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

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

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

Most kidneys from donors <9kgare not recovered

Tragic Trifecta3. The parents consent, the kidneys are recovered but

then discarded

50% discard rate if donor <9kg

Kidneys from very small donors: Few recovered, many discarded, few

transplanted

Could these kidneys be betterutilized?

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 <0.0001

10-14kg 708 0.97 0.84-1.12 0.66

15-19kg 406 0.83 0.68-1/01 0.06

20+ 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

Donation after circulatory death

A underutilized option for families with small children who

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

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 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

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

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

0 2 3 5 6 9Hours

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

UC Davis Deceased Donor Transplantation: Small pediatric donors

2003 2004 2005 2006 2007 2008 2009 2010 2011 20120

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

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 0.72

Recipient weight (kg) 60 66 0.04

Gender (% male) 32% 48% 0.25

Pediatric recipients 0 4.7% NS

Panel Reactive Antibody (%) 1.1% 10.0% 0.007

Recipient Characteristics

Allograft Survival

0 1 3 6 12

Months

<5kg donors

>5kg donors

p<0.048 p = NS p = NS

National Learning Congress 2010International Txp Society 2012

Short Term Allograft Function

1 3 6 12

Months

)<5kg donors

>5kg donors

p<0.048 p = NS p = NS

National Learning Congress 2010

* P <0.05

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

Richard V. Perez, M.D. Kidney Donation in the Very Small Pediatric Deceased Donor: Addressing the...

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