Randomized Case-Control Trial About the Impact of Targeted Physical Activity and Diet Modification on Kidney Transplant Recipients' Outcome
Phase: NA
Conditions: Kidney Transplant
Sponsor: University of Illinois at Chicago

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Randomized case-control trial about the impact of targeted physical activity and 
diet modification on kidney transplant recipients’ outcome 
 
Primary Investigator: Enrico Benedetti, MD 
 
BACKGROUND 
 
It is well known that in the general population, metabolic syndrome is tightly linked to 
obesity and is a strong risk factor for cardio-vascular disease and mortality. After renal 
transplantation, obesity and metabolic syndrome are prominent risk factors for post-
transplantation diabetes mellitus, chronic graft dysfunction, graft loss, and patient death 
in renal transplant recipients [1]. At the same time, obesity in the setting of end stage 
renal disease is associated with a condition called obese sarcopenia, which is 
characterized by protein energy wasting and thus a decreased ratio of lean body mass/fat 
body mass [2]. Both obesity and sarcopenia are associated with higher circulating 
concentrations of pro-inflammatory cytokines. These pro-inflammatory cytokines lead to 
systemic inflammation which contributes to cardio-vascular disease development and 
higher morbidity and mortality in patients with end-stage renal disease [3].   Behavioral 
changes to prevent or convert weight gain and improve the lean body mass rate may 
counteract the post-transplant development of obesity-related comorbidities and thereby 
improve renal graft function and survival in the long-term [4].  
 
It is well known that lifestyle factors such as physical activity and diet are important 
modifiable factors for insulin resistance, and have been associated with the risk of kidney 
disease. In the second National Health and Nutrition Examination, the risk of chronic 
kidney disease was related to physical inactivity, both with and without adjustment for 
age, sex, race and body-mass index [5]. In hemodialysis patients, exercise has been 
reported to enhance insulin sensitivity, improve lipid profile, increase hemoglobin, 
improve insulin-like growth factor 1 (IGF-1) status, increase muscle strength, decrease 
blood pressure, increase physical functionality and improve quality of life. Little is 
understood about the state of muscle mass following transplantation. While the patient is 
in renal failure, catabolism of muscle occurs due to protein processing derangements.  
 
Post-transplant, renal function is restored along with appropriate processing of protein 
and elimination of the catabolic state. Few studies have determined whether restoration of 
renal function allows the restoration of muscle mass, whether patients are sufficiently 
strong to accomplish activities of daily living,  whether the use of immunosuppressants 
impedes the ability to increase muscle mass, and whether increasing muscle mass can 
lead to reduction of medication side effects as has been shown recently with 
chemotherapy patients.  Further, little has been studied regarding protein content of post-
transplant diets and its manipulation to increase muscle mass. 
 
Furthermore, although recommendations to engage in physical exercise are routinely 
made by the Transplant Team, it has been extremely difficult to enroll post transplant 
recipients in regular exercise programs. Concern with performances, body images, 

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objective difficulty in performing physical exercise have all contributed to the low level 
of physical activity typical of this patient population. 
 
The present study aims to analyze the effectiveness of a specific physical 
activity/nutrition training program (for a detailed description of the GH method see 
Appendix 1) in comparison to the standard of care for renal transplantations in kidney 
transplant recipients.  
 
GH METHOD AND PHILOSOPHY  
 
There are four major components of the GH Method (also known as the Greg Hachaj 
Method): 
1) Become experts in our patients. 
 
 
 
The GH Method incorporates multiple disciplines including fitness, 
psychology and nutrition.  The efficacy of the GH Method is built around the 
application of standard processes and curriculum that are then customized to the 
particular physiology and psychology of each individual patient.  For the GH 
Method to work effectively, we must develop a comprehensive expertise in our 
patients that demands constant updating as the physiology, psychology and life 
circumstances of each patient evolves during the program.   
 
 
Typically, fitness programs are not customized to fit with a patients’ 
physical and emotional life resulting in a much more limited health impact, 
shorter term participation, unsustainable changes, and an eventual return to the 
patients’ status quo at the beginning of the program.  However, the effective 
interplay of the distinct disciplines of fitness, psychology and nutrition is critical 
to the GH Method’s success in achieving significant and sustainable health 
improvements in our patients measured in improved bodily function, mental 
health, and quality of life. 
 
2) Build and expand their life tissue. 
 
 
 
The physical exercise component of the GH Method focuses on using the 
least amount of a patients’ energy to achieve the maximum health improvements.  
We believe the most effective strategy for maximizing patient improvements with 
minimal energy is to focus on the building and expansion of patients’ life tissue or 
muscle mass.  This focus on the development of life tissue with minimal energy 
expenditure informs the strategy, intensity, techniques, and process of the 
physical exercise of the GH Method. 
 
Many exercise programs focus on improving many aspects of patients’ 
physical health, while the GH Method focuses on strategies designed to maximize 
the development of life tissue.  This systematic strategic focus on muscle mass 
development informs every aspect of the GH Method and is a critical driver of the 
significant measurable improvements experienced by patients.   
 

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3) Help them change their feelings and thinking patterns 
 
 
 
The GH Method is designed to engage patients in an ongoing re-
evaluation of their own health and behaviors, resulting in increased self-
awareness of the cause-effect relationship of their lifestyle choices on their overall 
health and well being.  While we use a range of strategies including cognitive 
behavior techniques, our more novel approach is to focus first on changing how 
patients physically feel and then engaging in cognitive therapy techniques to help 
them change their thinking and behaving patterns leveraging their already more 
positive feelings.  We believe the most effective way to help patients modify 
behaviors is focus on helping them achieve a paradigm shift in their feelings from 
passive and negative regarding their health towards more positive and empowered 
feelings about their health before embarking on more detailed thinking and 
behaving pattern changes.   
 
 
 
The inter-disciplinary approach of the GH Method requires us to patiently 
understand the mindset of our clients and then even more patiently work 
collaboratively with clients to change their mindset in order to achieve lasting 
lifestyle and behavioral changes.  We believe the key to sustainable improvements 
in our patients’ lives is working with them at this deeper psychological level 
rather than just focus on the behaviors we want to change.  Far too often, physical 
fitness is handled independently of psychology and often that is delivered 
independently of nutrition guidance resulting in a disjointed patient experience 
that is difficult for patients to navigate.  The GH Method integrates all of these 
resulting in deeper, more significant and more lasting measurable improvements 
in patient physical and mental health.  
 
