Solid organ transplantation (SOT) is a viable treatment option for end-stage disease. Posttransplant care requires adherence with a complex medical regimen for a successful outcome.
In addition, the immunosuppressant regimen can exacerbate pre-existing conditions that can adversely affect both quality of life and survival.
Many patients referred for transplantation have one or more chronic illnesses that might affect their candidacy for transplantation.
Therefore, it is paramount that patients be thoroughly evaluated to determine the appropriateness of proceeding with transplantation.
Additionally, the transplant evaluation may reveal problems amenable to interventions other than transplantation.
General procedures for all organs as well as organ-specific requirements
Waiting list criteria for specific organs
The role of the transplant coordinator includes overseeing the transplant process and providing education to patients and their families/members of their support system.
Often, the coordinator is the first contact that the patient may have with the transplant team.
The transplant coordinator presents an overview of the transplant evaluation process and discusses the role of the interdisciplinary transplant team so that patients and family members will know to whom they should address particular questions as they proceed through the evaluation process.
Patients and families should be given detailed information about each test and consult so they know what to expect and how to prepare.
Information may be obtained over the phone, prior to the patient’s initial appointment, for example:
Past medical history
Payer or insurance information
During the assessment process, the coordinator consults with the patient and family to provide education concerning the evaluation and transplant process.
This education should include information about
Names and roles of members of the interdisciplinary transplant team
Organ-specific United Network for Organ Sharing (UNOS) listing criteria
Transplant center-specific survival statistics as reported by the Scientific Registry for Transplant Recipients1
What the patient should expect during the evaluation process
The timeline for transplant team decision making regarding whether or not the patient meets eligibility criteria for placement on the UNOS waiting list
Issues concerning the waiting period for transplant
Estimated time to await an organ
Availability of hospital-based support groups or educational forums
The organ allocation process
What to expect after transplantation
Medications (particularly immunosuppressants)
Postdischarge follow-up and self-care management
Financial responsibility including insurance coverage, out-of-pocket costs for medications, clinic visits, and testing co-payment
The stress of the situation may interfere with the ability of patients and members of their support system to understand and/or retain information. Members of the interdisciplinary transplant team should frequently assess the patient’s and their support persons’ understanding and expect to repeat information throughout the evaluation process. Refer to the chapter on patient education for more detailed information on this topic.
General evaluation process
All patients referred for organ transplantation will undergo a general evaluation process prior to more specific and invasive testing.
This process begins with a thorough history and physical examination of the patient.
Following this, baseline lab work and consultations will be performed as outlined below.
Patients referred for SOT undergo a battery of lab tests to
Determine if the patient meets physiological eligibility criteria for transplantation.
Identify any comorbid conditions.
General lab work typically includes basic metabolic panel, hepatic panel, lipid profile, complete blood cell count, thyroid panel, rapid plasma reagin (RPR),
urinalysis, and estimated glomerular filtration rate (extrarenal transplant candidates only).
In addition, transplant-specific lab work is performed. This includes the following:
ABO blood typing. It is a UNOS requirement that prospective recipients have blood typing performed on two separate occasions.2
Both results should be recorded in the medical record.
At the time of listing, a second member of the transplant team will confirm the blood type in the UNOS UNet system.
Currently, neither Australia nor Canada has a written policy for blood type confirmation.
Panel reactive antibody (PRA).
In order to determine the likelihood of hyperacute rejection following SOT, the serum of a prospective recipient is tested for the presence of circulating antibodies reactive against human leukocyte antigens (HLA).
Different techniques can be utilized, but currently, most SOT programs use solid-phase immunoassays, composed of solubilized HLA molecules bound to polystyrene beads and performed on a fluoroanalyzer (Luminex).4
Other techniques used include enzyme-linked immunosorbent assay (ELISA), complement- dependent cytotoxicity (CDC), and flow cytometry.5
This result is generally expressed as a percent of panel reactivity (% PRA) between 0% and 99%. This percentage represents the proportion of the population to which the person being tested will react because of preformed antibodies.
Additionally, transplant programs may choose to determine the calculated PRA (cPRA).
This calculation specifically looks at antigens deemed unacceptable and determines risk. A cPRA calculator can be accessed online.6
Each program determines which antigens are considered unacceptable for a particular transplant candidate based on the degree of risk the program is willing to assume.
