Transplant Flashcards
Define transplantation
The moving of living cells, tissues or organs from a donor to a recipient, for the purpose of replacing the recipient’s damaged or absent organ
Describe the different body parts of transplant that can occur. Examples:
Organs:
Kidneys, heart, liver, lungs, pancreas, intestine, thymus
Tissues:
Bones, tendons, corneas, skin, heart valves and veins
Cells:
Stem cells, islet cells
Do transplants last forever? Can more than one organ be transplanted?
No
Transpplants doo not last forever
Can be multi-organ – common situation is to hae one organ
What are the different types of transplant that can occur?
Autograft
Allograft
Xenograft
Define autograft
Transplant that occurs within body (self to self) – skin graft, CABG (potentially)
Define Allograft
Transplant within two people within the same species (Twins)
Define xenograft
Transplant from one species to another ( Experiemental; working on this for decades, pig heart and kidney transplant)
Define the types of donor for a transplant
Living donor – Can donate one kidney, donate piece of liver
Deceased donor
Neurological determination of death (NDD)
Donation after circulatory death (DCD)
Are tissues for transplant immediately transplanted? Organs?
Tissues may be ‘banked’, however organs must be transplanted immediately, which poses surgical and geographic challenges
Transplants are considered a _______ procedure
Life-saving procedure for many
Describe the survival rates of various types of transplant
Lung Lowest 5 year survival rate
Survival rate varies depending on the type of transplant
Describe transplant of kidneys regarding duration and choice for patient
Kidneys
Dialysis; so there is a choice here
Kidney transplant –> 12-15 years – if have one really young, may need another one when you are older
Describe why lungs have the lowest survival rate out of all transplants
Lungs are finnicky: require more immunosuppression, contribute to more toxicities and rejections
Lungs are exposed to the external environment all day long so less barrier
What is the major barrier to transplant? How many Canadians are on the waitlist for a transplant?
Donor shortage is a huge barrier
~ 3500 Canadians are on the waitlist for organ transplant
Describe how organ sharing occurs in Canada?
Different centres across the country
Organ sharing occurs locally first, then if not a match to someone in SK, national sharing as well
Highly Sensitize Registry: Anytime an organ becomes available, scanned against everyone else to have the best chance of getting it
Healthcare is provincial so difference: Wait times may be different across the country
What is the most common type of transplant?
Kidney
Describe the average time for renal transplant in SK?
Average time:
workup – 1yr
wait – 2yrs
Describe a program in Sk for renal transplant reciepients
Medications covered under SAIL
Saskatoon Aid for Independent Living:
- program in sask that covers specific people; covers a lot of dialysis patients in SK (renal replacement therapy – transplant meets this criteria),
Immunosuppressive covered 100%, cover adjunctive meds as well
Describe where other organ transplants occur in Canada?
Transplanted out of province (usually Edmonton, occasionally Winnipeg)
Post-transplant care provided in SK
Livers, lungs, hearts
Adults, pediatrics
Medication coverage differences – not covered by SAIL; EDS: coverage same as every one else
Describe the function (s) of the immune system?
Recognition and protection against infection by infection causing organisms
Recognition and destruction of cells with mutations (e.g. cancer cells)
Cause cell injury and destruction to create inflammation and recruit further immune system response
How does recognition occur in the immune system?
Proteins produced by ’non-self’ organism
Signaling molecules created when inflammation is present
List the components of the immune system
Major histocompatibility complex (MHC)/Human leukocyte antigens (HLA)
Antigen presenting cells (APC)
T lymphocytes “cell-mediated”
B lymphocytes “Humoral” or “antibody-mediated”
Describe the role of the MHC/HLA. Where is it located?
Distinguishes ‘self’ from ‘non-self’
Expressed on surface of antigen presenting cells
Describe the role of APC
B cells, macrophages, dendritic cells
Displays HLA to host T-cells causing antigen-specific T-cell activation
Describe the role of T lymphocytes
T lymphocytes “cell-mediated”
CD4 (“Helper” or :TH”)
Recognize MHC class II
Stimulate B- and T-cells
CD8 (“Cytotoxic” or “Tc”)
Recognize MHC class 1
Kill infected cells
Describe B-lymphocytes
B lymphocytes “Humoral” or “antibody-mediated”
Responsible for antibody formation against antigen
Describe the role of MHC in the reciepient of the transplant
The recipient recognizes the the transplanted graft either as self or foreign based on the reaction to histocompatibility antigens
Describe histocompatability antigens and their role in the immune system
glycoproteins expressed on nucleated cells
major function is to bind peptides and present them at the cell surface for inspection by T-cells of the immune system
Are encoded by the major histocompatibility complex (MHC) genes that are referred to as the Human leukocyte antigen (HLA) in humans
What is the most important Hiscompatbility antigen? Describe its role in transplant?