4) Coach them to make sustainable improvements in their lifestyle 
 
Through the written assessment process supplemented by motivational 
interviewing and the use of cognitive therapy techniques, the GH Method 
identifies the most impactful behavior/lifestyle changes for a particular patient 
with particular emphasis on improving their optimum recuperation and therefore 
enhancing the development of their life tissue.  After evaluating the impact of 
each potential behavior change (the GH Method uses 17 commonly accepted 
improvements including:  reducing sodium intake, minimizing emotional eating, 
increasing protein to support muscle development, reducing cholesterol, eating 
more balanced meals), the GH Method then uses the Transtheoretical Model of 
Behavior Change to determine which external behavior changes should be 
introduced first.  While we begin testing our hypothesis developed with the help 
of the MIPS profiling of how to be the most effective coach from the beginning, 
we do not ask patients to make significant behavior changes until after they have 
experienced a paradigm shift in their feelings about their own health and 
empowerment.  Once we have initiated the phase of coaching external behavior 
changes, we stay focused on moving slowly so that the patient is only focused on 
one new behavior at a time, and they can connect that changed behavior with an 

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improved outcome in order to maximize sustainability and help the patient build 
momentum to increasingly more difficult external behavior changes. 
 
Often, the nutrition/lifestyle component of an exercise program is built on 
the assumption that patients foremost need knowledge of healthier living in order 
to help them improve their behaviors.  The focus on knowledge is often 
communicated to the patient, sometimes in writing, and is intended to help 
patients make significant changes to their daily lifestyle.  Said simply, many 
fitness programs simply put patients on a diet and focus on the desired outcome 
which is often weight loss.  This type of dieting often leads to a classic pattern 
where patients that do have success struggle to maintain their success and the rate 
of recidivism is high.  The GH Method emphasizes implementation over 
knowledge and we therefore focus our energy on identifying the easiest changes 
for that patient to implement that will have a significant impact, and then helping 
the patient methodically execute the agreed upon change.  We focus patients on 
the process not the outcome, because they can have more control over the process, 
and we make them responsible for observing the results of the behavior changes 
in terms of their energy, mood, and health. 
 
BECOME EXPERTS IN OUR PATIENTS 
The process of becoming an expert in our patients begins through the written assessment 
process and continues to evolve throughout their participation with the GH Method as 
their psychology and physiology continue to change.  We use five different written 
assessments, some given only at the beginning of the GH Method and some being given 
at multiple points in the process. 
 
BUILD AND EXPAND THEIR LIFE TISSUE 
At the core of the GH Method’s approach to exercise is to build and expand life tissue or 
muscle tissue with a minimal amount of energy expenditure.  The GH Method aims to 
increase individual muscle development by helping patients focus their energy on 
isolating the individual muscle that is being targeted through proper technique, improved 
self-awareness, active participation in the program, and a deepening understanding of 
their own physiology.  The education of the patient is paramount, as they must be 
technically engaged and develop an increased awareness of physical sensations in order 
to fully participate in the precision required to build and expand life tissue.  The GH 
Method requires such precision that it can only be delivered to one patient at a time with 
minimal distractions given the engagement and concentration required by both the coach 
and the patient.  The patient is re-assessed consistently throughout the program as their 
physiology changes and, therefore, the exercise needs to change as well to maximize the 
development and expansion of their life tissue.   
 
The GH Method is a systematic approach to increasing individual muscle development 
that is customized to each client based on the assessments completed as well as their 
energy and recuperation levels.  Throughout the GH Method, we are constantly 
evaluating the patients’ optimum recuperation level to determine the right intensity to 
achieve the exercise objective.  We define optimum recuperation as the intensity level 
where the patients’ body can effectively incorporate the workout.  For example, if the 

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objective of the GH Method for a week is to increase the thickness of muscle tissue then 
the intensity level must be set so that the exercise effectively tears the appropriate layer 
of the muscle cell fibers while leaving enough energy in the body to repair and rebuild 
the impacted muscles resulting in increased thickness.  Optimum recuperation levels are 
determined by a combination of a clients physiology, energy, strength, endurance, 
sleeping patterns, nutrition, and stress level. 
 
The GH Method defines in detail the strategy and objectives for each day of exercise, 
including intensity levels, duration, muscle groups, order of exercises, repetitions, speed, 
breaks, techniques to enhance the effectiveness, along with an accompanying educational 
curriculum and psychological strategy correlated with the workout program.  The detailed 
workouts are then customized to the individual patient based on the assessments of 
strength, recuperation, energy among others that are constantly updated throughout the 
program.  The GH Method is organized into Levels and all patients begin in Level 0.  For 
the purposes of this study, patients will experience at least 12 months of the GH Method 
which may incorporate the following levels: 
 
Level 0.   This level comprises approximately 8 separate weeks although many of the 
weeks may be repeated depending on the needs of a particular patient.  The major 
physical objective of Level 0 is to effectively engage their muscle fiber (without much 
breakdown) to activate their innate strength, endurance and cardiovascular capacity.  
Before the end of Level 0, we measure patient strength, endurance, and cardiovascular 
capacity to ensure we can train patients to their optimum recuperation level.  The major 
educational objective of this Level is to teach clients the technical form and self-
awareness that is mandatory before they can proceed to the next Level.  The major 
psychological objective of this Level is to establish a safe and caring environment for 
patients, to reframe how they think about exercise and their health, and for us to become 
experts in all aspects of the patient. 
 
Level 1.  This level comprises approximately 12 weeks although many of the weeks may 
be repeated depending on the needs of a particular patient.  The major physical objective 
of Level 1 is to begin the process of increasing the development of individual muscles 
and therefore increasing patients’ life tissue.  More energy is directed towards the larger 
muscle groups which can increase in size the fastest resulting in improvements in patients 
energy levels, physical symptoms, and other measures.  The major educational objective 
of this Level is to promote the patients autonomous relationship with their own body by 
increasing their own self-awareness of physical sensations during their exercise and 
recovery.  The major psychological objective of this Level is to leverage the improved 
energy and autonomy to collaboratively initiate the process of making 
lifestyle/behaviorial changes.  Before the end of Level 0, we measure patient strength, 
endurance, and cardiovascular capacity to ensure we can train patients to their optimum 
recuperation level. 
 
Level 2.  This level comprises approximately 20 weeks although many of the weeks may 
be repeated depending on the needs of a particular client.  The major physical objective 
of Level 2 is to continue the process of increasing the development of individual muscles 

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and therefore increasing the patients’ life tissue.  The Level includes weeks focused on 
improving muscle strength, muscle endurance, muscle size, muscle thickness, heart 
endurance, lung capacity, and resistance strength.  The main educational objective of this 
level is to promote patients awareness of the function of their bodies, including strength, 
energy, endurance, and recuperation so they feel more empowered and in-control of their 
physical health and aware of the improvements they are making.  The main psychological 
objective of this Level is to help patients use the increased self-awareness of their own 
body (the educational goal of Level 1) to understand the impact of the dietary and 
lifestyle changes they are making.  We aim to connect patients as closely as possible with 
feeling the impact of the individual changes they are making, as that is a key to both 
sustainability of the changes they have already made and empowerment to continue 
making more changes. 
 
