Immunosuppressant Nephrotoxicity

Question 1

Main calciurne inhibitors side effect?

Answer 1

Nephrotoxic and this is what we focus on for PGx

Question 2

What is the SNP for 3A5 for Tacrolimus?

Answer 2

Splicing defect with no enzyme activities

Question 3

3A5*1 Allele does what?

Answer 3

Having at least one will express the protein at significant levels

Question 4

3A5 EM is what?

Answer 4

1/1

Question 5

3A5 IM is what allele

Answer 5

1* + 3,6 or 7

Question 6

3A5 PM is what?

Answer 6

Any combo without a 1

Question 7

What is TACTICS study for Tac?

Answer 7

1 group get package dose Tac
1 group get genetic dosing Tac
*1 .3mg
PM got .15mg

Question 8

Outcome of TACTICS study for transplant?

Answer 8

Adaptive group more people were at goal and achieved target dosing faster
IM and PM had the most benefit in adjusted dosing
BUT NO DIFFERENCE IN REJECTION %

Question 9

CPIC for 3A5 EM Tacrolimus

Answer 9

Increase dose 1.5-2 times
DNE .3mg/kg a day

Question 10

CPIC for 3A5 IM Tacrolimus

Answer 10

Increase starting does 1.5-2
DNE .3/mg/kg

Question 11

CPIC 3A5 PM Tacrolimus

Answer 11

Standard dose

Question 12

Do we care about 3A4*1B in transplant?

Answer 12

No bc Linkage disequilibrium with 3A5 (mean the change is due to 3A5 not 3A4

Question 13

What does 3A4*22 do in transplant?

Answer 13

Reduce enzyme activity and reduce does by 33%

Question 14

What is ABCB1 PgP do in transplant?

Answer 14

Responsible for one factor of acute rejection
(Study was shown when combined with other factors it played a small role in acute rejection)

Question 15

CNI nephrotoxic acute rxn?

Answer 15

Sudden rise in Scr and occurs within days
A fervent arteriole w/ decrease renal and GFR

Question 16

Chronic CNI nephrotoxicity

Answer 16

Prolong exposure and slow rise
Bc hormones are released when taking tacrolimus

Question 17

Study in renal Allograft

Answer 17

Look at 3A5 with CNI toxicity
Then looked at the genome typing
Found that PM and IM were significantly significant

Question 18

What is the role of 3A5 in CNI nephrotoxicity?

Answer 18

Reduce function plays a significant role in nephrotoxicity

Question 19

ABCB1 study with Cyclosporine?

Answer 19

Donor ABCB1 a low expression (CNI going out)
Higher risk of nephrotoxicity
Also found that if receipt and donor have low expression you get a compounded risk

Question 20

DeKAF for immunosuppression study?

Answer 20

found that 3A4 and 3A5 were strongly associated for Trough concentrations
NOT FOR NEPHROTOXICITY bc it’s had to make that pin point on the genome stuff