Author(s): Maricarmen Cruz, MD, Isabel Borras, MD, Juan Carlos Lemos, MD, Fidel Chavez, MD, Francisco Merced, MD
Originally published: May 2, 2016 Last updated: July 11, 2024
Jump to:

Disease/Disorder

Definition

Transplantation medicine involves the surgical addition or transfer of a donated organ for an organ that has failed or is at its end stage. Kidney is the most transplanted major organ, followed by liver, heart, and lung. Organ transplantation is recognized as a treatment option in the end stage of failing organs.

Etiology

Common causes for renal transplantation include diabetes mellitus, chronic glomerulonephritis, polycystic kidney disease, nephrosclerosis, Lupus nephritis and interstitial nephritis. The most common reason for liver transplant is cirrhosis, which can be related to viral diseases such as hepatitis C and B, alcohol abuse, and hepatocellular carcinoma. However, the most common reason for liver transplant in children is biliary atresia.1

Epidemiology

Transplant registries show that transplant candidates and transplant procedures continue increasing, marked by the ceiling of available donors. More than 270,000 kidney transplants have been performed in the United States (US) and about 100,000 individuals are living with a functional kidney transplant. The stronger transplant registries are hold by the US and the United Kingdom (UK). This data shows that kidney, liver and heart represent the highest graft rate, respectively and represent the 98% of US transplants. In contrast, the UK has a low donation rate due to low consent rate among donor survivors. In the US, the pediatric population experiences a high transplant rate, 3-15% of the solid organ transplant population.2,3

The national rate of graft survival five years after first adult deceased donor kidney only transplant is 88%. These rates vary between 76% to 93% depending on the risk-adjustment. The equivalent rate after first pediatric deceased donor kidney only transplant is 86%, ranging from 79% to 100%. The national rate of graft survival five years after first adult living donor kidney only transplant is 93%; the rate varies when the risk is adjusted. The equivalent rate after first pediatric living donor kidney only transplant is 91%, ranging from 85% to 100%. In the US, the post-transplant mean survival for kidney transplants is 22.79 years, and 20.90 years for liver transplants.2,3

In 2021 there were 9,234 liver transplants in the US, 94.6 % in occurring in adults, and 5.4 % in pediatric population. Survival outcomes in adults have changed (decreased) in the first year, contrary to historic trends, and there is a coincidental relation to the onset of COVID-19 in 2020. This is not the case on the long term; post-transplant mortality rate is reported 13.3%, 18.6% and 35.9% at 3,5 and 10 years. The most common cause of failure for a successful transplant is rejection, which is seen in up to one in every three patients, usually within weeks or months after a transplant.4

Patho-anatomy/physiology                 

Once glomerular damage reaches a certain point, the progression of renal disease is irreversible. Tubulointerstitial injury is considered a mediator of kidney disease progression, resulting in the loss of peritubular capillaries, impairing blood flow delivery.5 However, age related kidney function failure, is associated with glomerulosclerosis, interstitial fibrosis, tubular atrophy and vascular sclerosis.6

In chronic liver disease there is permanent scarring of the liver tissue, or cirrhosis, which ends up affecting normal blood flow. The persistent affected circulation into the liver will lead to portal hypertension, and consequent varicosities. Varices break and produce serious bleeding. Blood flow into the liver will affect breakdown of substances leading to accumulation and toxicity.

Once there is significant loss of the liver metabolic and synthetic function, complications such as coagulopathies, metabolic encephalopathy, hemodynamics disturbances and predisposition to infection and systemic inflammations may occur independently or simultaneously. The loss of normal hemostasis and alteration of the coagulation pathways is the result of inadequate synthesis, enhanced consumption of clotting factors and their inhibitors, and platelet abnormalities. Pro-thrombin time is one of the best indicators of changing liver function, and therefore its prophylactic correction is contraindicated in patients who are been considered for liver transplant.7 Acute as well acute-on-chronic liver injury results in impairment of cerebral function that ranges from abnormal mentation, with drowsiness, euphoria and confusion that may progress to deep coma. Other important manifestation of patients with liver failure is the presence of a hyperdynamic circulation that resembles that of septic shock characterized by hypotension due to low systemic vascular resistance with increased cardiac output.

A proinflammatory state is also known to cause multisystem dysfunction that may also trigger injury to the others’ organs systems and not only the primary organ who is been considered for transplantation. Systemic inflammation can be induced by the presence in body fluids of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs).8 As an example, this inflammatory response may trigger a neurohormonal activation leading to intense vasoconstriction that may perpetuate kidney injury secondary to renal hypoperfusion.9

Disease progression

The progression of kidney and liver disease is managed differently.

Liver patients10

New onset/acute: Patients are often critically ill. Supportive measures are key to minimizing complications until an organ is available. Supportive measures include airway protection, management of hepatic encephalopathy, coagulopathy, detection of cerebral edema, and prevention of sepsis.

Chronic:11 A 3-month survival rate is estimated, using the Model for End stage Liver Disease (MELD). The MELD score is used to accurately gauge the severity of liver disease and effectively assess the risk of mortality. It also aids in determining organ allocation priority in patients on waiting list for liver transplant [LT] in the US as well as in other countries around the world. MELD score incorporates the international normalized ratio (INR), serum creatinine, and serum bilirubin.  Given hyponatremia’s role as a marker for the severity of cirrhosis, the MELD Na score was developed with the intention of including sodium as a factor.12 Currently, the average MELD score for a patient undergoing a liver transplant is 20 nationally. As a patient’s MELD score increases, the priority to receive a liver transplant increases. If a patient’s condition improves, and the MELD score decreases, the priority to receive a liver transplant decreases.

