Chapter 12: Transplantation Flashcards
Most important in recipient/donor matching
HLA-A, -B, and -DR
HLA: most important overall
HLA-DR
Generally required for all transplants (except liver)
ABO blood compatibility
Detects preformed recipient antibodies to the donor organ by mixing recipient serum with donor lymphocytes
Cross-match
What does a positive cross-match mean?
If antibodies are present, the cross-match is positive and a hyper acute rejection would likely occur with TXP.
Technique identical to cross-match; detects performed recipient antibodies use a panel of HLA typing cells
Panel reactive antibody (PRA)
Panel reactive antibody (PRA) which is a contraindication to transplant
> 50% (% of cell that the recipient serum reacts with) - > increased risk of hyper-acute rejection
What can increase the panel reactive antibody (PRA)?
Transfusion
Pregnancy
Previous transplant
Autoimmune diseases
Tx: mild rejection
Pulse steroids
Tx: severe rejection
Steroid and antibody therapy (ATG or daclizumab)
1 malignancy following any transplant
Skin cancer (squamous cell CA #1)
2 Next most common malignancy following transplant (Epstein-Barr virus related)
Post-transplant lympho-proliferative disorder (PTLD)
Tx: post-transplant lympho-proliferative disorder (PTLD)
Withdrawal of immunosuppression; may need chemotherapy and XRT for aggressive tumor
- Inhibits de novo purine synthesis, which inhibits growth of T cells
- Side effects: myelosuppression
- Used as maintenance therapy to prevent rejection
Mycophenolate (MMF, CellCept)
WBC: Mycophenolate
Need to keep WBC > 3
Inhibit inflammatory cells (macrophages) and genes for cytokine synthesis (IL-1, IL-6); used of induction after TXP, maintenance, and acute rejection episodes
Steroids
- Binds cyclophilin protein and inhibits genes for cytokine synthesis (IL-2, IL-4,etc); used for maintenance therapy
Cyclosporin (CSA)
Side effects: cyclosporin
Nephrotoxicity Hepatotoxicity Tremors Seizures Hemolytic-uremic syndrome
Tough: cyclosporin (CSA)
Trough 200-300
Pharm: cyclosporin (CSA)
Undergoes hepatic metabolism and biliary excretion (reabsorbed in the gut, get enter-hepatic recirculation)
- Binds FK-binding protein like FK-506 but inhibits mammalian target of rapamycin (mTOR); result is that it inhibits T and B cell response to IL-2
- Used as maintenance therapy
Sirolimus (Rapamycin)
- Equine (ATGAM) or rabbit (Thymoglobulin) polyclonal antibodies against T cell antigens (CD2, CD3, CD4)
- Used for induction and acute rejection episodes
- Is cytolytic (complement dependent)
Anti-thymocyte globulin (ATG)
Side effects: Anti-thymocyte globulin (ATG)
Cytokine release syndrome (Fevers, chills, pulmonary edema, shock)
What can prevent cytokine release syndrome from anti-thymocyte globulin (ATG)?
Steroids and benadryl
WBCs: anti-thymocyte globulin
Need to keep WBCs > 3
Human monoclonal antibody against IL-2 receptors
- Used for induction and acute rejection episodes
- Is not cytolytic
Zenapax (daclizumab)
- Occurs within minutes to hours
- Caused by preformed antibodies that should have been picked up by the cross-match
- Activates the complement cascade and thrombosis of vessels occurs
Hyperacute rejection
Tx: hyperacute rejection
Emergent re-transplant (or just removal of organ if kidney)
- Occurs
Accelerated rejection
Tx: accelerated rejection
Increase immunosuppression, pulse steroids, and possible antibody treatment
- Occurs 1 week to 1 month
- Caused by T cells (cytotoxic and helper T cells
Acute rejection
Tx: acute rejection
Increased immunosuppression, pulse steroids, and possibly antibody treatment
- Months to years
- Partially and type 4 hypersensitivity rejection (sensitized T cells)
- Antibody formation also plays a role
- Leads to graft fibrosis
Chronic rejection
Tx: chronic rejection
Increase immunosuppression - no really effective treatment
How long can a kidney be stored?
48 hours
Can you still use a kidney with a UTI?
Yes
Can you use a kidney with an acute increase in creatinine (1.0-3.0)?
Yes
Kidney transplant: what is mortality most likely from?
Stroke and MI
What do you attach the kidney to?
Attach to iliac vessels
Complications kidney transplant
Urine leaks, renal artery stenosis, lymphocele, postop oliguria, postop diuresis, new proteinuria, postop diabetes, viral infection, acute / chronic rejection
1 cause complication with kidney transplant
Urine leaks
Tx: urine leaks s/p kidney transplant
Drainage and stenting
Dx / Tx: renal artery stenosis s/p kidney transplant
Dx: US
Tx: PTA with stent