Richard V. Perez, M.D. Kidney Donation in the Very Small Pediatric Deceased Donor: Addressing the...
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Transcript of Richard V. Perez, M.D. Kidney Donation in the Very Small Pediatric Deceased Donor: Addressing the...
Richard V. Perez, M.D.Kidney Donation in the Very Small
Pediatric Deceased Donor: Addressing the Tragic Trifecta
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Outline1. Rationale for kidney transplantation2. What is the tragic trifecta?3. Challenges with small pediatric
donors4. Problems/potential in pediatric DCD5. An interesting case study6. A strategy to utilize small kidneys7. Outcomes
1. Very small <5kg donors2. Pediatric recipients3. DCD
8. Summary and call to action
Outline1. Rationale for kidney transplantation2. What is the tragic trifecta?3. Challenges with small pediatric
donors4. Problems/potential in pediatric DCD5. An interesting case study6. A strategy to utilize small kidneys7. Outcomes
1. Very small <5kg donors2. Pediatric recipients3. 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
Outline1. Rationale for kidney transplantation2. What is the tragic trifecta?3. Challenges with small pediatric
donors4. Problems/potential in pediatric DCD5. An interesting case study6. A strategy to utilize small kidneys7. Outcomes
1. Very small <5kg donors2. Pediatric recipients3. DCD
8. Summary and call to action
Pediatric Organ Donation More Common with Increasing Donor Weight
Pelletier, et al. Am J Transplant 2006
Tragic Trifecta1. The small child dies
Pelletier, et al. AJT 2006
Tragic Trifecta2. The parents consent, but the kidneys are not
recovered
Pelletier, et al. AJT 2006
Most kidneys from donors <9kgare not recovered
Tragic Trifecta3. The parents consent, the kidneys are recovered but
then discarded
Pelletier, et al. AJT 2006
50% discard rate if donor <9kg
Kidneys from very small donors: Few recovered, many discarded, few
transplanted
Pelletier, et al. AJT 2006
Could these kidneys be betterutilized?
Outline1. Rationale for kidney transplantation2. What is the tragic trifecta?3. Challenges with small pediatric
donors4. Problems/potential in pediatric DCD5. An interesting case study6. A strategy to utilize small kidneys7. Outcomes
1. Very small <5kg donors2. Pediatric recipients3. 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) Early Failure /Thrombosis
Beltran 2010 5 <1yr 20%
Balachandran 2010 11 <10 18%
Thomusch 2009 35 <1yr 34%
Sanchez 6 <1yr 33%
Hiromoto 2002 10 <1yr 12.6 40%
Gourlay 1995 3 <1yr 100%
Kidneys from donors <10kg have a higher failure rate
Group N Adj Hazard Ratio
95% CI P-value
Standard Criteria
34,527 Ref Ref Ref
5-9kg 293 1.50 1.23-1.84 <0.000110-14kg 708 0.97 0.84-1.12 0.6615-19kg 406 0.83 0.68-1/01 0.0620+ kg 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 post-
transplantation
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
Bretan, et al. Transplantation 1997
Pediatric kidneys rapidly grow after transplantation
Outline1. Rationale for kidney transplantation2. What is the tragic trifecta?3. Challenges with small pediatric
donors4. Problems/potential in pediatric DCD5. An interesting case study6. A strategy to utilize small kidneys7. Outcomes
1. Very small <5kg donors2. Pediatric recipients3. 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
Labrecque, et al. J Peds 2011
• 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
Results: 8% of NICU mortalities were potential candidates for DCD
Outline1. Rationale for kidney transplantation2. What is the tragic trifecta?3. Challenges with small pediatric
donors4. Problems/potential in pediatric DCD5. An interesting case study6. A strategy to utilize small kidneys7. Outcomes
1. Very small <5kg donors2. Pediatric recipients3. 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 MyrickDiana 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 3.6cm length– 6 weeks 5.4cm length– 1 year 7.6cm length
• Slow improvement in renal function with current serum creatinine 1.29 16 months post transplant
Outline1. Rationale for kidney transplantation2. What is the tragic trifecta?3. Challenges with small pediatric
donors4. Problems/potential in pediatric DCD5. An interesting case study6. A strategy to utilize small kidneys7. Outcomes
1. Very small <5kg donors2. Pediatric recipients3. 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
Machine preservation may increase availability of organs for
transplantation
vs.