CHANGE FEELING AND THINKING PATTERNS 
As we become experts in our clients through the use of assessments, motivational 
interviewing, and careful observation, we develop a deep understanding of how our 
patients see the world, their physical health, their mental health, their behavioral choices, 
and their future.  We use each session to add to the body of knowledge we have about 
each person, including their verbal and non-verbal communication, how they react to 
management and autonomy, their ability to execute behavior changes, their motivations 
and their outlook on the future.   
 
During Level 0, we are absorbing as much knowledge as possible about our patients.  
Often before the end of Level 0 patients feel some improvement in their daily function, 
whether its energy, attitude, or the reduction of pain.  We help patients listen to their own 
bodies and become aware of the changes they are experiencing.  When they confidently 
express on their own the changes they are feeling, we work closely to leverage those 
positive feelings into a paradigm shift in how patients may be viewing their physical and 
mental health.  This is a critical step in how the GH Method achieves changes in feeling, 
thinking, and then behavior patterns. 
 
Often, patients start out with a focus on negatives (concerns, fears, obstacles, limitations) 
which inform their cognitive thinking patterns and capacity for behavior change.  As 
patients become aware of changes in their body and life, we work to shift their paradigm 
from the negative to the positive (empowerment, sense of control, ability to improve 
symptoms, autonomy, hope for the future).  While each patient is different, a common 
early patient experience is improved energy, so that is a key point of focus and provides 
the most common pivot point in patients’ feelings moving from negative towards 
positive.  We use many motivational interviewing techniques to help maximize the 
impact of this shift.   
 
Cognitive behavior theory postulates that thinking patterns inform feeling and behavior 
patterns so changing the way we think can greatly impact how we feel and behave.  
While we use cognitive behavior techniques, our more novel approach is to focus first on 
changing how patients physically feel and then leveraging that momentum towards 
encouraging changes in thinking and then behaving.  We believe the most effective way 

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to modify behaviors is to work in a collaborative process with our patients and help them 
first achieve a paradigm shift from negative to positive before embarking on more 
detailed thinking and behaving pattern changes.  We incorporate cognitive therapy 
techniques with the workouts so that we can leverage the most teachable moments, set a 
slow and steady pace, and continue to learn more about the most effective techniques of 
cognitive therapy and motivational interviewing to create changes in each individual 
patient. 
 
The GH Method also utilizes Neuro Linguistic Programming (NLP) to better understand 
and then impact the outlook of patients and by maximizing the effectiveness of our 
communication with those patients.  We study the conscious and unconscious process of 
how our patients code and store their feelings, insights, obstacles and successes so that 
we can impact that coding and therefore influence their thinking.  The key components of 
NLP are: 
 
a) Neuro.  The key for this component is to understand how patients translate the 
experience of their key senses into thought processes, both conscious and 
unconscious.  We are trying to learn how their senses, their mind, their feelings 
combine to function as one system. 
b) Linguistic.  The key for this component is to understand how patients use 
language to make sense of their experiences and how they choose to communicate 
that experience to themselves and others.  Language patterns have an enormous 
impact on how a patient feels, thinks and ultimately behaves, so learning their 
language patterns positions us to have a more significant impact on our patients. 
c) Programming.  This is the coding of experience.  How patients mobilize their own 
experiences and vocabulary to attempt and execute changes in their own lives.  
Individuals typically demonstrate some consistency in patterns of success and 
patterns of failure, so we study how patients most effectively program themselves 
for success so that we can help them emulate or establish consistent and 
sustainable patterns of success. 
 
 
 
COACH THEM TO MAKE SUSTAINABLE IMPROVEMENTS IN THEIR 
LIFESTYLE 
We combine the written assessments with the knowledge we have accumulated about our 
clients behaving patterns, routines, capacity for behavior change and attitude towards 
change to establish the priorities for that client for behavior/lifestyle changes.  The GH 
Method includes a formulaic approach to identifying the order and speed of changes for 
each patient based on the clients need for independence in terms of agenda-setting 
(discovered in the MIPS), their evaluation of general health (PROMIS v.1.1 Global 
Health questionnaire), their evaluation of mental health and pain intensity (PROMIS 29 
Profile v2.0) their readiness to change according to the Transtheoretical Model of Change 
(discovered in the Lifestyle Inventory), their actual habits and routines (discovered in the 
Food Journal) and our ongoing motivational interviewing and assessment process. 
 

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The formulaic approach determines which of 17 possible behavior changes we will focus 
on first, and then we use the MIPS profiling, our identification of where they are in terms 
of their stage of change, our understanding of their Neuro Linguistic Programming, and 
the rapport we have established to coach patients to most effectively execute behavior 
change plans.  The integration of the coaching program from physical exercise to lifestyle 
changes is critical to the GH Method’s effectiveness. 
 
The GH Method targets only one behavior change at a time and does not move onto the 
second until patients have achieved some level of success with the behavior change and 
become aware of the impact that change has on their health.   This methodical and slow 
approach helps sustainability as patients feel the connection between the cause (the 
behavior change) and the effect (an improvement in their health).  After identifying the 
starting point for guiding the client through behavior changes, we use motivational 
interviewing to help the patient collaboratively accept the starting point or reject it and 
select another starting point where they are more ready to implement a change.  We then 
focus on helping patients develop a strategy and a plan for implementing the change, set 
their own goals for the change, and then we help create accountability for the 
implementation. 
 
Hypotheses: 
1. Counseling twice weekly on diet and nutrition will improve food choices to more 
healthy choices of fresh fruits and vegetables and low fat protein sources.    To test 
this hypothesis, patients will undergo a food frequency questionnaire at baseline to 
document choices prior to intervention. A food frequency questionnaire will be 
performed at the end of the intervention to determine the effect of counseling on protein 
source, number of calories, and frequency of fresh fruits and vegetables. Counseling will 
consist of the diabetes prevention program counseling which is a well-established, well-
verified intervention, commonly accepted as an effective means of providing a 
standardized nutritional education. 
 
2. The combination of exercise and dietary intervention positively affects body 
composition. With this hypothesis we will test whether muscle strength (Biodex 
measurements) and muscle mass (DEXA scan) changes after 12 months of an exercise 
intervention. We hypothesize that the transplant itself will not affect activity levels, 
strength levels or muscle mass. Baseline measurement will be performed before the 
intervention, at 6 months post intervention, and the final measurement would be taken at 
12 months with muscle mass measured by DEXA and strength measured again by 
Biodex. 
 
3. Patients receiving strength training will have significantly higher activity levels 
when compared with no intervention or physical therapy. The rationale for this 
hypothesis is that patients without strength training will fail to increase muscle mass and 
strength and this inability will translate to persistently lower activity levels than those 
patients with strength training.  Once again levels will be documented with an 
accelerometer and PROMIS questionnaires, 6 months and 12months to document the 
effect of intervention. In addition, if patients in the control group and GH group decide to 

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have the optional muscle biopsy, it will help evaluate how targeted exercise may change 
muscle development measuring expression of mature microRNAs using total RNA 
extraction. 
 