HLA matching here
HLA is the version of the MHC found in humans: HLA more specific as only found in humans
HLA: Most important antigens responsible for graft rejection
Describe the different HLA Classes
200 Genes located on chromosome 6
Describe the inheritance of HLA genes?
HLA genes are polymorphic and are genetically inherited as a haplotype (groups)
HLA alleles are polymorphic and are designated by a number (ie HLA –A1 or HLA-A2)
HLA-A identical: Perfect match (share all the same alleles)
Siblings: 25% the same alleles, 25% chance no same alleles, 50% chance of mixed alleles
Even though may have perfect allele match, other antigens (minor histocompability antigens) can provoke rejection
Describe the T-cell signal Model
Drugs that work differenytly: Wider coverage, prevent toxicity – use lower doses of each in combo (like acet and iBu hehe)
Describe the overall role of HLA-typing
In general, the closer the HLA match between the donor and the recipient, the better the outcome
Describe the role of B cells in transplant
Although allograft rejection was traditionally thought to be a t-cell related process, It is now recognized that B cells play a key role by the production of anti-donor antibodies that bind to allografts (termed Donor Specific Antibodies or DSA)
Rejection due to B-cell pathophysiology is termed B cell rejection or Humoral rejection
List the different types of compatability tests used for transplant
PRA (pannel reactive antibody test)
Lymphocyte cross-match
ABO blood typing
Describe PRA compability test
PRA (pannel reactive antibody test)
Blood sample from the potential recipient is cross-matched with cells from panel of previously typed donors selected to represent as many HLA antigens as possible.
PRA or panel reactive antibody = the percentage of positive reactions among the total cell panel.
A high PRA indicates broad sensitization, but it does not reflect antibody strength or titer.
Many reasons for sensitization, eg transfusions, transplants, pregnancies
Measure of sensitization
Describe an example of PRA compability tests
Tony crossed with a sample of many people: percentage of reactions Tony has to the sample
Tony: 88% - Reacting to 88% of people
Higher PRA: more sensitization: Not a good thing
Highly sensitized against panel cells: less chance of Tony getting a kidney
PRA: General measure of sensitization, does not represent antibody strength or titre
PRA: 99% -> Go on highly sensitized registry
Scanned across canada get organ: 1 in a million organ
Describe lymphocyte cross-match compatability testing
Directly tests the reactivity between a patient’s serum and a potential donor’s cells
Viable lymphocytes are isolated from samples of the donor’s blood, spleen or lymph nodes cross-matched with potential recipient blood to determine whether pre-formed antibodies to donor’s lymphocytes are present
+ test indicates the presence of cytotoxic IgG antibodies to the donor (+ is BAD!)
Virtual crossmatch
Not a contraindicatication with liver: More tolerogenic organ
Describe antibody testing timing prior to transplant
Antibody levels fluctuate, therefore tests are done continuously while the potential recipient is waiting for a transplant
Describe ABO blood typing
Matching of blood type is critical
Transplanting an organ with ABO incompatibility typically results in a hyperacute rejection and destruction of the graft
When is ABO blood typing not required in a transplant?
