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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5258_Библиотеки_им_академика_М_И_Перельмана.pdf
5© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2025
C. J. Wong (ed.), Primary Care of the Solid Organ Transplant Recipient,
https://doi.org/10.1007/978-3-031-98076-3_2
Chapter 2
Overview ofSolid Organ Transplantation
forPrimary Care Providers
DianaZhong andChristopherJ.Wong
2.1 Introduction
Solid organ transplantation is increasing in prevalence. With each passing year, it
becomes more likely that primary care providers will encounter patients who are
recipients of a solid organ transplant.
In the USA, the number of solid organ transplantations has risen steadily over the
past 20years (Fig.2.1), with 46,629 solid organ transplants performed in 2023 [1].
Remarkably, this overall increase has continued despite a small decrease in 2020
due to the COVID-19 pandemic. The number of deceased donors has been increas-
ing, including donors from circulatory death (as distinguished from brain death) [2].
The greatest increases have been in liver and kidney transplants (Fig.2.2). As the
actuarial survival has also increased over this period of time, so too has the overall
prevalence of living solid organ transplant recipients. The United Network for
Organ Sharing (UNOS) estimated that there were over 400,000 surviving organ
transplant recipients alive in the USA in 2022 [3], the majority of whom are kidney
transplant recipients (approximately 245,000in 2021) [4] and liver transplant recip-
ients (approximately 99,000in 2020) [5].
In addition to post-transplant patients, primary care doctors will likely care for
patients with end-organ disease in the pre-transplantation stage. As of September
2024, over 104,164 candidates were on the U.S. waiting list for all organ
D. Zhong
Division of Infectious Disease, School of Medicine, University of Pittsburgh,
Pittsburgh, PA, USA
e-mail: zhongdz@upmc.edu
C. J. Wong (
*)
Division of General Internal Medicine, Department of Medicine, University of Washington,
Seattle, WA, USA
e-mail: cjwong@uw.edu
6
0
5,000
10,0 00
15,0 00
20,0 00
25,0 00
30,0 00
35,0 00
40,0 00
45,0 00
50,0 00
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
2015
2016
2017
2018
2019
2020
2021
2022
2023
Fig. 2.1 Number of solid organ transplant recipients per year in the USA, 1988–2023. Based on
OPTN data from 2024, from https://optn.transplant.hrsa.gov/data/view- data- reports/national-
data/. Accessed 4 August 2024
transplants, with 89,937 awaiting kidney transplants. In 2023, over 70,000 patients
were added to the waiting list, a number that has increased steadily over time [6].
Internationally, transplantation is also increasing since the decrease in 2020 due
to the COVID-19 pandemic, with 173,785 solid organ transplants performed in
2023 [7].
There have been notable trends in organ transplantation over the past sev-
eral years:
• Age is no longer a contraindication to receive a solid organ transplant at many
transplant centers [8, 9], although practices vary by country. In the USA in 2023,
23.8% of transplants were received by recipients age 65 and over [1].
• In the USA, allocation criteria for potential transplant recipients continue to be
rened. There have been numerous recommendations for ways to reduce dispari-
ties associated with race, ethnicity, intellectual capacity, immigration status, and
geography [10].
• Criteria for donor assessment have also evolved. Donors with higher-risk condi-
tions such as age, medical comorbidities, and chronic infections have been used
successfully [11]. Using higher-risk donors has been driven by two factors: the
need for transplantation continues to outpace the supply of organs, and medical
advances have allowed mitigation of medical risks (for example, the use of
organs from donors who have hepatitis C as well as HIV-positive donors to HIV-
D. Zhong and C. J. Wong
7
0
5,000
10,000
15,000
20,000
25,000
30,000
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
2015
2016
2017
2018
2019
2020
2021
2022
2023
Kidney Liver Heart Lung
Fig. 2.2 Solid Organ Transplantation in the USA, by Organ, 1988–2023. Kidney-pancreas, pan-
creas, heart-lung, intestine, and other solid organ transplantation data not shown. Based on OPTN
data from 2024, from
https://optn.transplant.hrsa.gov/data/view- data- reports/national- data/.
Accessed 4 August 2024
positive recipients). Some transplantation experts have also advocated for the use
of continuous risk scores (such as the kidney donor prole index (KDPI) for
kidney transplant donor assessment) rather than dichotomous and potentially
stigmatizing terms such as “expanded criteria” donors.