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 non-
function (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
Improved renal microcirculation during pulsatile perfusion of pediatric en bloc kidneys
1516171819202122232425
0 2 3 5 6 9Hours
Flow
(cc/
min
)
0
0.5
1
1.5
2
2.5
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3.5
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Flow
Resistance
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
Outline1. Rationale for kidney transplantation2. What is the tragic trifecta?3. Challenges with small pediatric
donors4. Problems/potential in pediatric DCD5. An interesting case study6. A strategy to utilize small kidneys7. Outcomes
1. Very small <5kg donors2. Pediatric recipients3. DCD
8. Summary and call to action
UC Davis Deceased Donor Transplantation: Small pediatric donors
2003 2004 2005 2006 2007 2008 2009 2010 2011 20120
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Outcomes
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
Donors ≤5kg N=28
Donors>5kg N=63 P value
Age (months) 1.5 (5 hrs – 6 m) 22.8 <0.001
Weight (kg) 3.8(1.9 – 5) 10.7 <0.001
Terminal creatinine (mg/dL) 0.59 0.60 0.92
Imported 96% 83% 0.10Donation after Circulatory
Death 43% 24% 0.08
Donor Characteristics
International Txp Society 2012
Small pediatric kidney import sources
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♦ - ≤5kg
♦ - >5kg
Donors ≤5kg N=28
Donors >5kgN=63 P value
Recipient age (years) 50 50 0.72Recipient weight (kg) 60 66 0.04Gender (% male) 32% 48% 0.25Pediatric recipients 0 4.7% NSPanel Reactive Antibody (%) 1.1% 10.0% 0.007
Recipient Characteristics
International Txp Society 2012
Allograft Survival
50
60
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90
100
0 1 3 6 12
Months
Surv
ival
(%)
<5kg donors>5kg donors
p<0.048 p = NS p = NS
National Learning Congress 2010International Txp Society 2012
Short Term Allograft Function
0
0.5
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1 3 6 12
Months
Seru
m C
reat
inin
e (m
g/dL
)<5kg donors>5kg donors
p<0.048 p = NS p = NS
National Learning Congress 2010
*
** P <0.05
International Txp Society 2012
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
Study Cohort88 small pediatric donors (≤20kg) 2005-2011, single academic center
22 Pediatric DCD
66 Pediatric DBD Halsted, et al. ATC 2012
Donation after circulatory death vs brain death
Donor Characteristics
DCD (n=22) DBD (n=66) P-value
Donor age (months) 10 23 0.005
Donor weight (kg) 7.6 10 0.04
Donor terminal Creatinine (mg/dL)
0.44 0.76 0.006
Warm Ischemia (min)
34 n/a n/a
Imported graft (%) 91 73 0.03
NICU (%) 14 3 NS
Halsted, et al. ATC 2012
Study Outcomes
Outcomes DCD DBD P-value Delayed Graft Function (%)
23 14 0.37
Graft Survival (%) 100 92 0.24Patient survival (%) 100 97 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% 89%
Patients 76 36 24
Surgical ComplicationsPts (%)
Urinary leak/obstruction 11 (7.5)Thrombosis of one en bloc kidney 9 (6.2)Bleeding/Hematoma 5 (3.4)Thrombosis of both en bloc kidneys 4 (2.7)Surgical site infection 3 (2.1)Hematuria 1 (0.6)Lymphocele 1 (0.6)Renal artery stenosis 1 (0.6)
ATC 2013
Multivariate AnalysisRisk 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) 0.014Cold ischemia time ≥ 24h 4.54 (1.85 – 11.13) 0.001
* Logistic regression
Adjusted by all variables in univariate analysis with P<0.2Donor age and cold ischemia time treated as categorical variables
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
***, MDPediatric 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