4. Patients with strength training will activate type II macrophages which are anti-
inflammatory and pro-regenerative, tipping the balance away from inflammation 
towards regeneration when compared to the other treatment groups.  Since strength 
training is likely to initiate signals of muscle regeneration, and since type II macrophages 
play a key role in this effect, it is possible that increasing the signaling to the muscle for 
regeneration may also increase the proportion of active type II macrophages which are 
anti-inflammatory. To test this hypothesis, we will test the proportion of peripheral blood 
M1/M2 macrophages at baseline,6 months and 12 months after the initiation of the 
intervention. Recognizing that immunosuppression may significantly confound this 
proportion and overall suppress it, we will also test circulating levels of pro-inflammatory 
cytokines such as C-reactive protein(CRP), IL-6, IL-1, TNF-alpha, homocysteine, 
adiponectin, leptin, and resistin as well as pro-regenerative cytokines such as TGF-beta 
and IL-10.  
 
5. We expect patients with strength training will experience less renal dysfunction, 
decreased hemoglobin A1C, increased peripheral vascular function, decreased 
fasting blood sugar when compared to the other treatment groups. The rationale for 
this hypothesis is the finding that muscle mass provides active regulation of glucose and 
other metabolites. Therefore increasing this may provide improved metabolic function. 
These laboratory panels are part of the standard transplant follow-up labs and add no cost 
to the project.  
 
6. Patients with strength training will have an overall improved sense of well-being 
and energy level compared to those with physical therapy or no treatment.  With 
twice weekly counseling for activity and nutrition, patients will be asked about their 
general health, mental health and pain intensity using the PROMIS questionnaires. 
 
METHODS 
Setting: The study will include 225 patients, to achieve a goal of 180 patients in the GH 
study group and 45 patients in the control group.   Every patient will be followed for 3 
years after the start of the intervention. Patients will start the intervention at least 2 
months post-transplant; however they can be enrolled prior to transplant.    
 
Main Study Inclusion criteria: 
 -Successful kidney transplantation (KTx) with primary graft function 
- Age between 18 and 65 years 
- Adequate cognitive ability to complete the questionnaires, give consent for the study 
and follow the physical and diet instructions  
 
Main Study Exclusion criteria: 
- transplant of any other organ besides kidney alone or a combination of a 
kidney/pancreas  

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-non-ambulatory or significant orthopedic problems 
- cardiac/pulmonary disease that contraindicate the physical training 
- any contraindication to exercise testing per the American Heart Association  
-unable to comply with the training program 
 
Muscle Biopsy Inclusion: 
- Age between 18 and 65 years 
-Patients who have a brachial–cephalic arteriovenous fistula (AVF) in the elbow or 
brachial–basilic AVF in the arm  
-Exercise Arm- the biopsy will only be performed once, after the 12 month exercise 
intervention is completed (which will be longer than 1 year post transplant surgery)  
-Control Arm- this procedure will be performed once, around one year post transplant 
surgery (may occur at any time during the study) 
 
Muscle Biopsy Exclusion:  
-Patients that do not meet the inclusion criteria 
 
Identifying potential subjects for recruitment:  
A waiver for an alteration of consent and waiver of documentation of consent is being 
requested for review of medical records to identify potential patients for study 
recruitment and also for a telephone screening process for patients that response to a 
recruitment flyer.  The principal investigator already has access to these records as part of 
daily care for all patients seen in clinic.  This presents no more than minimal risk since 
this data will be kept confidential.   
 
Moreover, as part of the telephone screening process for patients interested in this study 
there will be oral consent obtained to start the screening process in order to determine if 
the patients are eligible to be in the study. If the patients are eligible, they will be 
schedule for a visit where they will be consented to be in the study. 
 
Randomization: All patients who meet the enrollment criteria will be randomized 4:1 to 
the GH group or the control group. 
• GH group: patients will be treated for 12 months with the GH method (Appendix 
1) for one hour twice a week 
• Control group: patient will be treated according to the standard of care for post-
transplant recipients; control patients will be offered the opportunity to undergo 
the GH regimen for the 1 year after their final visit as a control patient.  If the 
control patients chose to undergo the GH regimen, the extended follow up will be 
completed after 1 year from their final GH visit (totaling 4 years from the start of 
intervention).  
 
Long-term follow-up 
After the 12 month intervention period all patients will be followed for 2 additional years.  
Patients will be contacted by phone to assess current activity level, employment status, 
graft function and current weight.  Patient’s medical records will also be reviewed to 
confirm BMI and graft function. This will be done every 6 months.  

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A separate waiver of documentation of consent, for long-term follow up, is being 
requested for patients that have previously enrolled and completed the study (January 3, 
2012 to July 28, 2014). 
 
 
Parameters to analyze in all patients: 
 
The PROMIS v.1.1 - Global Health short form will be administered to all patients at the 
time of enrollment, 6 months and at the end of the study (12 months). The PROMIS v.1.1 
- Global Health short form will assesses health in general (i.e. overall health). The 
PROMIS Global Health short form is a 10-item instrument representing multiple domains 
(physical function, fatigue, pain, emotional distress, social health) as well as perceptions 
of general health that cut across domains. Global items allow respondents to weigh 
together different aspects of health to arrive at a “bottom-line” indicator of their health. 
Similar global health items have been found predictive of future health care utilization 
and mortality. 
 
 PROMIS 29 Profile v2.0 will be administered to all patients at the time of enrollment, 6 
months and at the end of the study (12 months). The PROMIS 29 Prolife v2.0 is a short 
form containing four items from seven PROMIS domains (Depression, Anxiety, Physical 
Function, Pain Interference, Fatigue, Sleep Disturbance, and Ability to Participate in 
Social Roles and Activities) along with a single item on Pain Intensity.  
 
Multiple studies have been conducted by the PROMIS Network validating these 
instruments. Studies are shown at: http://www.nihpromis.org/science/validitystudies.aspx 
 
 
Body composition and strength 
BMI will be calculated at the time of enrollment, at 6 months, and at the end of the study 
(12 months).The most exact method to determine body fat and lean body mass is DEXA, 
a method that has been validated in patients with renal failure before and after 
transplantation [6,7]. Waist circumference as well as blood pressure will be measured for 
general health markers. Muscle strength will be measured using a Biodex machine.  
Exercise capacity will be measure with a 6 minute walk test and an accelerometer.  
Fitness level will be measure with a maximal aerobic capacity test (VO2 max). These 7 
tests will be done at baseline, 6, and 12 months.    
 