Exceptions to this rule In pediatric herat transplants, can transplant a cross blood type Not an issue if less than one
Describe the role of immunosupression for organ transplantation
A complex regimen of medications is needed to prevent the recipient’s immune system from rejecting the new organ
Immunosuppressive regimens consist of drugs that work at different levels of the immune cascade
The amount of immunosuppression required will vary depending on the organ transplanted
(in general, lung> heart, kidney> liver)
Describe other factors that play a role in the immunosupression for organ trasnaplantation:
Many other factors also play a role, including:
Match between donor and recipient
Time post-transplant
- Immune system high post-transplant; increased risk of rejection, require induction therapy and decrease drugs over time
Underlying disease
- If reason for transplant is immunoreactive disease, need higher immunosupression
Patient history
Medication tolerance
Patient age, race
- Men aged 18-30 and African AMericans have more robust immune system
Descibe the diferrent types of rejection
Hyperacute
Acute Cellular Rejection (ACR)
Humoral Rejection/Antibody Mediated rejection
Chronic rejection
Describe hyperacute rejection
Uncommon, immediate immunological response
Describe acute cellular rejection
Occurs anytime
Mediated by alloreactive T lymphocytes
Describe humoral rejection/antibody mediated rejection
Humoral rejection/Antibody mediated rejection – ‘vascular rejection’
Antibody mediated process
Poorer prognosis
Define chronic rejection
most common cause of late graft loss
No effective treatment
(slow gradual decline/ process)
Describe the immunosupressive therapies (list) that can be used in transplant
Describe the approach to medication therapy in transplant
Multidrug approach utilized
2 phases:
1) INDUCTION THERAPY
- Risk of acute rejection is highest in first 1-3 months
2) MAINTENACE THERAPY
Why is induction therapy required?
The risk of acute rejection is highest in the first 1-3 months, so higher doses of immunosuppressants are used during this time
How does induction therapy occur?
Induction therapy is treatment with a biologic agent begun at the time of transplant to deplete or modulate t-cell response (done in hospital)
Describe the effect of induction therapy
Induction therapy improves the efficacy of immunosuppression by reducing acute rejection and allowing for the reduction in other maintenance medications
Gives us broad coverahe for. A short period of time
Describe the medication(s) used for induction therapy
Describe Basiliximab (Simulect): MOA, Dose, D.I.
Humanized, recombinant IgG1 interleukin-2 receptor monoclonal antibody
MOA: Binds to IL-2 receptor on activated lymphocytes preventing IL-2 binding to the receptor – prevents cellular proliferation – maintained for 4-6 weeks
No DIs, usually well tolerated, can have acute hypersensitivity (rare)
Usual Dose: 20mg IV pre-transplant, and again on Day 4 or 5
- Standard dose to everyone – not weight based dose
Describe anti-thymocyte Globulin (ATG, thymoglobulin) MOA, S/E, Dose
Polyclonal antibody
MOA: The antibodies in ATG bind to antigens found of the surface of t-cells and depletes t-cells from circulation
For induction or rejection (cell mediated)
SE: bone marrow suppression, anaphylaxis, hepatic, infusion related reactions (premed to help prevent this)
- Count the lifetime doses for rejection and induction: Incraese side ffects, increased risk of cancers, infection
Dose: 1-1.5mg/kg (ABW) daily (x3-10days)
- Weight based dosing (IV)
Describe maintenace immunkosupressive regimens
Prednisone MOA, Dosing
MOA:
Bind to the glucocorticoid receptor, which in turn, up-regulates the expression of anti-inflammatory proteins in the nucleus and represses the expression of proinflammatory proteins in the cytosol by presenting the translocation of other transcription factors from the cytosol into the nucleus
Inhibit antigen presentation, cytokine production, and proliferation of lymphocytes.
Dosing:
IV initially
switched to oral prednisone and tapered to the lowest effective dose
Adverse EFfects of CS’s
Insomnia
Personality changes
Adrenal suppression
Acne, moon facies, bruising, hirsutism
Gastrointestinal
Glucose alterations
Hyperlipidemia/accelerated athersclerosis
Impaired wound healing
Infection
Musculoskeletal changes
Osteoporosis
Pancreatitis
Cataracts, glaucoma
Describe teh short term and long term side effects of CS
Short term effects e.g.
Insomnia
Personality changes
Gastrointestinal
Glucose alterations
Long term effects e.g.
Musculoskeletal changes
Osteoporosis
Cataracts
How can osteoporosis of CS be managed?
Routine bone density measurements
Pharmacotherapy to prevent or treat osteoporosis
Calcium, Vitamin D
bisphosphonates
How can hyperglycmeia of CS be managed?
hope it resolves with tapering doses
diet, oral hypoglycemics, insulin if needed,
?stop tacro?
