current trends in transplantation karin true md, fasn assistant professor unc kidney center may 23,...

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

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

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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.

8

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

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

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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