12 Transplantation Flashcards by Ryan Bird

Most important markers in recipient/donor matching?

HLA-A, HLA-B, HLA-DR

HLA-DR is most important overall

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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

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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

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What can increase a PRA?

Transfusions
Pregnancy
Previous transplant
Autoimmune disease

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Treatment of mild transplant rejection?

Pulse steroids

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Treatment of severe transplant rejection?

Steroids and antibody therapy (ATG or daclizumab)

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Number one malignancy following any transplant?

Squamous cell skin cancer

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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

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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)

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Steroids

Inhibits inflammatory cells (macrophages) and genes for cytokine synthesis (IL-1, IL-6)
Used for induction after transplant, maintenance and acute rejection episodes

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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)

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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

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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

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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

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Zenapax (daclizumab)

Human monoclonal antibody against IL-2 receptors
Used for induction and acute rejection episodes
Not cytolytic

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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)

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Accelerated rejection

Occurs within the first week
Sensitized t-cells to donor antigens
Tx - increase immunosuppresion, pulse steroids, possibly antibody tx

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Acute rejection

Within 1 week to 1 month
T-cells (cytotoxic and helper)
Tx - increase immunosuppression, pulse steroids, possibly antibody tx

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Chronic rejection

Month to years
Type IV hypersensitivity reactions (sensitized T-cells) and antibody formation
Leads to graft fibrosis
Tx - increase immunosuppression

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How long can you store a transplant kidney?

48 hours

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If a donor has a UTI, can you still use the kidney?

Yes

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If a donor has an acute increase in Cr, can you still use the kidney?

Yes

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Primary mortality associated with kidney transplants?

Primarily from stroke and MI

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Where do you attach the donor kidney?

To the iliac vessels

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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