Before a candidate with a cPRA score >98% receives offers in allocation classifications per UNOS guidelines updated with the new kidney allocation, the transplant program’s HLA laboratory director and the candidate’s transplant physician or surgeon must review and sign a written approval of the unacceptable antigens listed for that candidate. A member of the transplant team must document this approval in the candidate’s medical record.
Antigens may be considered unacceptable based on the level of HLA-specific antibody binding, which is expressed as the mean fluorescence intensity (MFI) of the reporter signal.4
A prospective crossmatch may be performed at the time of transplantation based on center- and organ-specific determination of risk of hyperacute rejection.
Additionally, specific therapies may be attempted to desensitize the recipient prior to transplantation. This, too, is center and organ specific.
HLA typing. HLA is the term that describes six separate polymorphic genetic loci clustered together in a single area of the human genome and expressed on the lymphocyte that can predict rejection.4
HLA is assessed preoperatively and is used in the allocation of deceased donor kidneys and pancreata. HLA typing is required by UNOS when listing patients as kidney, kidney/pancreas, and pancreas transplant candidates.7
Eurotransplant requirements: “Every potential transplant recipient should be HLA typed on two different occasions using two different samples. Every recipient and every organ donor must be typed for HLA-A, -B, -DR, HLA-C, and -DQ.”8
In other organs, it is considered useful information to predict rejection and is a necessary step in determining crossmatch positivity but may not be performed until the time of transplant.
The increased use of molecular testing to determine HLA can lead to confusion in the setting of recent blood transfusions.
The sensitivity of this method can identify antigens from the transfusion and obscure the HLA.
For that reason, it is best to avoid HLA testing within 72 hours of a blood transfusion.4
Virology screening. Virology screening is performed to determine a patient’s suitability for transplantation and posttransplant infection risk. As a result of their immunosuppressive status, organ transplant recipients are at greater risk for developing more severe viral infections than healthy individuals. Assessment includes
Human immunodeficiency virus (HIV). The initial test for HIV is done by enzyme immunoassay.
Equivocal or positive results are confirmed by Western blot.
Currently, most centers consider the presence of HIV a contraindication to transplantation.
However, with the advent of highly active antiretroviral therapy to treat HIV and the improved survival of HIV-infected individuals, some centers are performing transplants on patients who are HIV positive.9
Hepatitis screening. Hepatitis screening is performed both to determine previous exposure to hepatitis and the need for further testing or treatment for those who may have been infected in the past.
Chronic hepatitis B or C infection is an indication for liver transplantation.
However, any active hepatitis infection is typically a contraindication to the transplantation of other solid organs.
Initial hepatitis screening consists of the convalescent battery (Table 1-1).
To determine candidacy, further testing will be necessary if initial hepatitis B results are positive (Table 1-2).
Patients may need to be referred to a hepatologist to determine appropriate treatment prior to listing for extrahepatic transplantation.
TABLE 1-1 Convalescent Hepatitis Battery for Screening
Positive Results Indicate
Anti-HCV (Hepatitis C antibody)
Exposure to hepatitis C
HBsAg (Hepatitis B surface antigen)
Infection with hepatitis B
HBsAb (Hepatitis B surface antibody)
Immunity to hepatitis B
HBcAb IgG (Hepatitis B core antibody)
Previous hepatitis B infection/exposure
Herpes virus screening.
The herpes family of viruses are the most common disease-causing viral pathogens in the transplant population.12
Knowledge of a patient’s previous exposure and immune status may direct the acceptance of donor organs as well as determine the need for prophylactic therapy.
Cytomegalovirus (CMV) screening. CMV is a member of the Betaherpesvirinae family.
Approximately 80% of adults are exposed to CMV during the first two decades of life either as an asymptomatic infection or as a benign infectious mononucleosis-like syndrome.13
At the time of infection, cell-mediated immune responses develop but do not completely eradicate the virus.
CMV establishes latency and may therefore reactivate later in life.
Historically, up to 85% of SOT recipients who are CMV seronegative and receive an organ from a CMV-seropositive donor develop CMV disease.14
CMV status is established by testing the patient’s blood for the presence of CMV antibodies, specifically immunoglobulin G (IgG).
