12: Transplantation

Question 1

What are the following characteristics of the immunosuppresive agent FK-506 (Prograf, Tacrolimus)?

• Mechanism of action
• Side effect

Answer 1

• Mechanism of action: Binds FK-binding protein with actions similar to, but more potent than Cyclosporin (inhibition of cytokine synthesis)
• Side effect: Nephrotoxicity, more GI symptoms and mood changes than Cyclosporin

[Much less entero-hepatic recirculation compared to Cyclosporin. Less rejection episodes in kidney transplants with FK-506 compared to Cyclosporin. Need to keep trough between 10 and 15.]

Question 2

What is the most common complication following a pancreas transplant?

Answer 2

Venous thrombosis

[Pancreas transplant rejection is hard to diagnose if the patient does not also have a kidney transplant. Signs of rejection may include increased glucose or amylase, fever, or leukocytosis.]

Question 3

ABO blood compatibility is generally required for all transplants except which one?

Answer 3

Liver transplant

Question 4

What is the criteria for an urgent liver transplant?

Answer 4

Fulminant hepatic failure (encephalopathy: stupor, coma)

Question 5

What is the likely cause of the following postoperative conditions after a kidney transplant?

• Postoperative Oliguria
• Postoperative diuresis
• New proteinuria
• Postoperative diabetes

Answer 5

• Postoperative Oliguria: Usually due to acute tubular necrosis (pathology shows hydrophobic changes)
• Postoperative diuresis: Usually due to urea and glucose
• New proteinuria: Suggestive of renal vein thrombosis
• Postoperative diabetes: Side effect of Cyclosporin, Tacrolimus, or steroids

Question 6

What is the most common complication and most common cause of death for a living kidney donor?

Answer 6

• Most common complication: Wound infection (1%)
• Most common cause of death: Fatal pulmonary embolism

[The remaining kidney hypertrophies.]

Question 7

What is the 5-year kidney graft survival in the following circumstances?

• Cadaveric graft
• Living donor graft
• Overall 5-year survival

Answer 7

• Cadaveric graft: 65%
• Living donor graft: 75%
• Overall 5-year survival: 70%

Question 8

What are the 2 most common malignancies following any transplant?

Answer 8

1. Skin cancer is #1 (squamous cell cancer is most common)
2. Post-transplant lympho-proliferative disorder (PTLD) is #2 (Epstein-Barr virus related)

Question 9

How do the effects of early hepatic artery thrombosis differ from late hepatic artery thrombosis in a liver transplant patient?

Answer 9

• Early hepatic artery thrombosis leads to fulminant hepatic failure
• Late hepatic artery thrombosis leads to biliary strictures and abscesses but not fulminant hepatic failure

[Early hepatic artery thrombosis will likely need emergent re-transplantation for ensuing fulminant hepatic failure (revision of the anastomosis or a stent can be attempted).]

Question 10

What are the below characteristics of acute liver transplant rejection?

• Clincal
• Labs
• Pathology
• Timing

Answer 10

• Clincal: Fever, jaundice, decreased bile output
• Labs: Leukocytosis, eosinophilia, increased LFTs, increased total bilirubin, and increased PT
• Pathology: Shows portal triad lymphocytosis, endotheliitis (mixed infiltrate), and bile duct injury
• Timing: Usually occurs in first 2 months

[Chronic rejection is unusual after liver transplant. When it occurs, it causes disappearing bile ducts, gradually leading to bile duct obstruction with increases in alkaline phosphatase and portal fibrosis.]

Question 11

What are the below characteristics of a liver transplant:

• How long can it be stored?
• Contraindications to liver transplant?
• Most common reason for liver transplant in adults?

Answer 11

• How long can it be stored? 24 hours
• Contraindications to liver transplant? Current ethanol abuse, acute ulcerative colitis
• Most common reason for liver transplant in adults? Chronic hepatitis C

Question 12

How long can the following be stored prior to transplantation?

• Heart
• Lung

Answer 12

Both can be stored for 6 hours

Question 13

What is the treatment for the following types of rejection?

• Hyperacute rejection
• Accelerated rejection
• Acute rejection
• Chronic rejection

Answer 13

• Hyperacute rejection: Emergent re-transplantation or just removal of organ if kidney
• Accelerated rejection: Increase immunosuppression, pulse steroids, and possibly antibody treatment
• Acute rejection: Increase immunosuppression, pulse steroids, and possibly antibody treatment
• Chronic rejection: Increase immunosuppression (no really effective treatment)

Question 14

What is the treatment for post-transplant lympho-proliferative disorder (PTLD)?