Describe aziathioprine (AZA) MOA, DOSE
MOA: Purine analog, likely affects purine synthesis & metabolism, suppresses T & B cells (Pro-drug of 6-mercaptopurine)
Dose: ranging from 25-150mg once daily
Describe the adverse effects of azathioprine. Drug Inetraction(s)?
Adverse effects:
bone marrow suppression
skin lesions
hepatic
pancreatitis,
alopecia, etc…..
Drug interactions: remember Allopurinol
Largely replaced by Mycophenolic acid derivatives
Describe the drug interaction between Aziathioprine and ALoopurinol
Allopurinol: Gout (used in gout) – quite common in transplant patients
Can cause myelosuppression –>Severe
Call in check or see if transplant centre: Can be used together but need to adjust doses
Allopurinil inhibites glutathione-S-transferase: Incraeses plamsa levels of 6-mercaptopurine
Describe the MOA of Mycophenolic ACid Derivatives
Purine analog: affects purine synthesis and metabolism, suppresses T & B cells
more specific than azathioprine (does not affect other rapidly dividing cells)
Describe the formulations of mycophenolic acid derivatives
Formulations: (both oral)
Mycophenolate mofetil (MMF) (Cellcept®)
Prodrug: rapidly converted to mycophenolic acid (MPA) via first pass metobolism
IV form also available
Mycophenolate sodium (EC-MPS) (Myfortic®)
Enteric coated tablets , deliver active moiety (MPA)
Dosing of Mycopheolic ACid Derivatives
Dosing: Empiric, Based on type of organ (q12)
Standard dose: Cellcept 1g bid =Myfortic 720mg bid (kidney)
It is possible to do mycophenolic acid levels, but they are not routinely done
Adverse EFfects of Mycophenolic Acid Derivatives
Adverse effects:
GI: diarrhea, nausea, indigestion (MAJOR)
Neutropenia - Must monitor WBC count in individuals who have received a transplant
Teratogenic: birth control for males and females
Describe the drug inetractions of Mycophenolic ACid Derivatives
divalent cations (iron, calcium)
Cholestyramine, colestipol
food decreases the rate but not the extent of absorption
Describe how the GI side effects of Mycophenolic acid can be managed
Food may decrease absorption
Adherence is extremely important
Will still space with medications to twice a day
- often say take with food to help alleviate GI side effects
Do a lot of counselling on this front here as can be confusing for the patient
How can the GI adverse effects of mycophenolic acid be managed? (more in depth here)
rule out infectious cause
administer with food
Use of acid suppressive medications (PPI, H2RA)
divide total daily dose into 3 or 4 doses (or decraese if possible)
try alternate formulation (ie, Cellcept to Myfortic)
loperamide for diarrhea if non-infectious
consider change to azathioprine if unable to manage
How cxan neutropenia due to mycophenolic acid be managed?
reduce dose if possible (not always the case).
look for other drug causes and eliminate if possible (incraesed risk when given concurrently with valganciclovir)
Filgrastim/GCSF if needed
What are the two calcicneurin inhibitors?
Tacrolimus and cylosporine
Calcineurin Inhibitors MOA. CAn they be userd tohgetehr?
Forms a complex with their cytoplasmic receptor proteins (cyclophilin) that binds with calcineurin. Inhibition of calcineurin impairs the expression of several cytokine genes that promote T-cell activation
Cyclosporine & tacrolimus should not be prescribed concurrently
Describe cyclosporine formulation
Cyclosporine (NeoralR) supplied at 10, 25, 50, 100mg capsules. Should stay in the foil package prior to administration.
Q12h dosing
Suspension available, IV available (conversion iv:po = 1:3)
Pharamcokinetics of cyclosporine
Bioavailbility: ~ 60-80%, t1/2 (mean) 8h
Lipid soluble
Extensive binding to plasma proteins (90-98%)
Metabolism –cyp3A4 and pgp
Cyclosporine Drug Levels
Drug Levels:
can do trough (C0) level or 2 hour post dose (C2) level.
C2 preferably no more than 15 minutes from the 2 hour mark. C0 – 11.5-12.5 hours after last dose.
Level range is dependent on various patient factors such as time since transplant, match, side effects, history, organ
Earlier on: More immunosuprression; higher levels and then overtime we will decrease
Levels are patient specific
When is the certain timing of cyclosporine levels preferred for specific transplants?
