Solid Organ Transplant

Transplant definition

- take a diseased organ out and putting a healthier organ in

Allograft definition

- donation of organ from a different human

- live donor

- deceased donor

Xenograft definition

- donation of organ from different species

Heterotropic transplant definition

- leaves diseased organ in place while transplanting new organ

Orthotopic transplant definition

- removes diseased organ and new organ is placed in same location

Rejection definition

- body's immune system and attacks the foreign organ

Tolerance definition

- requiring less immunosuppression over time (chimerism)

- transplanted organ has phenotype similar to the host

Common transplanted organs

- kidney

- liver

- heart

- lungs

Common causes of kidney transplant

DPH

- diabetic nephropathy

- polycystic kidney disease

- hypertension

Common causes of liver transplant

- hepatitis C

- alcoholic cirrhosis

- hepatotoxic medications (APAP)

Common causes of heart transplant

- cardiomyopathy

- coronary artery disease

- congenital heart disease

Common causes of lung disease

CIA

- COPD

- idiopathic pulmonary fibrosis

- alpha-1 antitrypsin deficiency

What are other organs that are transplanted and causes?

- pancreas = diabetes

- skin = burns or necrosis

United Network for Organ Sharing (UNOS)

- non-profit, scientific

- responsible for organ matching process

- holds waiting list

Organ Procurement and transplantation network (OPTN)

- responsible for delivering transplanted organs throughout US

Induction regimens

- methylprednisolone +

One of the following: BAT

- basiliximab

- anti-thymocyte globulin

- thymoglobulin

Which medications do you need to premedicate for infusion rxns w/ APAP, diphenhydramine?

- thymoglobulin

- anti-thymocyte globulin

What are the precautions when using antibody-targeted drugs?

- increased risk of viral infections and malignancies

Maintenance medications (primary, secondary, +/-)

Primary:

- calcineurin inhibitor

Secondary: One of these

- mTOR inhibitors

- antimetabolites

+/- prednisone

Calcineurin inhibitors

- cyclosporine

- tacrolimus

mTOR inhibitors

- sirolimus

- everolimus

Antimetabolites

- azathioprine

- mycophenolate

What do you always have to monitor with these patients?

- CBC for overimmunosuppression

Cyclosporine brand names

- Gengraf, Neoral = equivalent

- Sandimmune

Cyclosporine has a

Lower incidence of:

- hyperglycemia

- tremor

Cyclosporine BBW

- hypertension

- nephrotoxicity

- skin cancer

Tacrolimus brand names

- Prograf, astagraf XL, envarsus XR

Tacrolimus has

Lower incidence of:

- hypertension

- gingival hyperplasia

- hirsutism

- neurotoxicity

Does cyclosporine or tacrolimus have more consistent levels?

- tacrolimus has more consistent levels

Does cyclosporine or tacrolimus have superior effects to prevent rejection in kidney/liver transplants?

- tacrolimus

Both cyclosporine and tacrolimus

- requires peak/trough levels

- acute and chronic nephrotoxicity

- absorption by food

- narrow therapeutic range

- CYP3A4 substrates

Cyclosporine and tacrolimus SE and BBW

- SE = hyperlipidemia

- BBW = infection and malignancy

Prograf

Tacrolimus IR

- given BID

Astagraf XL and Envarsus XR

given once daily

Prograf TDD to Astagraf XL TDD

- 1:1

Envarsus XR to Prograf

Envarsus XR = 0.8 x Prograf TDD

Tacrolimus IV

- 1/4 x Tacrolimus IR TDD as a continuous infusion over 24 hours

i.e. Tacrolimus 5 mg BID = 10 mg TDD = 2.5 mg IV over 24 hours

T/F: Tacrolimus trough levels change proportionately to the dose given.

- true

Everolimus is associated w/

Ever PPED your pants

- pnemonitis

- pulmonary fibrosis

- edema

- dyslipidemia

What is unique about everolimus?