Merion and colleagues evaluated the survival benefit of Liver Transplant [LT]. They reported that the benefit of LT at 1 year was highest among those with MELD scores > 18. Recipient mortality was higher among candidates with low MELD scores. For example, for patients with MELD scores between 6 and 11, the risk of mortality was 3.6 times higher by undergoing LT rather than remaining on the waitlist. For MELD 12–14, the risk remained significantly increased. Subsequently, these findings led to a change in allocation policy – an organ would need to be shared within the larger region prior to use for a local candidate with a MELD score <15.13

Pre-Terminal: characterized by recurrent hospitalizations. To decrease morbidity and mortality associated with wait time, the possibility of accepting organs from high risk deceased donors or from living donor allograft is contemplated.

Kidney patients14

The National Kidney Foundation (NKF) has divided chronic kidney disease (CKD) into five stages, using GFR for each stage

1. Normal or high GFR (>90ml/min)
2. Mild CKD (GFR=60-89 ml/min)
3A. Moderate CKD (GFR=45-59 ml/min)
3B. Moderate CKD (GFR=30-44 ml/min)
4. Severe CKD (GFR=15-29 ml/min)
5. End Stage CKD (GFR<15 ml/min)

Albuminuria and eGFR are independently associated with progression to ESRD. Reduced eGFR should be complemented with urinary albumin to predict progression to ESRD.15 As the disease progresses in stages, morbidity and mortality increase, and the patient’s functional status declines. The levels of albumin in urine in healthy people are generally in the range within 0 to 8 mg/dl. Urine samples accumulated over a time frame of 24 hours should not have albumin levels in excess of 150 mg.

Specific secondary or associated conditions and complications16

Complications associated to solid organ transplant vary depending upon the organ transplanted and these may include cardiac, renal, neurologic, infectious, and gastrointestinal, all which may impact morbidity and mortality. Still, rejection is the most common complication and occurs in one in every three people following transplant surgery.17 To prevent the body from rejecting the new organ, immunosuppressants medications are used to suppress the immune response that rejects the foreign tissue. Immunosuppressants in turn can cause hypertension, kidney failure, hyperlipidemia and diabetes. The risk of infection from bacteria and viruses is greatest in the early period after transplant, when immune suppressant dosages are at their highest, making the patient more vulnerable to infection. People with organ transplantations have an increased risk of developing some types of cancers, such as non-melanoma skin cancer, melanoma skin cancer, cervical cancer or post-transplant lymphoproliferative disorder. After a liver transplant, more than one person in every 10 people experiences a problem affecting their biliary tract, such as a bile leak or an obstruction caused by scar tissue in the bile ducts. The ureter can become blocked after a kidney transplant. It can be blocked soon after the transplant, for example by blood clots, or this can happen months or even years later, usually due to scar tissue forming. There is also an increase in acute and chronic kidney injury among this population, despite advances in pre and post-transplant care. Neurologic complications are also commonly seen and include cerebrovascular events, encephalopathy, CNS infection and seizures.17 Overall, complications after transplantation do not seem to vary from center to center nor on the experience of clinicians. The success rate of organ transplantation depends more so on whether the donated organ is from a living or a deceased donor and the medical circumstances of the recipient.16,18

History: Patients who require solid organ transplant have chronic diseases pre-operatively leading to muscle weakness, fatigue, de-conditioning, gait abnormalities, anemia, and cardiopulmonary dysfunction. Sequelae to organ transplant are immobility leading to deconditioning and debility, neurological complications (neuropathies, myopathies), medications side effects and cognitive impairments based on the nature of the disease and its treatment.19

Physical examination: A comprehensive examination should be performed, before and after surgery. Patients that undergo transplantation have associated co-morbidities involving multiple organ systems, due to which impairments will not be limited to the type of transplant performed. Full examination should include: (1) Cardiovascular System for heart rate, blood pressure and auscultation-bruits may indicate renal artery stenosis/A-V malformations (2) Respiratory System for respiratory rate and air exchange. (3) Musculoskeletal System for ROM, joint stability, muscle strength and endurance. (4) Neurological System for mental status, speech/language, cranial nerves, reflexes, sensation, coordination, muscle tone or involuntary movements. (5) Psychiatric exam for behavioral symptoms of anxiety, depression, and suicidal risk. (6) Additionally, the graft site should be palpated for any tenderness, swelling, erythema/warmth, color changes, which may be signs of rejection.20

Clinical functional assessment: Functional evaluation should be performed, and not merely estimated. This includes a comprehensive ADL and IADL evaluation. Deficits and preserved function should be quantified for optimization and/or compensation in order to achieve maximal independence.

Standardized scales assist in evaluation of current status, monitor progress and aid in prognosis. Examples are the 6-minute walk test, Fatigue Severity Scale (FSS), Visual Analog Scale and Systematic Isokinetic. Current literature reports the use of the 6-minute walk test as a submaximal exercise test to measure functional exercise capacity (i.e., the ability to engage in physically demanding activities of daily living) in individuals with a wide variety of characteristics. It is a practical and simple test that can be repeated to determine changes associated with the implementation of an intervention designed to improve functional capacity.21 The FSS scale is a self-reported scale that is easy to administer. The scale has been shown to be both valid and reliable with a variety of populations. It has been shown to have good internal consistency and is sensitive to change in fatigue levels over time.22 In general there are many other instruments available such as the Functional assessment of Cancer Therapy (FACT) scales, its abridge version FACT-G7, Two Minute Step Test, Gait speed, Timed Up and Go.23 Regardless of the tool selected, consistency with its use is crucial for accurate assessment.22

Lab studies24,25,26,27

A thorough evaluation for both transplant donor and recipient prior solid organ transplantation is essential for optimal outcomes. Initial evaluation consists of detailed medical history, including prior infections, immunization status, travel history, exposure to animals or environmental pathogens, toxic habits, sexual practices, among other information in order to create strategies and preventive measures to help quality of life during posttransplant period. In some cases, pre-transplant screening helps to exclude potential deceased donor to avoid donor-derived infections.

