Current Trends inTransplantation

Karin True MD, FASNAssistant ProfessorUNC Kidney Center

May 23, 2011

ESRD Treatment Modalities

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Prevalent patientsIncident patients

USRDS 2010 ADR

Incident ESRD patients receiving a transplant within three years of ESRD

registration

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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

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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

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Donor Outcomes

• Survival similar to matched controls

• ESRD in 11 donors» 180 per

million/yr» In general

population• 286 per

million/yr

7NEJM 2009; 360: 459-

469

Donor Outcomes cont.

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Quality of life scores

Donors perception ofbenefit to recipient

AJT 2011; 11:463-469

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

9Br J Surg 2010; 97: 21-28

Living Donor Relationships

10USRDS 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

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Positive CrossmatchPredicts rejection

Negative CrossmatchProceed with transplant

Crossmatch

IgGto A2

IgGto A2

A2

A2

A2

Blood Type Compatibility

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30-35% chance a given pair will beABO incompatible

Median waittime for a deceased

donor

5.1 years

3.3 years

5.3 years

2.3 years

Paired Donation

Recipient A Donor A

Recipient B Donor B

X

X

Transplants done witha 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

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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

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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: $90,300 + 68,100» ABOC: $52,500 + 25,300» Differential $37,800

• Less than the cost of a year of hemodialysis

18Transplantation 2006; 82:155-163

Curr Op Tx 2010; 15:526-530

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,

splenectomy19

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

20CJASN 2011; 6:922-936

ECD and DCD Donation

22USRDS 2010 ADR

Incidence of delayed graftfunction (DGF)

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Patient survival Graft survival

Post-Transplant Malignancy

VIRAL INFECTIONASSOCIATEDMALIGNANCY

Epstein-Barr Virus (EBV)Post-transplant

lymphoproliferative disorder (PTLD)

Human papillomaviruses 5 and 8

Skin and lip cancersquamous > basal cell

Hepatitis B and C Hepatoma

Human herpesvirus (HHV) 8

Kaposi’s sarcoma

Human papillomavirus (HPV) and herpes

simplex virus (HSV)

Cervical and vaginalcancer

Medicare Costs by Modality

25USRDS 2010

ADR