Nephrology - Renal Transplant

Question 1

What is the mechanism of action of induction agents for renal transplant?

Answer 1

1. Basiliximab - anti IL2 receptor and anti CD25 on activated T cells. Very costly. Minimal side effects.
2. anti thymocyte globulin (ATG) - rabbit thymoglobulin polyclonal antibody and targets T cells. Increases risk of infections and malignancies esp in EBV positive donor recipient negative cases which increases post transplant lymphoproliferative disorder. Usually used in treatment of steroid resistant rejection. Superior in higher immunological risk group but unclear on long term graft survival.

Question 2

What is the mechanism of action of tacrolimus and cyclosporin and the pros and cons of each?

Answer 2

Tacrolimus - Calcineurin inhibitor. Causes less acute rejection and early graft loss and less de novo DSA. Associated with chronic rejection and graft loss.
Can be nephrotoxic. No bone marrow suppression. Causes hypertension and lipids. More post transplant diabetes. More low mg and low phosphate. More hair loss. Less drug interactions. More tremor and neurotoxicity.

Cyclosporin - calcineurin inhibitor.
Can be nephrotoxic. No bone marrow suppression. Causes hypertension and lipids. More gum hypertrophy and hirsutism.

(CNI sparing causes less cancer in the long term)

Question 3

What is the mechanism of action of anti metabolite and pros and cons in renal transplant?

Answer 3

1. Mycophenolate - inhibits IMDPH (inosine-5-monophodphate dehydrogenase) involved in purine synthesis. Levels lowered in cyclosporin but not tacrolimus: bone marrow suppression - commence valganciclovit and bactrim.
   Teratogenic - switch to azatioprine in pregnancy.
   More diarrhoea.
2. Azathioprine - inhibit purine synthesis
   - associated with skin cancer

Question 4

When to switch/use mTORi such as sirolimus/everolimus?

Answer 4

Previously to avoid CNI nephrotoxicity and late graft lost but noted more rejection and graft loss and high discontinuation rate. Non inferior to CNI + prednisolone (to replace mycophenolate). Usually has less viral infection like CMV, less skin malignancy, less neutropaenia and diarrhoea.

Question 5

What are the most common causes of graft loss?

Answer 5

1. Death with graft function.
2. In first year - cardiovascular
3. After first year - cancer

Question 6

What are the common causes of graft loss?

Answer 6

First year - graft thrombosis/technical.

Beyond first year - chronic allograft nephropathy