Waist Circumference: 
Waist circumference will be measured at the narrowest part of the torso (above the 
umbilicus and below xiphoid process) in the standing position using a tape measure. This 
will be completed at baseline, 6 months and 12 months post-intervention.  
Blood Pressure: 
Blood pressure will be measured in the supine position (lying on back) in a dimly lit 
room after resting for fifteen minutes. This will be completed at baseline, 6 months and 
12 months post-intervention.  
 

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DEXA Scan:  We will determine percent body fat via a whole body scan by dual energy 
x-ray absorptiometry (GE, IDXA, Madison, Wi), which will be operated and calibrated 
using the manufacturer’s stated guidelines.  The duration of the scan will be less than 10 
min and the subject will be exposed to a radiation dose of ≤0.3 mrem based upon the 
manufacturer’s specifications and calculations from Standford Dosiometry, LLC 
RADAR Medical Procedure Radiation Dose Calculator.  This amount of research 
protocol radiation exposure is minimal given the estimated effective equivalent dose is 
below the 100 mrem per year, a limit set by the Nuclear Regulatory Commission for 
“general public” exposure. 
 
Biodex: Bilateral isometric knee extensor and flexor peak torque will be measured using 
a Biodex System 3 dynamometer (Shirley, NY). Participants will be positioned in the 
dynamometer according to the manufacturer’s recommendation. Briefly, the axis of 
rotation of the machine will align with the lateral epicondyle of the femur. The calf pad 
against which the participant exerts force will be positioned halfway between the lateral 
malleolus of the fibula and lateral epicondyle of the femur, and securely attached using 
straps. Straps will be placed over the thighs, pelvis, and torso regions to minimize 
movement during the test. We will use an anatomical reference position of 90° knee 
flexion, and isometric torque will be assessed at joint angles of 45°, 60°, and 75°. Peak 
torque will be obtained by having the participant perform 3 maximal contractions with 
the knee extensors for 5 seconds, which will be immediately followed by a 5 second 
maximal contraction with the knee flexors; 1 set will be performed. There will be no rest 
period between contractions within a set, and the rest period between each angle set will 
be 3 minutes. The highest recorded peak torque will be used as a measure of knee 
extensor and flexor isometric strength, and expressed as strength per body weight.  
 
The 6 minute walk test involves walking as far as possible (down the hallway) over a six-
minute period with distance recorded by researchers on one trial.  During this test the 
subjects will wear a mask on their face that measures how much oxygen their body uses 
during this task (Cosmed K4b2, Rome, Italy). VO2 will be assessed during this test to 
evaluate the amount of oxygen the subject’s body utilizes during acts of regular daily 
activity, such as walking, which will be completed on a treadmill (as described below).  
Distance will also be collected as a way to measure the subject’s functional capacity and 
to track progression.  This test will be completed at baseline, 6 months and 12 months 
post-intervention.  
 
 
Maximal aerobic capacity test (VO2 max):  For subjects over 55 yrs or that are classified 
as moderate to high risk according to ACSM’s risk stratification scale, this will occur in 
the presence of a physician. We will use a modified Balke Treadmill protocol: the 
treadmill will be set at a constant speed (3.3 mph) while the incline is increased by 2% 
every two minutes. This protocol is selected to ensure that the elderly subjects will be 
able to perform a maximal aerobic test. For younger (18-35 yr) subjects, the test will 
begin at a 10% grade and increase 2% every 2 minutes.  If maximal effort is not reached 

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by minute 10 and a 20% grade, speed will be increased by 0.3 mph until maximal effort 
is achieved. 
 
Accelerometer: subjects will be given an accelerometer with instructions for use and be 
asked to wear it around their waist for 1 week while awake to measure their level of 
physical activity.  This will be completed at baseline, 6 months and 12 months post-
intervention.  
  
Muscle Biopsy  
Optional muscle biopsies for GH group and control group, will be performed to measure 
expression of mature microRNAs using total RNA extraction, which will help evaluate 
how targeted exercise may change muscle development.  The muscle biopsy will be 
performed by Dr. Ivo Tzvetanov, Dr. Benedetti, Dr Di Bella, and/or Dr Spaggari, all of 
which areexperienced surgeons with prior experience performing muscle biopsies. The 
muscle biopsy will be performed at the University of Illinois at Chicago Outpatient 
Clinic, with an address at 1855 W Taylor St, Chicago, IL 60612.   
 
Prior to kidney transplantation many patients undergo hemodialysis treatments to sustain 
life. Hemodialysis is a process of purifying the blood of a person whose kidneys are not 
working normally. Arteriovenous fistula provides an access route for hemodialysis to be 
possible, by providing a direct connection of an artery to a vein. As part of standard of 
care at UIC, the AV fistula is ligated (a surgical procedure of closing off a blood vessel) 
at around one year post-transplant. As a way to retrieve bicep muscle biopsy samples we 
will retrieving samples during the closing AV fistulas (ligation) in kidney transplant patients 
with stable renal function. Patients will be consented with a supplemental consent for the 
bicep muscle biopsy.  
 
In the upper extremities, the typical sites for muscle biopsy are deltoid or biceps. We want to 
focus on the bicep muscle only and we will include only patients with brachial–cephalic AVF 
in the elbow or brachial–basilic AVF in the arm will be selected in order to have easily 
access to the biceps muscle.  
 
The skin incision for closing brachial–cephalic or brachial–basilic AV fistula in the upper 
extremity is made over the area of the arteriovenous anastomosis: in the elbow for brachial–
cephalic AVF or in the arm for brachial–basilic AVF. 
 
After shaving and disinfection of the external part of the surgical site, local subcutaneous 
anaesthesia is achieved using 4 mL of lidocaine (2%) with special attention to ensure that no 
lidocaine is injected in the muscle. Thus, injection of lidocaine is done superficially and 
obliquely.  
 
In case of voluminous fistula, a regional anesthesia via peripheral nerve block is preferred. In 
these cases, the anesthetic (a mix of lidocaine and ropivacaine) is injected by anesthesiologist 
near the brachial plexus to block sensations of pain from a specific area of the body. Nerve 
blocks usually last longer than local anesthesia. 
 

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A small cutaneous incision (about 4-5 cm) is made in the antecubital fossa, over the area of 
the arteriovenous anastomosis, following the medial border of the biceps muscle. The 
muscle is retracted slightly laterally in order to allow access to the thin aponeurotic 
sheath which contains the neuro-vascular bundle.  Biceps brachii muscle is visualized and 
cut. Muscle fibres are carefully dissected in their longitudinal axis away from the tendon 
insertion, to obtain a sample of 300 mg. This is about the size of 2-3 grains of rice. Both ends 
are immediately clipped and hemostasis is controlled. The bundle is fixed on a cork support 
at its apparent resting length. 
 
The skin incision is closed with 3.0 Nylon suture and pressure is applied to the incision site.  
 
This procedure will be done once at 12 months for patients randomized to the exercise arm 
(after the exercise intervention is completed) and once at any time during the 12 month study 
duration for the control arm as long as the patient is at least one year post transplant.  
 
