Transplant Immunosuppression

Question 1

What type of induction would you use in a patient with a high KDPI?

Answer 1

Depleting agents

Question 2

What are the MoAbs used in transplant induction?

Answer 2

• Alemtuzumab

- Basilixumab

Question 3

What is the MoA of basilixumab?

Answer 3

• Inhibitor of IL-2 receptor

Question 4

What is more efficacious? Rabbit or Horse ATG?

Answer 4

• Rabbit ATG; leads to reconstitution of immune system with more suppressor T-cells

Question 5

What are the main side effects of ATG induction?

Answer 5

• Myelosuppression (50%)
• Cytokine Release
• Serum sickness (rare)

Question 6

When should the first dose of ATG be given?

Answer 6

• Before graft reperfusion (ideally)

Question 7

What is the MoA of alemtuzumab?

Answer 7

• anti-CD52 MoAb

- Complement-mediated cell depletion

Question 8

What are the side effects of alemtuzumab?

Answer 8

• Myelosuppression
• AIHA
• Higher rate of ABMR?
• Infusion reactions

Question 9

What percentage of patients on tacrolimus will develop some degree of alopecia?

Answer 9

20%

Question 10

What is the conversion factor for envarsus?

Answer 10

0.8mg envarsus to 1mg tac

Question 11

Why does MMF not cause systemic side effects?

Answer 11

It specifically inhibits the B- and T- cell IMPDH; neither of these cell types has a salvage pathway, whereas other cell types do.

Question 12

What practical advice would you give a patient taking Ca supplementation and MMF?

Answer 12

Separate taking medications by 1-2 hours.

Question 13

What is the effect of PPIs on MMF (specifically cellcept) metabolism?

Answer 13

Decrease the GI absorption of MMF by 20%; not a factor with enteric coated formulation (myfortic)

Question 14

What is an important DDI with azathioprine?

Answer 14

Allopurinol

Febuxostat

Question 15

What is an important consideration with mTORi?

Answer 15

Wound healing

Question 16

What is one of the main drawbacks to belatacept?

Answer 16

Associated with increased rates of cellular rejection

Question 17

What is the treatment of ACMR?

Answer 17

1. Pulse methylprednisolone

2. rATG

Question 18

What is the treatment of ABMR?

Answer 18

Adapted from UptoDate Article:

Patient presenting with ABMR within one year of transplant:

1. Pulse methylprednisolone
2. TPE every other day for 6 sessions, replacing 1.5 times plasma volume with albumin in the first session and 1 times plasma volume in subsequent sessions
3. IVIg 100mg/kg after each TPE session
4. Add rituximab as a single dose post TPE and IVIG if there is evidence of microvascular inflammation on biopsy

Patient presenting with ABMR beyond one year of transplant:

1. Pulse methylprednisolone
2. No role for TPE, give IVIg every two weeks for total of 3 doses (200mg/kg)
3. Rituximab as a single dose 375mg/m2 at end of course of IVIg

Bortezomib can be considered in patients who have failed to respond to the above measures

Question 19

What are the indicators of success in management of ABMR?

Answer 19

1. Decrease in sCr to within 20-30% of baseline
2. Decrease in proteinuria to pre-ABMR baseline
3. Decrease in dominant DSA by >50%
4. Resolution of changes of ABMR on biopsy