There are many implications of the high prevalence of surviving solid organ
transplant recipients for the practice of primary care. First, the high volume of solid
organ transplant recipients will likely lead to more primary, urgent, and emergent
medical care taking place outside of a transplant center. The approximately 248
transplant centers in the USA who are members of the Organ Procurement &
Transplantation Network (OPTN) [12] are unlikely to be able to provide complete
primary care to the over 400,000 living transplant recipients in addition to the grow-
ing pre-transplant population. Second, patients often live far from their transplant
center, making it imperative to have effective local care. Most data regarding patient
geography are derived from the pre-transplant population—assuming that the
majority of patients do not move permanently closer to the transplant center after
2 Overview ofSolid Organ Transplantation forPrimary Care Providers
8
transplantation, then there is ample evidence that patients often live far from their
transplant centers. In the United Kingdom, the median distance to the transplant
center for liver transplant recipients was 67km [13]. In the United States, a study of
patients in the Veterans Affairs system found that the vast majority of pre-liver
transplant candidates resided over 100 miles from a transplant center [14]. In
another study of patients in the United States listed for liver transplant, 28% lived
over 100miles from the transplant center [15]. A study of lung transplant recipients
found a median distance of 70miles to a patient’s transplant center [16]. Kidney
transplant recipients may live a shorter distance to their transplant center (median
30km in a Canadian study, 23miles in a United States study), but there has also
been shown to be a wide range of travel distance [17, 18]. Third, removal of age
requirements and improved overall survival are resulting in an increasingly older
population of solid organ transplant recipients. The general practitioner, experi-
enced in the comorbidities of aging, is well-suited to provide care for these patients.
2.2 Pre-transplant Evaluation
2.2.1 Overview
While this book focuses on the primary care of patients after receiving a solid organ
transplant, knowledge of the pre-transplant process is useful to provide context to
their ongoing treatment.
The pre-transplant process begins when a patient with end-stage organ failure is
referred to a transplant specialist. This referral may arise from outpatient primary or
specialty care or during an acute-care hospitalization. Pre-transplant testing can
take place in a variety of settings, including outpatient clinics (not necessarily only
in the transplant center) and inpatient hospital stays.
The transplant team typically includes a medical and surgical team (for example,
both a transplant hepatologist and a transplant surgeon, in the case of end-stage liver
disease) as well as a social worker and other team members to assess social support
and psychological health. Other specialists, such as an infectious disease specialist,
psychiatrist, dietician, cardiologist, and/or pulmonologist, may be involved depend-
ing on the patient’s needs and comorbidities. Testing generally includes laboratory
studies, assessment of cardiac tolerance for surgery (other than for heart transplant),
and cancer screening. Treatment often includes vaccinations and medication adjust-
ments for medical optimization. The workup required for each patient is dependent
on the transplant center, the extent of illness, the urgency of transplant, the affected
organ(s), and the individual patient’s needs.
If no contraindications are discovered in the initial assessment, a transplant com-
mittee then evaluates a patient’s candidacy for transplantation. The evaluation
encompasses many factors, including the indication for transplant, medical comor-
bidities, results of medical testing, suitability for major surgery, psychiatric evalua-
tion, and psychosocial considerations. If a patient is accepted as a candidate for
transplantation, the patient is most commonly placed on a waiting list.
D. Zhong and C. J. Wong
9
Table 2.1
Pre-transplant
evaluation
History and exam
Laboratory testing
Functional status
Nutrition and body mass index
Bone density
Cardiopulmonary assessment
Dental evaluation
Family planning (if applicable)
Infection screening
Immunizations
Cancer screening
Surgical evaluation
Psychosocial evaluation
The transplant evaluation and candidate selection process vary depending on
the transplant center, organ(s) affected, the patient’s underlying disease, and many
other individual patient factors. The information provided here is not intended to
be comprehensive; rather, it will hopefully serve as an overview of the process for
the primary care provider who is taking care of a patient either pre- or
post-transplantation.
Components of the typical pre-transplant evaluation are summarized in Table2.1.