The CMV status of the recipient and donor will determine the need for, and the length of, prophylactic therapy.15
Epstein-Barr virus (EBV) screening. EBV is a member of the Gammaherpesvirinae family and is acquired in adolescence or early adulthood.
EBV is responsible for the infectious mononucleosis syndrome.
EBV is classified as a group 1 carcinogen and is strongly associated with Burkitt’s lymphoma, nasopharyngeal carcinoma, Hodgkin’s disease, and immunosuppression-related lymphoproliferative disease.16
TABLE 1-2 Hepatitis B Surface Antigen Positive (HBsAg+): Further Testing*
Hepatitis B e antigen (HBeAg)
Hepatitis B e antibody (HBeAb)
Hepatitis B virus DNA (HBV DNA)
Hepatitis B core antibody IgM (HBcAb IgM) = acute hepatitis B or reactivation of virus
*Suggest referral to a hepatologist for further assessment and management of hepatitis.
Posttransplant lymphoproliferative disease can affect both graft and patient survival.
EBV status is established by testing the patient’s blood for the presence of EBV antibodies, specifically IgG.
Herpes simplex type 1 (HSV1) screening. HSV is an Alphaherpesvirinae, which is also acquired in childhood or young adulthood.
Impairment of the immune response as a result of immunosuppression predisposes transplant recipients to reactivation infection.
HSV status is established by testing the patient’s blood for the presence of HSV antibodies, specifically IgG.
Toxoplasma screening. Toxoplasma gondii is a coccidian parasite of the cat population for which humans are intermediate hosts.17
Although a large proportion of the population is infected by Toxoplasma gondii, toxoplasmosis is an uncommon disease.
In immunocompromised individuals, however, toxoplasmosis can be life threatening.
Toxoplasma-negative patients who receive an organ from a donor with prior exposure are at high risk for developing toxoplasmosis after transplantation.
Patients with prior exposure to Toxoplasma gondii are at risk for developing an active infection after transplant.
Toxoplasma status is established by testing the recipient’s blood for the presence of Toxoplasma antibodies, specifically IgG.
Tuberculosis (TB) testing. All patients should be tested for TB.
The most commonly performed test is the purified protein derivative (PPD), an intradermal skin test.
Those patients with a prior TB exposure or those who have been vaccinated with bacille Calmette-Guérin (BCG) may have a positive PPD test. Therefore
A chest radiograph is indicated.
A QuantiFERON Gold test may be indicated.
Consultation by an infectious disease physician is recommended to determine need for treatment in the event of a positive test.
Patients who are extremely ill may be anergic, meaning they cannot respond appropriately to immune stimuli.
Therefore, it is best to apply a control test at the same time as the PPD to determine response.
Candida and mumps are two commonly used PPD controls because most people have been exposed to these two organisms.
Cancer screening. Transplant recipients are at increased risk of developing cancer because of their immunosuppressive regimen.
Any undetected, pre-existing cancer, in the setting of immunosuppressive medications, may become untreatable and lead to the recipient’s death.
Patients should be screened based on
Past medical history (e.g., history of colon polyps, family history of cancer)
History of exposure to carcinogens
Age- and gender-appropriate screening as outlined by the American Cancer Society.18 This includes
Cervical cancer screening for women older than 21 (younger if sexually active), mammography for women older than 40, and colonoscopy for men and women older than 50
Prostate-specific antigen (PSA) blood test and digital rectal examination for men over 50
All candidates should have a chest radiograph performed, although this is a poor method for detecting lung cancer.
Osteoporosis screening. All postmenopausal women, as well as all candidates with a smoking history, chronic corticosteroid use, or cholestatic liver disease, should be assessed for osteopenia or osteoporosis by bone densitometry.
SOT recipients are at increased risk of developing bone loss as a result of the immunosuppressive regimen.19
All abnormal findings should be treated appropriately.
This is an integral part of the pretransplant evaluation process.
The purpose is to assess a patient’s
Appropriateness for transplantation
Ability to give informed consent
Past adherence history
Ability to adhere to the complex postoperative regimen
Social support structure20
Patients are screened for any current and/or past history of substance abuse. Additional laboratory screening may be required to determine if the patient is currently smoking or using illegal drugs or alcohol.