Answer 14

• Withdrawal of immunosuppression
• May need chemotherapy and XRT for an aggressive tumor

[PTLD is Epstein-Barr virus related.]

Question 15

What is the #1 cause of early mortality following lung transplant and what is the treatment?

Answer 15

• Reperfusion injury
• Treatment is similar to ARDS

Question 16

What are the appropriate steps to take in approaching kidney transplant rejection?

Answer 16

1. Ultrasound with duplex to rule out vascular problems and ureteral obstruction
2. Renal biopsy
3. Empiric decrease in cyclosporin or Tacrolimus (these can be nephrotoxic)
4. Empiric pulse steroids

[Chronic rejection rarely seen until after 1 year, and there is no good treatment.]

Question 17

What is the treatment of choice for the below conditions?

• Mild transplant rejection
• Severe transplant rejection

Answer 17

• Mild transplant rejection: Pulse steroids
• Severe transplant rejection: Steroid and antibody therapy (ATG and daclizumab)

Question 18

What are the following characteristics of steroids as an immunosuppresive agent?

• Mechanism of action
• Use

Answer 18

• Mechanism of action: Inhibit inflammatory cells (macrophages) and genes for cytokine synthesis (IL-1, IL-6)
• Use: Induction therapy after transplant, mantenance therapy, and acute rejection episodes

Question 19

What are the 3 components of the MELD score and what is it used for?

Answer 19

• Creatinine, INR, and bilirubin
• Predicts if patients with cirrhosis will benefit more from liver transplant than from medical therapy (MELD > 15 benefits from liver transplant)

[Wikipedia: The MELD score was initially developed to predict mortality within three months of surgery in patients who had undergone a transjugular intrahepatic portosystemic shunt (TIPS) procedure, and was subsequently found to be useful in determining prognosis and prioritizing for receipt of a liver transplant. This score is now used by the United Network for Organ Sharing (UNOS) and Eurotransplant for prioritizing allocation of liver transplants instead of the older Child-Pugh score.]

Question 20

What is the most common complication of a kidney transplant and what is the treatment?

Answer 20

Urine leak (treat with drainage and stenting)

[Other side effects include renal artery stenosis (diagnosed with U/S) and lymphocele (treat with percutaneous drainage, if it fails, need peritoneal window).]

Question 21

What are the 3 most important antigens to match when performing recipient/donor matching for transplantation?

Answer 21

1. Human leukocyte antigen DR (HLA-DR)
2. Human leukocyte antigen A (HLA-A)
3. Human leukocyte antigen B (HLA-B)

[HLA-DR is the most important overall. Cross-match is performed by mixing recipient serum with donor lymphocytes to detect pre-formed recipient antibodies to the donor organ.]

Question 22

What is the most common hepatic arterial anomaly?

Answer 22

Replaced right hepatic artery coming off the SMA

Question 23

What is the retransplantation rate and 5-year survival rate of liver transplant?

Answer 23

• Retransplantation rate = 20%
• 5-year survival rate = 70%

Question 24

What are the following characteristics of the immunosuppresive agent Anti-thymocyte globulin (ATG)?

• Mechanism of action
• Side effects
• Use

Answer 24

• Mechanism of action: Equine (ATGAM) or rabbit (Thymoglobulin) polyclonal antibodies against T cell antigens (CD2, CD3, CD4). It is cytolytic (complement dependent)
• Side effects: Cytokine release syndrome (fever, chills, pulmonary edema, shock)
• Use: Induction and acute rejection episodes

[Steroids and Benadryl can be given before drug to try to prevent cytokine release syndrome. Need to keep WBCs > 3.]

Question 25

What are the following characteristics of the immunosuppresive agent Cyclosporin (CSA)? * Mechanism of action * Side effect * Use

Answer 25

* Mechanism of action: **Binds cyclophilin protein and inhibits genes for cytokine synthesis** (IL-2, IL-4, etc.) * Side effect: Nephro/hepato-toxic, tremors, seizures, hemolytic-uremic syndrome * Use: Maintenance therapy [Need to keep trough 200-300. Cyclosporin undergoes hepatic metabolism and biliary excretion (reabsorbed in the gut, get entero-hepatic recirculation).]

Question 26

What is the most common complication of a liver transplant and what is the treatment?

Answer 26

* Bile leak * Treatment is to place a drain and then ERCP with stent across the leak

Question 27

What 2 agents can be administered to patients with hepatitis B following liver transplant to prevent reinfection?

