BCTXP cheat sheet
BCTXP · Keep the key ideas within reach.
Clinical Foundations and Transplant Immunology
Hyperacute rejection is antibody-mediated, complement-dependent, and occurs within minutes to hours; it is prevented by pretransplant crossmatch.
Acute cellular rejection is mediated by recipient T cells recognizing donor alloantigen via direct or indirect pathways; direct pathway predominates early.
Chronic rejection is characterized by alloantibody-mediated vascular changes (transplant vasculopathy) and fibrosis; donor-specific antibody (DSA) is a major risk factor.
ABO blood group compatibility: recipients with blood group O have anti-A and anti-B antibodies; group AB recipients have no anti-A or anti-B antibodies.
HLA matching: HLA-A, -B, -DR are most immunogenic; zero HLA mismatch is associated with superior graft survival, but matching is weighted by other factors.
Panel-reactive antibody (PRA) or calculated PRA (cPRA) estimates the percentage of the donor pool to which a recipient has antibodies; higher cPRA reduces acceptable donor offers.
Complement-dependent cytotoxicity (CDC) crossmatch detects complement-fixing antibodies; flow cytometry crossmatch is more sensitive and detects non-complement-fixing antibodies.
Immunosuppression principles: induction (e.g., basiliximab, antithymocyte globulin) at transplant, maintenance (calcineurin inhibitor, antimetabolite, steroid), and treatment of rejection.
Pre-Transplant Evaluation and Candidate Selection
Absolute contraindications to transplantation include active malignancy (except selected skin cancers), active uncontrolled infection, and severe irreversible organ failure not amenable to transplant.
Cardiac evaluation before kidney transplant: stress testing is indicated for candidates with diabetes or age >50 and no symptoms, per guidelines.
Pulmonary evaluation: forced expiratory volume in 1 second (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) guide candidacy for lung transplant; values <20% predicted increase risk.
Liver transplant candidates are prioritized by Model for End-Stage Liver Disease (MELD) score (or MELD-Na); exceptions exist for hepatocellular carcinoma within Milan criteria.
Psychosocial evaluation assesses adherence, social support, substance use, and mental health; active substance use may require abstinence period before listing.
Obesity (body mass index >35-40 kg/m2) is a relative contraindication for some organs; weight loss may be required before listing.
Infectious screening includes HIV, hepatitis B and C, CMV, EBV, syphilis, and tuberculosis; vaccination status should be updated before transplant.
Geriatric assessment: frailty and functional status predict post-transplant outcomes; chronological age alone is not an absolute contraindication.
Organ Procurement, Preservation, and Donor Management
Donation after brain death (DBD) and donation after circulatory death (DCD) are the two deceased donor categories; DCD organs have higher risk of delayed graft function.
Cold ischemia time (CIT) is the time from organ procurement to reperfusion; prolonged CIT increases delayed graft function and primary nonfunction.
Static cold storage uses preservation solutions (e.g., University of Wisconsin, histidine-tryptophan-ketoglutarate) at 4°C to reduce metabolic demand.
Machine perfusion (hypothermic or normothermic) may improve organ preservation and allows assessment of organ viability, especially for marginal grafts.
Donor management goals: maintain mean arterial pressure 60-80 mm Hg, urine output 0.5-1 mL/kg/h, normoglycemia, and normothermia; hormonal resuscitation (thyroid hormone, vasopressin, steroids) may be used in brain-dead donors.
Organ procurement follows standardized surgical technique; in DCD, warm ischemia time (from withdrawal of life support to cold perfusion) should be minimized (<30 minutes preferred).
Donor-derived infection screening includes blood cultures, serologies, and nucleic acid testing for HIV, HBV, HCV, and other pathogens.
Preservation solution composition: UW solution contains lactobionate, raffinose, glutathione, and adenosine; HTK contains histidine buffer, tryptophan, and ketoglutarate.
Perioperative and Surgical Management of the Transplant Recipient
Kidney transplant: extraperitoneal iliac fossa placement; vascular anastomoses to external iliac vessels; ureteroneocystostomy with anti-reflux technique.
Liver transplant: orthotopic replacement with caval anastomosis (piggyback or conventional), portal vein, hepatic artery, and biliary reconstruction (duct-to-duct or Roux-en-Y).
Heart transplant: orthotopic technique with bicaval or biatrial anastomoses; postoperative management includes inotropic support and monitoring for right heart failure.
Lung transplant: single or bilateral; bronchial anastomosis at risk for dehiscence and stenosis; immunosuppression and infection prophylaxis are critical.
Pancreas transplant: usually simultaneous pancreas-kidney (SPK); exocrine drainage via enteric or bladder; vascular thrombosis is a major complication.
Perioperative antibiotic prophylaxis is given before incision and continued for 24-48 hours; antifungal prophylaxis may be used in high-risk patients.
Postoperative complications include bleeding, vascular thrombosis, anastomotic leak, ureteral stricture, and delayed graft function; early imaging with ultrasound or CT is used for diagnosis.