 
 
Status of systemic inflammation 
At baseline, after the patients have fasted overnight, blood samples will be drawn for 
analyses of pro-inflammatory cytokines such as C-reactive protein (CRP), IL-6, IL-1, 
TNF-alpha, homocysteine, adiponectin, leptin, and resistin as well as pro-regenerative 
cytokines such as TGF-beta and IL-10. Peripheral blood M1/M2 macrophages will also 
be measured.  These tests will be performed at baseline, 6 months and 12 months post-
intervention. Blood sampling will require approximately 20ml of blood at each blood 
draw. The total amount of blood drawn will be about 60 ml. 
 
Metabolism and renal function changes 
All patients will be monitored for fasting plasma Glucose, HbA1c, Lipid profile (Serum 
Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol), and serum creatinine 
during the study per standard of care for kidney transplant patients.    
 
Vascular Function and Vascular Stiffness 
Brachial FMD will be used to assess macrovascular endothelial function. This method 
involves the measurement of vascular reactivity of the brachial artery using non-invasive 
ultrasound technique. While the subject rests in the supine position, an 11 MHz probe will be 
used to determine brachial artery diameter above the antecubital fossa in the non-dominant 
arm. In addition, continuous wave Doppler will be used to determine brachial artery blood 
flow velocity. Brachial artery diameter and blood flow velocity will be measured under the 
following conditions: 1) At rest, 2) During reactive hyperemia produced by a five minute 
interruption of flow with a blood pressure cuff inflated >50mmHg above systolic pressure, 3) 
For three minutes after reactive hyperemia (30-second intervals for the first minute and 1-
minute intervals thereafter).  
 
Assessment of vascular stiffness using peripheral tonometery and ultrasound imaging 
Upon entering the lab, participants will be required to rest quietly in the supine position in a 
dimly lit room for 10 minutes.  Arterial size and stiffness will then be measured via 
ultrasonography using several different methodologies:   1) Pulse wave velocity:  this test 

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allows for a non-invasive way to measure arterial stiffness.  Three disposable electrodes will 
be placed on the subject's torso.  A pen-shaped transducer is placed over the carotid artery 
(side of the neck), over the femoral artery (top of the leg), over the anterior tibialis artery 
(inner ankle), and over the radial artery (wrist).  The distance between each of these sites will 
be measured using a tape-measure.   2) Arterial Distensibility and function by ultrasound 
imaging:  this test allows for non-invasive imaging of the carotid, brachial, and femoral 
arteries.  Central blood pressure will be determined using the aforementioned pulse-wave 
analysis method (SphygmoCor SCOR, PWV Medical, Sydney, Australia).  In brief, the 
pressure waveforms that are obtained at the radial artery site are subjected to a generalized 
transfer function to derive the corresponding central arterial waveforms 
 
 Cardio-ankle vascular index (CAVI) and Ankle Brachial Index (ABI) 
CAVI and ABI will be assessed by pulse wave velocity analysis at the brachial and ankle 
arteries (VaSera VS 1500AU, Fukuda Denshi, Japan). The CAVI measurement requires 
the placement of ECG electrodes on both wrists, and a microphone for 
phonocardiography on the sternum in the second intercostal space, and 4 blood pressure 
cuffs.  CAVI between the heart and ankle arteries is assessed using measurements of 
 time between heart sound II and plethysmograms taken at the brachial 
and ankle arteries. This will be done to measure the stiffness of arteries and is 
independent of blood pressure. This test will be performed at baseline, 6 months and 12 
months post-intervention. 
 
Wrist Artery Stiffness 
A very sensitive pen-shaped microphone will be placed on the subject’s wrist (radial 
artery).  This microphone measures how stiff the radial artery is.  This test will be 
performed at baseline, 6 months and 12 months post-intervention. 
  
Central Artery Stiffness 
The same pen-shaped microphone used before will be placed on  the subject’s neck and 
then the artery at the top of their thigh.  We will use these  measurements to measure how 
stiff their central arterial system (the arteries in the midsection of the body) is. This test 
will be performed at baseline, 6 months and 12 months post-intervention. 
   
Carotid Artery Stiffness and Compliance 
We will look at the artery in the subject’s neck using an ultrasound machine.  This 
machine is similar to what doctors use to look at babies within the womb.  We will place 
a small amount of gel on their neck to help us get a clearer picture.  This gel is 
hypoallergenic and washes off very easily.  We will place the probe on their skin, over 
the artery on the inside of their right neck.  This probe will allow us to look at the carotid 
artery and see how it moves with each heart beat.  This test will be performed at baseline, 
6 months and 12 months post-intervention. 
 
Cardiac Ultrasound 
We will measure the subject’s heart function with ultrasonography using ultrasound gel 
and a probe.  It is the same probe used to visualize babies in the womb.  We will measure 

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how quickly the subject’s heart contracts and relaxes.  This test will be performed at 
baseline, 6 months and 12 months post-intervention. 
 
Other measurements: Resting heart rate will be measured in the supine position.  
Resting blood pressure will be measured in the brachial artery using a digital 
sphygmomanometer in the supine position according to the guidelines of the American 
Heart Association. Blood pressure will be measured twice, one minute apart, and the 
average of the two values will use as resting blood pressure. Body mass index will be 
calculated as weight (kg) divided by height (m) squared. Employment status will be 
confirmed. These measures will be completed at baseline, 6 months and 12 months post-
intervention.  
 
GH subjects only: 
Personality Assessment 
Millon Index of Personality Styles (MIPS) is a 180 question true/false questionnaire that 
can typically be completed in approximately 30 minutes and was developed to evaluate 
normally functioning adults who may be experiencing problems in various aspects of 
their lives.  The MIPS addresses three key dimensions of normal personalities:  
motivating styles, thinking styles, and behaving styles.  Based on the patients motivating 
style we learn how to balance coaching with autonomy, and how patients engage 
emotionally with their surrounding environment. The outcome of thinking styles helps us 
understand the patients’ cognitive processes and prepares us for effectively influencing 
their cognitive thinking patterns.  The outcome of behaving styles helps us understand the 
patients’ way of interrelating with others so we can be the most effective coach when it’s 
time to help them change their behaviors. This will only be administered to the GH 
patients at the time of enrollment.  
 
Lifestyle Inventory 
The GH Lifestyle Inventory was developed by GH as a lifestyle inventory questionnaire 
combining factual assessment questions regarding their lifestyle, as well as questions 
evaluating their emotional relationship with their health, and finally a series of questions 
evaluating their readiness to change informed by the Transtheoretical Model of Behavior 
Change.  The tool typically takes 8 – 10 minutes for completion, involves 26 questions 
many of which are multiple choice but some free form fields.  The GH Lifestyle 
Inventory is primarily used to: allow patients to self-report lifestyle habits, understand 
their emotional relationship with their health and with their lifestyle. And develop 
hypothesis for where the patient is in terms of behavior change stages according to the 
Transtheoretical Model of Behavior Change (pre-contemplative, contemplative, 
preparation, action, maintenance). This will only be administered to the GH patients at 
the time of enrollment.  
 
