation
to transplant
Replace all urine output (cc for cc) for initial hours
Maintain: CVP 8-12
BP 90th-95th% tile for age
HR within normal range
“Third-space” fluid losses are common in first hours
after intraperitoneal transplant (bowel manipulation results
in bowel wall edema)
Colloid (albumin) is often necessary to maintain adequate BP and CVP

30. Adult kidney into small infant

31. > 900 Pediatric Kidney Transplants

32. Comparison of Pediatric Renal Txs 1984-2006
Age (yrs)
<1
1-5
6-10
11-17
Total
Nation
105
2618
2806
8589
14,118
U of MN 36
146 94
179
450
% U of MN 34 6 3 2

33. Trends in Pediatric Kidney Transplantation 1996-2006
The Good
Trends in Pediatric Kidney Transplantation

38. Impact of ESRD on Growth
Younger subjects have greater height deficits at transplantation
0-1 years: -2.21
2-5 years: -2.26
6-12 years: -2.00
13-17 years: -1.41
2008 NAPRTCS Annual Report

39. Trends in Height Z Scores after Kidney Transplant
2004 NAPRTCS Annual Data Report

40. The Good: Conclusions
Compared to chronic dialysis, kidney transplantation leads to improved patient survival
Children aged 0-5 years have the best long-term (5 year) graft survival rates of all kidney transplant recipients
Improvement in linear growth after transplant is associated with age < 6 years

41. Infection Rates are Up in Young Pediatric Kidney Transplant Recipients
The Bad
Infection Rates are Up in Young Pediatric Kidney Transplant Recipients

42. Infectious hospitalization rates in pediatric vs
Infectious hospitalization rates in pediatric vs. adult ESRD patients, by modality: any infection
Figure 8.23, 2004 USRDS ADR
Incident dialysis patients & first-time, kidney-only transplant patients, with Medicare as primary payor; unadjusted. Infectious hospitalizations represent inpatient claims with a principal diagnosis code for infection.

43. Admissions for infection (overall), by age, gender, and time on ESRD: transplant
Figure 6.17, incident & prevalent transplant patients, 1997–1999 combined, 2001 USRDS ADR

44. Cause-specific hospitalization rates in months 6-24 by selected characteristics at month 6 post-transplant (%)
Viral
Bacterial
Age at transplant
0-1 years
27.1
25.3
2-5 years
24.5
23.0
6-12 years
14.6
13.3
> 12 years
10.0
11.6
Dharnidharka et al, AJT 4:384, 2004

45. Prevention of infection after transplant
Screening of donor and recipient for infections before transplant
CMV, EBV, HIV, Hepatitis A/B/C
Pretransplant serology
Ensuring up-to-date immunizations including influenza
Prophylaxis
Antiviral: ganciclovir, valganciclovir
Antibacterial
Antifungal

47. The Bad: Conclusions Infection after kidney transplantation
Largest cause of death in pediatric first kidney transplant recipients -Infection 28.9% (NAPRTCS 2008 ADR)
The smallest children have the greatest number of infections after kidney transplantation
Immunizations help prevent vaccine preventable infection posttransplant
Co-infection is common

48. The Ugly
PTLD Rates are Unacceptable in Young Pediatric Kidney Transplant Recipients

49. Posttransplant Lymphoproliferative Disorder (PTLD)
4 -5 x more common in children after kidney transplant than adults
Usually caused by proliferation of Epstein Barr virus (EBV) infected B cells
Symptoms
Infectious mononucleosis
Lymphoid hyperplasia
Invasive malignant lymphoma

50. Posttransplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression
Patient characteristics
Data obtained from the USRDS
25,127 Medicare patients aged 1-98 years, transplanted between 1996 and 2000, 80% with grafts from deceased donors
344 (1.4%) developed PTLD (non Hodgkin lymphoma) within the first 3 years of transplant. Mean time to onset was 12 months. 27% mortality
The incidence in pediatric patients (< 20 years) was 5.8%
Caillard, et al Transplantation 80:1233, 2005

51. Posttransplant lymphoproliferative disorders after renal transplantation3
Caillard, et al Transplantation 80:1233, 2005

52. Posttransplant lymphoproliferative disorders after renal transplantation
Caillard, et al Transplantation 80:1233, 2005

53. 7% incidence in 274 recipients Rate varied by age
Incidence of PTLD in Pediatric Renal Transplant Recipients Receiving Basiliximab, Calcineurin Inhibitor, Sirolimus and Steroids
7% incidence in 274 recipients
Rate varied by age
12% in 0-5 years
7% in 6-10 years
3% in years
0% in > 17 years
McDonald, et al AJT 8:984, 2008

54. Malignancy Prevention in Pediatric Kidney Transplant Recipients
Pretransplant serology on donor and recipient
Viral load monitoring in high risk patients
EBV seronegative recipient
Children < 1 year at transplant
Children tested after receiving blood products that might transiently confer EBV positivity
Reduce immunosuppression if positive
Monitor uric acid, LDH, CT scans

55. The Ugly: Conclusions Malignancy in Pediatric Kidney Transplant Recipients
Third largest cause of death in first kidney transplant recipients
Malignancy 10.6%
Highest rates are seen in the young
Mean 3-year posttransplant malignancy rates have increased % % %
≥ %
2008 NAPRTCS ADR

56. Conclusions: Pediatric Kidney Transplantation in Infants and Small Children
Young children have excellent long-term outcomes after kidney transplantation
Improvement in linear growth after transplant is associated with age < 6 years
Infectious complications of immunosuppression are highest in young children
Highest rates of PTLD are seen in young kidney transplant recipients age ≤ 5 years

57. Acknowledgements
Katherine Tabaka
Jerry Vincent
Jensina Ericksen