Transplantation

Question 1

Transplantation

Answer 1

• Removal of a tissue or an organ from a body and placing it in the same or in an other body with maintaining its function.

Question 2

Source of donor organs

Answer 2

•	Deceased donor
–	Brain dead
–	Non heart beating
•	Living donor
–	Living-related (parents, siblings, children) 
–	Living emotionally related (spouses)
–	Living unrelated
–	Brain Death

Question 3

Indication to renal transplantation:

Answer 3

• Progressive, irreversible chr. renal failure
  serum creatinine > 600-800 mmol/l,
  GFR < 15 ml/min

Question 4

Contraindications

Answer 4

	Malignancy
	Active infection (HIV, TBS, hepatitis) 
	Obesity (BMI>35) 
	Severe atherosclerosis
	Noncompliance
	Psychiatric illness

Question 5

Donation criteria

Answer 5

• age:
• Kidney: 4-75 years
• Liver: < 300
• HBsAg, HCV és HIV negative

Question 6

Contraindications of donation

Answer 6

• Known renal, liver, heart, lung, pancreas disorder
• Injury
• Malignancy
• Infection
• Smoking (lung)
• Long (>7 days) mechanical ventillation
• Alcohol/drug abuse (liver, pancreas)
• long (>60 min) hypotension (RR<60)
• Malignant hypertension
• IDDM (type I)
• Immunology

Question 7

Donor / Recipient

Answer 7

HISTOCOMPATIBILITY
ABO (Rh ?)
MHC (Major Histocompatibility Complex)
•	MHC I  (all nucleated cells) 
	Presents endogen peptides
	Activation of CD8+ cytotoxic T cells
•	MHC II  (APC: B lymphocyte, macrophag, dentritic cells)
	presents exogen oligopeptides
	Activation of CD4+ helper T cells

Principles of immunologic allocation
	Blood Group Identity ( A-A, B-B, etc)
	HLA A, B, DR mismatch 
			importance of B, DR matching
	Negative crossmatching
	To exclude recipients who bear pre-existing antidonor immunity likely to cause graft failure.

Question 8

Rejection

Answer 8

Hyperacute rejection (0-24 h) V
• (preformed Ab, no therapy)
Accelerated acute rejection (within 5 days) C, V
• (low affinity antidonor Ab, generation of cytotoxic T cells from memory elements.
• Th: ATG, plasmapheresis, cyclophosphamide)
Acute rejection C (V) (5-28. days, later )
• Alloantigen-specific T cells, th: steroids, antilymphocyte Abs (Histology)
cellular, interstitital (C)
humoral, vascular (V)

Question 9

Immunosuppression Ideal ISU agent

Answer 9

•	Prevention of graft rejection
•	No immunologic side effect 
(infection, tumour)
•	No toxic side effect
•	Induction of tolerance

Question 10

Basic ISU (long term)

Answer 10

1. Corticosteroids
2. Inhibitors of IL-2 synthesis:
   • Calcineurin inhibitors (CNI):
   Cyclosporin-A
   Tacrolimus
   • mTOR inhibitors:
   Rapamycin
   everolimus
3. Inhibitors of lymphocyte proliferation
    Azathioprin
    Mycofenolate-mofetil (MMF)
    Mycophenol acid (MPA)

Question 11

Induction and Anti-rejection therapy (Short Term)

Answer 11

1. Polyclonal immunglobulins 
	antilymphocyte globulin (ALG)
	antithymocyte globulin (ATG)
2. Monoclonal immunglobulins
	anti-CD3 IgG (OKT-3)
	 anti - IL-2 receptor Ab 
(anti C D25, anti Tac)
•	Basiliximab
•	Daclizumab

Question 12

ISU side effects

Answer 12

•	CNI
–	Nephrotoxicity
–	Hypertrichosis (Cya)
–	Gingival hyperplasia (CyA)
–	Hyperlipidemia (CyA>Tac)
–	Glucose intolerance, DM (Tac>CyA)
–	Neurotoxicity (temor)
–	Hyperuricemia, gout
•	MMF
–	GI (diarrhea, nausea, vomiting)
–	Leukopenia, anemia, thrombocytopenia
–	CMV infection
•	Sirolimus
–	Hypercholesterolemia, hypertrigliceridemia
–	Leukopenia, anemia, thrombocytopenia

Question 13

Relative risk of malignancy

Answer 13

• CNS-lymphoma > 1000
• Kaposi sarcoma > 1000
• pajzsmirigy 323
• ureter 198
• vulva ,vagina 35,5
• vese 9,2
• máj 9,2
• pleura 8,5
• oesophagus 8,0
• lymphoma 7,2