kidney transplantation an overview mark w. johnson, md, assoc. professor of surgery director of...
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Kidney TransplantationKidney TransplantationAn Overview An Overview
Mark W. Johnson, MD, Assoc. Professor of Surgery
Director of Liver Transplantation University of North Carolina
Chapel Hill
Kidney Transplantation Kidney Transplantation Surgical MilestonesSurgical Milestones
Ulman, 1902 – kidney to neck vessels Carrel, 1912 – vascular techniquesKolff, 1940’s – dialysis machineHume, 1947 – kidney to arm vesselsMurray, 1956 – identical twin transplant
Non-Uremic PatientsNon-Uremic Patients
Sequellae of diabetes have to be considered worse than short term surgical risks and the long term risks of chronic immunosuppression.
History of Pancreas History of Pancreas TransplantationTransplantation
1913 Hedon: pancreas segment to neck of dog
1921 Banting & Best: extraction of insulin
1966 Kelly/Lillehei: 1st clinical pancreas tx 60 grafts/56 pts. 3% graft/39% pt @ 1 yr.
1978 Introduction of cyclosporin295grafts/276 pts. 40% graft/77% pt @ 1 yr
History of Pancreas History of Pancreas Transplantation (cont’d)Transplantation (cont’d)
since 1984: improved vascular techniques (“Y” graft) drainage of exocrine function (bladder vs. enteric) improved immunosuppression (FK506, MMF) improved rejection therapy (OKT3) improved antibiotics (anti-viral, fungal agents)
P. B. Medawar, 1953:P. B. Medawar, 1953:
““Actively Acquired Actively Acquired Tolerance of Tolerance of
Foreign Cells.”Foreign Cells.”
Major Histocompatibility ComplexMajor Histocompatibility Complex
Class I MW 45k
single polymorphic chain
ß-2 microglobulin
A, B, and C loci
Expressed on all cells
Class II MW33k and 28k
two polymorphic chains
DP, DQ, and DR loci
Expressed on macrophages, B cells, activated T cells, dendritic cells, etc.
Varieties of RejectionVarieties of Rejection
Type of Rejection
Time course Cause
Hyperacute Minutes-hours Pre-formed antibodies (humoral)
Acute Days - weeks Cell mediated
chronic Months - years Humoral and cell mediated
ImmunosuppressionImmunosuppression
EvolutionEvolution
1960 1970 1980 1990 2000 2010
Cyclosporin
OKT3
TacrolimusMycophenolate mofetil Rapamycin Brequinar Leflunomide
IL2r antibodies monoclonal antibodies
Steroids
Azathioprine
ATGALG ?????
Progress in ImmunosuppressionProgress in Immunosuppression
1950 vs. 2000
Ready-Fire-Aim Ready-Aim-Fire
Renal Transplant Graft SurvivalsRenal Transplant Graft Survivals
0
20
40
60
80
100
1 YEAR 2YEARS
3YEARS
4YEARS
UNC CAD (N=190)
UNC LD (N=163)
UNOS CAD(N=51830)UNOS LD(N=15480)
Pancreatic Graft SurvivalsPancreatic Graft Survivals
0
20
40
60
80
100
1st YR 2nd YR 3rd YR 4th YR
UNC (n=50)
UNOS (n=3733)