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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 - PowerPoint PPT Presentation
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Kidney Transplantation in Infants and Small Children
Blanche Chavers, M.D.Professor of Pediatrics
University of Minnesota Amplatz Children’s Hospital
The Good, The Bad, and the Ugly
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 agefigure 6.1, per million population, adjusted for gender & race
(2001 USRDS ADR)
0.0
5.0
10.0
15.0
20.0
25.0
30.0
35.0
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Rate
Per
Mill
ion
Popu
lati
on
Ages 0-4Ages 5-9Ages 10-14Ages 15-19
Incidence of Pediatric End-Stage Renal Incidence of Pediatric End-Stage Renal Disease by RaceDisease by Race
(per million age adjusted population per year, 2008 USRDS ADR)(per million age adjusted population per year, 2008 USRDS ADR)
• Black 24
• Native American 19
• Asian/Pacific Islander 15
• White 13
Renal dysplasia/hypoplasia
Intrauterine bladder outlet obstruction associated with• renal dysplasia• hypoplasia of abdominal musculature
Prune-belly syndrome
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, highmorbidity/mortality from infection, thrombosis
Excellent survival, QOL with BNx @ 4-6 mos, aggressivenutrition, transplant @ 8-10 kgs
42234
6891011
1826
4262
0 10 20 30 40 50 60 70
Unknown
Anatomic
Jeune's
Steroid res neph s
Hypoxia at birth
Drash
Glomerulonephritis
Hemolytic Uremic S
Polycystic
Cortical Necrosis
Oxalosis
Cong Nephrotic Synd
Obstructive Uropathy
Hypoplasia
Number
Etiology of Kidney Disease in 207 Infants
Treatment Options for ESRD
• Dialysis– Peritoneal– Hemodialysis
• Kidney transplantation
Benefits of transplantation• Improved patient survival
Special issues in 0-5 year olds
• Improved growth and development
• Improved quality of life
• Avoidance of dialysis complications
• ESRD unresponsive to medical management
• Progressive growth failure
• Developmental delay
• Progressive renal osteodystrophy
• Failure to thrive
Indications 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
Contraindications for Kidney Transplantation in Children
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
• Adult-sized kidney• Big Kidney: Hemodynamics
– Blood flow– Blood pressure– Blood volume
Very Big Kidney-->Infant & Small Child
Note: The kidney will shrink to size and GROW with child
Special issues in 0-5 year olds: Risks -Graft thrombosis
Consequences of Hypovolemia
Hypovolemia Hypotension
Acute tubular necrosis Renal hypoperfusion
Graft thrombosis/infarction
Protecting intravascular volume followingkidney transplantation
• Vigorous volume-expansion prior to establishing circulation to transplant
• Replace all urine output (cc for cc) for initial 48-72 hours
• Maintain: CVP 8-12BP 90th-95th% tile for ageHR 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
Trends in Pediatric Kidney Transplantation 1996-2006
The Good
Impact of ESRD on Growth
»0-1 years: -2.21
»2-5 years: -2.26
»6-12 years: -2.00
»13-17 years: -1.41 2008 NAPRTCS Annual Report
Younger subjects have greater height deficits at transplantation
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
Infection Rates are Up in Young Pediatric Kidney Transplant Recipients
The Bad
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.
Infectious hospitalization rates in pediatric vs. adult ESRD patients,
by modality: any infection
Figure 8.23, 2004 USRDS ADR
Admissions for infection (overall), by age, gender, and time on ESRD: transplant
0-4 5-9 10-14 15-190
10
20
30
40
50
60
70
80
< 1 year 1 to < 2 years 2 to <5 years 5+ years
Male Female
Age Gender
Adm
issi
ons
per 1
00 p
atie
nt y
ears
at r
isk
Figure 6.17, incident & prevalent transplant patients, 1997–1999 combined, 2001 USRDS ADR
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
Cause-specific hospitalization rates in months 6-24 by selected characteristics at month 6 post-
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
PTLD Rates are Unacceptable in Young Pediatric Kidney
Transplant Recipients
The Ugly
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 aTIFF (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
3
Posttransplant lymphoproliferative disorders after renal transplantation
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 TabakaJerry VincentJensina Ericksen