This evaluation is performed by a social worker with input from a psychologist or psychiatrist. Some centers require a psychologist to perform a separate mental health evaluation.
See the chapter on Psychosocial Issues in Transplantation for additional information on this topic.
Pre-, peri-, and postoperative transplant care is expensive. Therefore, private or public insurance is a requisite.
Third-party payors may have their own transplant eligibility criteria and may refer patients to their designated transplant centers of excellence.
In the United States, Medicare (the federally funded program that provides medical insurance for the elderly and disabled) funds transplants only at transplant programs that have been approved by the Centers for Medicare and Medicaid Services (CMS).
Medicaid is a state program; requirements and provisions vary from state to state.
Requirements in countries other than the United States will vary depending on each country’s payment system.
The purpose of the financial evaluation is to determine if the patient has access to sufficient financial resources to facilitate a positive outcome following transplantation.
All patients referred for SOT should undergo a nutritional assessment with a registered dietitian.
This is especially important for patients who are either overweight or underweight or who may have impaired digestion.
This evaluation also includes educating the patient about risks for posttransplant disorders such as immunosuppressant-induced hyperlipidemia or diabetes mellitus (DM) and the need for a heart healthy diet.
The increasing prevalence of nonalcoholic fatty liver disease as an indication for liver transplantation means many patients have features of metabolic syndrome that results in the development of DM.25
Patients may be poor surgical candidates for a variety of reasons such as contraindications identified by pretransplant testing and consultations, as well as anatomic barriers to transplantation, most notably from previous surgeries.
The transplanting surgeon must determine if the intended procedure can be done safely.
Cardiac evaluation. All patients, regardless of age, should have an electrocardiogram.
More extensive testing should be done based on the patient’s medical history and age.26
An echocardiogram should be performed on any patient for extracardiac transplantation who complains of shortness of breath or who has a murmur noted on physical examination.
Patients who are currently smoking or those with a history of coronary artery disease, hypertension, diabetes, or smoking will require a cardiac stress test to evaluate myocardial perfusion.
Exercise stress testing is the most accurate; however, many patients with end-stage organ disease are unable to walk on a treadmill.
In those cases, adenosine, dipyridamole, or dobutamine stress testing is appropriate.
Patients with a positive stress test should be referred to a cardiologist for further evaluation, including cardiac catheterization.
All patients referred for transplantation should have a chest radiograph and oxygen saturation evaluated by pulse oximetry.
In addition, patients with a smoking history or a history of chronic obstructive lung disease should undergo pulmonary function testing.
Any patient with abnormal findings should be referred to a pulmonologist for further evaluation.
Most organ transplant programs require a period of smoking cessation before listing patients who are currently smoking or who have a recent smoking history. Smoking cessation is confirmed by random urine cotinine testing.
Effects of smoking in specific transplant populations
Heart transplant recipients with a smoking history have an increased risk of developing coronary atherosclerosis, graft dysfunction, and loss after transplantation.26
Cigarette smoking has been implicated in a number of adverse outcomes in liver transplant recipients including cardiovascular mortality and an increased incidence of hepatic artery thrombosis.27
Kidney transplant recipients who smoke are at increased risk for cardiovascular events, renal fibrosis, rejection, and malignancy.27
All patients with a history of diabetes, coronary artery disease, claudication, or cerebrovascular accident should undergo Doppler imaging and anklebrachial index testing.
This should include at least bilateral lower extremity and bilateral carotid artery imaging.
Abnormal results may indicate the need for angiography and/or referral to a vascular surgeon.
Patients referred for specific types of SOT may require additional consultations with medical specialists based on clinical findings, test results, and comorbid conditions.
Cardiac transplantation is indicated for patients with end-stage heart failure and advanced congestive heart failure (New York Heart Association Class III to IV) for whom there are no other medical or surgical options to improve quality of life and survival.
