Editing Immunosuppression


Must constantly weigh risk of rejection against risk from immunosuppression

* No real way to measure an individual's need for immunosuppression


Corticosteroids

* Common in induction, maintenance and rescue therapies
* '''Prednisone''' most common
* May need stress dosing in emergencies
* Suppresses lymphocyte activation and promotes lymphocyte apoptosis
* Reduces production of cytokines and suppresses inflammatory response

Rabbit anti-thymocyte globulin (rATG)

* Polyclonal Ab against human T cells
* Depletes T cells
* Effectively reduces the risk of acute rejection

Basilixumab

* Alternative to rATG


Antimetabolites - inhibit lymphocyte clonal expansion

* '''Azathioprine''' (Imuran)
* '''Mycophenolate mofetil''' (Cellcept)
** Don't need to stop if patient has another surgical condition e.g. appendicitis
** Can be given IV
* '''Cyclophosphamide'''

Calcineurin inhibitors

* Mainstay of most multimodal immunosuppressive regimens (used in 95% of patients)
* Inhibit calcineurin, which has downstream affect of limiting T cell activation
* '''Cyclosporin'''
* '''Tacrolimus'''
*** Especially liver transplant
*** Don't need to stop if patient has another surgical condition e.g. appendicitis
*** Needs close monitoring if giving IV
*** The IV dose is approximately one third of the oral dose
*** Target concentration varies significantly depending on patient and transplant factors. Trough concentrations are used. Steady state is reached after 3-5 days.
*** Be careful of risk of AKI if dosing is slightly wrong during acute illness - use levels if necessary

Lymphocyte-depleting agents

* Often used as induction
* Antilymphocyte globulin
* OKT3
* Anti-Il2 receptor antibodies

Inhibitors of mammalian target of rapamycin (mTOR)

* Alternative to calcineurin inhibitors
* Prevents IL-2 stimulated proliferation of T cells
* Significant impairment of wound healing
* No IV equivalents
* '''Everolimus'''
** Stop 5 days before elective surgery
** In emergencies, stop on admission and restart when wound heals
* '''Sirolimus'''


== Induction ==

* Aim is to prevent acute rejection
* Give at the time of transplant

== Maintenance ==

* Start at the time of transplant, and continue for the life of the graft
* Suppress multiple pathways with subtoxic doses of medications

== Complications of immunosuppression ==

* Malignancy
** Mechanism
*** Impaired immunosurveillance of neoplastic cells
*** Reduced antiviral immune activity
*** Direct mutagenic effects
** Types
*** Skin - primarily SCC, but also BCC/melanoma
*** Kaposi's sarcoma
*** Lymphoproliferative disease (related to EBV)
*** Lymphoma
*** Cervical cancer
*** Anogenital cancer
*** TVV
*** HCC
*** Lung cancer
** Management
*** Treat malignancy as required
*** Avoid carcinogens carefully
*** Switch immunosuppressant to mTOR, especially for skin cancers
* Infection
** Atypical presentations, opportunistic, reactivation of chronic infections
** C diff
** CMV
** Viral gastro
* Metabolic
** Diabetes
** Hypertension
** Dyslipidaemia
** CVD
** OP/osteonecrosis

== Screening in immunosuppressed patients ==

* Skin exam annually
* Pelvic exam and pap smear every 1-3 years
* Mammogram same as population
* HCC annual USS and AFP if cirrhosis present
* FOBT/CRC same as population

[[Category:Transplant]]