TRANSPLANTATION TODAY

1. TRANSPLANTATION TODAY LILLY BARBA, M.D. MEDICAL DIRECTOR RENAL TRANSPLANT PROGRAM HARBOR-UCLA MEDICAL CENTER APRIL 12, 2010

2. THE HISTORY OF TRANSPLANTATION AS DEPICTED IN ART • The possibility to transplant limbs and organs predates the modern technology of organ transplantation. • The legend of the “Miracle of the Black Leg” describes two surgeon brothers, who lived during the 3rd century in Asia Minor. • The legend relates their miraculous removal of the diseased leg of a Caucasian Roman named Justinian and its replacement with the leg of a recently deceased black African. The Miracle of Cosmas & Damian (15th c.)

3. SIGNIFICANT EVENTS IN TRANSPLANTATION • AS EARLY AS THE 6TH CENTURY BC THE INDIAN SURGEON SUSHRUTA DESCRIBED RECONSTRUCTION OF DISFIGURING FACIAL WOUNDS BY TRANSPLANTATING SKIN AND CARTILAGE • EARLY INTEREST IN THE POSSIBILITY OF TRANSPLANTATION

4. TRANSPLANTATION AS A VIABLE CLINICAL PROCEDURE • 1905 FIRST SUCCESSFUL HUMAN CORNEAL TRANSPLANT • 1930’S HISTOCOMPATIBILITY ANTIGENS DISCOVERED IN MICE • 1954 FIRST SUCCESSFUL KIDNEY TRANSPLANT PERFORMED BETWEEN IDENTICAL TWINS • 1957 AZATHIOPRINE DEVELOPED

5. TRANSPLANTATION AS A VIABLE CLINICAL PROCEDURE • 1962 FIRST SUCCESSFUL DECEASED DONOR KIDNEY TRANSPLANT • 1963 DR. HARDY PERFORMS FIRST SUCCESSFUL LUNG TRANSPLANT • 1966 FIRST SUCCESSFUL PANCREAS TRANSPLANT • 1967 DR. BARNARD PERFORMS THE FIRST SUCCESSFUL HEART TRANSPLANT. DR. STARZL PERFORMS THE FIRST SUCCESSFUL LIVER TRANSPLANT

6. TRANSPLANTATION AS A VIABLE CLINICAL PROCEDURE • 1981 DR. SHUMWAY PERFORMS THE FIRST HEART/LUNG TRANSPLANT • 1983 CYCLOSPORINE APPROVED FOR PREVENTION OF REJECTION • 1988 FIRST SUCCESSFUL SMALL INTESTINE TRANSPLANT • 1990 TACROLIMUS APPROVED FOR PREVENTION OF REJECTION • 1995 MYCOPHENOLATE APPROVED

7. TRANSPLANTATION AS A VIABLE CLINICAL PROCEDURE • 1996 USE OF SPLIT LIVERS • 1997 DACLIZUMAB APPROVED FOR PREVENTION OF ACUTE REJECTION • 1999 SUCCESSFUL ISLET CELL TRANSPLANTATION USING THE EDMONTON PROTOCOL • 2005 FIRST SUCCESSFUL PARTIAL FACE TRANSPLANT PERFORMED

8. TRANSPLANTATION TODAY • THE WAITING LIST • SUCCESS RATE OF ORGAN TRANSPLANTATION • REVIEW OF TRANSPLANTATION 2009

9. THE OPTN • The Organ Procurement and Transplantation Network (OPTN) was established by Congress under the National Organ Transplant Act (NOTA) of 1984 • The OPTN is operated by a private, non-profit organization under federal contract.

10. UNOSUNITED NETWORK FOR ORGAN SHARING • UNOS was awarded the first OPTN contract in 1986 • UNOS has continued to administer the OPTN under contract with the Health Resources and Services Administration of the U.S. Department of Health and Human Services (HHS) for more than 20 years.