Food Journal 
The Food Journal was developed by GH as to allow client self-reporting of actual eating 
and sleeping habits.  This is typically administered for two consecutive weeks at various 
times in their participation with the GH Method, but never earlier than four consecutive 
weeks of participation.  The food journal is used to: validate or disprove the patients self-

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reporting done via the Lifestyle Inventory, understand their eating and sleeping patterns 
in greater detail by eliminating their opinions and emotional relationship and just 
focusing on actual intake, and provide a tool for ongoing monitoring and an opportunity 
for increasing patient’s self-reflection on their food and sleeping habits. This will only be 
administered to the GH patients. Importantly, this is not a measurement tool that we 
would give at a specific time during the study; it is being used during the study by the 
research personnel and GH Method personnel to help manage self-reported behavior 
changes with the patients.  
 
Counseling 
Patients in the both arms will be counseled regarding weight loss per standard of care 
which consists of a pre-transplant and a post-transplant nutrition evaluation and 
education. 
 
Video recording (optional) 
Video recordings will be an option on the consent form for patients that are randomized 
into the GH exercise group. The option to be video recorded by the GH team at the 
beginning and end of the patient’s 12 months of training.  The recordings will be used to 
compare the progress of the patient from the beginning and end of GH training.     
 
GH Study Visits: 
At least one week prior to the first GH session with a patient, the written assessments will 
be completed and returned to GH personnel for scoring and processing. The first four GH 
sessions (over 2 weeks) for any patient will be 75 minutes.  Following the first 4 sessions, 
ongoing patients will be slotted into recurring 60 minute time slots for the remaining 50 
weeks. All of these visits will occur in the UIC Disability Health and Social Policy 
Building (DHSP) located at 1640 W. Roosevelt Road in Suites 158, 190, and 195. The 
procedure visits at baseline, 6 and 12 months will take 2-3 hours.   
 
At least twice per week, GH personnel will attempt to follow-up with patients via text 
message, email or a phone call to evaluate their physical recuperation and overall health 
and energy or to track their performance with a behavior change goal.  
 
Patients will be asked to complete a physical regimen based on the following: 
 
Summary of GH Study Visits: 
• Patients may be asked to repeat previous weeks and/or skip a particular week 
depending on their energy, progress, and overall health.  
• Depending on a patient’s individual physical need, mobility, the program may be 
slightly modified (number of repetitions, number of exercises, etc...) to be safe 
and appropriate for that individual. 
• Each week comprises two different exercise days, each incorporating 
approximately 5-10 minute light warm-up plus stretching and then the exercises. 
• Unless specified as a cardio or endurance week, all weeks consist of basic 
strength training/resistance workouts. 

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• The attached exercise list includes all possible strength training exercises, and 
clients complete the appropriate exercises for that week during their two, one-
hour appointments each week.  Depending on a patients particular physical health 
(e.g. shoulder problems) certain exercises may be eliminated or modified in terms 
of the safe range of motion and intensity. 
• These sessions can be directly supervised by the GH instructors or performed by 
trained personnel implementing written instructions given by the instructors.   
 
Week 
Overview 
Intensity/Weight 
Breaks 
Week 1 
1st Set:  30 Seconds with Only 
Safety Instruction 
2nd Set:  90 Seconds with More 
Focus on Form 
Light 
2 or more minutes 
Week 2 
1st Set:  Holding at top and bottom 
of range (20 seconds each hold) 
2nd Set:  20 rep’s and possible to 
add plus 5 depending on energy 
Light 
2 or more minutes 
Week 3 
1st Set:  Warm-Up of 15 repetitions 
2nd Set:  Resistance focused 60 
seconds, possible plus 5 
Light/Moderate 
2 or more minutes 
Week 4 
3 Sets for every exercise.  Each set 
is 12 repetitions with some holding 
for five seconds.   
Moderate 
30 seconds 
between sets.  2 
minutes between 
exercises. 
Week 5 
1 Warm Up Set of 15 repetitions. 
1 Heavier Set of 11 Repetitions. 
Moderate/Heavy 
3 minute breaks 
Week 6 
Cardio Exercises (e.g. run in 
place).  5 different exercises are 
done as one round and two rounds 
total. 
Light/Moderate 
2 minutes between 
exercises and 4 
minutes between 
rounds. 
Week 7 
1st Set:  Warm up of 12 repetitions. 
2nd Set: 6 repetitions 
Moderate/Heavy 
3 minutes 
Week 8 
1 Set:  90 seconds 
Light 
3 minutes 
Week 9  
1 Warm Up Set of 15 Repetitions. 
3 Sets of 6-8 repetitions 
(depending on exercise) 
Moderate/Heavy 
3 minutes 
Week 10 3 Sets of Declining Heaviness with 
6 reps, 8 reps, and 10 reps 
Moderate 
3 minutes 
Week 11 2 Sets Per Exercise without break 
between:  18 reps and 16 reps 
Moderate/Light 
2 minutes 
Week 12 1 Set of 25 - 30 repetitions 
Moderate/Light 
2 minutes 
Week 13 Cardio Exercises (e.g. run in 
place).  7 different exercises are 
done as one round and three rounds 
total. 
Moderate 
2 - 3minutes 

