Northwestern University Feinberg School of Medicine New Trends in organ donation and Transplantation Juan Carlos Caicedo, MD FACS Director, Hispanic Transplant Program Adult transplant Surgeon (NMH) Pediatric Transplant Surgeon (LCH)

Overview Introduction Kidney ( Living / deceased/ combined stem cell) Liver: whole, split, reduce size, living donor 2

Who Needs a Transplant? Transplantation is offered to patients who: are in end-stage organ failure have no other surgical or medical option available to them have a limited life expectancy without a transplant have undergone a rigorous and thorough assessment process and meet all necessary criteria

4 Type of donors Deceased (dead) donors -Brain dead donors: intact heartbeat & circulation, on ventilator less than 3% of all deaths -Donors after cardiac death: occurs in hopeless cases in the hospital where the decision to withdraw life-support is made (decision is independent of the decision to donate). Organ donation occurs immediately once the heart has stopped and the patient is declared dead Living donor -Patient chooses to donate one or part of an organ to someone on a transplant waiting list can only occur with organs when removal will NOT cause grave harm to the donor-

Northwestern University Feinberg School of Medicine United States Organ Transplantation OPTN & SRTR Annual Data Report, 2011

Patients on the waiting list on December 31 of the year (active listings only)

Transplants performed during the year (adult & pediatric combined)

First-year all-cause graft survival

Northwestern University Feinberg School of Medicine Adult Kidney Transplantation

End Stage Renal Disease Dimension of the problem > people in US Options: Dialysis and kidney transplantation US kidney waiting list: people / 2013

Kidney Failure: Treatment Kidney Transplantation “ Best option” -Replace all functions of the kidney -Increase survival and quality of life -Decrease complications -Cost effective

Incident ESRD Rate and Transplant Rate 12 USRDS 2010 ADR

Northwestern University Feinberg School of Medicine 2013: Waiting list 2012: Transplanted 758 ( 4.5%) Pediatric pts Whites :38% AA: 34% Hispanics: 19% Asian: 8%

Distribution of adult patients waiting for a kidney transplant

Deceased donor kidney donation rates

Cause of death among deceased kidney donors

Organs recovered per donor (ORPD), by SCD, DCD, & ECD status

Delayed graft function among adult kidney transplant recipients

Kidney donations from living donors

Living kidney donation Laparoscopic vs Open - Safe - Less pain - Fast recovery - POD 1: Home - Smaller Incisions

Intended kidney transplant procedure type, & percent of intended laparoscopic procedures converted to open

Number of transplants from living donors, by donor relation All patients receiving a living donor kidney transplant. USRDS 2010 ADR

Kidney Transplantation

Sensitized Patients Sensitized Very Highly Sensitized36% Sensitized Total = 17,814 pts 2010: 25% Sensitized

Options for Sensitized and ABO incompatible Patients Wait and hope Desensitization Live Donor Deceased Donor Live Donor Paired Exchange List Exchange Wait and hope Desensitization Live Donor Deceased Donor Live Donor Paired Exchange List Exchange

Paired kidney donations

Basic Kidney Paired Donation (KPD)

Northwestern University Feinberg School of Medicine

Desensitization 30 N Engl J Med 365;4 July 28, 2011

Trends in Transplant Medications 31

Immunosuppression use in adult kidney transplant recipients

Initial immunosuppression regimen in adult kidney transplant recipients, 2011

Acute rejections within the first year post-transplant 34 First-time, kidney-only transplant recipients, age 18 & older, with functioning graft at discharge. Source: USRDS 2010 ADR

Trends in Transplant Research 35

The co-existence of two genetically different components in one organism Chimerism induces tolerance Mixed Chimeras How can we make it safe?

Northwestern Clinical Tolerance Protocols Sequential kidney/HSC in HLA matched related Simultaneous kidney/HSC in HLA mismatched 37

HLA-Matched Protocol Current Enrollment – 20/20 First patient enrolled January 2008 HLA identical siblings Excluded if high risk of recurrent disease in the allograft (role of immunosuppression in preventing disease recurrence) 38 PI: Joshua Miller

39 HSCT mobilized, collected, processed, & cryopreserved (> 2 wks before Tx) Conditioning Fludarabine, cytoxan, 200 cGy TBI Perform Transplant Processed donor leukopheresis product/marrow enriched for HSC, FC and progenitors (FCRx) Simultaneous FCRx +Kidney Transplant d0d +1

Adult kidney transplants

Outcomes among adult kidney transplant recipients: deceased donor

Outcomes among adult kidney transplant recipients: living donor

Half-lives for adult kidney transplant recipients

Liver Transplantation Type of donor: Living vs deceased donor Type of graft: Partial vs whole organ

Whole Organ Orthotopic Liver Transplant Standard technique. This figure illustrates a completed liver transplant with vascular and biliary anastomoses.

Partial Grafts / Liver transplantation (LTX) -Reduce Size Ltx -Split LTx -Living Donor Ltx

Partial Liver Transplantation The split through midplane with right and left lobe grafts Reference: Humar A, et al. Amer J Transpl 2001;1: Schematic drawing of the right lobe after transplantation into the recipient. The major vascular anastomosis and drainage of the bile duct into a Roux loop of bowel is illustrated

Northwestern University Feinberg School of Medicine Adult Liver Transplantation 48

Distribution of adult patients waiting for a liver transplant

Liver donors who are DCD

Liver transplants from living donors, by donor relation

Living donor liver transplant graft type

Total adult liver transplants

Adult liver transplants

Graft failure among adult liver transplant recipients: deceased donor

Immunosuppression use in adult liver transplant recipients

59 Conclusion Transplantation offers a second chance at life to thousands of people. It has been proven over and over again to be very successful. However, transplantation can only occur if someone consents to the ultimate gift – organ and tissue donation. liver transplant recipient Kidney donor and recipient

Northwestern University Feinberg School of Medicine Thank you 60