11. What is the purpose of the OPTN? • The OPTN is a public-private partnership linking all of the professionals involved in the donation and transplantation system. • The primary goals of the OPTN are to: • increase and ensure the effectiveness, efficiency and equity of organ sharing in the national system of organ allocation • increase the supply of donated organs available for transplantation

12. THE WAITING LIST • Initiated on October 25, 1999, UNet contains data regarding every organ donation and transplant event occurring in the U.S. since 1986. • UNet enables the nation's organ transplant institutions to: • register patients for transplants • match donated organs to waiting patients • manage the clinical data of all patients, before and after their transplants

13. UNOS

14. Transplants performed January 2010UNOS

15. DONORSUNOS

16. Waitlist and Transplant Activity for Liver, 1999-2008

17. Waitlist and Transplant Activity for Kidneys, 1999-2008

18. Waitlist and Transplant Activity for Heart, 1999-2008

19. Waitlist and Transplant Activity for Lung, 1999-2008

20. TRANSPLANTATION TODAY • THE WAITING LIST • SUCCESS RATE OF ORGAN TRANSPLANTATION • REVIEW OF TRANSPLANTATION 2009

21. Patient Survival Until Five Years After Transplant Patients Transplanted 2001-2007

22. One Year Unadjusted Graft Survival by Year,Living and Deceased Donor Kidney Transplants

23. One Year Unadjusted Graft Survival by Year, Living and Deceased Donor Liver Transplants

24. One Year Unadjusted Patient Survival by Year, Living and Deceased Donor Liver Transplants

25. One Year Unadjusted Graft Survival by Year,Deceased Donor Heart Transplants

26. One Year Unadjusted Patient Survival by Year,Deceased Donor Heart Transplants

27. One Year Unadjusted Graft Survival by Year, Deceased Donor Lung Transplants

28. One Year Unadjusted Patient Survival by Year, Deceased Donor Lung Transplants

29. Annual Report of the OPTN and SRTR Trends in K and P Transplants 1998 to 2007 • The number of patients awaiting transplantation increased from 40,825 to 76,070 (86%) between 1998 and 2007, reflecting an increase in the number of patients listed “inactive status”. Active patients increased by 4,510 between 2002 and 2007, from 44,263 to 48,773. • There were 6,037 living donor and 10,082 deceased donor kidney transplants in 2007. Patient and allograft survival was best for recipients of living donor kidneys, least for expanded criteria donor (ECD) deceased donor kidneys, and intermediate for non-ECD kidneys. • The total number of pancreas transplants peaked at 1,484 in 2004 and has since declined to 1,331. Among pancreas recipients, those with simultaneous pancreas-kidney (SPK) transplants experienced the best pancreas graft survival rates: 86% at one year and 53% at 10 years.

30. Liver and Intestine Transplantation In the United States, 1998-2007 • Liver transplantation numbers in the United States remained constant from 2004-2007, while the number of waiting list candidates has trended down. • In 2007, the waiting list was its smallest since 1999, with adults ≥50 years representing the majority of candidates. Most age groups had decreased waiting list death rates, however, children <1 year had the highest death rate. • Non-cholestatic cirrhosis was most commonly diagnosed. Hepatocellular carcinoma exceptions increased slightly.

31. Liver and Intestine Transplantation In the United States, 1998-2007 • Use of liver allografts from donation after cardiac death donors increased in 2007. • Model for End-stage Liver Disease (MELD)/Pediatric Model for End-stage Liver Disease (PELD) scores <15 accounting for 75% of the waiting list. • Over the same period, the number of transplants for MELD/PELD <15 decreased from 16.4% to 9.8%. • The intestine transplantation waiting list decreased from 2006, with the majority of candidates being children <5 years old. • Death rates remain at about 14 % . Policy changes have been implemented to improve allocation and recovery of intestine grafts to positively impact mortality

32. Heart Transplantation in the U.S., 1998-2007 • The number of candidates actively awaiting heart transplantation has declined steadily, from 2,525 in 1998 to 1,408 in 2007, a 44% decrease. • Despite this decline, a larger proportion of patients are listed as either Status 1A or 1B, likely secondary to increased use of mechanical circulatory support.

