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

1. Next Speaker: Richard V. Perez, M.D. Kidney Donation in the Very Small Pediatric Deceased Donor: Addressing the Tragic Trifecta Sponsored by

2. Outline 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 Very small <5kg donors Pediatric recipients DCD Summary and call to action

3. Outline 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 Very small <5kg donors Pediatric recipients DCD Summary and call to action

4. Rationale for Kidney Transplantation • Children • Optimize growth and development • Adults • Survival benefit vs dialysis • Improvement in quality of life

5. Our Goal To make transplantation a safe option for as many patients as possible

6. Patients waiting for kidney transplantation on October 2, 2013 97,916

7. Outline 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 Very small <5kg donors Pediatric recipients DCD Summary and call to action

9. Pediatric Organ Donation More Common with Increasing Donor Weight Pelletier, et al. Am J Transplant 2006

10. Tragic Trifecta1. The small child dies Pelletier, et al. AJT 2006

11. Tragic Trifecta2. The parents consent, but the kidneys are not recovered Most kidneys from donors <9kg are not recovered Pelletier, et al. AJT 2006

12. Tragic Trifecta3. The parents consent, the kidneys are recovered but then discarded 50% discard rate if donor <9kg Pelletier, et al. AJT 2006

13. Kidneys from very small donors: Few recovered, many discarded, few transplanted Could these kidneys be better utilized? Pelletier, et al. AJT 2006

14. Outline 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 Very small <5kg donors Pediatric recipients DCD Summary and call to action

15. 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

16. Inferior outcomes when donor is <10kg or <1yr: A disincentive to transplant small kidneys

17. Kidneys from donors <10kg have a higher failure rate Kayler, et al. Am J Transplant 2009

18. 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

19. 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

20. Pediatric kidneys rapidly grow after transplantation Bretan, et al. Transplantation 1997

21. Outline 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 Very small <5kg donors Pediatric recipients DCD Summary and call to action

22. Donation after circulatory death A underutilized option for families with small children who die?

24. DCD in the small infant is uncommon Dagher, et al. Transplantation 2011 • UNOS national experience 2000 – 2009 • 12207 pediatric kidneys recovered • 765 (6.3%) pediatric DCD • 88 (0.7%) DCD less 5 years old

25. J Pediatrics 2011

26. What is the potential for DCD in the small neonate? Labrecque et al., J Pediatrics 2011 • Retrospective review of 192 deaths in 3 Harvard Neonatal ICUs

27. 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

28. Outline 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 Very small <5kg donors Pediatric recipients DCD Summary and call to action

29. Case Study: Donation after Circulatory Death in an Anencephalic Newborn Acknowledgement to: Intermountain Donor Services Angela Ortega Craig Myrick Diana Alonso

30. 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

31. 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)

32. 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

33. 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

36. Recipient • 38 year old woman • Renal failure secondary to focal segmental glomerulosclerosis • Pre-dialysis • Weight 56kg, PRA 0%

38. 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

39. Outline 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 Very small <5kg donors Pediatric recipients DCD Summary and call to action

40. 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

41. Donor Operation

45. Organ preservation method matters vs. Machine preservation may increase availability of organs for transplantation

46. 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)

47. 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

48. Pulsatile Pump Preservation Optimize vascular back bench preparation Improves renal hemodynamics

49. Improved renal microcirculation during pulsatile perfusion of pediatric en bloc kidneys

50. Improved renal hemodynamics after pulsatile perfusion Before pumping After pumping