Transplant

Question 1

When your kidneys don’t work, you need to pick your poison. Explain the cons for immunosuppression vs dialysis

Answer 1

Immunosuppression (after transplant)

• infection
• cancer
• drug-specific side effects

Dialysis

• chronic “uremia”
• cardiac disease
• decreased quality of life

Question 2

Does transplant or dialysis have a better survival benefit?

Answer 2

Transplant has a better survival benefit after a period of increased risk due to surgery and immunosuppression (about 3 months).

Transplant roughly doubles your life expectancy compared to dialysis.

Question 3

Does hemodialysis cost more or peritoneal dialysis? How about transplant?

Answer 3

Hemodialysis costs more than peritoneal dialysis which costs more than transplant.

Question 4

Moving a kidney from one individual to another results in variable degrees of ischemia. Explain the two types

Answer 4

Warm ischemia: time from cardiac death (deceased donor) or cross-clamp (live donor) to cold perfusion (max ~60 minutes until it can’t be used anymore)

Cold ischemia (on ice): time from cold perfusion to recipient anastomosis (max 24-36 hours)

Question 5

True or False: kidneys from living donors have longer graft survival than deceased donors

Answer 5

True

12-14 years vs 8-10 years

Question 6

What is longevity matching?

Answer 6

You try to give the healthiest kidney to the healthiest person in need.

KDPI = kidney donor profile index. The lower the KDPI number, the healthier the kidney.

Question 7

True or False: Unless donor/recipipent are HLA identical, recipient T cells will recognize foreign donor HLA antigens as “non-self” and mount a response (rejection)

Answer 7

TRUE

Question 8

What are the 2 pathways for T cell activation in organ transplant rejection?

Answer 8

• Direct activation
  
  • recipient T cells recognize in-tact donor HLA antigens on donor APCs
  • 99% of early rejection episodes
  • Biological phenomenon only happens in setting of organ transplantation
• Indirect activation
  
  • recipient T cells recognize donor HLA antigen fragments presented by host APCs.
  • “Normal” mechanism of T cell activation
  • Largely class II MHC presenting to CD4+ Th cells.

Question 9

True or False: Patients with low levels of anti-HLA antibodies have longer waiting times for organs

Answer 9

False. It’s patients with high levels of anti-HLA antibodies that have longer waiting times for organs because they have higher rates of graft rejection. High levels of anti-HLA antibodies is called sensitization and can happen as a result of organ transplant, transfusions, or pregnancy.

Question 10

True or False: It’s okay to transplant in the setting of HLA mismatch.

Answer 10

True.

We don’t refuse transplants due to HLA mismatch. While mismatching causes higher chance of transplant rejection, it’s not by much anymore since we have better immunosuppressant drugs.

Question 11

What are the 2 types of T cell rejection?

Answer 11

Tubulitis (Banff class I)

Vasculitis (Banff class II)

Question 12

How do you treat T cell (Cellular) rejection vs B cell (antibody) rejection?

Answer 12

T Cell rejection is treated with IV steroids for Banff Ia and Ib. Banff IIa/IIb are treated with T cell-depleting therapy.

B cell rejection is treated with plasmapheresis and IVIG, rituximab, bortezomib, eculizimab, or splenectomy.

Question 13

Immunosuppression is required to limit graft damage by the recipient’s immune response. This is typically done with what 3 drugs? What are side effects?

Answer 13

• 1st agent: calcineurin inhibitor (side effects are nephrotoxicity, HTN, and diabetes)
  
  • Cyclosporine
  • Tacrolimus
• 2nd agent: proliferation inhibitor (side effects are cytopenias and GI toxicity)
  
  • MMF
  • Sirolimus
• 3rd agent (side effects are weight gain, HTN, diabetes, hyperlipidemia, bone loss, and cataracts)
  
  • Prednisone

Bolded ones are used most in USA* (all 3 at once)