Challenges with small pediatric donors Problems/potential in

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Next Speaker:
Richard V. Perez, M.D.
Kidney Donation in the Very Small
Pediatric Deceased Donor:
Addressing the Tragic Trifecta
Sponsored by
Outline
1.
2.
3.
4.
5.
6.
7.
Rationale for kidney transplantation
What is the tragic trifecta?
Challenges with small pediatric donors
Problems/potential in pediatric DCD
An interesting case study
A strategy to utilize small kidneys
Outcomes
1. Very small <5kg donors
2. Pediatric recipients
3. DCD
8. Summary and call to action
Outline
1.
2.
3.
4.
5.
6.
7.
Rationale for kidney transplantation
What is the tragic trifecta?
Challenges with small pediatric donors
Problems/potential in pediatric DCD
An interesting case study
A strategy to utilize small kidneys
Outcomes
1. Very small <5kg donors
2. Pediatric recipients
3. DCD
8. Summary and call to action
Rationale for Kidney
Transplantation
• Children
–Optimize growth and
development
• Adults
–Survival benefit vs dialysis
–Improvement in quality of life
Our Goal
To make transplantation a
safe option for as many
patients as possible
Patients waiting for kidney
transplantation on
October 2, 2013
97,916
Outline
1.
2.
3.
4.
5.
6.
7.
Rationale for kidney transplantation
What is the tragic trifecta?
Challenges with small pediatric donors
Problems/potential in pediatric DCD
An interesting case study
A strategy to utilize small kidneys
Outcomes
1. Very small <5kg donors
2. Pediatric recipients
3. DCD
8. Summary and call to action
Pediatric Organ Donation More Common with
Increasing Donor Weight
Pelletier, et al. Am J Transplant 2006
Tragic Trifecta
1. The small child dies
Pelletier, et al. AJT 2006
Tragic Trifecta
2. The parents consent, but the kidneys are not
recovered
Most kidneys from donors <9kg
are not recovered
Pelletier, et al. AJT 2006
Tragic Trifecta
3. The parents consent, the kidneys are recovered but
then discarded
50% discard rate if donor <9kg
Pelletier, et al. AJT 2006
Kidneys from very small donors:
Few recovered, many discarded, few
transplanted
Could these kidneys be better
utilized?
Pelletier, et al. AJT 2006
Outline
1.
2.
3.
4.
5.
6.
7.
Rationale for kidney transplantation
What is the tragic trifecta?
Challenges with small pediatric donors
Problems/potential in pediatric DCD
An interesting case study
A strategy to utilize small kidneys
Outcomes
1. Very small <5kg donors
2. Pediatric recipients
3. DCD
8. Summary and call to action
Unique challenges with kidneys
from very small pediatric donors
•
•
•
•
Small vessels that are very vasoactive
Reduced renal mass
Short ureters
High risk of early allograft loss
Inferior outcomes when donor is <10kg or <1yr: A disincentive
to transplant small kidneys
Author
#pts
Age
Wt (kg)
<1yr
Early Failure /
Thrombosis
Beltran 2010
5
20%
Balachandran 2010
11
Thomusch 2009
35
<1yr
34%
Sanchez
6
<1yr
33%
Hiromoto 2002
10
<1yr
Gourlay 1995
3
<1yr
<10
12.6
18%
40%
100%
Kidneys from donors <10kg have a higher failure rate
Group
Standard
Criteria
5-9kg
10-14kg
15-19kg
20+ kg
N
95% CI
P-value
34,527
Adj
Hazard
Ratio
Ref
Ref
Ref
293
708
406
1.50
0.97
0.83
1.23-1.84
0.84-1.12
0.68-1/01
<0.0001
0.66
0.06
169
0.82
0.60-1.10
0.18
Kayler, et al. Am J Transplant 2009
Factors involved in early loss of
small pediatric kidneys
• Technical problems
• Increased vasospasm in renal
vasculature
• Relative decrease in renal perfusion
prior to procurement
• Decreased allograft perfusion posttransplantation
Rationale for use of kidneys from
very small pediatric donors
• Excellent quality of kidneys
• High capacity to recover from acute
stress/injury
• Kidney allografts will grow with time
Pediatric kidneys rapidly grow after
transplantation
Bretan, et al. Transplantation 1997
Outline
1.
2.
3.
4.
5.
6.
7.
Rationale for kidney transplantation
What is the tragic trifecta?
