12 Transplantation Flashcards
Most important markers in recipient/donor matching?
HLA-A, HLA-B, HLA-DR
HLA-DR is most important overall
Cross-match
Detects preformed recipient antibodies to the donor organ by mixing recipient serum with donor lymphocytes
If antibiodies are present, it is a positive cross-match - likely for hyperacute rejection to occur
Panel reactive antibody
Identical technique to cross-match: detects preformed antibodies
Can get percentage of cells that the recipient serum reacts with
High PRA (>50%) has increased risk of hyperacute rejection
What can increase a PRA?
Transfusions
Pregnancy
Previous transplant
Autoimmune disease
Treatment of mild transplant rejection?
Pulse steroids
Treatment of severe transplant rejection?
Steroids and antibody therapy (ATG or daclizumab)
Number one malignancy following any transplant?
Squamous cell skin cancer
Post-transplant lympho-proliferative disorder (PTLD)
Second most common malignancy following transplant
Associated with EBV
Tx withdrawal of immunosuppression, may need chemotherapy and XRT for aggressive tumor
Mycophenolate (MFF, CellCept)
Inhibits de novo purine synthesis - inhibits growth of T-cells
AE: myelosuppression
Keep WBCs >3
Used as maintenance therapy to prevent rejection
(Similar - Azathioprine)
Steroids
Inhibits inflammatory cells (macrophages) and genes for cytokine synthesis (IL-1, IL-6)
Used for induction after transplant, maintenance and acute rejection episodes
Cyclosporin (CSA)
Binds cyclophilin protein and inhibits genes for cytokine synthesis (IL-2, IL-4)
Used for maintenance therapy
AE: Nephrotoxicity, Hepatotoxicity, Tremors, Seizures, HUS
Keep trough 200-300
Undergoes hepatic metabolism and biliary excretion (reabsorbed in the gut, entero-hepatic recirculation)
Fk-506 (Prograf, Tacrolimus)
Binds FK-binding protein - actions similar to CSA, but more potent
AE: nephrotoxicity, more GI symptoms, more mood changes, less entero-hepatic recirculation
Keep trough 10-15
Sirolimus (Rapamycin)
Binds FK-binding protein like FK-506 but inhibits mammalian target of rapamycin (mTOR) - inhibits T and B cell response to IL-2
Maintenance treatment
Anti-thymocyte globulin (ATG)
Polyclonal antibodies against T-cell antigen (CD2, CD3, CD4)
Used for induction and acute rejection episodes
Cytolytic (complement dependent)
Keep WBCs >3
AE: Cytokine release syndrome (fever, chills, pulmonary edema, shock); pre-treat with steroids and benadryl
Zenapax (daclizumab)
Human monoclonal antibody against IL-2 receptors
Used for induction and acute rejection episodes
Not cytolytic
Hyperacute rejection
Occurs within minutes to hours
Preformed antibodies (failure of cross-match)
Complement cascade –> thrombosis
Tx - emergent re-transplant (or removal of the transplanted organ)
Accelerated rejection
Occurs within the first week
Sensitized t-cells to donor antigens
Tx - increase immunosuppresion, pulse steroids, possibly antibody tx
Acute rejection
Within 1 week to 1 month
T-cells (cytotoxic and helper)
Tx - increase immunosuppression, pulse steroids, possibly antibody tx
Chronic rejection
Month to years
Type IV hypersensitivity reactions (sensitized T-cells) and antibody formation
Leads to graft fibrosis
Tx - increase immunosuppression
How long can you store a transplant kidney?
48 hours
If a donor has a UTI, can you still use the kidney?
Yes
If a donor has an acute increase in Cr, can you still use the kidney?
Yes
Primary mortality associated with kidney transplants?
Primarily from stroke and MI
Where do you attach the donor kidney?
To the iliac vessels
Number one complication from kidney transplant?
Urine leak
Tx - drainage and stenting
Renal artery stenosis
Dx - ultrasound
Tx - PTA with stent
Lymphocele
Most common cause of external ureter compression
Tx:
- Percutaneous drainage
- Peritoneal window
Kidney transplant patient - postop oliguria?
ATN (hydrophobic changes)
Kidney transplant patient - post-op diuresis?
Due to urea and glucose
Kidney transplant patient - new proteinuria?
Suggestive of renal vein thrombosis