The primary indication for heart transplantation has shifted away from an equal distribution between ischemic and nonischemic cardiomyopathy. Currently, the majority (54%) of patients who receive a heart transplant have a diagnosis of nonischemic cardiomyopathy.28
Nonischemic cardiomyopathy includes the diagnoses of
Cardiomyopathy associated with valvular disease or congenital heart disease
Restrictive cardiomyopathies, such as certain infiltrative diseases (amyloidosis, sarcoidosis)
Patients referred for cardiac transplantation will have a thorough evaluation of cardiac function and anatomy to determine if another procedure, such as coronary artery bypass grafting or valve repair/replacement will relieve symptoms and improve quality of life. Patients will also undergo testing to determine the severity of their illness and the urgency for transplantation. These tests include
Cardiac catheterization: Patients referred for cardiac transplantation will require both a right and left heart catheterization.
Right heart catheterization is performed to determine right heart function and degree of pulmonary hypertension.
Severe, fixed pulmonary hypertension (typically pulmonary vascular resistance >5 Wood units or transpulmonary gradient >20) is a contraindication to heart transplantation; therefore, those patients with pulmonary hypertension may require additional therapy to determine if the hypertension can be reversed.
This may include the use of vasodilators, such as oxygen, nitric oxide, nitroglycerin, milrinone (Primacor), nesiritide (Natrecor), or prostaglandin (Flolan) during the catheterization procedure.
Oral pulmonary hypertension therapy may be initiated with the intention to re-evaluate the patient’s hemodynamic parameters to determine if there has been an improvement.29
Once a patient is listed for heart transplantation, right heart pressures should be re-evaluated at regular intervals to detect changes in the patient’s condition as well as to direct therapy.
Coronary angiography, or left heart catheterization, is performed to determine if there are any lesions amenable to intervention that would relieve the patient’s symptoms and obviate the need for transplantation. Angiography need not be repeated unless changes in the patient’s symptoms warrant additional investigation.
Cardiopulmonary exercise testing (CPET) with direct measurement of ventilatory gas exchange provides the most reliable determination of functional capacity in patients with congestive heart failure.30
The test is performed by exercising the patient on either a treadmill or bicycle ergometer using a standard protocol of increasing workload.
During exercise, the patient will breathe through a mouthpiece, which allows for the continuous measurement of gas exchange to determine the patient’s aerobic capacity.
CPET is used to assess progression of disease and determine timing for transplantation as well as to provide an exercise prescription for cardiopulmonary rehabilitation.
Computerized tomography (CT) scanning of the chest may be performed to identify thoracic anatomic abnormalities, especially in patients who have had previous surgery.
Cardiac magnetic resonance imaging (MRI) or positron emission tomography scan: Patients who are being considered for revascularization or ventricular aneurysmectomy may require more extensive testing to determine myocardial viability. Both tests are limited by the patient’s suitability for the procedure (presence of MRI contraindications such as a pacemaker, stent, metal implants in the body) and availability of scanners.
Waiting list criteria for cardiac transplantation vary from country to country.
These criteria play an instrumental role in organ allocation, regardless of location.
Policies for allocation of donor hearts are reviewed by a committee of transplant specialists on a regular basis to ensure equitable distribution. The goal of these policies is to provide suitable donor hearts to individuals with the greatest need and the greatest chance of survival.
Allocation systems are frequently reviewed and revised in order to ensure that the systems are just and make judicious use of a scarce national resource.
For additional information, see the chapter on Heart Transplantation
Lung transplantation is indicated for patients with end-stage pulmonary disease who are sick enough to need a transplant but well enough to survive a transplant.
The most common indications for lung transplantation are non α-1 antitrypsin disease, chronic obstructive pulmonary disease (COPD), interstitial lung disease, bronchiectasis associated with cystic fibrosis, pulmonary hypertension, and COPD associated with α-1 antitrypsin disease.33
As with heart transplantation, there are patients who may benefit from a procedure other than lung transplantation.
Some patients with emphysema may be suitable candidates for lung volume reduction surgery.34 The decision to perform this surgery is based on the results of pulmonary function testing, functional capacity as determined by a 6-minute walk test, quantitative ventilation perfusion scan, and oxygen requirements. Unfortunately, few patients qualify for lung volume reduction surgery.
There is no alternative surgical therapy for patients with end-stage lung disease caused by pulmonary fibrosis, cystic fibrosis, pulmonary hypertension, or connective tissue disorders.
Patients referred for lung transplantation will undergo additional testing. This includes35
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