C2 correlated better with AUC Standard practice Kidney and live r
CO Heart and lUngs
Describe the different formulations of tacrolimus
AdvagrafR and PrografR are NOT bioequivalent
AdvagrafR is an extended-release product intended for once daily dosing, while PrografR is intended for q12h dosing
Both are available in the SAME strengths (0.5,1, 5mg)
EnvarsusR (new) prolonged release formulation; also dosed once daily
IV available (approximately 25% of po Prograf dose)
PK of tacrolimus
Bioavailability: ~ 25%; t1/2 (mean) 8 -11h
Bound primarily to albumin(99%)
Metabolism – cyp3A4
Describe the differences between the different formualtions of tacrolimus
- Advagraf : OD
- prpgraf : BID
- equivalency: Under dose by 50%
Envarsus: OD –> Samller dose; less variability in peak to trough ratio
Prograf to Advagraf: adherence: If miss the dose, missing whole day dose
Drug Levels of Tacrolimus
Trough level only (C0)
Timing preferably no more than 30minutes from the CO hour mark.
Level range is dependent on various patient factors such as time since transplant, match, side effects, history, organ
Ex kidney
New transplant: >10ug/L; after 1 year ? 6-9 ug/L
Adverse Effects of Calcineurin Inhibitors
Describe the difference in potency between TAC and Cyclosporine
Tacrolimus is more potent; stronger
Mainly use tacrolimus now; cyclosporine sometimes
What is a warning sign of calcineurin toxicity?
Headache Warning sign, go get level checked as can be that level if too high (dose-dependent)
Describe the differences in adverse effects of cyclosporine and tacrolimus
How can HTN cause by calcineurin inhibitors be managed?
CCB, ACEIs, ARBs, B blockers….
How can blood sugar increases by calcineurin inhibiotrs be managed?
oral hypoglycemics, insulin
How can increased lipids by calcineurin inhbitors be managed?
statins – use lowest dose possible, monitor liver enzymes, creatinine kinase, patient (? Seem to experience muscle aches/weakness frequently)
– drug int., start low and monitor (still appropriate to do so)
atorvastatin, pravastatin, simvastatin, rosuvastatin?
Cyclosporine and Tacrolimus Drug Interactions
Describe MOA of Sirolimus
mTor Inhibitor
Macrolide Antibiotic structurally related to tacrolimus
MOA:
Binds to FKBP but does not block calcineurin - engages the TOR which reduces the cytokine-dependent cellular proliferation of the G1-S phase of the cell division cycle. Both hematopoietic and non-hematopoietic cells are affected.
Formulation of Sirolimus
Supplied as 1mg tablets
Available as a liquid that requires refrigeration
Mix dose with 60ml water or OJ. Stir vigorously and drink immediately. Rinse container, stir and drink. Mix in hard plastic or glass cup. Protect from light
Sirolimus PK
Poorly absorbed (F ~ 15%); Long t1/2 (60 h)
Extensive binding to plasma proteins (92%)
Metabolism –cyp3A4 *Drug interactions = SAME AS Calceurin Inhibitors
Drug Monitoring Sirolimus
Trough levels (Range: usually 8-15 ug/L)
When is sirolimus used?
To replace the calcineurin inhibitor (Declining renal function due to calcineurin inhibitors) - Does not have nephrotoxicity
Malignancy (?anti-tumor properties)
Potentially (used rarely) an add on therapy for those that need increased immunosuppression (lung transplants with declining therapy despite triple therapy)
Sirolimus Adverse Effects
How can hyperlipiemia of Sirolimus be managed?
Hyperlipidemia: most will need treatment
How can anemia of sirolimus be managed?
Anemia: treat, thrombocytopenia (stop?)
How can HTN of sirolimus be managed?
Hypertension: treat as previous
How can rash of sirolimus be managed?
Rash: ?dose related, reduce if possible, if significant and non-resolving stop drug
How can mouth sores of sirolimus be managed?
Mouth sores: reduce dose if possible, various mouthwashes, stop drug
How can peripheral edema of sirolimus be managed?
Peripheral edema: reduce dose, d/c calcium channel blocker if on, stop drug
How can proteinuria of sirolimus be managed?