Challenges with small pediatric donors
Problems/potential in pediatric DCD
An interesting case study
A strategy to utilize small kidneys
Outcomes
1. Very small <5kg donors
2. Pediatric recipients
3. DCD
8. Summary and call to action
Donation after circulatory death
A underutilized option for
families with small children who
die?
DCD in the small infant is uncommon
–UNOS national experience 2000 –
2009
• 12207 pediatric kidneys recovered
• 765 (6.3%) pediatric DCD
• 88 (0.7%) DCD less 5 years old
Dagher, et al. Transplantation 2011
J Pediatrics 2011
What is the potential for DCD in the
small neonate?
–Retrospective review of 192 deaths
in 3 Harvard Neonatal ICUs
Labrecque et al., J Pediatrics 2011
Results: 8% of NICU mortalities were
potential candidates for DCD
• 161 of 192 deaths during the study period
leaving 31 theoretically eligible donors
• 16 infants died with a warm ischemic time of
< 60 minutes
• Establishment of infant DCD protocols for
level III NICUs should be considered
Labrecque, et al. J Peds 2011
Outline
1.
2.
3.
4.
5.
6.
7.
Rationale for kidney transplantation
What is the tragic trifecta?
Challenges with small pediatric donors
Problems/potential in pediatric DCD
An interesting case study
A strategy to utilize small kidneys
Outcomes
1. Very small <5kg donors
2. Pediatric recipients
3. DCD
8. Summary and call to action
Case Study: Donation after
Circulatory Death in an
Anencephalic Newborn
Acknowledgement to:
Intermountain Donor Services
Angela Ortega
Craig Myrick
Diana Alonso
Case History
• 24 year old Hispanic woman
• Married with 2 small children and pregnant with 3rd
• At 12 weeks gestation routine ultrasound showed that
the baby was anencephalic
• Grim prognosis given by obstetrician
• Offered option to terminate pregnancy
Case History
• Mother decided to carry the baby to
term and donate whatever organs and
tissues
• Intermountain Donor Services
contacted
• Team assembled to offer support and
coordinate a plan (L & D, NICU, OR,
Hosp admin, social workers,
physicians)
Hospital Course
• Elective C-section at term
• Birthweight 1.9 kg
• Immediate airway support necessary intubation
• Hemodynamically unstable requiring
pressors and transfusion
• Blood drawn for serology and tissue
typing
Organ Donation
• Withdrawal of support in NICU 5 hours
after birth
• Death declared 47 minutes after
extubation
• Aortic cross clamp after 56 minutes of
warm ischemia
• Kidneys removed en bloc
Recipient
• 38 year old woman
• Renal failure secondary to focal
segmental glomerulosclerosis
• Pre-dialysis
• Weight 56kg, PRA 0%
Post-transplant Course
• Initial admission without complication
• Discharged on POD 6
• Follow up ultrasound at 6 weeks showed
thrombosis of one kidney
• Remaining kidney allograft patent and left in place
• Growth of remaining kidney assessed by
ultrasound
– POD#1
– 6 weeks
– 1 year
3.6cm length
5.4cm length
7.6cm length
• Slow improvement in renal function with current
serum creatinine 1.29 16 months post transplant
Outline
1.
2.
3.
4.
5.
6.
7.
Rationale for kidney transplantation
What is the tragic trifecta?
Challenges with small pediatric donors
Problems/potential in pediatric DCD
An interesting case study
A strategy to utilize small kidneys
Outcomes
1. Very small <5kg donors
2. Pediatric recipients
3. DCD
8. Summary and call to action
An overall approach that addresses the
unique challenges with very small
pediatric en bloc kidneys
•
•
•
•
•
•
Donor operation
Pulsatile perfusion preservation
Back bench preparation
Recipient selection
Recipient operation
Immunosuppression
Donor Operation
Organ preservation method
matters
vs.