Fluid management: maintain adequate intravascular volume to ensure graft perfusion; avoid nephrotoxic agents in kidney transplant recipients.
Immunosuppression and Rejection Management
Calcineurin inhibitors (tacrolimus, cyclosporine) inhibit T-cell activation by blocking calcineurin; tacrolimus is preferred in most protocols due to lower rejection rates.
Antimetabolites (mycophenolate mofetil, azathioprine) inhibit purine synthesis and lymphocyte proliferation; mycophenolate is associated with gastrointestinal side effects and teratogenicity.
mTOR inhibitors (sirolimus, everolimus) block cytokine-driven proliferation; they may be used in patients with calcineurin inhibitor nephrotoxicity but can impair wound healing.
Corticosteroids have broad anti-inflammatory effects; they are used for induction, maintenance, and treatment of acute rejection.
Induction therapy with basiliximab (IL-2 receptor antagonist) or antithymocyte globulin reduces early acute rejection; ATG is more potent but increases infection and malignancy risk.
Acute cellular rejection is treated with high-dose corticosteroids; steroid-resistant rejection may require antithymocyte globulin or OKT3.
Antibody-mediated rejection (AMR) is treated with plasmapheresis, intravenous immunoglobulin (IVIG), and rituximab; bortezomib may be used in refractory cases.
Therapeutic drug monitoring is essential for calcineurin inhibitors and mTOR inhibitors due to narrow therapeutic index and drug interactions (e.g., CYP3A4 inhibitors/inducers).
Infectious Disease and Post-Transplant Complications
Timeline of infections: early (<1 month) bacterial and fungal; intermediate (1-6 months) opportunistic (CMV, Pneumocystis, Aspergillus); late (>6 months) community-acquired and late opportunistic.
CMV infection: prophylaxis with valganciclovir for 3-6 months in high-risk (D+/R-) patients; treatment with intravenous ganciclovir for CMV disease.
Pneumocystis jirovecii pneumonia (PJP) prophylaxis with trimethoprim-sulfamethoxazole for 6-12 months after transplant; alternative dapsone or atovaquone.
Epstein-Barr virus (EBV) is associated with post-transplant lymphoproliferative disorder (PTLD); management includes reduction of immunosuppression and rituximab.
BK virus nephropathy: screen with plasma BK viral load; reduce immunosuppression as first-line treatment; cidofovir or leflunomide may be used.
Fungal infections: Candida and Aspergillus are common; prophylaxis with fluconazole or voriconazole in high-risk patients.
Surgical complications: anastomotic stricture, biliary leak, vascular thrombosis, lymphocele, and wound infection; early recognition and intervention are critical.
Vaccination after transplant: inactivated vaccines are safe; live vaccines are generally contraindicated; pre-transplant vaccination is preferred.
Long-Term Follow-Up and Outcomes
Graft survival rates: kidney transplant >90% at 1 year and ~70% at 5 years; liver transplant ~85% at 1 year and ~70% at 5 years; heart and lung lower.
Chronic allograft dysfunction: characterized by progressive functional decline; causes include chronic rejection, calcineurin inhibitor toxicity, and recurrent disease.
Post-transplant malignancy: skin cancers (squamous cell carcinoma) are most common; immunosuppression increases risk; regular skin examinations are recommended.
Cardiovascular disease is a leading cause of late mortality; management includes blood pressure control, lipid management, and diabetes screening.
Adherence to immunosuppression is critical; non-adherence is a major risk factor for late acute rejection and graft loss.
Monitoring of kidney function: serum creatinine and estimated glomerular filtration rate (eGFR); proteinuria may indicate chronic allograft nephropathy.
Post-transplant diabetes mellitus (PTDM) is common; screening with fasting glucose or oral glucose tolerance test; management includes lifestyle and pharmacotherapy.
Bone disease: osteoporosis is common due to corticosteroids; calcium and vitamin D supplementation, and bone density monitoring.
Ethics, Policy, and Regulatory Aspects of Transplantation
Organ Procurement and Transplantation Network (OPTN) operates under federal contract; United Network for Organ Sharing (UNOS) is the current contractor.
National Organ Transplant Act (NOTA) of 1984 prohibits the sale of human organs and established the OPTN.
Uniform Anatomical Gift Act (UAGA) governs organ donation; first-person consent laws allow donation without family consent if the deceased registered as a donor.
Allocation policies are based on medical urgency, waiting time, and geographic proximity; the kidney allocation system uses estimated post-transplant survival (EPTS) and kidney donor profile index (KDPI).
Informed consent for transplant includes discussion of risks, benefits, alternatives, and the need for lifelong immunosuppression.
Ethical principles: autonomy, beneficence, nonmaleficence, justice; allocation should be fair and transparent.
Regulatory oversight: Centers for Medicare & Medicaid Services (CMS) Conditions of Participation for transplant centers; Joint Commission accreditation.
Living donation: must be voluntary and altruistic; donor advocate teams ensure informed consent and protect donor interests.