Kidney TransplantationKidney TransplantationAn Overview An Overview

Mark W. Johnson, MD, Assoc. Professor of Surgery

Director of Liver Transplantation University of North Carolina

Chapel Hill

History of TransplantationHistory of Transplantation

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

Alexis Carrel 1912Alexis Carrel 1912

Kolff, 1940’s : Kolff, 1940’s : Hemo-dialysis Hemo-dialysis

machinesmachines

Hume, 1950’s – kidney to femoral vesselsHume, 1950’s – kidney to femoral vessels

Murray, 1956 – current transplant positionMurray, 1956 – current transplant position

Murray, 1956 – Murray, 1956 – current transplant current transplant

positionposition

Renal transplant:Renal transplant:Venous anastomosisVenous anastomosis

Renal transplant:Renal transplant:

Arterial anastomosisArterial anastomosis

Renal transplant:Renal transplant:

ReperfusionReperfusion

Renal transplant:Renal transplant:

Ureteral anastomosisUreteral anastomosis

Kidney-Pancreas Kidney-Pancreas transplantationtransplantation

Why?Why?

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)

Pancreas transplant: Vascular anatomyPancreas transplant: Vascular anatomy

Lillehei 1966: Lillehei 1966: current transplant current transplant

positionposition

Pancreas transplant:Pancreas transplant:

enteric anastomosisenteric anastomosis

“You are about to experience something rare in your life, Stan – Rejection.”

P. B. Medawar, 1953:P. B. Medawar, 1953:

““Actively Acquired Actively Acquired Tolerance of Tolerance of

Foreign Cells.”Foreign Cells.”

Recognizing Non-selfRecognizing Non-self

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)

The SolutionThe Solution