Pre-transplant: Organ donors are divided between living donor and deceased donor. Screening for living donors can be completed weeks to months prior the schedule transplantation. For living donors, testing for HBV, HCV and HIV needs to be performed within 28 days prior organ transplantation. In contrast, screening for decease donor it takes hours, and a complete evaluation needs to be done and completed as fast as possible. Variables as cause of death, age, medical conditions and increased risk for transmissible disease are taken into consideration to accept or reject the organs. Screening tests include routine blood tests such as complete blood count (CBC), comprehensive metabolic panel (CMP), coagulation factors, infective pathogens serologic testing and immunologic assessment (ABO, HLA typing, Antibodies to HLA and cross-matching). Some screening tests are recommended based on epidemiologic risk. Transplant candidates or recipients will benefit to receive recommended immunizations prior transplantation. Both donors and recipients viral serologies helps to design pharmacologic prophylaxis or preemptive approach based on risk for reactivation of latent infections.

Post-transplant: After solid organ transplantation, recipients are followed closely weekly or bi-weekly for the firsts 3 months. Frequency of testing will depend on risk for allograft rejection, infection reactivation and doses of immunosuppressive therapy. Routine tests include CBC, CMP, infection testing (BK virus PCR testing only monitoring in kidney transplant), natriuretic peptide test (exclusive for heart transplant), immunosuppressive drug levels, donor specific antibodies and molecular expression testing for detection of rejection of allografts.

Imaging20

Close monitoring of patients after transplant is imperative since most are on complex immunosuppressive agents that will make them more susceptible to infections, cardiovascular complications and in certain cases, malignancy.

Pre-transplant: ECG, CXR, Exercise/pharmacology test, echocardiogram. If indicated consider coronary arteriography, endoscopy/colonoscopy, ultrasound of native kidneys, peripheral arterial doppler, Pulmonary function test, carotid doppler, voiding cystourethrography, and urodynamic pressure flow studies.

Post-transplant: ultrasound to diagnose possible obstruction, fluid collections, abscess, pyelonephritis, and infection, color flow doppler to diagnose possible vascular occlusion or stenosis, bone density scan, CT or MRI as indicated and ultimately biopsy to diagnose graft dysfunction.

Supplemental assessment tools

Selection of an assessment tool has to be based on the outcomes that are to be measured. Good pre-screening instruments include: Psychosocial Assessment of Candidates for Transplantation and the Transplant Evaluation Rating Scale which are useful for identifying areas of particular concern or areas requiring additional information from patients and/or families.28 The health care professional performing the evaluation (e.g., social worker, psychiatrist, psychiatric nurse practitioner) should be knowledgeable of and experienced in the psychosocial aspects of transplantation.29 For functional capacity or mobility, the 6 Minute Walk Test and Timed Up and Go are good choices. Appropriate Quality of life assessment instruments include Medical Outcomes Study Short Form-36 (SF-36). Nutritional evaluation tools include global assessment and mid-upper arm circumference. Imaging studies serve as prognosticators. In kidney transplants, the Nuclear renal scan reflects early renal function and Doppler ultrasonography and Resistive and Pulsatile Index assist in predicting early and long-term outcomes.20 Depending on the pattern of liver test, magnetic resonance imaging, computed tomography, endoscopic retrograde cholangiopancreatography, and sonography may be appropriate in liver transplant recipients.16

Early prediction of outcomes: Several circumstances may be used for early outcome prediction, such as the trend in need of renal replacement therapy after allograft transplantation; urine output creatinine level, especially in the first 6 months after kidney transplantation. For liver, post-operative day one is used to predict morbidity and mortality using serum bilirubin (for morbidity) and aspartate-aminotransferase (AST) (for mortality).

Environmental: Allograft recipients are counsel after transplantation to incorporate life changes strategies to ensure safety with the goal to regain normal function and return to an active and productive life. Simple practices such as washing hands frequently, clean surfaces, keep immunizations updated, avoid exposure to sick contacts, among others are imperative to decrease risk to acquire infections. Patients are advised to protect themselves from sun exposure due to the increased risk of skin cancer. Drinking water should be filtered; raw food is discouraged and avoid consumption of unpasteurized foods. Travel should be halted at least for six months after the transplant and travel to third world countries is discouraged due to immunosuppression and the risk of infections.16 Transplant Centers are incorporating educational information to increase the knowledge of the risk of food, animal exposures, and other environmental exposures for the transplant recipient to stay healthy and prevent hospital admission.

Social role and social support: Demand for solid organ transplantation is higher than the existent capacity. Efforts to increase awareness are necessary to support volunteerism in organ donation. However, there are still ethical issues around having family members approve to donate, even when the donor has already expressed his/her wish.

Professional issues30,31               

There are several professional and ethical dilemmas associated to solid organ donation. Among these are reported (1) the potential disagreements that may exist between the clinical team and the patient/family/non-transplant healthcare providers about the treatment goals and/or intensity of care that will be provided to the recipient (2) decision making about maximizing years before the transplant (3) altruistic donations versus paid living donations, and (4) health equity, among some.32

Another dilemma is the clinical competency in the early identification of brain death which can become a professional issue and this is key for the early preparation of the donor, the donor’s family, and the consequent timely match of the recipient. It is imperative that the physician who determines brain death should not be associated with the transplant team, and he should be consistent with the institutions clinical and ethical standards. Communication is another area that should not be overlooked; patients have the right to receive information and ask questions about the transplant procedure and give voluntary consent. In the setting of directed donation, organs for transplantation should be allocated to recipients on ethically sound criteria (e.g., urgency of need, change in quality of life, likelihood of benefit). Physicians should place candidates on a single waiting list, instead of multiple transplant centers.