Machine preservation may increase
availability of organs for
transplantation
Pulsatile Pump Preservation:
Rationale
– Simulates normal circulation
– Continuous provision of micronutrients
– Removal of toxic waste and free radicals
– Able to exclude kidneys at high risk for nonfunction (low flow and high resistance)
– Pulsatile flow stimulates endothelial
expression of vasoprotective genes (TGF-,
Kruppel-like factor 2)
Factors involved in early loss of small pediatric
kidneys
• Technical problems
• Increased vasospasm in renal vasculature
• Increased systemic and local inflammation from brain
death
• Relative decrease in renal perfusion
• Potential beneficial effect of pulsatile perfusion
Pulsatile Pump Preservation
• Optimize vascular back bench preparation
• Improves renal hemodynamics
Flow (cc/min)
Improved renal microcirculation during pulsatile perfusion of
pediatric en bloc kidneys
25
4
24
3.5
23
22
3
21
2.5
Flow
20
2
19
Resistance
1.5
18
1
17
16
0.5
15
0
0
2
3
5
Hours
6
9
Improved renal hemodynamics after pulsatile perfusion
Before pumping
After pumping
Recipient Selection
•
•
•
•
Low body weight
Low immunologic risk
Low risk of recurrent disease
Minimize cold ischemia time
– Frequent transplantation without
prospective crossmatch
Recipient Operation
Standard pediatric en bloc kidney
transplanation
Working with very small ureters: “Single
stitch technique” to minimize ischemic
injury
Immunosuppression Protocol
• Goals
– Avoid early rejection during allograft
growth
– Avoid early biopsy
• Agents
– Thymoglobulin 1-1.5mg/kg/d x 5 days
– Methylprednisolone x 3 d (250-125-75mg)
– Tacrolimus and MMF maintenance
Post-operative Management
• Post-operative ultrasound to
confirm perfusion to both
allografts
• Aspirin 81mg QD
• Aggressive management of
hypertension
Outline
1.
2.
3.
4.
5.
6.
7.
Rationale for kidney transplantation
What is the tragic trifecta?
Challenges with small pediatric donors
Problems/potential in pediatric DCD
An interesting case study
A strategy to utilize small kidneys
Outcomes
1. Very small <5kg donors
2. Pediatric recipients
3. DCD
8. Summary and call to action
Outcomes
UC Davis Deceased Donor Transplantation:
Small pediatric donors
80
70
60
50
40
30
20
10
0
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Very Small (≤5kg)
vs
Small (5-20kg) Donors
Study Cohort
• 91 small pediatric donors (≤20kg)
• Single academic center
• June 1, 2007 – March 1, 2012
• 28 pediatric donors ≤5.0kg
• 63 pediatric donors >5.0-20kg
International Txp Society 2012
Donor Characteristics
Donors ≤5kg
N=28
1.5
(5 hrs – 6 m)
3.8
(1.9 – 5)
Donors>5kg
N=63
P value
22.8
<0.001
10.7
<0.001
Imported
0.59
96%
0.60
83%
0.92
0.10
Donation after Circulatory
Death
43%
24%
0.08
Age (months)
Weight (kg)
Terminal creatinine (mg/dL)
International Txp Society 2012
Small pediatric kidney import sources
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♦ - >5kg
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Recipient Characteristics
Recipient age (years)
Recipient weight (kg)
Gender (% male)
Pediatric recipients
Panel Reactive
Antibody (%)
Donors ≤5kg Donors >5kg
P value
N=28
N=63
50
50
0.72
60
32%
66
48%
0.04
0.25
0
4.7%
NS
1.1%
10.0%
0.007
International Txp Society 2012
Allograft Survival
100
Survival (%)
90
>5kg donors
<5kg donors
80
70
60
p<0.048
p = NS
p = NS
50
0
1
3
6
12
Months
International
Txp Society
2012
National
Learning
Congress
2010
Short Term Allograft Function
Serum Creatinine (mg/dL)
4
3.5
*
>5kg donors
<5kg donors
3
2.5
*
2
* P <0.05
1.5
1
0.5
p<0.048
p = NS
p = NS
1
3
6
0
12
Months
International
TxpCongress
Society 2012
National
Learning
2010
Are children able to receive
these pediatric kidneys?
