Transplant Flashcards
Tacrolimus
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.
Cyclosporin
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.
Mycophenolate mofetil
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
Azathioprine
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
Pred / steroids
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
Muromonab CD3/ OKT 3
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)
Basiliximab
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
HLA mismatch
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.
Types of rejection
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.
Survival after renal transplantation
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.
Absolute contra-indications for donation
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
Relative contra-indications
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
Most comman cause for renal transplant
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.
Infection prophylaxis in renal transplant
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.
Cytokine release syndrome - OKT 3
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.