33. Heart Transplantation in the U.S., 1998-2007 • The overall death rate among patients awaiting heart transplantation fell from 220 to 142 patients per 1,000 patient-years at risk. • Likely reflects better medical and surgical options for those with end-stage heart failure. • This trend was noted across all racial groups, both sexes, all disease etiologies (re-transplantation excepted), and all status groups.

34. Heart Transplantation in the U.S., 1998-2007 • Recipient numbers were relatively stable over the past decade. In 2007, 2,207 transplants were performed, although the proportion of patients transplanted as Status 1A shifted from 34% to 50%. A trend toward transplanting more patients above 65 years of age was seen. • Adjusted patient (and graft) survival at three months, one, five, and 10 years after transplantation has gradually, but significantly, improved during the same period. • Current patient survival estimates are 93%, 88%, 74%, and 55%, respectively (for 3m, 1yr, 5 yr, 10 y).

35. Lung Transplantation in the United States,1998-2007 • The most significant change in lung transplantation over the last decade was implementation of the Lung Allocation Score (LAS) allocation system in May 2005. • Subsequently, the number of active wait-listed lung candidates declined 54% from pre-LAS (2004) levels to the end of 2007. There was also a reduction in median waiting time, from 792 days in 2004 to 141 days in 2007. • The number of lung transplants performed yearly increased through the decade to a peak of 1,465 in 2007; the greatest single year increase occurred in 2005.

36. Lung Transplantation in the United States,1998-2007 • Despite higher LAS scores being transplanted in the LAS era, recipient death rates have remained relatively stable since 2003, and better than in previous years. • Idiopathic pulmonary fibrosis (IPF) became the most common diagnosis group to receive a lung transplant in 2007. Emphysema was the most common diagnosis in years prior. • The number of re-transplants and transplants in those >65yrs have increased significantly since 1998, up 295% and 643%, respectively. • A decreasing percentage of lung transplant recipients are children (3.5% in 2007, n=51).

37. TRANSPLANTATION TODAY • THE WAITING LIST • SUCCESS RATE OF ORGAN TRANSPLANTATION • REVIEW OF TRANSPLANTATION 2009

38. Review of topics in transplantation • Machine Perfusion or Cold Storage in Deceased-Donor Kidney Transplantation(NEJM 360:7,2009) : randomized, controlled trial showed machine perfusion associated with a reduced risk of delayed graft function and improved graft survival in the first year post transplant (94 % vs 90 %)

39. Review of topics in transplantation • Outcomes and Utilization of Kidneys from Deceased Donors with Acute Kidney Injury (AJT 2009:9):The relative risk of graft loss was similar for recipients of SCD kidneys with sCr of 1.6–2.0 and >2.0 mg/dL, compared to ≤1.5 mg/dL. For ECD recipients, the relative risk of graft failure significantly increased with increasing sCr • Calculating Life Years from Transplant (LYFT): Methods for Kidney and Kidney-Pancreas Candidates (AJT 2008:8:997) :Prioritizing candidates with higher LYFT scores for each available kidney could substantially increase total years of life among both transplant candidates and recipients

40. Other topics in transplantation • PAIRED EXCHANGE/CHAIN DONORS • SURVIVAL OF KIDNEY DONORS • PREGNANCY IN YOUNG WOMEN AFTER DONATION

41. CONCLUSIONS: • TRANSPLANTATION SAVES LIFES, IMPROVES THE QUALITY OF LIFE • ALLOGRAFT AND PATIENT SURVIVALS HAVE IMPROVED • MORE DONORS ARE NEEDED