Proteinuria: monitor albumin/Creatinine ratio, stop drug
How can acute ceelular rejection be treated?
Generally responds well
High dose steroids (ex methylpred 500-1000mg iv od x 3 d)
Antibody therapy (anti-thymocyte globulin)
How can humoral rejection/antibody mediated rejection be treated?
Less responsive
Plasmapheresis, corticosteroids, anti-thymocyte globulin, IV immune globulin
Rituximab
chimeric monoclonal antibody directed against CD20 antigen on B lymphocytes
Tocilizumab, Bortezomib
How can chronic rejection be treated?
Most common cause of late graft loss, no effective treatment
Increase maintenance immunosuppression
Try your best; post-pone as long as possible
Describe blood work requirement in transplant
All patients are required to have bloodwork for life!
The frequency will depend on the time post transplant, the clinical status of the patient and the type of organ
At minimum most people will have bloodwork q monthly (exception heart transplants)
Bloodwork helps us to monitor for rejection (exception hearts) & to monitor for toxicity from immunosuppressive medications
Describe what may be included in blood work for an individual who recieved a transplant
Arguments in favour for generic immunosupressants
Significant cost savings/economic benefits
Same active ingredient and stringent testing required by Heath Canada to show bioequivalence
Generic immunosuppressants have been used widely in other countries and to date there is no evidence to suggest harm
Other critical dose drugs are generic (eg, warfarin, digoxin)
Aruguments against the use of generics in transplant
Lack of published evidence in transplant populations (bioequivalency studies are performed in healthy patients)
The potential for uncontrolled product switching is a concern, since generic preparations are not required to demonstrate bioequivalence with each other.
Switches are likely to occur without prescriber knowledge.
Generics will lead to more therapeutic drug and clinical monitoring, and increased patient education will be needed.
What transplants is live donation possible for?
With kidney and liver transplants living donation is possible
What is teh difference in pharamcotherapy between the types of transplant?
Same immunosuppressant drugs used, same principles.
Differences in outcomes, monitoring, immunosuppressant regimens, etc.
What are some of the pros and cons of a kidney transplant?
Who is elegible for a kidney transplant?
What are some common indications for. akidney transplant?
Diabetes
Hypertension
Glomerulonephritis
Polycystic kidney disease
Describe the outcomes of kidney transplnat? KP?
Immunosupression Regimen in KIdney
In general kidney transplants will follow the previously discussed regimen
(biologic therapy for induction + maintenance triple therapy
What can occur after a kidney transplant is indicative of good prognosis?
Copious amounts of urine is a good sign after a kidney transplant
How can monitoring for rejection occur in a kidney transplant?
Routine bloodwork including SCr, urea, lytes, drug levels can help us to monitor for rejection
What are some of the symptoms that indicate rejection in kidney transplant?
WHat are some other cocnerns in a kidney transplant?
Delayed Graft Function
BK Virus/Polyoma Virus
Describe delayed graft function in kidney transplant
The need for dialysis in the first week post transplant
Original cause of renal failure can be an issue
DGF – has transplant, no pee
Diaysis to kick stsrat things
10-50% of people – slower return to function
Describe BK virus/polyoma virus in kidney transplant
Opportunistic infection which is a major cause of graft loss
Associated with increased levels of immunosuppression
Who is eleigible for a liver transplant?
Patients with advanced disease with impaired, non-reversible liver disease (decompensated)
What are some of the common inidcations for a liver transplant?
chronic viral hepatitis C and B
autoimmune hepatitis
primary biliary cirrhosis (PBC)
primary sclerosing cholangitis (PSC)
alcoholic liver disease
Hepatocellular carcinoma
Kids: biliary atresia
Outcome of Liver transplant
5-year survival for a liver is roughly 82-87%
Immunosupression Regimen in Liver transplant
The liver is the least immunogenic organ
Complete steroid weaning is almost always the goal
While induction and triple therapy is used initially, it is often possible to taper this to one agent over time (ex TAC)
Steroid usually weaned first
Mycophenolic acid derivative usually tapered around 1 year
Tacrolimus only and then get the levels down
Monitoring of liver transplant
Routine bloodwork including including liver enzyme tests can help us monitor for rejection (ALP, AST, ALP, GGT)
rejection Sx in Liver transplant
What is another issue in liver transplant?
