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
Kidney transplant patient - post-op diabetes?
Side effect of CSA, FK, steroids
Viral infections seen in kidney transplant patients? Treatment?
CMV - ganciclovir
HSV - acyclovir
Kidney transplant - acute rejection
Presents within first six months
Pathology shows tubulitis (severe form of vasculitis)
Kidney rejection workup?
Performed for an increase in creatinine or poor UOP
- US with duplex (rule out vascular or ureteral problems)
- Biopsy
- Empiric decrease in CSA, FK (can be nephrotoxic)
- Empiric pulse steroids
Kidney transplant - chronic rejection
After 1 year
No good treatment
Kidney transplant - 5-year graft survival overall?
70%
Cadaveric 65%, living donor 75%
Most common complication for living kidney donors?
Wound infection (1%)
Most common cause of death for living kidney donors?
Fatal PE
How long can you store a transplant liver?
24 hours
Contraindication to liver transplant?
Current ETOH abuse
Acute ulcerative colitis
Most common reason for liver transplant in adults?
Chronic hep C
MELD score?
Creatinine, INR, bilirubin (>15 will benefit more from liver transplant than medical management)
Criteria for urgent liver transplant?
Fulminant hepatic failure (encephalopathy - stupor, coma)
Preventing Hep B reinfection after liver transplant?
HBIG and lamivudine (protease inhibitor)
Reduces reinfection rate to 20%
What disease is most likely to recur in the new liver allograph?
Hepatitis C
When can you use liver transplantation in liver cancer?
No vascular invasion or mets
Blood supply for the biliary system?
Hepatic artery blood supply
Most common arterial anomaly in the liver?
Right hepatic coming off SMA
Liver transplant - bile leak?
Most common complication
Tx - drain, then ERCP with stent across leak
Liver transplant - primary nonfunction
First 24 hours: - Total bilirubin >10 - Bile output <20cc/12hr - Elevated PT and PTT After 96 hours: - Mental status changes - Increased LFTs - Renal failure - Respiratory failure Tx - Re-transplantation
Liver transplant - early hepatic artery thrombosis
Most common early vascular complication
Increased LFTs, decreased bile output, fulminant hepatic failure
Tx - emergent re-transplantation (possible stenting of vessel)
Liver transplant - late hepatic artery thrombosis
Causes biliary structure and abscesses (NOT fulminant hepatic failure)
Liver transplant - abscesses
Most commonly from late (chronic) hepatic artery thrombosis
Liver transplant - IVC stenosis/thrombosis
Rare
Edema, ascites, renal insufficiency
Tx - Thrombolytics, IVC stent
Liver transplant - Portal vein thrombosis
Rare
Early - abdominal pain
Late - UGI bleeding, ascites, poss asymptomatic
Tx: if early - re-op thrombectomy, revise anastomosis
Liver transplant - Cholangitis
Get PMNs around portal triad
NOT mixed infiltrates
Liver transplant - acute rejection
T-cells mediated against blood vessels
Clinical - fever, jaundice, decreased bile output
Labs - leukocytosis, eosinophilia, increased LFTs, increased total bili, increased PT
Path - portal triad lymphocytosis, endothelitis, bile duct injury
Occurs within first 2 months
Liver transplant - chronic rejection
Unusual after liver transplant
Get disappearing bile ducts (antibody and cellular attack on bile ducts)
Get bile duct obstruction, with increased alkaline phosphatase
Portal fibrosis
Retransplantation rate in liver transplants
20%
5-year survival rate in liver transplants
70%
What do you need for vascular supply in a pancreas transplant?
Donor celiac artery and SMA
What do you need for venous drainage in a pancreas transplant?
Donor portal vein
Where do you attach a transplant pancreas?
Iliac vessels
How do you create enteric drainage for a transplant pancreas?
Second portion of duodenum from donor along with ampulla of vater and pancreas
Then perform anastomosis of donor duodenum to recipient bowel
Benefits of successful pancreas/kidney transplantation?
Stabilization of retinopathy Decreased neuropathy Increased nerve conduction velocity Decrease autonomic dysfunction (gastroparesis) Decreased orthostatic hypotention
NO reversal of vascular disease
Pancreas transplant - venous thrombosis
Most common
Hard to treat
Pancreas transplant - rejection
Hard to diagnosis if patient does not also have a kidney transplant
Sx: increased glucose or amylase, fever, leukocytosis
How long can you store a transplant heart?
6 hours
Heart transplant - pulmonary hypertension
Associated with early mortality
Tx: inhaled NO, ECMO
Heart transplant - acute rejection
Perivascular lymphocytic infiltrate
Myocyte inflammation and necrosis
Heart transplant - Chronic allograft vasculopathy
Progressive, diffuse coronary artherosclerosis
MMC of death
How long can you store transplant lungs?
6 hours
Number one cause of early mortality in lung transplantation?
Reperfusion injury
Tx - same as ARDS
Number one reason for double lung transplant?
Cystic fibrosis
Exclusion criteria for transplant lungs?
Aspiration Moderate to large contusions Infiltrates Purulent sputum PO2 < 350 on 100% FiO2 and PEEP 5
Lung transplant - acute rejection
Perivascular lymphocytosis
Lung transplant - chronic rejection
Bronchiolitis obliterans
MCC of death