Rehabilitation Management and Treatments

Available or current treatment guidelines

Patients who undergo a solid organ transplant are living longer lives making the short- and long-term recovery the most important priority; rehabilitation will play a critical role in this goal, seeking to take these patients to their highest level of function.

The existing clinical guidelines will provide direction on the anticipated morbidity areas that these survivors may encounter throughout their life span, including organ rejection, infections, cardiovascular/renal disease, diabetes, osteoporosis, and cancer, among some. Rehabilitation specialists should take into consideration these potential complications in all stages of care to timely refer and/or a adjust treatment plans.16,33 From the rehabilitation perspective, it is recommended that a functional and medical baseline be established before surgery, which includes mobility status, use of assistive devices, level of independence in activities of daily living, community and household activities, cognition, communication, as well as vocation.34

At different disease stages

Due to the duration of time a patient may be waiting for a donor, physical deconditioning may play a role on the patient’s decremental functional activity. In both end-stage kidney disease and end-stage liver disease, frailty, cardiovascular fitness and sarcopenia will not only influence the patient’s ability to recovered functional abilities but may play a role as well on the post – surgical clinical and functional outcomes and mortality risk.35 Prehabilitation has acquired a critical role previous to the surgical procedure, influencing the patient’s general state and physical condition. Scholarly work has significantly expanded and shows that Prehabilitation protocols can improve physical fitness, exercise capacity, decrease the hospital post operatory length of stay, the educational awareness about the role of conditioning and nutrition, and consequently the patient’s quality of life.36

Adjusted exercise routines and training, even of two weeks duration, before surgical events may improve the patient’s physiologic state. Pre-operative routines can include daily pedometer-based-walking routines, breathing exercises, flexibility training, aerobic training, resistance training, movement of the thorax, warm up and cool downs, and mindfulness activities, among others.36 In general Prehabilitation has shown to improve cardiorespiratory fitness, self-reported physical function and pain.37 Benefits of prehab is stronger for liver than for kidney transplanted patients.38

New onset/acute
Rehabilitation after solid organ transplant starts immediately after surgery, where the initial focus is on maintenance of bodily systems, as well as pulmonary hygiene and chest wall mobility in order to assist with the ventilator/supplemental oxygen weaning process.34 The rehabilitation team must take into consideration that this population has more immediate transfers or readmissions to an acute hospital within the first week of its rehabilitation admission.39

Preventive measures towards complications from immobilization such as contractures, DVT, pulmonary embolism, as well as skin maintenance and preservation of bowel/bladder function are imperative. The use of bedside isometric exercise protocols may help in the prevention of disuse atrophy of major muscle groups.34 Rehabilitation programs include maintaining and improving ROM, transfer/gait training, posture, and pulmonary toileting assuring adequate gas exchange through airway clearance, endurance/activity tolerance and functional mobility.

Patient’s heart rate, rating the perceived excretion, blood pressure, dyspnea index, and signs of fatigue as well as signs suggesting acute rejection should be monitored. In renal patients, acute rejection is often heralded by anorexia, malaise, fever, hypertension, leukocytosis, blood urea nitrogen (BUN) elevation, and enlarged tender kidney.34 In the liver patient, fatigue, fever, dark yellow/orange urine, clay-colored stools, decreased exercise tolerance and abdominal pain/tenderness may occur. Special considerations to have with patients after liver transplant are delayed cognitive recovery, malnutrition, delayed liver function, primary graft nonfunctioning and side effects of immunosuppressive therapy.

Subacute
In the subacute phase, exercise capacity increases significantly to near-normal values for sedentary healthy individuals. Exercise tolerance can be improved through low to moderate intensity exercise and activities of daily living (ADL’s). During this stage, activities are aimed at increasing MET level, improving ADL independence, increasing endurance, and discharge education including home exercise programs. The goal is to continue with progression of exercises to preserve muscle strength/endurance, emphasizing proximal muscles groups to preserve upper and lower extremity function as well as counteracting the effects of corticosteroids and decreased mobility.40

Chronic/stable
Priorities should include restoration of muscle mass and strength, enhancement of aerobic endurance leading to increase in tolerance to functional activities. Even though quality of life on organ survivors persists in the long term, the rehabilitation team should keep in mind common morbidities associated to long term surgical complications or immunosuppression. Other manifestations to monitor are insomnia and neuropathy, which may interfere with rehabilitation efforts. Neuromusculoskeletal complications such as paraparesis, delirium, stroke, peripheral neuropathy, tremors, myopathy, contractures, and osteoporotic should be monitored.34

Pre-terminal or end of life care
At this stage, palliative care will play a critical role in caring for this population with its main goal focused on providing comfort measures and the best quality of life possible. An interdisciplinary approach is used permitting comprehensive conversations between the patient and the treating team that allow improved advanced care planning, symptoms management, lower healthcare utilization, and enhanced patient and caregiver satisfaction.41

Coordination of care              

Transplant teams are composed of interdisciplinary services, including immunologists, internists, nephrologists, hematologists, surgeons, anesthesiologist, and physiatrists, among some. The team helps assess patients, retrieve organs, monitor immunologic status, transplant the new organ, provide immunosuppression, and assure adequate rehabilitation. Other team members may include nurses, physical and occupational therapists, social workers, and respiratory technologists, among others.