2.2.2 History andExamination
The initial pre-transplant medical evaluation will include a detailed history and
physical examination. Active or chronic medical conditions are treated and opti-
mized prior to transplantation. Severe medical conditions may be contraindications
to transplantation, including untreatable signicant dysfunction of another major
organ system (unless combined organ transplantation can be performed), uncor-
rected atherosclerotic disease with end-organ ischemia or coronary disease not ame-
nable to revascularization, and other severe and uncorrectable diseases that may
lead to a signicantly shortened life expectancy [19, 20].
2.2.3 Laboratory Testing
Typical laboratory testing is given in Table 2.2. In addition to routine testing,
patients are evaluated for their risk of prior sensitization, including whether they
have a history of blood or platelet transfusions, pregnancies, pregnancy termina-
tions, or previous transplants [19]. Patients are screened prior to transplant to help
identify and treat active infections pre-transplant, to recognize infectious risks
2 Overview ofSolid Organ Transplantation forPrimary Care Providers
10
Table 2.2
Typical pre-transplant laboratory tests
Routine tests [19, 21, 22]
• Complete blood count
• Kidney function, electrolytes, glucose
• Liver function panel
• Coagulation studies
• Urinalysis and urine culture
• Pregnancy test (if applicable)
• Urine drug screen
Compatibility tests [19]
• ABO-Rh blood type
• Human leukocyte antigen (HLA) type
• Panel reactive antibody assay (PRA)
• Crossmatching
Infectious disease tests [23]
• Human immunodeciency virus (HIV): HIV antibody/antigen screening
• Cytomegalovirus (CMV): CMV IgG
• Hepatitis B virus (HBV): HBV surface antigen (HBsAg), HBV core antibody (HBcAb-IgM
and IgG, or total core antibody), HBV surface antibody (HBsAb)
• Hepatitis C virus (HCV): HCV antibody, HCV nucleic acid amplication testing (NAAT)
• Epstein-Barr virus (EBV): EBV antibody (EBV viral capsid antigen IgG, IgM)
• Toxoplasma gondii: Toxoplasma IgG antibody
• Syphilis: Methodology varies by institution (treponemal, non-treponemal)
• Tuberculosis: Puried protein derivative (PPD) or interferon gamma release assay (IGRA)
• Additional testing as indicated by exposures and risk factors (e.g., Strongyloides, HTLV-I,
HTLV-II, latent bacterial and fungal colonization and infection when applicable)
This list is meant for general education; testing will vary by transplant center and by an individual
patient’s needs
including latent infections, and to help prevent and manage post-transplant infec-
tions [23]. Additional testing may be specic to the organ(s) being transplanted or
to individual transplant centers.
2.2.4 Cardiopulmonary Screening
Screening is performed to evaluate for many cardiopulmonary conditions, including
coronary artery disease, cardiomyopathy, heart failure, pulmonary hypertension,
cardiac arrhythmias, valvular heart disease, and congenital heart disease [24].
Testing may vary by center, organ transplanted, and a patient’s individual clinical
features. Examples of cardiopulmonary testing are given in Table2.3.
2.2.5 Functional Status, Nutrition, andBone Density
Impaired functional status with limited rehabilitation potential may be a contraindi-
cation to transplantation. A patient’s frailty can be assessed by whether they need
assistance with activities of daily living (ADL), the sit-to-stand test, as well as
D. Zhong and C. J. Wong
11
Table 2.3
Pre-transplant cardiopulmonary screening tests
Most patients [25]
• Chest radiography (X-ray)
• Electrocardiogram (ECG)
Depending on age and comorbidities, many patients will undergo further evaluation [25]
• Transthoracic echocardiogram (TTE)
• Cardiac stress testing
• Coronary angiography (if abnormal stress testing or echocardiogram)
Other testing considered may include [24]
• Cardiopulmonary exercise testing (CPET)
• 6-min walk test (6 MWT)
• Noninvasive coronary CT angiography (CCTA)
• Coronary artery calcium (CAC) score
• Right heart catheterization
Some patients may have additional pulmonary evaluation [21]
• Pulmonary function tests (PFTs)
• Chest computed tomography (CT) scanning
This list is an overview; testing for an individual patient will vary by transplant center and
patient factors
whether they have unintentional weight loss and low physical activity [26]. Older
age is not a contraindication by itself, but is considered in the context of a patient’s
functional status and comorbidities [27].
