Immunosuppressive therapy in renal disease

Question 1

Interstitial nephritis pathophysiology

Answer 1

acute inflammatory infiltrate (often eosinophils) in interstitium

Question 2

What treatment is interstitial nephritis often responsive to?

Answer 2

steroid therapy

Question 3

Describe hyperacute transplant rejection

Answer 3

due to pre-formed anti-donor antibodies in recipient eg. from blood transfusion, pregnancy, previous transplant

can cause graft loss in mins-hours

avoided by pre-operative crossmatch

untreatable

Question 4

Describe acute transplant rejection

Answer 4

days onwards
cell or antibody-mediated
usually responds to additional immunosuppression

Question 5

Describe ‘chronic’ transplant rejection

Answer 5

usually used non-specifically to include non-immunological causes of chronic damage

does not usually respond to additional immunosuppression

Question 6

What is plasma exchange?

Answer 6

removal of plasma together with plasma proteins
replacement with human albumin solution or FFP

Question 7

When can plasma exchange be used in renal disease?

Answer 7

useful in conditions mediated by abnormal circulating proteins such as antibodies

eg. Goodpasture’s (anti-GBM), systemic vasculitis (ANCA)

Question 8

Corticosteroids examples

Answer 8

prednisolone
methylprednisolone

Question 9

Antiproliferative agents (immunosuppressants) examples

Answer 9

azathioprine
mycophenolate mofetil

Question 10

Calcineurin inhibitors (immunosuppressants) examples

Answer 10

ciclosporin
tacrolimus

Question 11

IL-2 pathway inhibitor (immunosuppressant) example

Answer 11

sirolimus

Question 12

Alkylating agent (immunosuppressant) example

Answer 12

cyclophosphamide

Question 13

Main site of action of corticosteroids

Answer 13

cell nucleus

Question 14

Corticosteroids side effects

Answer 14

impaired glucose tolerance
gastric irritation
osteoporosis
thinning of skin
easy bruising

Question 15

How do calcineurin inhibitors work?

Answer 15

eg. ciclosporin, tacrolimus

inhibit transduction of signal from T cell surface receptors to nucleus

Question 16

Calcineurin inhibitors side effects

Answer 16

nephrotoxicity
fluid retention/hypertension
hirsutism
gum hypertrophy
diabetes (particularly tacrolimus)

Question 17

Which system are calcineurin inhibitors metabolised by?

Answer 17

cytochrome P450 (many drug interactions)

Question 18

Azathioprine MOA

Answer 18

antiproliferative
nucleic acid analogue: inhibits DNA synthesis

Question 19

Azathioprine side effect

Answer 19

bone marrow suppression

Question 20

Azathioprine important drug interaction

Answer 20

allopurinol

Question 21

Main side effects of mycophenolate mofetil

Answer 21

bone marrow suppression
diarrhoea

Question 22

Sirolimus MOA

Answer 22

inhibits signal transduction pathway from IL-2 receptor back to nucleus

Question 23

Side effects of sirolimus

Answer 23

hyperlipidaemia
impaired wound healing
acne
mouth ulcers
lung infiltrates

Question 24

Side effects of cyclophosphamide

Answer 24

haemorrhagic cystitis
bone marrow suppression
nausea
hair loss
infertility

Question 25

Pneumocystis jiroveci treatment

Answer 25

cotrimoxazole

Question 26

How can CMV infection present?

Answer 26

pneumonitis
gastritis
colitis
hepatitis
bone marrow suppression
retinitis (mainly AIDS patients)

Question 27

CMV infection treatment

Answer 27

antivirals
eg. ganciclovir, valganciclovir

Question 28

What is the most common skin cancer in an immunocompromised individual?

Answer 28

SCC

Question 29

Complications of excessive immunosuppression

Answer 29

infections
malignancy (skin tumours, lymphomas)