immunosuppressive therapy in renal disease

Question 1

what are the 2 classes of immune mediated renal disease

Answer 1

1. native kidney autoimmune e.g. glomerulonephritis, tubulointerstitial nephritis
2. transplant kidney -> graft rejection

Question 2

what are the 3 types of graft rejection

Answer 2

1. hyperacute
2. acute
3. chronic

Question 3

what is a systemic cause of tubulointerstitial nephritis

Answer 3

sarcoidosis ->affects tubules but spares glomeruli

Question 4

3 common immunosuppressants used in renal disease

Answer 4

1. steroids
2. DMARDs
3. biologics

Question 5

types of biologics (2)

Answer 5

1. monoclonal andibodies
2. polyclonal antibodies -> less specific

Question 6

what is the gold standard renal replacement therapy

Answer 6

transplant

Question 7

how much does dialysis increase GFR by

Answer 7

10

Question 8

what individuals are high risk for kidney transplant (4)

Answer 8

1. untreated coronary artery disease
2. active infection
3. recent malignancy
4. other co-morbidities

Question 9

what is hyperacute transplant rejection

Answer 9

graft loss within minutes to hours due to pre-formed anti-donor antibodies i the recipient

Question 10

how is hyperacute transplant rejection avoided

Answer 10

pre-operative cross match

Question 11

what is acute transplant rejection

Answer 11

rejection that occurs a few days later -> due to cell or antibody mediated reaction

Question 12

acute rejection mgx

Answer 12

additional immunosuppression

Question 13

what is chronic transplant rejection

Answer 13

rejection that occurs years later -> organ slowly loses its function and symptoms start to appear

Question 14

how does plasma exchange result in immunosuppression

Answer 14

plasma exchange removes antibodies and other plasma proteins

Question 15

what is plasma replaced with in plasma exchange

Answer 15

human albumin or fresh frozen plamsa

Question 16

what is the mechanism of T cell activation (7)

Answer 16

1. peptide-MHC complex binds to corresponding T cell receptor complex
2. costimulatory signals bind (must bind to activate response)
3. signal transduction
4. nucelic acid synthesis
5. proetin synthesis
6. secretion of cytokines
7. T cell proliferation

-> help is provided to other cells

Question 17

where do azathioprine, MMF, cyclophosphamide etc. act to extert their action

Answer 17

in the nucleus to inhibit nucleic acid synthesis

Question 18

what does ciclosporin inhibit

Answer 18

calcinerurin (stops signal transduction from surface of T cell to nucleus and enzyme activation)

Question 19

where does belotacet exert its action

Answer 19

inhibits the binding of the costimulatory factors at the T cell

Question 20

side effects of corticosteroids

Answer 20

1. impaired glucose tolerance
2. gastric irritation
3. osteoporosis
4. thinning of skin
5. easy bruising

Question 21

why is neutropenia seen in immunosuppression

Answer 21

the cells with the highest proliferation rate are bone marrow -> their action is downregulated and so less neutrophils are produced

Question 22

side effects of calcineurin inhibitors

Answer 22

1. nephrotoxicity
2. fluid retention/hypertension
3. hirstuisim
4. gum hypertrophy
5. diabetes (esp w tacrolimus)

Question 23

via what system are calcineurin inhibitors metabolised

Answer 23

cyt P450 -> multiple drug interactions

Question 24

what common drug does azothiorpine interact with

Answer 24

allopurinol - inhibits metabolism, increasing the drug levels in the body

Question 25

Mycophenolate mofetil MOA

Answer 25

The active metabolite of mycophenolate, mycophenolic acid, prevents T-cell and B-cell proliferation and the production of cytotoxic T-cells and antibodies via the inhibtion of monophosphate dehydrogenase (required for de novo purine synthesis)

Question 26

how is the action of MMF mainly lymphocyte sepcific

Answer 26

inhibits only de novo purine synthesis -> most cells have both de novo and salvage pathways while lympocytes only have de novo

Question 27

rapamycin/sirolimus MOA

Answer 27

inhibits signal transduction from IL-2 receptors back to the nucleus -> inhibiting T-lymphocyte activation and proliferation

Question 28

what is the most feared side effect of long term immunosuppression

Answer 28

malignancy

Question 29

side effects of rapamycin (5)

Answer 29

1. hyperlipidaemia
2. impaired wound healing
3. acne
4. mouth ulcers
5. lung infiltrates

Question 30

cyclophosphamide MOA (3)

Answer 30

an alkylating agent which works by:
1. attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes -> preventing DNA synthesis and RNA transcription from the affected DNA;
2. DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription;
3. the induction of mispairing of the nucleotides leading to mutations

Question 31

5 side effects of cyclophosphamide

Answer 31

1. haemorrhagic cyctitis
2. bone marrow suppression
3. nausea
4. hair loss
5. infertility

Question 32

what abx is used for pneumocystis jiroveci penumonia mgx

Answer 32

cotrimoxazole

Question 33

what skin cancer is seen more frequently in immunosuppressed ppl

Answer 33

squamous cell carcinoma -> incidence of BCC are also increased but SCC are more common

Question 34

what is EBV-related post transplant lymphoproliferative disorders

Answer 34

excessive proliferation of EBV infected B cells due to lack of T cell control -> B cell lymphoma