Chapter 12: Transplantation Flashcards by Minh Nguyen

Most important in recipient/donor matching

HLA-A, -B, and -DR

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HLA: most important overall

HLA-DR

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Generally required for all transplants (except liver)

ABO blood compatibility

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Detects preformed recipient antibodies to the donor organ by mixing recipient serum with donor lymphocytes

Cross-match

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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.

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Technique identical to cross-match; detects performed recipient antibodies use a panel of HLA typing cells

Panel reactive antibody (PRA)

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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

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What can increase the panel reactive antibody (PRA)?

Transfusion
Pregnancy
Previous transplant
Autoimmune diseases

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Tx: mild rejection

Pulse steroids

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Tx: severe rejection

Steroid and antibody therapy (ATG or daclizumab)

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1 malignancy following any transplant

Skin cancer (squamous cell CA #1)

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2 Next most common malignancy following transplant (Epstein-Barr virus related)

Post-transplant lympho-proliferative disorder (PTLD)

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Tx: post-transplant lympho-proliferative disorder (PTLD)

Withdrawal of immunosuppression; may need chemotherapy and XRT for aggressive tumor

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Inhibits de novo purine synthesis, which inhibits growth of T cells
Side effects: myelosuppression
Used as maintenance therapy to prevent rejection

Mycophenolate (MMF, CellCept)

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WBC: Mycophenolate

Need to keep WBC > 3

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Inhibit inflammatory cells (macrophages) and genes for cytokine synthesis (IL-1, IL-6); used of induction after TXP, maintenance, and acute rejection episodes

Steroids

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Binds cyclophilin protein and inhibits genes for cytokine synthesis (IL-2, IL-4,etc); used for maintenance therapy

Cyclosporin (CSA)

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Side effects: cyclosporin

Nephrotoxicity
Hepatotoxicity
Tremors
Seizures
Hemolytic-uremic syndrome

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Tough: cyclosporin (CSA)

Trough 200-300

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Pharm: cyclosporin (CSA)

Undergoes hepatic metabolism and biliary excretion (reabsorbed in the gut, get enter-hepatic recirculation)

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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)

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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)

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Side effects: Anti-thymocyte globulin (ATG)

Cytokine release syndrome (Fevers, chills, pulmonary edema, shock)

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What can prevent cytokine release syndrome from anti-thymocyte globulin (ATG)?

Steroids and benadryl

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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

MCC external ureter compression s/p kidney transplant

Lymphocele

Tx: lymphocele s/p kidney transplant

1st try percutaneous drainage; if that fails, then need peritoneal window (make hole in peritoneum, lymphatic fluid drains into peritoneum and is reabsorbed - 95% successful)

Usually due to ATN (pathology shows hydrophobic changes) s/p kidney transplant

Postop oliguria

Usually due to urea and glucose s/p kidney transplant

Postop diuresis

Suggestive of renal vein thrombosis s/p kidney transplant

New proteinuria

Side effect of CSA, FK, steroids s/p kidney transplant

Postop diabetes

Viral infections s/p kidney transplant

CMV - Tx: ganciclovir | HSV - Tx: acyclovir

Time / path: acute rejection s/p kidney transplant

- Time: usually occurs in first 6 months | - Path: tubulitis (vasculitis with more severe form)

Kidney rejection workup (usually for increase in creatinine or poor urine output)

- US with duplex (r/o vascular problem and ureteral obstruction) and biopsy - Empiric decrease in CSA or FK (can be nephrotoxic) - Empiric pulse steroids

When do you see chronic rejection s/p kidney transplant?

Usually do not see until after 1 year; no good treatment

5-year graft survival overall: kidney transplant

70% (cadaveric 65%, living donors 75%)

Living kidney donors: MC complication

Wound infection (1%)

Living kidney donors: MCC death

fatal PE

Living kidney donors: outcome remaining kidney

Hypertrophy

How long can a liver be stored?

24 hours

Contraindications for liver transplant

Current EtOH abuse, acute ulcerative colitis

MC reason for liver transplant in adults

Chronic hepatitis C

Uses creatinine, INR, and bilirubin to predict if patients with cirrhosis will benefit more from liver transplant than from medical therapy

MELD score

MELD score: benefits from liver transplant

MELD score > 15

Criteria for urgent liver transplant

Fulminant hepatic failure (encephalopathy - stupor coma)

Tx: patients with hepatitis B antigenemia after liver transplant to help prevent reinfection

HBIG (hepatitis B immunoglobulin) and lamivudine (protease inhibitor)

Reinfection rate is reduced to 20% with use of HBIG and lamivudine s/p liver transplant

Hepatitis B

Disease most likely to recur in the new liver allograft; reinfects essentially all grafts s/p liver transplant

Hepatitis C

Liver TXP: if no vascular invasion or metastases can still consider transplant

Hepatocellular CA

Not a contraindication to liver transplant

Portal vein thrombosis

Definition: recidivism

20% will start drinking again s/p liver transplant

Extracellular fat globules in the liver allograft

Macrosteatosis

Macrosteatosis: risk-factor for primary non-function

If 50% of cross-section is macrosteatatic in potential donor liver, there is a 50% chance of primary non-function.