Recurrence of disease is possible with some conditions
Ex Hepatitis B&C, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis
Who is eleigible for a heart transplant?
Advanced heart failure, non-responsive to medical therapy, but otherwise healthy
Common Indication for Heart Transplant
Cardiomyopathy
Severe coronary artery disease with scar tissue
Congenital defects
Heart Transplant O8uctome
5-year survival for a heart transplant is around 75%
Immunosupression in heart transplant
In general heart transplants will follow the previously discussed regimen
(biologic therapy for induction + maintenance triple therapy)
IS levels are similar to kidneys but prednisone is eventually often tapered
Issues with heart transplant
The transplanted heart is denervervated
Increased resting heart rate (90-110bpm), decreasing ability to rise quickly with exercise
MI may be asymptomatic
Altered response to drugs that work via the autonomic nervous system
Not able to recognize rejection symptoms
Additional Drugs in a Heart TRansplant
All adult patients should receive a statin, (regardless of LDL) to prevent CVD, plus ASA & ACE inhibitor for cardioprotection
Monitoring of Heart Transplant for Rejection
No great way to monitor! Labs are not helpful
Protocol biopsies are scheduled depending on the time post transplant (no marker to check)
Heart Transplant rejection Sx
Eligibility of Lung Transplant
healthy younger patients with chronic, end-stage lung disease who are failing maximal medical therapy.
Potential candidates should be well informed and demonstrate adequate health behavior and a willingness to adhere to health care guidelines
Indications of lung transplant
Cystic fibrosis
COPD
Pulmonary fibrosis
Pulmonary hypertension
Outcome Lung Transplant
5-year survival for a lung transplant in Canada is roughly 65%
Immunosupression Regimen Lung Transplant
High levels of immunosuppressants are necessary to prevent rejection
Induction therapy + triple therapy maintenance is almost always necessary. (sometimes even quadruple therapy used - sirolimus)
Lung Transplant Monitoring
Routine pulmonary function tests can help us to monitor for rejection, bloodwork can help us monitor for toxicity
Rejection Sx Lung TRansplant. Tx?
Other issues of lung tranplant. Risk factors and Tx?
Describe infection in transplant patients
Describe the treatmen tof infections in transplant? Sx?
What are some of the infections of concern in transplant?
1) CMV (cytomegalovirus)
2) Pneumocyitis Jiroveci pneumonia (PJP)
3) Herpes Simplex Reactivation
4) Epstein Barr Virus
5) Fungal
6) Polyoma BK Virus (Kidney)
How can CMV be manged categories?
Prophylaxis
Treatment
What is the prophylaxis of CMV?
Usually valganciclovir 900mg od x 100-200 days, or screening with CMV PCR and pre-emptive treatment
Treatment of CMV
-IV ganciclovir, po valganciclovir,
-?CMV immunoglobulin as an adjunct?
-?letermovir ?maribavir
What is the prophylaxis of PJP?
Prophylaxis with co-trimoxazole x 6-12 months (perhaps indefinitely in lungs)
Various dosing regimens (ie SMX-TMP 400/80mg od or 800/160mg 3x week)
Options for sulfa allergies – Dapsone, Aerosolized pentamidine
What is CMV?
Most common opportunistic infection post transplant
Risk is dependent on donor/recipient serology
D+R- > D+R+ > D-R-
Oppurtunistic Infections – suppress immune system these come up
Test for prior to the transplant
Most risky with Donor positive, and Recipient has not been exposed
Describe the presentation of CMV?
What is Epstein Barr Virus?
A major cause of post transplant hypoproliferative disorder (PTLD)
Prophylaxis or monitoring is common for D+R-
More monitoring in pediatrics as likely to not be exposed to the virus
What type of fungal infections can occur with transplant?
Candida, aspergillus
What is polyoma BK virus?
-Associated with nephropathy and graft loss
Describe maliganncy after transplant
Increased risk (3-4x general population)
Skin, cervical & anorectal cancer, lymphoma, PTLD (post transplant lymphoproliferative disorder)
Prevention of maliganncy after transplant
Encourage routine screening & lifestyle factors:
Protect from Sun/Sunscreen
Regular pap & colonoscopy
Regular dermatologic exams
What is PTLD?
