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
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
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
Incident ESRD rates, by age
figure 6.1, per million population, adjusted for gender & race
(2001 USRDS ADR)
35.0
Rate Per Million Population
30.0
25.0
Age s 0-4
Age s 5-9
20.0
Age s 10-14
Age s 15-19
15.0
10.0
5.0
0.0
90 991 992 993 994 995 996 997 998 999 000 001 002 003 004 005 006 007
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
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
Renal dysplasia/hypoplasia
Prune-belly syndrome
Intrauterine bladder outlet obstruction associated with
• renal dysplasia
• hypoplasia of abdominal musculature
Posterior Urethral Valves
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 BNx @ 4-6 mos, aggressive
nutrition, transplant @ 8-10 kgs
Etiology of Kidney Disease in 207 Infants
62
Hypoplasia
42
Obstructive Uropathy
26
Cong Nephrotic Synd
18
Oxalosis
11
Cortical Necrosis
10
Polycystic
9
Hemolytic Uremic S
8
Glomerulonephritis
6
Drash
4
Hypoxia at birth
3
Steroid res neph s
Jeune's
2
Anatomic
2
4
Unknow n
0
10
20
30
40
Numbe r
50
60
70
Treatment Options for ESRD
• Dialysis
– Peritoneal
– Hemodialysis
• Kidney 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
Indications for Kidney
Transplantation in Children
• ESRD unresponsive to medical management
• Progressive growth failure
• Developmental delay
• Progressive renal osteodystrophy
• Failure to thrive
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
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
• 8 - 10 kg in body size
Transplant
Surgeon is key
Transplant
Nephrologist is key
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
Transplant the patient under the best
possible conditions
Optimize medical management pretransplant
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
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
Technically Challenging
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
Consequences of Hypovolemia
Hypovolemia
Acute tubular necrosis
Graft thrombosis/infarction
Hypotension
Renal hypoperfusion
Protecting intravascular volume following
kidney transplantation
• Vigorous volume-expansion prior to establishing circulation
to transplant
• Replace all urine output (cc for cc) for initial 48-72 hours
• Maintain:
CVP 8-12
BP 90th-95th% tile for age
HR within normal range
• “Third-space” fluid losses are common in first 24-72 hours
after intraperitoneal transplant (bowel manipulation results
in bowel wall edema)
• Colloid (albumin) is often necessary to maintain adequate BP and CVP
Adult kidney into small infant
> 900 Pediatric Kidney Transplants
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
3
The Good
Trends in Pediatric Kidney
Transplantation 1996-2006
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
Trends in Height Z Scores after Kidney Transplant
2004 NAPRTCS Annual Data Report
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
The Bad
Infection Rates are Up in
Young Pediatric Kidney
Transplant Recipients
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.
Admissions per 100 patient years at risk
Admissions for infection (overall), by age,
gender, and time on ESRD: transplant
80 Age
Gender
70
< 1 year
1 to < 2 years
2 to <5 years
5+ years
60
50
40
30
20
10
0
0-4
5-9
10-14
15-19
Male
Female
Figure 6.17, incident & prevalent transplant patients, 1997–1999 combined, 2001 USRDS ADR
Cause-specific hospitalization rates in months 6-24
by selected characteristics at month 6 posttransplant (%)
Viral
Bacterial
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
Age at transplant
Dharnidharka et al, AJT 4:384, 2004
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
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
The Ugly
PTLD Rates are Unacceptable
in Young Pediatric Kidney
Transplant Recipients
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
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
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
Posttransplant lymphoproliferative
disorders after renal transplantation
3
Caillard, et al Transplantation 80:1233, 2005
Posttransplant lymphoproliferative
disorders after renal transplantation
Caillard, et al Transplantation 80:1233, 2005
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 11-17 years
– 0% in > 17 years
McDonald, et al AJT 8:984, 2008
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
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
–
–
–
–
1987-1990 1.05%
1991-1994 1.4%
1995-1998 2.93%
≥ 1999 3.0%
2008 NAPRTCS ADR
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
Acknowledgements
Katherine Tabaka
Jerry Vincent
Jensina Ericksen