- has antiviral properties = beneficial for CMV + patients

Sirolimus is associated with

HAD

- hypertriglyceridemia

- angioedema

- diabetes

Sirolimus has and does not have

Has:

- anti-fibrotic properties

- anti-atherogenic prop

- anti-cancer properties

Does not cause:

- nephrotoxicity

Both everolimus and sirolimus

- long half-life = 4-7 days

- CYP3A4 substrated

mTOR inhibitors are associated w/

- decreased wound healing

- proteinuria

- stomatitis

Types of mycophenolate and dose conversion

- MMF

- MPA

- 250 mg MMF = 180 mg MPA

Mycophenolate info

- dose limiting N/V/D (less w/ MPA)

- decreased absorption w/ < 4 hours apart from antacids

- TERATOGENIC

Azathioprine SE

- pancreatitis

- LFT elevations

Mycophenolate and azathioprine both have

- dose-limiting myelosuppression

How often is infection prophylaxis done?

- up to 6 months

Cytomegalovirus and Herpes simplex virus prophylaxis (Donor +/Recipient -): what type of risk and medication?

- high: primary infection

- valganciclovir

***donor has but, recipient never has been exposed/have antibodies to CMV

Cytomegalovirus and Herpes simplex virus prophylaxis (Donor -/Recipient -): what type of risk and medication?

- low: HSV prophylaxis only

- acyclovir

Cytomegalovirus and Herpes simplex virus prophylaxis (Donor +/Recipient +): what type of risk and medication?

- moderate: reactivation or superinfection

- valganciclovir

Cytomegalovirus and Herpes simplex virus prophylaxis (Donor -/Recipient +): what type of risk and medication?

- moderate: reactivation or superinfection

- valganciclovir

Candida prophylaxis for organ transplant

- fluconazole 400 mg PO daily

Pneumocystis jiroveci prophylaxis for organ transplant

Test for G6PD: BDA

- not deficient = bactrim

- not deficient, sulfa allergy = dapsone

- deficient = atovaquone

Classification of rejection

- hyperacute

- accelerated

- acute

- chronic

Hyperacute (time, mediators)

- minutes to hours

- caused by preformed donor-specific cytotoxic antibodies (tested prior to transplant)

Accelerated (time, mediators)

- 2-6 days

- prior sensitization. patients with high PRA

Acute (time, mediators)

- up to 1 year

- T cells, antibodies

Chronic (time, mediators)

- past 1 year

- T cells, antibodies

Diagnosis of rejection (how to confirm rejection)

- biopsies are done regularly to identify rejection

Clinical presentation of kidney rejection

- BP increase

- edema

- fever

- graft tenderness

Clinical presentation of liver rejection

- change in color of bile

- increased WBC

- confusion

- jaundice

- graft tenderness

Treatment of rejection (1st line)

Steroid pulse therapy:

- methylprednisolone 0.5-1 gram for QD 3-7 days

Post-transplant management for

- hypertension

- diabetes

- hyperlipidemia

Hypertension causes and treatment

Causes:

- cyclosporine, tacrolimus

- corticosteroids

Treatment:

- ACE/ARB

- CCB

***thiazides discouraged d/t hyperglycemia risk

Diabetes causes and treatment

Causes:

- corticosteroids, tacrolimus

Treat: consider T2DM

- metformin

- insulin

Hyperlipidemia causes and treatment

Causes:

- sirolimus

- cyclosporine

- tacrolimus

- prednisone

Treat:

- statins

Counseling points for organ transplant pts

- use sunscreen outside

Immunosuppression increases the risk of

- infection

Donor (+) / Recipient (-) CrCl > 60 ml/min

Valganciclovir 900 mg Daily

Donor (+) / Recipient (-) CrCl 40 - 59 ml/min

Valganciclovir 450 mg daily

Donor (+) / Recipient (-) CrCl 25 - 39 ml/min

Valganciclovir 450 mg every 2 days

Donor (+) / Recipient (-) CrCl 10-24 and < 10 ml/min

Valganciclovir 450 mg 2x/week

Donor (-) / Recipient (-) CrCl > 10 ml/min

Acyclovir 800 mg q8h

Donor (-) / Recipient (-) CrCl < 10 ml/min

Acyclovir 200 mg q12h

Donor (+) / Recipient (-) Risk

High Primary infection

Donor (-) / Recipient (-) Risk

Low HSV prophylaxis only