Due to the vast number of providers involved, coordination of care is usually carried by a single individual who may assume the role of a transplant coordinator as well. This role is important in facilitating communication between the interdisciplinary team, the patient, and the donor during the whole transplant process. The transplant process includes organ recovery, preservation, and recipient management. After the transplant, care coordinators help the patient adapt and/or transition to their new lifestyle, provide education on what to expect and about preventable medical complications, and assist on the tracking of laboratories and diagnostic studies, for timely actions.42 Care coordination is identified by the Institute of Medicine as core for improved safety and clinical outcomes.43 

Patient & family education

The physiatrist must consider the psychological aspects of each patient and the impact it will have on their quality of life and function, particularly when living with highly impairing chronic disease. Patients and their families may experience confusion and emotional burden associated to waiting for a donor, but in addition, there may be other stressors like loss of roles, loss of work, sexual dysfunction and marital issues among others.44 Emphasis on the underlying functional, medical, socioeconomic, and psychological needs of the patient should be performed.6 Family education is crucial to provide the support needed.

Measurement of Treatment Outcomes including those that are impairment-based, activity participation-based and environmentally based.

Medical outcomes have significantly advanced and improved for patients who undergo a solid organ transplant due to improvements in immunosuppression therapy, diagnostic studies, and the pairing of the donor-recipient match, among some. Costs continue high for this type of care in the United States. 

When liver transplantation is successful the recipient is usually fully rehabilitated, and quality of life is improved.45 Most patients return to a regular lifestyle six months to a year after a successful liver transplant. Programs specialized on organ transplant rehabilitation have shown up to 91% improvement in mobility, and at discharge, over 80% of patients demonstrated improvements in self-care, functional ability, locomotion, communication, and cognition. Beyer et al showed that a liver transplant combined with a supervised post-transplant exercise program improves physical fitness, muscle strength and functional performance in individuals with chronic liver diseases. Additionally, other studies have shown that aerobic exercise training provides improvement in muscle strength, cardiovascular condition, mental health status and overall wellbeing.46

To improve environmental outcomes, patients are recommended to practice frequent handwashing to minimize infections with direct contact pathogens, wear sock and long pants and sleeves in activities in which soil exposure is possible, avoid exposure to large groups in periods of immunosuppression, avoid consumption of unfiltered water, avoid smoking, and to avoid sun exposure, among some.16 Facilities that perform SOT should have specifically designated isolated rooms that use laminar airflow and / or high efficiency filtration systems. Furniture should have smooth nonporous easy to clean surfaces; carpets should be avoided as well as objects that may be prone to collect dust. Routine surveillance of potable water systems in the facilities as well as plumbing fixtures, sink sprouts, showerheads, ice machines and drinking water should be performed as needed.47

Exercise capacity improves soon after successful kidney transplant, with removal of uremia.28 Exercise capacity is measured by maximal oxygen uptake (VO2), improved muscle strength, blood pressure control, and evidence of bone remodeling, which also improve with successful transplantation.48 High frailty scores are associated to lower survival rates. There are objective assessments that could be used to measure frailty and cardiovascular fitness changes like the short physical performance battery (SPPB), activities of daily life (ADL), instrumental ADL (IADL) scales and the 6-minute walk test.35

Translation into Practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills              

Scholarly work in solid organ transplantation continues expanding. As discussed under rehabilitation management, Prehabilitation has greatly expanded evidence-based recommendations using strategies before the transplant that produce clinical improvements that are captured using objectives outcomes measures.

Medical advancements have improved allogenic organ transplanted women to have increased chances of conceiving and carrying a pregnancy to its full term. Still, women seeking to get pregnant after a solid organ transplant should receive contraception counseling since immunosuppressant medications are associated to teratogenicity and because the pregnancy by itself is considered high risk. These pregnancies require close monitoring by a specialized team. In liver recipients, organ failure is fairly uncommon. Some recommendations for this population include daily blood pressure monitoring, close monitoring of graft function, and regular obstetric evaluations among many others.49,50

Cutting Edge/Emerging and Unique Concepts and Practice

Despite advancements in pairing the donor to the recipient, rejection continues being an important complication after the transplant. Investigators discuss the role of preoperative desensitization in kidney transplant candidates and the role of pre-operative monitoring of donor-specific antibodies with the expectation to improve transplantation rate success and patient survival.51 Clinical outcomes don’t show yet the superiority that desensitization may have on recipient patients, yet investigation in this field is active and promising.52,53

Biotechnology is expanding its research in finding opportunities to address the shortage of organs necessary to manage the number of patients in waiting lists. Interestingly, this field is using 3-D printing to create veins, arteries and capillaries that imitate the organ vascular system that permits circulation to a lab-grown organ. Although this technology is not yet ready to be translated to a clinical application, the implications, and possibilities that this path is aspiring is promising to end-stage patients.54,55

Although there is a limited number of randomized controlled trials on exercise interventions after a solid organ transplant, these show that exercise increases VO2 exercise capacity, quadriceps muscle strength and improvements in the diastolic blood pressure when compared to controls, and that exercise should be an essential component of the post-transplant recovery phase.56

Exercise may benefit obese renal transplant patients by incorporatingindividualized physical training using low-impact, low-repetition, resistance-based weight training with two one-hour sessions each week.44 Results showed a 100% adherence to training in the intervention group compared to 25% in control group; also, higher glomerular filtration, greater improvement in quality of life and a higher employment rate in the intervention group. Painter et al., demonstrated that an individualized home program improved peak VO2, muscle strength and self-reported physical functioning.28 Ferreira et al., concluded that exercise training should be offered in the pre- and post-transplant phases for both adult and children.57 

Technology and robotics continue being incorporated. Examples include, antigravity treadmills and weight supported systems for gait retraining and increasing aerobic functional capacity; task oriented arm movements systems and touch screen computer systems which help with visuomotor training, improve hand-eye coordination, upper extremity coordination/movement, problems solving and pose cognitive challenges and visual-vestibular integration.58  Such technology continues evolving, improving, helping or compensating for functions that patients might have lost, therefore promoting independence and the decreasing the need for assistance.