Butani et al, Pediatric Transplantation 2013
Pediatric Recipients
• 8 pediatric recipients of ped en bloc
kidneys from 2007-2012 (25% of
pediatric transplants)
• Recipient age 7.5 – 18 yrs
• Donor age 2wks – 48months
• Donor weight 4 - 22kg
Pediatric Recipients
•
•
•
•
Immediate function of all grafts
No post op dialysis
All allografts increased in size
Surveillance biopsies at 6 months
normal vs glomerulomegaly
• 100% allograft survival
• Median serum creatinine 0.67mg/dL
Donation after circulatory
death vs brain death
Study Cohort

88 small pediatric donors (≤20kg)
2005-2011, single academic center
 22
Pediatric DCD
 66
Pediatric DBD
Halsted, et al. ATC 2012
Donor Characteristics
DCD (n=22) DBD (n=66) P-value
Donor age (months)
Donor weight (kg)
Donor terminal
Creatinine (mg/dL)
Warm Ischemia
(min)
Imported graft (%)
NICU (%)
10
23
0.005
7.6
10
0.04
0.44
0.76
0.006
34
n/a
n/a
91
73
0.03
14
3
NS
Halsted, et al. ATC 2012
Study Outcomes
Outcomes
Delayed Graft
Function (%)
Graft Survival (%)
Patient survival (%)
DCD
23
DBD
14
P-value
0.37
100
100
92
97
0.24
0.16
Halsted et al., ATC 2012
Risk Factors Associated with
Surgical Complications in Recipients
of Kidneys from Very Small
Pediatric Donors
American Transplant Congress 2013
Study Objectives
• Characterization of surgical complications
• Identification of risk factors associated
with occurrence of complications
• Development of strategies to minimize
future complications
ATC 2013
Study Patient Cohort
• Recipients of deceased donor kidneys from
small pediatric donors (<20kg) from June
2007 to November 2012
ATC 2013
Graft survival of kidneys from small
pediatric donors
93%
Patients
76
89%
36
24
Surgical Complications
Urinary leak/obstruction
Thrombosis of one en bloc kidney
Bleeding/Hematoma
Thrombosis of both en bloc kidneys
Surgical site infection
Hematuria
Lymphocele
Renal artery stenosis
Pts (%)
11 (7.5)
9 (6.2)
5 (3.4)
4 (2.7)
3 (2.1)
1 (0.6)
1 (0.6)
1 (0.6)
ATC 2013
Multivariate Analysis
Risk for Surgical Complications
Hazard Ratio*
(95% Confidence Interval)
P value
Recipient weight (per Kg)
0.96 (0.92 – 0.99)
0.015
Donor Age ≤ 6 months
3.18 (1.26 – 8.01)
0.014
Cold ischemia time ≥ 24h
4.54 (1.85 – 11.13)
0.001
Adjusted by all variables in univariate analysis with P<0.2
Donor age and cold ischemia time treated as categorical variables
* Logistic regression
Surgical Complications
• Increased risk of complications in recipients
of kidneys from small pediatric donors
• Short term allograft function and survival
acceptable
• Longer term follow up warranted
ATC 2013
Optimizing outcomes
• Minimization of cold ischemia time
• Recipient selection/focus on nutritional status?
• Improve surgical technique and perioperative
management in smallest donors (<6 month)
– Optimization of donor operation
– Optimization of recipient perioperative
hemodynamic status
– Selective use of anticoagulation
– Improved technique with bladder anastomoses
ATC 2013
What is the effect of
donation on the donor family?
Hospital Critical Care Medicine Additional Care Note
**/**/2012 05:59AM
Per the parents request, and with them and about 10 family members and friends at the
bedside, we removed all life support from …She was having dyspnea and apneic
breathing …and was given several doses of morphine and ... ativan over the next 30
minutes to treat this discomfort. Heart rate dropped... Evntually, she was apneic,
pulseless, asystolic and without heart tones and I pronounced her dead at 0537.
We moved her to the operating room and …the body was handed off to the organ
procurement team who only at that point entered the OR.
I came back up and met with the family to tell them that organ porcurement had started.
I outlined the next steps for them of finding a funeral home, the ME autopsy process,
and going home safely. Both mom and dad reiterated multiple times their thanks in
"helping something good come out of this tragedy". ***(OPO) representatives as well
as staff remain at the bedside to provide additional support for this family in this
obviously difficult time.
On an organizational note, I really appreciate all of the varying members of the hospital
and ***(OPO) team helping accomplish this family's goal of organ donation.
Signed
***, MD
Pediatric Critical Care Attending
Utilization of Very Small Pediatric
Donor Kidneys
• Utilization of DBD and DCD kidneys
from the small infant is possible
• Kidneys can be transplanted into adult
or pediatric recipients
• Acceptable short term outcomes
• Renal allograft function improves
gradually for at least one year
• More surgical complications with small
donors
Current inclusion criteria for small
pediatric kidney donors
•
•
•
•
Full term infant
Weight > 2.5 kg
Acute injury ok if not anuric
Consider cold ischemia time up to 48
hours
• Consider DCD warm ischemia up to 120
minutes
Questions and Considerations
• What is the true potential for donor
expansion in this patient population?
• How many families are never approached
due to the perception that these organs are
not transplantable?
• Optimal end of life care in this patient
population should include donation option
• Education necessary: PICU, NICU, OPO,
transplant team

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