Solid Organ Transplant Rehabilitation

Author(s): Isabel Borras-Fernandez, MD, Maricarmen Cruz, MD, Brenda Castillo, MD, Nataly Montes, MD

Originally published:05/02/2016

Last updated:05/02/2016

1. DISEASE/DISORDER

Definition

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

Etiology

Common causes for renal transplantation include diabetes mellitus, chronic glomerulonephritis, polycystic kidney disease, nephrosclerosis, Lupus 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 atresia1.

Epidemiology

More than 250,000 kidney transplants have been performed in the U.S. and about 100,000 individuals are living with a functional kidney transplant. One-year survival is 92% for first time recipients of deceased donor transplants and 96% for living donor transplants. Five-year survival is 70% and 83% respectively.

Six thousand liver transplants are performed annually in the U.S.; approximately 17% of listed patients die annually while waiting for transplantation. Liver transplant patients have approximately 90% one-year survival rate for both deceased and living donor. Patients who receive a liver from a living donor have higher survival rates with the five-year survival rate being 78% and 71% for deceased donor recipients2. 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 transplant3.

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 delivery4. However, age related kidney function failure, is associated with glomerulosclerosis, interstitial fibrosis, tubular atrophy and vascular sclerosis5.

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. Regardless of the etiology, impaired blood flow delivery is the leading cause of organ damage both in kidney and liver failure.

Disease Progression

The progression of kidney and liver disease is managed differently.

Liver patients6:

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

Chronic: A 3-month survival rate is estimated, using the Model for End stage Liver Disease (MELD). The MELD score has the ability to accurately gauge the severity of liver disease and effectively assess the risk of mortality. It also helps 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 three incorporates the international normalized ratio (INR), serum creatinine, and serum bilirubin. The four MELD levels are: greater than or equal to 25, 24-19, 18-11 and less than or equal to 10. 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 decreases7.

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 an MELD score < 15. 8

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 patients9:

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 ESRD10. 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 complications:

Rejection is the most common complication, and occurs in one in every three people following transplant surgery. 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.  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 recipient11,12.

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 treatment13.

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; which may be signs of rejection13,14,15.

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 capacity16. 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. Regardless of the tool selected, consistency with its use is crucial for accurate assessment17.

Lab studies18:

Pre-transplant: Chemistries, LFT, CBC, coagulation profile, infectious profile (Hepatitis B and C, EBV, CMV and Varicella Zoster serology, RPR, HIV, PPD skin test), and immunologic (ABO, HLA typing, Antibodies to HLA, cross-matching).

Post-transplant: HbA1c, Vitamin D, PTH, Urinalysis/protein to creatinine ratio, CBC, CMP/eGFR, LFT, immunosuppressive agent levels, CPK, INR and cultures.

Imaging15:

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 families19. 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 outcomes15.

Early prediction of outcomes: Several things may be used for early outcome prediction, such as the trend in 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: 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. 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 infections1.

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 issues:

Clinical competency in the early identification of brain death is key for early preparation of the donor, the donor’s family, and the consequent timely match of the recipient.

2. REHABILITATION MANAGEMENT AND TREATMENTS

Available or current treatment guidelines

Because transplant rehabilitation is a relatively nascent field, the literature outlining the principles of transplant rehabilitation is scarce. However, generalized guidelines for solid organ transplantation have been studied and discussed in the past. 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, vocation20.

At different disease stages

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 process20,21.

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 groups20. Rehabilitation programs include maintaining/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 kidney20.  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 21.

Subacute
In the subacute phase, exercise capacity increases significantly to near-normal values for sedentary healthy individuals22. Exercise tolerance can be improved through low to moderate intensity exercise and activities of daily living (ADL’s). For kidney transplants, treatment with recombinant human erythropoietin may be useful23. 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 mobility24.

Chronic/stable
Priorities should include restoration of muscle mass and strength, enhancement of aerobic endurance leading to increase in tolerance to functional activities20. The rehabilitation team should monitor for adverse effects of immunosuppressive medications, such as 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 monitored20.

Pre-terminal or end of life care
The main goal of this stage is to provide comfort measures and the best quality of life possible. Pain management is crucial as well as preservation of function.

Coordination of care

An interdisciplinary multi-organ transplant team of physicians include immunologists, internists, nephrologists, hematologists, surgeons and physiatrists, who work to assess patients, retrieve organs, monitor immunologic status, provide immunosuppression, and assure adequate rehabilitation. Designated nurses, physical and occupational therapists, social workers and respiratory technologists also care for these patients24.

Patient & family education

The physiatrist must consider the psychological status of each patient and the impact that the impairment will have on their quality of life and function.  Emphasis on the underlying functional, medical, socioeconomic, and psychological needs of the patient should be done25. 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.

When liver transplantation is successful the recipient is usually fully rehabilitated. Most patients return to a regular lifestyle six months to a year after a successful liver transplant. Eating a healthy diet, exercising regularly, and taking recommended medications are important factors to staying healthy. Nearly 90% of liver transplant patients are alive at one year after their transplant having resumed their normal activities without any restrictions and nearly 75% are alive five years after their transplants23,26.

Exercise capacity, improves soon after successful kidney transplant, with removal of uremia19. 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 transplantation27.

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

In 2004, St. John’s Rehab Hospital in Canada launched a program specialized on organ transplant rehabilitation.  According to their study, patients showed up to a 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. A well-programmed physical rehabilitation protocol is essential to provide organ transplant patients an opportunity to regain and have an enhanced quality of life21,28.

3. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE

Guidelines regarding physical rehabilitation programs in kidney and liver transplant recipients are limited. In a randomized controlled study by Tzvetanov et al.29 they applied the Greg Hachaj (GH) method as a program for rehabilitation in obese renal transplant patients; that incorporated physical fitness, psychology, and nutrition. It consisted of individual physical training using low-impact, low-repetition, resistance-based weight training with two one-hour sessions each week. 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 functioning19.

4. GAPS IN THE EVIDENCE-BASED KNOWLEDGE

Controversies and gaps in the evidence-based knowledge

There is limited evidence-based medicine available to follow in rehabilitation protocols after solid organ transplantation. Many transplant centers have established rehabilitation programs but there is not much information with regards to standard rehabilitation or exercise outcome measures regarding both renal and kidney transplant. Potential barriers for such may be lack of funding, shortage of qualified personnel, compliance issues, low volume of patients and insufficient standardized rehabilitation protocols22. 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.

REFERENCES

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  34. Benjamin French,  Peter Abt, and Kim Olthoff.  Liver Transplant Patients Who Receive Organs from Living Donors More Likely to Survive than Those Who Receive Organs from Deceased Donors.July 16, 2014. http://www.uphs.upenn.edu/news/News_Releases/2014/07/ goldberg/

Author Disclosure

Isabel Borras-Fernandez, MD
Nothing to Disclose

Maricarmen Cruz, MD
Nothing to Disclose

Brenda Castillo, MD
Nothing to Disclose

Nataly Montes, MD
Nothing to Disclose

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