Answer 27

1. HBIG (hepatitis B immunoglobulin) 2. Lamivudine (protease inhibitor) [Hepatitis B reinfection rate is reduced to 20% with use of HBIG and lamivudine. Hepatitis C is the disease that is most likely to recur in the new liver allograft (reinfects essentially all grafts).]

Question 28

What are the best indications of primary nonfunction of a liver transplant at the below time points? * First 24 hours * After 96 hours

Answer 28

* 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 [Treatment of primary nonfunction usually requires re-transplantation.]

Question 29

What are the following characteristics of the immunosuppresive agent Sirolimus (Rapamycin)? * Mechanism of action * Use

Answer 29

* Mechanism of action: Binds FK-binding protein like FK-506 (Tacrolimus) but inhibits mammalian target of rapamycin (mTOR), resulting in inhibition of T and B cell responses to IL-2 * Use: Maintenance therapy

Question 30

Which donor vessels are needed for a pancreas transplant and to which recipient vessels should the pancreas be attached?

Answer 30

* Donor celiac artery * Donor superior mesenteric artery * Donor portal vein * Attach to iliac vessels [Most use enteric drainage for pancreatic duct. This is accomplished by taking the second portion of the duodenum from the donor along with the ampulla of Vater and pancreas, then perform anastomosis donor duodenum to recipient bowel.]

Question 31

Which process is identical to cross-matching, but yields a percentage of cells that the recipient serum reacts with and what is considered a high percentage?

Answer 31

Panel reactive antibody (PRA) High PRA \> 50% [This process detects preformed recipient antibodies using a panel of HLA typing cells. It yields a parcentage of cells that the recipient serum reacts with. A high PRA is suggestive of an increased risk of hyper-acute rejection and is often a contraindication to transplantation. Transfusions, pregnancy, previous transplant, and autoimmune diseases can all increase PRA.]

Question 32

What are the most common opportunistic infections in immunosuppressed patients (IE transplant patients)? * Viral * Protozoan * Fungal

Answer 32

* Viral: CMV, HSV, VZV * Protozoan: Pneumocystis jiroveci pneumonia * Fungal: Aspergillus, candida, cryptococcus

Question 33

What is the cause of the following types of rejection? * Hyperacute rejection * Accelerated rejection * Acute rejection * Chronic rejection

Answer 33

* Hyperacute rejection: Caused by **pre-formed antibodies** that should have been picked up on cross-match and results in the activation of the complement cascade, causing thrombosis of vessels * Accelerated rejection: Caused by **sensitized T cells** to donor antigens * Acute rejection: Caused by T cells (**Cytotoxic and helper T cells**) * Chronic rejection: Partially caused by type **IV hypersensitivity reaction** (sensitized T cells) and partially from **antibody formation** which together lead to graft fibrosis

Question 34

What are the below characteristics of a kidney transplant: * How long can it be stored? * What are the two primary causes of postoperative mortality? * Which vessels should the kidney be attached to?

Answer 34

* How long can it be stored? **48 hours** * What are the two primary causes of postoperative mortality? **Stroke and MI** * Which vessels should the kidney be attached to? **Iliac vessels** [Need ABO type compatibility and cross-match. Can still use a kidney from a patient diagnosed with a UTI or with an acute increase in creatinine (1.0-3.0).]

Question 35

What are the following characteristics of the immunosuppresive agent Mycophenolate (MMF, CellCept)? * Mechanism of action * Side effect * Use

Answer 35

* Mechanism of action: **Inhibits de novo purine synthesis** which inhibits growth of T cells * Side effect: Myelosuppression * Use: Maintenance therapy to prevent rejection [Must keep WBCs \> 3. Azothioprine (Imuran) has similar action.]

Question 36

What is associated with early mortality following a heart transplant and what is the treatment?

Answer 36

* Persistent pulmonary hypertension * Treatment is inhaled nitric oxide, and ECMO if severe

Question 37

What is the most common cause of late death and overall death for the following? * Heart transplant * Lung transplant

Answer 37

* Heart transplant: **Progressive diffuse coronary atherosclerosis** (chronic allograft vasculopathy) * Lung transplant: **Bronchiolitis obliterans** (characterized by dyspnea, airflow limitation that is not reversible by inhaled bronchodilator, and a chest radiograph that shows normal or hyperinflated lungs)

Question 38

What are the following characteristics of the immunosuppresive agent Zenapax (Daclizumab)? * Mechanism of action * Use

Answer 38

* Mechanism of action: Human monoclonal antibody against IL-2 receptors * Use: Induction and acute rejection episodes [Daclizumab is not cytolytic.]