Another unique concept to consider is that of diversity and the need of donors from different ethnic groups. In 2019, 67% of patients waiting over 5 years for an organ where of ethnic or multiracial backgrounds whereas, 67% of those who were solid organ donors were of Caucasian decent.59 Successful organ transplantation depends on a strong tissue match which many times occurs within the same ethnic groups. In addition, health disparities among races places certain groups (i.e.., African America, Hispanics) at a higher risk of subsequently needing a solid organ transplant due to a higher incidence or prevalence of conditions such as hypertension, diabetes, or even inadequate/limited access to healthcare or education in regards to transplant option.

Gaps in the Evidence-Based Knowledge

Randomized controlled trials studying the effects of exercise interventions in the post-transplant period are expanding but still limited. There are opportunities to establish rehabilitation programs using standardized protocols with objective outcome measures.

Potential barriers for such may be lack of funding, shortage of qualified personnel, compliance issues, low volume of patients and insufficient standardized rehabilitation protocols. This in turn causes a gap in allowing research and/or evaluation of transplanted patients’ response to a rehabilitation protocol to improve evidence-based knowledge.

Solid organ transplant was dramatically impacted by the COVID-19 pandemic; it affected transplant donors, candidates, recipients and transplant related research. Factors contributing included decline on trauma death donors, donor screening excluding survivors of SARS-CoV-2 infection, delays in completing a transplant, increments in costs due to diagnostic testing, therapies, resource allocation, admissions and availability of intensive care beds, and patient’s preference, among some. This resulted in decreased numbers of transplants and an increased mortality in the early post-transplant period. There is still a need to create vaccination protocols for this population, and to understand how COVID-19 vaccination can reduce the burden of the infection in post-transplant patients.47,61