Body composition: Obesity can be a contraindication to transplantation due to
concern for worse outcomes, especially for lung and heart transplant recipients,
although data vary by series and BMI cutoff [28]. Historic body mass index (BMI)
cutoffs for transplantation include ≥35kg/m
2
for heart and lung transplant candi-
dacy and BMI ≥40kg/m
2
for liver transplant candidacy. However, transplant cen-
ters have begun to reassess how best to optimize transplant candidates who have
obesity, including changing the BMI cutoff and using other body composition met-
rics rather than BMI, especially for kidney transplantation [29–31]. Furthermore,
transplant centers and primary care providers can work with patients to meet body
composition requirements for transplantation, including referral to multidisci-
plinary weight loss programs. Conversely, malnourished patients are usually con-
sidered poor candidates and transplant teams work to optimize nutrition prior to
transplantation [20, 21].
Most patients will have bone densitometry measured with dual-energy X-ray
absorptiometry (DEXA). As patients will take chronic glucocorticoids post-
transplantation, having baseline data is helpful for follow-up testing and manage-
ment (see Chap. 11) [21].
2.2.6 Dental Evaluation
A dental evaluation is performed to evaluate for dental abscesses, dental caries, buried
roots, and gum disease. Dental problems can be a source of post-transplant infection.
Dental procedures are performed prior to transplantation whenever possible [21].
2 Overview ofSolid Organ Transplantation forPrimary Care Providers
12
2.2.7 Family Planning
Pregnancy in the rst 12months following transplantation is associated with both
an increased risk of preterm delivery as well as graft dysfunction or rejection. It is
therefore recommended to avoid pregnancy in the rst year after transplantation
[32]. A patient’s family planning goals should be addressed prior to transplantation,
including contraception. Intrauterine devices (IUD) are a preferred and effective
method of long-acting reversible contraception that will avoid interactions with
medications—if placed, identifying the type of IUD and date of implantation is
needed for future management.
2.2.8 Organ-Specic Testing
Further organ-specic testing is performed in conjunction with specialist consultation.
While all such testing is not necessary to review in primary care post- transplantation,
especially if no longer relevant (e.g., the organ is removed), some tests may be helpful
for future management. For example, a patient with end-stage liver disease will likely
have had esophagogastroduodenoscopy (EGD) performed to evaluate for esophageal
varices—having the results of these evaluations may be useful for comparison if a repeat
EGD is needed. Sometimes the workup for organ failure may uncover other syndromes
that should be followed. For example, a monoclonal gammopathy may be identied
during workup for chronic kidney disease; even if it was not the underlying etiology for
the patient’s kidney disease, it will still need to be followed post-transplantation. Finally,
the explanted organ pathology may sometimes be useful. For example, a heart transplant
recipient may have had negative biopsies but on explant the nding of non-caseating
granulomas may suggest sarcoidosis, a condition which could arise in other organs after
transplantation.
2.2.9 Vaccines andPre-transplant Prophylaxis
In most cases, the transplant team will ensure that patients are as up to date as pos-
sible on vaccines prior to transplant [33]. Both inactivated and live-attenuated vac-
cines can be given to patients pre-transplant. However, live vaccines are usually
contraindicated post-transplant due to the risk of disseminated infection.
Additionally, vaccines have variable immunogenicity after transplant due to immu-
nosuppression and thus may be less effective. Therefore, the pre-transplant window
is a crucial time for most vaccines to be administered, ideally earlier in a patient’s
disease course as immunogenicity can also decline due to the relative immunocom-
promise from organ failure. It is recommended that live vaccines be administered by
≥4weeks prior to immunosuppression, and that inactivated vaccines be adminis-
tered ≥2weeks prior to immunosuppression [33, 34]. All vaccines that are appropri-
ate for age, exposure history, and immune status should be administered prior to
D. Zhong and C. J. Wong
13
transplantation according to the Centers for Disease Control (CDC) guidelines. In
addition to the usual vaccine schedule, there are further recommendations for
patients awaiting solid organ transplantation, which include hepatitis A, herpes zos-
ter, and pneumococcal vaccination, as given in Table2.4 [34]. If a patient is unable
to receive vaccinations prior to transplantation, an infectious disease specialist will
typically assist with post-transplant vaccination decisions. (For post-transplant
guidelines, see Chap. 14).