Surgery: liver transplant

Duct to duct anastomosis is performed. Hepaticojejunostomy in kids. Right sub hepatic, right, and left sub diaphragmatic drains are placed.

Liver transplant: depends on hepatic artery blood supply

Biliary system (ducts, etc)

Liver transplant: MC arterial anomaly

Right hepatic coming off SMA

Complications liver transplant

Bile leak, Primary nonfunction, early / late hepatic artery thrombosis, abscesses, IVC stenosis/thrombosis, portal vein thrombosis, cholangitis, acute rejection

#1 complication liver transplant

Bile leak | - Tx: place drain, then ERCP with stent across leak

DX: s/p Liver transplant: | - 1st 24 hours: total bili > 10, bile output

DX: Primary non-function

Tx: primary non-function s/p liver transplant

Re-transplantation

MC early vascular complication s/p liver transplant

Early hepatic artery thrombosis

Dx: s/p liver transplant: | - Increased LFTs, decreased bile output, fulminant hepatic failure

Dx: early hepatic artery thrombosis

Tx: early hepatic artery thrombosis

MC will need emergent re-transplantation for ensuing fulminant hepatic failure (can try to stent or revise anastomosis)

Complication s/p liver TXP: results in biliary strictures and abscesses (not fulminant hepatic failure)

late hepatic artery thrombosis

MC'y from late (chronic) hepatic artery thrombosis s/p liver transplant

Abscesses

Dx: s/p liver transplant - (rare) edema, ascites, renal insufficiency - Tx: thrombolytics, IVC stent

IVC stenosis / thrombosis

Dx: s/p liver transplant - (rare) Early - abdominal pain. Late - UGIB, ascites, may be asymptomatic - Tx: if early, re-op thrombectomy and revise anastomosis

Portal vein thrombosis (rare)

Dx: s/p liver transplant - get PMNs around portal triad (not mixed infiltrate)

Cholangitis

Dx: s/p liver transplant - T cell mediated against blood vessels. - Clinical: fever, jaundice, decreased bile output - Labs: leukocytosis, eosinophilia, increased LFTs, increased total bilirubin, and increasedPT - usually occurs in 1st 2 months.

Acute rejection s/p liver transplant

Pathology: acute rejection liver transplants

Shows portal triad lymphocytosis, endotheliitis (mixed infiltrate) and bile duct injury

Unusual after liver transplant; get disappearing bile ducts (antibody and cellular attack on bile ducts); gradually get bile duct obstruction with increase in alkaline phosphatase, portal fibrosis

Chronic rejection

Liver TXP: Retransplantation rate

20%

Liver TXP: 5-year survival rate

70%

Pancreas TXP: donor arterial supply

Need both donor celiac artery and SMA for arterial supply

Pancreas TXP: donor venous drainage

Need donor portal vein for venous drainage

Where do you attach pancreas TXP?

Attach to iliac vessels

How do you drain pancreatic duct s/p pancreas TXP?

Most use enteric drainage for pancreatic duct. Take 2nd portion of duodenum from donor along with ampulla of Vater and pancreas, then perform anastomosis of donor duodenum to recipient bowel.

Successful pancreas/kidney TXP results in..

Stabilization of retinopathy, decreased neuropathy, increased nerve conduction velocity, decreased autonomic dysfunction (gastroparesis), decreased orthostatic hypotension. No reversal of vascular disease.

Complications: pancreas TXP

- Venous thrombosis (#1) - hard to treat - Rejection - hard to diagnosis if pt does not also have a kidney transplant. (Can see increased glucose or amylase; fever, leukocytosis)

How long can a heart store for TXP?

Can store for 6 hours

s/p heart transplant - Associated with early mortality after heart TXP - Tx: inhaled nitric oxide, ECMO if severe

Persistent pulmonary hypertension after heart transplantation

s/p heart transplant | - Shows perivascular lymphocytic infiltrate with varying grades of myocyte inflammation and necrosis

Acute rejection

s/p heart TXP | - MCC of late death and death overall following heart TXP

Chronic allograft vasculopathy (progressive diffuse coronary atherosclerosis)

How long can you store a lung?

Can store for 6 hours

Lung TXP: | - #1 cause of early mortality

Reperfusion injury (Tx: similar to ARDS)

Indication for double-lung TXP

Cystic fibrosis

Lung TXP: exclusion criteria for using lungs

Aspiration, moderate to large contusion, infiltrate, purulent sputum, PO2

Lung transplant: perivascular lymphocytosis

Acute rejection

Lung TXP: bronchiolitis obliterans. MCC of late death and death overall following lung TXP

Chronic rejection

Opportunistic infections: - Viral? - Protozoan? - Fungal?

- Viral: CMV, HSV, VZV - Protozoan: Pneumocystis jiroveci pneumonia (reason for Bactrim prophylaxis) - Fungal: Aspergillus, Candida, Cryptococcus

Hierarchy for Permission for Organ Donation from Next of Kin

1) Spouse 2) Adult son or daughter 3) Either parent 4) Adult brother or sister 5) Guardian 6) Any other person authorized to dispose of the body