References

  1. Definition & Facts of Liver Transplant | NIDDK (nih.gov). National Institute of Diabetes and Digestive and Kidney Diseases. March 2017. Accessed on March 21, 2021. 
  2. Lentine KL et al. OPTN/SRTR 2021 Annual Data Report: kidney. US Department of Health and Human Services.   Kidney (hrsa.gov)
  3. Graham CN, Watson C, Barley A, Stevenson M, Dharnidharka VR. Mean lifetime survival estimates following solid organ transplantation in the US and UK. J of Medical Economics. 2022. 25 (1) 230-237. https://doi.org/10.1080/13696998.2022.2033050
  4. Kwong AJ, Ebel NH, Kim WR, Lake JR, Smith JM, Schladt DP, Schnellinger EM, Handarova D, Weiss S, Cafarella M, Snyder JJ, Israni AK, Kasiske BL. OPTN/SRTR 2021 Annual Data Report: Liver. Am J Transplant. 2023 Feb;23(2 Suppl 1):S178-S263. doi: 10.1016/j.ajt.2023.02.006. PMID: 37132348.
  5. Nangaku M. Mechanisms of Tubulointerstitial Injury in the Kidney: Final Common Pathways to End-stage Renal Failure. Internal Medicine.43 (1): 9-17, 2004.
  6. Anderson S, Halter JB, Hazzard WR, Himmelfarb J, Horne FM, Kaysen GA. Prediction, progression, and outcomes of chronic kidney disease in older adults. Journal of the American Society of Nephrology. 20(1) :1199-1209. June 2009
  7. Pyleris, Emmanouil & Giannikopoulos, G & Dabos, Konstantinos. (2010). Pathophysiology and management of acute liver failure. Annals of Gastroenterology. 23(4), 257-265.
  8. Zaccherini, Giacomo, Weiss, Emmanuel & Moreau, Richard. Acute-on-chronic liver failure: Definitions, pathophysiology and principles of treatment. JHEP Reports, Volume 3, Issue 1, 100176 JHEP Rep. 2021 Feb; 3(1): 100176. doi: 10.1016/j.jhepr.2020.100176
  9. Arroyo V, Moreau R, Jalan R. Acute-on-Chronic Liver Failure. N Engl J Med. 2020 May 28;382(22):2137-2145. doi: 10.1056/NEJMra1914900. PMID: 32459924.
  10. Rudow DL, Goldstein MJ. CS. Critical Care Management of the Liver Transplant Recipient.
  11. Everson, GT. “Hepatic Failure and Liver Transplantation.” Goldman-Cecil Medicine, by Lee Goldman and Andrew I. Schafer, Elsevier, 2020, pp. 998–1004.
  12. Leise MD. A revised model for end-stage liver disease optimizes prediction of mortality among patients awaiting liver transplantation. Gastroenterology, US National Library of Medicine. June 2011.
  13. Asrani SK, Kim WR. Model for End Stage Liver Disease: End of the First Decade. Clin Liver Dis. 2011 November; 15(4): 685–698.
  14. Renal Association Clinical Practice Guideline Development Manual – September 2016.
  15. Hallan SI, Ritz E, Lydersen S, Romundstad S, Kvenild K, Orth SR. Combining GFR and Albuminuria to Classify CKD Improves Prediction of ESRD. Journal of the American Society of Nephrology.20 (5): 1069-1077, 2009.
  16. Lucey MR, Terrault N, Ojo L, Hay JE, Neuberger J, Blumberg E, Teperman LW. Long-Term Management of the Successful Adult Liver Transplant: 2012 Practice Guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. LIVER TRANSPLANTATION 19:3-26, 2013
  17. Sen A, Callisen H, Libricz S, Patel B. Complications of Solid Organ Transplantation. Critical Care Clinics. 2019-01-01. Vol 35 Issue 1, Pages 169-186
  18. Baker RJ, Mark PB, Patel, RK et al. Renal association clinical practice guideline in post-operative care in the kidney transplant recipient. BMC Nephrol 18, 174 (2017). https://doi.org/10.1186/s12882-017-0553-2
  19. VanDen Berg-Emons R, van Ginneken B, Wijffels M, Tilanus H, Metselaar H, Stam MH, Kazemier G. Fatigue Is a Major Problem After Liver Transplantation.
  20. DeLisa’s Physical Medicine & Rehabilitation,Prnciples and practices. Fifth ed, Philadelphia, PA Lippincott Williams & Wilkins 2010:1207-1226
  21. American College of Rheumatology.2015. Available at: http://www.rheumatology.org/I-Am-A/Rheumatologist/Research/Clinician-Researchers/Six-Minute-Walk-Test-SMWT#sthash.po23bnQz.dpuf.
  22. Evidence Based Review of Moderate to Severe Acquired Brain Injury. Fatigue Severity Scale. 2015. Available at: http://www.abiebr.com/set/17-assessment-outcomes-following-acquiredtraumatic-brain-injury/fatigue-severity-scale.
  23. Ramos Emos M, Purewal-Kossack A, Parke S, Cheng J. Functional Measures in Cancer Rehabilitation. PMR Knowledge Now. December 2023.
  24. http://www.uptodate.com/contents/overview-of-care-of-the-adult-kidney-transplant-recipient?source=search_result&search=renal+transplant&selectedTitle=1%7E150. Up to Date Overview of care if the adult kidney transplant recipient. Anil Chadraler, MD. March 29,2015
  25. Malinis M, Boucher HW. Screening of donor and candidate prior to solid organ transplantation. Guidelines from the Amertican Society of Transplantation Infectious Diseases Community of Practice. March 2019.
  26. Avery RK, Michaels MG. Strategies for safe living following solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. March 2019.
  27. Marie Dirix, Ester Philipse, Rowena Vleut, Vera Hartman, Bart Bracke, Thierry Chapelle, Geert Roeyen, Dirk Ysebaert, Gerda Van Beeumen, Erik Snelders, Annick Massart, Katrien Leyssens, Marie M Couttenye, Daniel Abramowicz, Rachel Hellemans, Timing of the pre-transplant workup for renal transplantation: is there room for improvement?, Clinical Kidney Journal, Volume 15, Issue 6, June 2022, Pages 1100–1108, https://doi.org/10.1093/ckj/sfac006
  28.  Painter PL, Hector L, Ray K, et al. A randomized trial of exercise training after renal transplantation, Transplantation 74(1):42-8, 2002.
  29.   Kidney Disease: Improving Global Outcomes (KDIGO) Kidney Transplant Candidate Work Group. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation. 2020;104: S1–S103.
  30. Guidelines for Organ Transplantation. (n.d.). Retrieved March 14, 2021, from https://www.ama-assn.org/delivering-care/ethics/guidelines-organ-transplantation
  31. Informed Consent. (n.d.). Retrieved March 14, 2021, from https://www.ama-assn.org/delivering-care/ethics/informed-consent
  32. Courtwright AM, Erler KS, Bandini JI, Zwirner M, Cremens MC, McCoy TH, Robinson EM, Rubin E. Ethics Consultation for Adult Solid Organ Transplantation Candidates and Recipients: A Single Centre Experience. J Bioeth Inq. 2021 Jul;18(2):291-303. doi: 10.1007/s11673-021-10092-5. Epub 2021 Feb 26. PMID: 33638124; PMCID: PMC7908944.
  33. 2021 AMERICAN SOCIETY OF TRANSPLANTATION. Guidelines for Post-Kidney Transplant Management in the Community Setting | American Society of Transplantation (myast.org)