PTLD = Post-transplant lymphoproliferative disorder
Describe Post-transplant lymphoproliferative disorder
Diverse spectrum of disease with varied clinical presentation
May be nodal/extranodal, may localize in allograft or be disseminated; may be indistinguishable from Non-Hodgkin’s lymphoma
Highest risk in pediatrics
Monitoring = EBV viral load
Tx of PTLD
Decrease immunosuppression, rituximab??
Describe osteoporosis/osteopenia after transplant
a metabolic complication of transplantation
Regular bone densities
Optimize Vitamin D& calcium
Targeted treatment for high risk patients (ie: bisphosphonate)
Describe GI side effects transplant
H2 antagonist or PPI for dyspepsia or to minimize side effects from intensive immunosuppression (continued forever or d/c after)
PPI prophylaxis routine in many centers
describe GI side effects and drugs
Describe CVD in transplant
Major cause of morbidity and mortality
Framingham underestimates risk
Decrease risk factors (control BP, diabetes, stop smoking, weight loss, manage hyperlipidemia)
Describe Hyperlipidemia in Transplant
SRL»_space;CSA, TAC
Statins 1st line but increased risk of myopathy/rhabdomyalysis
Drug Int Hyperlipidemia MEds
increased levels of statins, start at ½ dose & titrate pending effect and tolerance
Cholestyramine/colestipol adversely affect absorption of MMF, CSA
Ezetimibe in combo with CSA can increase levels of both drugs – caution with CNIs!
Hypertension Transplant
Occurs in 50-90% kidney & liver & almost all hearts
CSA, TAC
May be difficult to treat
Optimal target unknown, extract from general population and tx to high risk (130/80?)
Tx HTN in Transplant
Anemia in Transplant and TX
Describe renal insufficiency in transplant
Complication of all solid organ transplant
CKD affects 30-50% of non-renal transplants
Modify medications/procedures to minimize renal adverse effects DO not want to use NSAIDs here, radiocontrast with imaging
What is NODAT?
NEW ONSET DIABETES AFTER TRANSPLANT (NODAT)
Describe NODAT and TX
Describe GOut in TX
Tx of Gout in Transplant
Avoid NSAIDS
counsel on diet
may use steroids, colchicine or allopurinol but dose adjust based on renal function & manufacturer recommendation
Electrolyte Disturbance in Transplant
Oral or IV supplementation
correct underlying cause if possible
IV supllementation – earlier post-transplant – first year
Sorts its self out over time
What are the electrolytes of cocnern post-transplant?
Magnesium, Phosphate and Calcium Supllementation (CNI decraese Mg and PO4)
K+ increased by CNI and high after transplant
Kaxylate, Sodium polystyrene sulfonate
Fertility Consideration Transplant
Pregnancy should NOT be considered without consultation from transplanting center
Pregnancy may pose risk to mother and organ
Improved health post transplant may lead to return to fertility
Immunizations in Transplant
No live vaccines!
Vaccine response post transplanted is often blunted
Influenza yearly is recommended for all patients
Drug Inetractions Transplant
Herbal Products Transplant
Non-adherence in Transplant
Which adjunct medications are often started after a transplant?
Labetalol and clonidine or Nifedipine –> Blood Pressure control and Protect the kidney
ACEi and Arb not started right after transplant –>More often than not, will not start it until after
CCB
ACE/ARBs are first line eventually
ASA sometimes prophylactically prescribed to prevent bleeding
Role of Community Pharamcist in Transplant
Identify and address drug interactions
Assess adherence
Identify and triage red flags
Liaison for communication
Types of Living Donors
Paired Exchange: An incompatible donor/ recipient pair (such as a mother and son that don’t have compatible blood types) are matched with another incompatible donor/recipient pair for a “swap”
Altrusitic DOnor: a person who wishes to donate a kidney to a person with advanced kidney disease, who he or she does not know
Risks of donating a KIdney
Risks of surgery
Slight increased risk of high blood pressure
Slight increased incidence of kidney failure
Possibility of injuring the remaining kidney
Slight risk of developing a disease of the remaining kidney
Some people also experience psychological difficulties, although most donors are satisfied with their decision to donate a kidney
Allocation of Organs
In Canada, opt-in system for donation
Nova-Scotia - Opt-out system
