Immunosuppressive therapy in renal disease Flashcards
Interstitial nephritis pathophysiology
acute inflammatory infiltrate (often eosinophils) in interstitium
What treatment is interstitial nephritis often responsive to?
steroid therapy
Describe hyperacute transplant rejection
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
Describe acute transplant rejection
days onwards
cell or antibody-mediated
usually responds to additional immunosuppression
Describe ‘chronic’ transplant rejection
usually used non-specifically to include non-immunological causes of chronic damage
does not usually respond to additional immunosuppression
What is plasma exchange?
removal of plasma together with plasma proteins
replacement with human albumin solution or FFP
When can plasma exchange be used in renal disease?
useful in conditions mediated by abnormal circulating proteins such as antibodies
eg. Goodpasture’s (anti-GBM), systemic vasculitis (ANCA)
Corticosteroids examples
prednisolone
methylprednisolone
Antiproliferative agents (immunosuppressants) examples
azathioprine
mycophenolate mofetil
Calcineurin inhibitors (immunosuppressants) examples
ciclosporin
tacrolimus
IL-2 pathway inhibitor (immunosuppressant) example
sirolimus
Alkylating agent (immunosuppressant) example
cyclophosphamide
Main site of action of corticosteroids
cell nucleus
Corticosteroids side effects
impaired glucose tolerance
gastric irritation
osteoporosis
thinning of skin
easy bruising
How do calcineurin inhibitors work?
eg. ciclosporin, tacrolimus
inhibit transduction of signal from T cell surface receptors to nucleus
Calcineurin inhibitors side effects
nephrotoxicity
fluid retention/hypertension
hirsutism
gum hypertrophy
diabetes (particularly tacrolimus)
Which system are calcineurin inhibitors metabolised by?
cytochrome P450 (many drug interactions)
Azathioprine MOA
antiproliferative
nucleic acid analogue: inhibits DNA synthesis
Azathioprine side effect
bone marrow suppression
Azathioprine important drug interaction
allopurinol
Main side effects of mycophenolate mofetil
bone marrow suppression
diarrhoea
Sirolimus MOA
inhibits signal transduction pathway from IL-2 receptor back to nucleus
Side effects of sirolimus
hyperlipidaemia
impaired wound healing
acne
mouth ulcers
lung infiltrates
Side effects of cyclophosphamide
haemorrhagic cystitis
bone marrow suppression
nausea
hair loss
infertility
Pneumocystis jiroveci treatment
cotrimoxazole
How can CMV infection present?
pneumonitis
gastritis
colitis
hepatitis
bone marrow suppression
retinitis (mainly AIDS patients)
CMV infection treatment
antivirals
eg. ganciclovir, valganciclovir
What is the most common skin cancer in an immunocompromised individual?
SCC
Complications of excessive immunosuppression
infections
malignancy (skin tumours, lymphomas)
