Current Trends in Transplantation Karin True MD, FASN Assistant Professor UNC Kidney Center May 23, 2011

ESRD Treatment Modalities 2 Prevalent patientsIncident patients USRDS 2010 ADR

Incident ESRD patients receiving a transplant within three years of ESRD registration lla illi lla illi USRDS 2010 ADR

Advantages of Living Donor Reduced time to transplant »Fewer deaths awaiting transplant »Pre-emptive transplant possible »Reduced time on dialysis Hospital stays shorter Graft and patient survival rates higher 5

The Living Donor Free of disease associated with development of kidney dysfunction Acceptable risk for surgery Free of diseases which could be transferred to the recipient Financial gain for the donor is prohibited 6

Donor Outcomes Survival similar to matched controls ESRD in 11 donors » 180 per million/yr » In general population 286 per million/yr 7 NEJM 2009; 360:

Donor Outcomes cont. 8 Quality of life scores Donors perception of benefit to recipient AJT 2011; 11:

Laprascopic Donor Nephrectomy Advantages »Pain control »Decreased hospital stay »Earlier return to ADLs »Better wound cosmesis Disadvantages »Increased warm ischemia time »Smaller surgical field Hand assisted technique may aid in hemorrhage control »Difficult in obese donors 9 Br J Surg 2010; 97: 21-28

Living Donor Relationships 10 USRDS 2010 ADR

HLA Matching The Major Histocompatibility Complex (MHC) is a large cluster of closely linked genes on the short arm of chromosome 6 These genes code for a group of proteins called the Human Leukocyte Antigens (HLA) » determine the rejection or acceptance of tissue grafts » involved in antigen presentation » markers of cellular identity, self-recognition Transplant focuses on HLA –A, -B and –DR » specific HLA alleles are numbered » one from each parent » Ex. of HLA type: A1 A2 B51 B60 DR7 DR11

12 Positive Crossmatch Predicts rejection Negative Crossmatch Proceed with transplant Crossmatch IgG to A2 IgG to A2 A2

Blood Type Compatibility % chance a given pair will be ABO incompatible Median wait time for a deceased donor 5.1 years 3.3 years 5.3 years 2.3 years

Paired Donation Recipient ADonor A Recipient B Donor B X X Transplants done with a negative crossmatch

Disadvantages Pairs with type O recipients less likely to match » Type O donors usually compatible » Match rates only ~ 15% ~ 50% for those with non-type O recipients Ideally surgeries occur simultaneously » Donors have autonomy to withdraw consent » Not always possible with bigger chains Geographic barriers » May separate donor from recipient at time of surgery Lack of national registry » Need maximum number of pairs for success 15

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ABO Incompatible Transplant Use isohemaglutinin techniques to measure titers of anti-A and anti-B antibodies present Need to eliminate these antibodies to have a successful transplant Strategies » Therapeutic plasma exchange centrifuge separation of plasma w/ removal of immunoglobulin, complement, clotting factors can run concurrent with hemodialysis » IVIG downregulates antibody production usually used as an adjunct to plasma exchange Once titer is low enough (center specific) can proceed with transplant 17

Disadvantages Antibody mediated rejection » 10-30% early » 0-10% irreversible leading to graft loss » > 1 month survival similar to routine transplants Cost from POD -14 to +90 » ABOI: $90, ,100 » ABOC: $52, ,300 » Differential $37,800 Less than the cost of a year of hemodialysis 18 Transplantation 2006; 82: Curr Op Tx 2010; 15:

Desensitization Therapies to reduce/eliminate the HLA antibodies the recipient has to the donor Done prior to transplant over a period of weeks to months Treatment options » Plasmapheresis » IVIG » Rituximab » Other – bortezemib, eculizumab, splenectomy 19

Desensitization Outcomes » At 2 years Patient survival 95% Graft survival 86% » Decreased compared to traditional transplants Consider paired donation first Disadvantages » Rejection 36% acute rejection (28% antibody mediated) Higher rate of transplant glomerulopathy » Once develops is poor prognosis » More immunosuppression » Cost 20 CJASN 2011; 6:

ECD and DCD Donation 22 USRDS 2010 ADR Incidence of delayed graft function (DGF)

23 Patient survivalGraft survival

Post-Transplant Malignancy VIRAL INFECTION ASSOCIATED MALIGNANCY Epstein-Barr Virus (EBV) Post-transplant lymphoproliferative disorder (PTLD) Human papillomaviruses 5 and 8 Skin and lip cancer squamous > basal cell Hepatitis B and CHepatoma Human herpesvirus (HHV) 8Kaposi’s sarcoma Human papillomavirus (HPV) and herpes simplex virus (HSV) Cervical and vaginal cancer

Medicare Costs by Modality 25 USRDS 2010 ADR