current trends in transplantation karin true md, fasn assistant professor unc kidney center may 23,...
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Current Trends inTransplantation
Karin True MD, FASNAssistant ProfessorUNC Kidney Center
May 23, 2011
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ESRD Treatment Modalities
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Prevalent patientsIncident patients
USRDS 2010 ADR
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Incident ESRD patients receiving a transplant within three years of ESRD
registration
lla
illi
lla
illi
USRDS 2010 ADR
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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
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Donor Outcomes cont.
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Quality of life scores
Donors perception ofbenefit to recipient
AJT 2011; 11:463-469
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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
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Living Donor Relationships
10USRDS 2010
ADR
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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
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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
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Paired Donation
Recipient A Donor A
Recipient B Donor B
X
X
Transplants done witha negative crossmatch
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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
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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
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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
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ECD and DCD Donation
22USRDS 2010 ADR
Incidence of delayed graftfunction (DGF)
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Patient survival Graft survival
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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
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Medicare Costs by Modality
25USRDS 2010
ADR