Guidelines for Transplantation

Induction of Immunosuppression

IV anti-thymocyte globulin: not used in liver transplant; Corticosteroids: 10 mg/kg IV once → decrease by 2 mg/kg IV daily until 1 mg/kg oral; Mycophenolate mofetil: 600 mg/m²/dose PO BID; Tacrolimus: 0.075-0.2 mg/kg/dose PO BID

Maintenance of Immunosuppression

Calcineurin inhibitors, mTOR inhibitors, Anti-proliferative, Corticosteroids

Anti-Rejection Agents

Calcineurin inhibitor, mTOR inhibitor, T-cell costimulation blocker, Anti-proliferative, Corticosteroid

Anti-Infective Agents

Antifungal, antiviral, antibacterial

Anti-Thrombotic Agents

Anticoagulant, antiplatelet

Most Common Regimen

CNI + Mycophenolate + Corticosteroid (Tacrolimus + Mycophenolate mofetil + Prednisone/Prednisolone)

Calcineurin Inhibitors (CNI)

Lifelong therapy; includes Tacrolimus and Cyclosporine

Tacrolimus Dosing

0.075-0.2 mg/kg PO q12h

Tacrolimus Monitoring

Serum trough concentrations, CYP3A4 and P-glycoprotein interactions

Tacrolimus Side Effects

Nephrotoxicity, post-transplant diabetes, hair loss, diarrhea

Cyclosporine Dosing

2-5 mg/kg PO q12h

Cyclosporine Monitoring

Serum trough concentrations, CYP3A4 and P-glycoprotein interactions

Cyclosporine Side Effects

More nephrotoxicity, hirsutism, gingival hyperplasia, hyperlipidemia

CNI Counseling/Monitoring

Formulations not interchangeable; do not miss or double doses; avoid grapefruit

Post-Transplant Lymphoproliferative Disorder (PLTD)

Caused by too much immunosuppression, often from EBV

PLTD Cause and Pathophysiology

EBV infection → ↓ T-cell surveillance → EBV B-cell proliferation → B-cell transformation → lymphoma

PLTD Symptoms

Asymptomatic → fatigue, fever, lymphadenopathy, splenomegaly, hepatomegaly, rash

mTOR Inhibitors

Sirolimus and Everolimus; preferred in PLTD; delay >1 year post-transplant

Sirolimus Dosing

<40 kg: 3 mg/m² load → 1 mg/m² daily; ≥40 kg: 6 mg load → 2 mg daily

Everolimus Dosing

Adjunct or monotherapy; ~0.75-1.5 mg BID

mTOR Inhibitor Side Effects

Headache, hypertension, edema, pleural effusions, pain, constipation, mucositis, proteinuria, ↑SCr, hyperlipidemia, anemia, thrombocytopenia, leukopenia, delayed wound healing

mTOR Counseling/Monitoring

Don't miss doses; monitor levels; report mouth sores

T-cell Costimulation Blocker (Belatacept)

Must be EBV+; selective T-cell stimulation blocker; dosed every 14 days

Belatacept in Kidney Transplant

Higher eGFR, better graft survival; EBV+ required

Belatacept in Liver Transplant

Higher rejection, graft loss, and death; trial terminated

Anti-Proliferative Agents

Mycophenolate & Azathioprine (~6 months)

Mycophenolate Mofetil Dosing

600 mg/m² PO BID

Mycophenolate Side Effects

Diarrhea, neutropenia, teratogenic

Mycophenolate Conversion

500 mg MMF = 360 mg mycophenolic acid

Mycophenolate REMS

Teratogenicity risk; ↑ miscarriage and malformations; report pregnancy to registry

Corticosteroids (~3 months)

Used for maintenance and T-cell rejection; taper within 3 months post-transplant

Post-Op Steroid Dosing

Start 10 mg/kg IV day 0 → taper to 1 mg/kg PO by day 5

Steroid Monitoring/Counseling

↑ blood sugar, ↓ natural steroid production, mood changes, don't stop abruptly

T-cell Mediated Cellular Rejection

Methylprednisolone 10 mg/kg IV x3d → 5 mg/kg x2d → 2 mg/kg x2d → 2 mg/kg PO taper outpatient

Antithrombotic Therapy

Enoxaparin and Aspirin

Antithrombotic Concerns

Bleeding (varices, ↑PT/INR), clotting (↓ portal flow, ↑ vascular resistance), risk of HAT/PVT

Antithrombotic Management

Aspirin ↓ HAT risk without ↑ bleeding; PVT: LMWH or UFH preferred

Pediatric Enoxaparin Dosing

0.5 mg/kg SQ q12h (3-6 mo), monitor Anti-Xa 0.1-0.4 IU/mL

Pediatric Aspirin Dosing

1-5 mg/kg PO daily (max 81 mg, lifelong); monitor VerifyNow or platelet aggregation

Enoxaparin Counseling

Inject into fatty tissue, rotate sites; 90° injection; engage safety; dispose in sharps; seek ER for bleeding

Anti-Infective Prophylaxis

Covers antifungal, antiviral, antibacterial

Antifungal Prophylaxis (oral candidiasis)

Azoles (fluconazole, clotrimazole): CYP3A4 inhibitors, CNI toxicity risk; Nystatin: bad taste, avoid food/drink near dosing

Antiviral Prophylaxis (CMV)

Valganciclovir; medium risk 3 mo, high risk 6 mo; monitor hematologic toxicity, fertility, fetal risk

Antibacterial Prophylaxis (PJP)

SMX-TMP for 6-12 months; high mortality if untreated

SMX-TMP Side Effects

Hyperkalemia, neutropenia, thrombocytopenia

SMX-TMP Counseling

Take w/ 8 oz water, avoid if sulfa allergy, risk in early/late pregnancy, photosensitivity

Alternative PJP Agents

Atovaquone, Dapsone, Pentamidine

Summary

Main anti-rejection: Tacrolimus + Mycophenolate + Steroids; Anti-thrombotic: Enoxaparin + Aspirin; Anti-infective: up to 1 year post-transplant