Table 2.4 Typical vaccination recommendations prior to solid organ transplantation
a
Vaccine Type
Evaluate for
serologic
response? Notes
Inuenza inactivated
(IIV)
Inactivated No High-dose formulation often used
Inuenza live-
attenuated (LAIV)
Live-attenuated No Intranasal vaccine
Hepatitis B Inactivated Yes Various formulations (2-dose, 3-dose,
or 4-dose series)
Hepatitis A Inactivated Sometimes Sometimes given in combined
formulation with hepatitis B vaccine
Tetanus Inactivated No
Pertussis (Tdap) Inactivated No If no tetanus booster in the past
10years, administer Tdap. At least
one dose of acellular pertussis should
be given in adulthood, especially
women of child-bearing age and
individuals in contact with infants
Inactivated polio Inactivated No
H. inuenzae type B Inactivated Yes
S. pneumoniae Inactivated No Conjugated vaccine, generally PCV20
or PCV21
Dosing schedules are complex
depending on prior immunization—
see reference or consult with local
infectious disease experts [35]
Human papilloma
virus (HPV)
Inactivated No Indicated for age 9–45years
Measles, mumps,
rubella (MMR)
Live-attenuated Yes
Varicella (VAR or
Varivax
®
)
Live-attenuated Yes Given if not immune
Herpes zoster
(recombinant zoster
vaccine, RZV or
Shringrix
®
)
Inactivated No Recommended for patients ≥50years
old. This is generally the preferred
form of zoster vaccination due to its
higher efcacy as compared with the
live-attenuated vaccine, and because it
is inactivated it will not delay
transplantation
(continued)
2 Overview ofSolid Organ Transplantation forPrimary Care Providers
14
Table 2.4
(continued)
Vaccine Type
Evaluate for
serologic
response? Notes
Herpes zoster (live
zoster vaccine, LZV or
Zostavax
®
)
Live-attenuated No Two doses should be administered
≥3months apart, while considering
that live vaccines should be given
≥4weeks prior to transplant [33]
Coronavirus disease
2019 (COVID-19)
(SPIKEVAX
®
,
COMIRNATY
®
,
Novavax Covid-19
vaccine)
mRNA
(SPIKEVAX
®
,
COMIRNATY
®
)
or protein
subunit
(Novavax)
No Recommended for everyone 6months
of age or older, especially for those
with highest risk of severe COVID-19
(including those 65years and older
and with medical comorbidities) [36]
Respiratory syncytial
virus (RSV) (Arexvy
®
,
mResvia
®
, Abrysvo
®
)
Recombinant
antigen
(Arexvy
®
and
Abrysvo
®
) or
mRNA vaccine
(Mresvia
®
)
No Recommended for all adults aged
75years and older, and for adults aged
60–74years with increased risk of
severe RSV (including those with risk
factors such as chronic lung or heart
disease)
a
Recommendations change and should be reassessed periodically
Less common vaccines that may have been given prior to transplant include
meningococcus, BCG, smallpox, anthrax, rabies, yellow fever, Japanese encephali-
tis, typhoid, and cholera, depending on a patient’s exposures and travel [34].
2.2.10 Infections
Transplant candidates are assessed for past infections and a detailed exposure his-
tory (travel, residence, occupation, lifestyle, animal, and environmental) [23]. In
addition to the routine laboratory testing given in Table2.2, further testing may be
performed for patients with certain exposures or from endemic areas, including
assessment for Strongyloides, Trypanosoma cruzi, and Coccidioides species [23,
37]. A rigorous separate screening process is used for potential organ donors.
Well-controlled HIV infection does not preclude receiving transplantation [38].
Patients with hepatitis B and chronic hepatitis C can still be considered for trans-
plantation but are evaluated for liver cirrhosis and considered for antiviral treatment
prior to transplant [20, 27].
Viral serologies such as CMV and EBV testing can be used to guide donor selec-
tion and to stratify risk. Transplant recipients who are CMV seronegative are at
higher risk for CMV infection if the donor is CMV seropositive; similarly, recipi-
ents who are EBV seronegative are at higher risk for EBV infection and post-
transplant lymphoproliferative disorder (PTLD) if the donor is EBV seropositive
(see Chap. 10). These situations require additional post-transplant monitoring and
prevention strategies [23].
D. Zhong and C. J. Wong