  34. Braddom RL. Transplantation of Organs: Rehabilitation to Maximize Outcomes. Ed. In Braddom RL, Physical Medicine & Rehabilitation. 4th ed. Philadelphia, PA, Elsevier Saunders, 2011: 1439-1456.
  35. Williams AM, Waits S, Englesbe MJ. The Importance of Prehabilitation in Liver Transplantation Curr Transpl Rep (2015) 2:312–315. DOI 10.1007/s40472-015-0080-7
  36. Quint EE, Ferreira M, van Munster BC, Nieuwenhuijs-Moeke G, Te Velde-Keyzer C, Bakker SJL, Annema C, Mathur S, Pol RA. Prehabilitation in Adult Solid Organ Transplant Candidates. Curr Transplant Rep. 2023;10(2):70-82. doi: 10.1007/s40472-023-00395-4. Epub 2023 Mar 25. PMID: 37124070; PMCID: PMC10039771.
  37. Mitra R. Book: Rehabilitation Medicine, Chapter 86 Rehabilitation of the Organ Transplant Patient by Dorianne R. Feldman; Stephanie Van; Travis Edmiston; R. Samuel Mayer. ISBN: 978-0-07-179333-9
  38. Cheng XS, Myers JN, Chertow GM, Rabkin R, Chan KN, Chen Y, Tan JC. Prehabilitation for kidney transplant candidates: Is it time? Clinical Transplantation. 2017;31:e31020. DOI: 10.1111/ctr.13020
  39. Patcai JT, Disotto-Monastero MP, Gomez M, Adcock LE. Inpatient rehabilitation outcomes in solid organ transplantation: Results of a unique partnership between the rehabilitation hospital and the multi-organ transplant unit in an acute hospital. Open Journal of Therapy and Rehabilitation. Vol.1, No.2, 52-61 (2013) http://dx.doi.org/10.4236/ojtr.2013.12009
  40. Mitchell L. H News. Returning to life after organ transplant rehab. 2009. Available at: http://hospitalnews.com/returning-to-life-after-organ-transplant-rehab.
  41. Wentlandt K, Weiss A, O’Connor E, Kaya E. Palliative and end of life care in solid organ transplantation. Am J Transplant. 2017 Dec;17(12):3008-3019. Doi: 10.1111/ajt.14522. Epub 2017 Nov 15. PMID: 28976070.
  42. Transplant Care Team | Stanford Health Care
  43. Care Coordination | Agency for Healthcare Research and Quality (ahrq.gov)
  44. Engle D. Psychosocial aspects of the organ transplant experience: what has been established and what we need for the future. J Clin Psychol. 2001 Apr;57(4):521-49. Doi: 10.1002/jclp.1027. PMID: 11255205.
  45. Bobel M. Lever Transplants. Advance for Physical Therapy & Rehab Medicine.2001;12(6):33.
  46. National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Care Services; Cooper R, Snair M, Denning LA, editors. Exploring the State of the Science of Solid Organ Transplantation and Disability: Proceedings of a Workshop. Washington (DC): National Academies Press (US); 2021 Jun 30. 5, Treatments, Technologies, and Interventions Affecting Function After Transplantation. Available from: https://www.ncbi.nlm.nih.gov/books/NBK573862/
  47. Banach DB, Seville MTA, Kusne S. Infection Prevention and Control Issues After Solid Organ Transplantation. Transplant Infections. 2016 Feb 15:843–67. doi: 10.1007/978-3-319-28797-3_46. PMCID: PMC7123530
  48. Kempeneers G, Myburgh KH, Wiggins T, Adams B, vanZyl-Smith R, Noakes TD. Skeletal muscle factors limiting exercise tolerance of renal transplant patients: effects of a graded exercise training program. Am J Kidney Dis 1990; 14: 57
  49. Ahmad M. Pregnancy After Transplantation. Pregnancy After Transplantation: Practice Essentials, Overview, Important Points to be Considered in Female Transplant Recipients (medscape.com)
  50. Al-Badri M, Kling JM, Vegunta S. Reproductive planning for women after solid organ transplant. Cleveland Clinic J of Medicine. Vol 84; No 9, Sept. 2017. doi:10.3949/ccjm.84a.16116
  51. Thongprayoon C, Kaewput W, Pattharanitima P, Cheungpasitporn W. Progress and Recent advances in solid organ transplantation. . Clin. Med. 2022, 11, 2112. https://doi.org/10.3390/jcm11082112 https://www.mdpi.com/journal/jcm
  52. Sinangil A, Ucar ZA, Koc Y, Barlas S, Abouzahir S, Ecder ST, Akin EB. Outcome of Desensitization Therapy in Immunologically High-Risk Kidney Transplantation: Single-Center Experience. Transplant Proc. 2019 Sep;51(7):2268-2273. doi: 10.1016/j.transproceed.2019.04.068. Epub 2019 Jul 26. PMID: 31358450.
  53.  DD Kuppachi S, Axelrod DA. Desensitization strategies: is it worth it? Transpl Int. 2020 Mar;33(3):251-259. doi: 10.1111/tri.13532. Epub 2020 Feb 5. PMID: 31553805.
  54. Nelson J. Revolutionizing organ transplant with 3D bioprinting: a new technique using ice moulds. Medriva. February 2024.
  55. Song D, Xu Y, Liu S, Wen L, Wang X. Progress of 3D Bioprinting in Organ Manufacturing. Polymers (Basel). 2021 Sep 18;13(18):3178. doi: 10.3390/polym13183178. PMID: 34578079; PMCID: PMC8468820.
  56. Janaudis-Ferreira, T., Tansey, C.M., Mathur, S., Blydt-Hansen, T., Lamoureaux, J., Räkel, A., de Sousa Maia, N.P., Bussières, A., Ahmed, S. and Boruff, J. (2021), The effects of exercise training in adult solid organ transplant recipients: A systematic review and meta-analysis. Transpl Int, 34: 801-824. https://doi.org/10.1111/tri.13848
  57. Janaudis-Ferreira T, Mathur S, Deliva R, Howes N, Patterson C, Räkel A, So S, Wickerson L, White M, Avitzur Y, Johnston O, Heywood N, Singh S, Holdsworth S. Exercise for Solid Organ Transplant Candidates and Recipients: A Joint Position Statement of the Canadian Society of Transplantation and CAN-RESTORE.. Transplantation: September 2019 – Volume 103 – Issue 9 – p e220-e238doi: 10.1097/TP.0000000000002806
  58. https://www.upmc.com/services/rehab/rehab-institute/conditions/transplant
  59. https://connect.mayoclinic.org/page/transplant/newsfeed-post/the-important-of-diversity-among-organ-donors/#
  60. Azzi Y, Bartash R, Scalea J, Loarte-Campos P, Akalin E. COVID-19 and Solid Organ Transplantation: A Review Article. Transplantation: January 2021 – Volume 105 – Issue 1 – p 37-55 doi: 10.1097/TP.0000000000003523
  61. Danziger-Isakov L, Blumberg EA, Manuel O, Sester M. Impact of COVID-19 in solid organ transplant recipients. Am J Transplant. 2021 Mar;21(3):925-937. doi: 10.1111/ajt.16449. Epub 2021 Feb 26. PMID: 33319449; PMCID: PMC9800718

Original Version of the Topic

Isabel Borras-Fernandez, MD, Maricarmen Cruz, MD, Brenda Castillo, MD, Nataly Montes, MD. Solid Organ Transplant Rehabilitation. 5/2/2016

Previous Revision(s) of the Topic

Maricarmen Cruz, MD, Isabel Borras-Fernandez, MD, Francisco Merced-Ortiz, MD, Carolina Diaz, MD, Juan Vazquez-Fuster, MD. Solid Organ Transplant Rehabilitation. 6/8/2021

Author Disclosure

Maricarmen Cruz, MD
Nothing to Disclose

Isabel Borras, MD
Nothing to Disclose

Juan Carlos Lemos, MD
Nothing to Disclose

Fidel Chavez, MD
Nothing to Disclose

Francisco Merced, MD
Nothing to Disclose