Transplant Flashcards

1
Q

Tacrolimus

A

Calcineurin inhibitor prevents T cell signal transduction and IL2 production

Agent of choice in liver and renal transplant recipients

Long term increased risk of malignancy
Nephrotoxic
Electrolyte disturbance

Diabetes is a well recognised complication of tacrolimus therapy and may occur in up to 50% of patients receiving the drug. It may be partly reversed on cessation of therapy.

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2
Q

Cyclosporin

A

Calcineurin inhibitor prevents T cell signal transduction and IL2 production

Used for solid organ transplants although generally has inferior outcomes compared with tacrolimus

Hyperkalaemia
Nephrotoxicity
Increased risk of malignancy

Hirsuitism may occur in association with cyclosporin therapy. Other adverse effects include impairment of renal function and gingival hyperplasia.

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3
Q

Mycophenolate mofetil

A

Inhibits inosine monophosphate dehydrogenase, the enzyme that controls the rate of synthesis of guanine monophosphate in the pathway of purine synthesis used in the proliferation of B and T lymphocytes

May be used as a substitute for calcineurin inhibitors or in combination with them for resistance cases of rejection

Diarrhoea
Less nephrotoxic than cyclosporin and tacrolimus

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4
Q

Azathioprine

A

Inhibitor of purine synthesis

Most commonly used in post transplant regimes though remains widely used for treatment of inflammatory bowel disease

Bone martow suppression
Nausea
Less effective in solid organ transplant recipients

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5
Q

Pred / steroids

A

Binds to cellular
glucocorticoid receptors and inhibits cell signaling pathways on multiple levels resulting in attenuation of the immune response

Commonly used as an induction agent following solid organ transplants, often weaned thereafter

Aside from immune
suppression it can cause diabetes, osteoporosis, adrenal suppression, pancreatitis, changes to dermal collagen and increase the risk of peptic ulcers

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6
Q

Muromonab CD3/ OKT 3

A

Binds to T cell CD3 complex resulting in apoptosis of T cells

Used to prevent acute organ rejection in patients in whom steroids have failed

Tachyphylaxis
Cytokine release syndrome when therapy is initiated
(stimulates T cells initially)

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7
Q

Basiliximab

A

Antagonist at the IL 2 binding site of T lymphocytes

Currently agent of choice for prevention of acute graft rejection following renal transplantation

Tachyphylaxis (though only needs two doses)
Usually well tolerated

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8
Q

HLA mismatch

A

The effect of HLA-DR mismatches are the most clinically significant, since HLA-DR mismatch increases graft loss five fold. HLA-B increases graft loss three fold and HLA-A increases the risk two fold. Rhesus is not used to match organs to recipients. Kidd is a minor group and of no significance.

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9
Q

Types of rejection

A

Types of organ rejection
• Hyperacute. This occurs immediately through presence of pre formed antibody (such as ABO incompatibility).
• Acute. Occurs during the first 6 months and is usually T cell mediated. Usually tissue infiltrates and vascular lesions.
• Chronic. Occurs after the first 6 months. Vascular changes predominate.

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10
Q

Survival after renal transplantation

A

The survival following renal transplantation is lower than the general population but currently sits at 95% at one year. The three leading causes of death include; cardiovascular disease, (50% of deaths), malignancy (25% of deaths) and infections.
The rise in malignancies is multifactorial and due in part to stronger immunosuppression coupled with longer survival. The most common malignancies are skin cancers. In contrast to malignancy, infection, which accounts for approximately 15% of deaths is declining. Where infective deaths occur, these typically happen early.

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11
Q

Absolute contra-indications for donation

A

Absolute contra indications
• Known or suspected new variant CreutzfeldtJakob disease (nCJD) and other neurodegenerative diseases associated with infectious agents
• Known human immunodeficiency virus (HIV) disease

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12
Q

Relative contra-indications

A

Relative contra indications
In addition, it is highly likely that donors with the following conditions will also be declined, although there may be occasions when organs are accepted if the alternative for a specific recipient is imminent death (e.g. from fulminant hepatic failure):
• Disseminated malignancy
• Melanoma (except local melanoma treated > 5 years before donation)
• Treated malignancy within 3 years (except non-melanoma skin cancer)
• Age > 90 years
• Known active tuberculosis
• Untreated bacterial sepsis
• Infection with hepatitis B and C

CNS TUMOURS ARE NOT CONTRAINDICATIONS

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13
Q

Most comman cause for renal transplant

A

Diabetes and chronic glomerulonephritis compete as the leading cause of renal failure.
Globally diabetes is the most common cause and type I diabetics may benefit from associated pancreatic transplant.

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14
Q

Infection prophylaxis in renal transplant

A

Infection Prophylaxis
In recipients who are either CMV positive, or in those who are negative but receiving a kidney from a positive donor, receive valganciclovir prophylaxis for 3-6 months.
In addition, patients are given co-trimoxazole for PJP prophylaxis for 3 months.

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15
Q

Cytokine release syndrome - OKT 3

A

Especially during the first infusion, the binding of muromonab-CD3 to CD3 can activate T cells to release cytokines like tumor necrosis factor and interferon gamma. This cytokine release syndrome, or CRS, includes side effects like skin reactions, fatigue, fever, chills, myalgia, headaches, nausea and diarrhea, and could lead to life-threatening conditions like apnea, cardiac arrest, and flash pulmonary edema. To minimize the risk of CRS and to offset some of the minor side effects patient experience, glucocorticoids (such as methylprednisolone), paracetamol, and diphenhydramine are given before the infusion.

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16
Q

Cancer and renal transplant

A

Renal transplantation can be considered provided there is no active disease and the patient is fit enough for treatment. Patients who are at risk of disease relapse should be carefully screened.

17
Q

Graft rejection and dysfunction process

A

The role of T cells in graft rejection is well established. There is considerable interest in the role of B cells (which play a major role in innate immunity), as they can have an impact on how the T cells present antigen. In the context of this question, the contribution by the T cells (especially given the timeframe) is more significant).