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Week 14 1 Set of 12 - 16 Repetitions 
Moderate 
2 minutes 
Week 15 3 Sets of declining heaviness with 
8, 10 and 12 repetitions 
Moderate 
3 minutes 
Week 16 3 Exercises in Each Set and 7 sets 
Moderate 
3 minutes 
Week 17 1 Set 90 Seconds 
Moderate/Light 
3 minutes 
Week 18 Cardio Exercises (e.g. run in 
place).  3 different exercises per 
set.  3 Sets equal one Round.  
Three Rounds total 
Light 
2 minutes 
Week 19 1 Warm-Up Set of 12 repetitions 
1 Set of 7 Repetitions 
Moderate/Heavy 
3 Minutes 
Week 20 1 Set of 25 - 30 Repetitions 
Moderate 
3 Minutes 
Week 21 1st Set:  Warm up of 12 repetitions. 
2nd Set: 6 repetitions 
Moderate/Heavy 
3 minutes 
Week 22 1 Set:  35 - 40 repetitions  
Moderate/Light 
3 minutes 
Week 23 1 Warm Up Set:  15 repetitions 
1 Heavier Set 8 - 10 repetitions 
Moderate/Heavy 
3 minutes 
Week 24 1 Set of 90 Seconds focused on 
resistance 
Moderate 
3 minutes 
Week 25 Cardio Exercises.  10 exercises in a 
set.  2 Sets. 
Moderate 
3 minutes 
Week 26 3 Exercises in 1 Set.  9 Sets. 
Moderate 
3 minutes 
Week 27 1 Warm Up Set:  8 – 12 reps. 
1 Heavy Set:  8 – 12 reps.  Slower 
Speed. 
Moderate/Heavy 
2 minutes 
Week 28 1 Warm Up Set 8 reps 
1 Heavy Set 8 reps.  Medium 
speed. 
Heavy 
3 minutes 
Week 29 3 Sets on each exercise of 6, 8, 12 
repetitions. Lower weights each 
set.  Medium speed. 
Moderate 
3 minutes 
Week 30 1 set 90 seconds.  Medium speed. 
Lighter 
2 minutes 
Week 31 1 Warm Up Set:  8 – 12 reps. 
1 Heavy Set:  8 – 12 reps.  Slower 
Speed. 
Moderate/Heavy 
2 minutes 
Week 32 3 Sets on each exercise of 6, 8, 12 
repetitions. Lower weights each 
set.  Medium speed. 
Moderate 
3 minutes 
Week 33 1 set 90 seconds.  Medium speed. 
Lighter 
2 minutes 
Week 34 1 Warm Up Set:  8 – 12 reps. 
1 Heavy Set:  8 – 12 reps.  Slower 
Speed. 
Moderate/Heavy 
2 minutes 
Week 35 3 Sets on each exercise of 6, 8, 12 
repetitions. Lower weights each 
set.  Medium speed. 
Moderate 
3 minutes 

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Week 36 1 set 90 seconds.  Medium speed. 
Lighter 
2 minutes 
Week 37 1 Warm Up Set:  8 – 12 reps. 
1 Heavy Set:  8 – 12 reps.  Slower 
Speed. 
Moderate/Heavy 
2 minutes 
Week 38 2 Sets Per Exercise without break 
between:  18 reps and 16 reps 
Moderate/Light 
2 minutes 
Week 39 3 Sets on each exercise of 6, 8, 12 
repetitions. Lower weights each 
set.  Medium speed. 
Moderate 
3 minutes 
Week 40 1 set 90 seconds focused on 
resistance.  Medium speed. 
Lighter 
2 minutes 
Week 41 Cardio Exercises.  10 exercises in a 
set.  2 Sets. 
Moderate 
3 minutes 
Week 42 1 Warm Up Set:  8 – 12 reps. 
1 Heavy Set:  8 – 12 reps.  Slower 
Speed. 
Moderate/Heavy 
2 minutes 
Week 43 3 Sets on each exercise of 6, 8, 12 
repetitions. Lower weights each 
set.  Medium speed. 
Moderate 
3 minutes 
Week 44 1 set 90 seconds focused on 
resistance.  Medium speed. 
Lighter 
2 minutes 
Week 45 1 Warm Up Set:  8 – 12 reps. 
1 Heavy Set:  8 – 12 reps.  Slower 
Speed. 
Moderate/Heavy 
2 minutes 
Week 46 3 Sets on each exercise of 6, 8, 12 
repetitions. Lower weights each 
set.  Medium speed. 
Moderate 
3 minutes 
Week 47 1 set 90 seconds focused on 
resistance.  Medium speed. 
Lighter 
2 minutes 
Week 48 1 Warm Up Set:  8 – 12 reps. 
1 Heavy Set:  8 – 12 reps.  Slower 
Speed. 
Moderate/Heavy 
2 minutes 
Week 49 3 Sets on each exercise of 6, 8, 12 
repetitions. Lower weights each 
set.  Medium speed. 
Moderate 
3 minutes 
Week 50 1 set 90 seconds focused on 
resistance.  Medium speed. 
Lighter 
2 minutes 
Week 51 1 Warm Up Set 8 reps 
1 Heavy Set 8 reps 
Heavy 
3 minutes 
Week 52 Cardio Exercises.  10 exercises in a 
set.  2 Sets. 
Moderate 
3 minutes 
 
GH Method:  List of Strength/Resistance Exercises 
MEN   
 
 
 
 
 
 
WOMEN  
Exercise 
Exercise 

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Chest:  Smith Bench Press/Incline 
Glutes:  Abductor 
Glutes:  Abductor 
Biceps:  Cable Easy Curl / Free Bar 
Biceps:  Cable Easy Curl/Free Bar 
Quads:  Leg Extension 
Quads:  Leg Extension 
Chest:  Smith Press 
Calves:  Calf Machine 
Abs:  Decline  
Biceps:  Preacher 
Quads:  Leg Press 
Quads:  Leg Press 
Back:  Pull Down Behind 
Quads:  Leg Extension 
Hamstring:  Machine  
Abs:   Decline 
Shoulders:  Dumbbell Press / Smith 
Press 
Back:  Pull Down Behind 
Triceps:  Push Down / Kick Back / Rope 
Pull down 
Hamstring:  Curl Machine 
Back:  Low Roll  
Shoulders:  Dumbbell Press / Smith Press 
Abs:  Sit-Ups  
Back:  Low Roll  
Shoulders:  Side Raise with Dumbbells 
Hamstring:  Good Morning with Dumbbell/ 1 Leg 
Hamstring Curl 
Triceps:  Close Grip 
Shoulders:  Side Rise with Dumbbells 
Hamstring:  Good Morning with 
Dumbbells/1 Leg Hamstring 
Triceps:  Push Down / Kick Back 
Triceps:  Push Down / Kick Back 
Abs:  Sit Ups 
Abs:  Sit Ups 
Triceps:  Close Grip 
Triceps:  Close Grip 
 
5)Statistical analyses: 
 
The efficacy of the methods will be determined by:  
 
1. a significant difference in term of pre and post treatment perception of well being 
between the groups 
 
2.a  significant difference in the lean/fat body mass ratio between the groups 
 
3. a significant difference in BMI between the groups 
 
 
 
 
 
 
4. a significant difference between the inflammatory parameters between the groups 
 
 
 
 
 
 
5. a significant difference between the metabolic parameters between the groups 
 
The data will be entered into an Excel spreadsheet and stored on the UIMCC hospital 
server. The patient data, including age, sex, race, underlying kidney disease, length of 
hospital stay, rejection episode, comorbidities, and medications will be coded and patient 
names will not be included in the datasheet.   
The de-identified collected data will be entered into a SAS database. Initial descriptive 
analysis will include calculating means, standard deviations, ranges and frequencies. T-
tests for continuous variables and Chi Square or Fischer exact tests of association for 

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categorical variables will be used to compare results of the study between the two groups 
for the efficacy parameters listed above. A P value<0.05 will be considered significant. 
 
 
6) Benefits/risks 
The main risk of this research is loss of confidentiality of medical information.  Consent 
will be obtained for all patients. Master patient code list will be kept in a separate file 
accessible only by the primary investigator. A member of the transplant team will be 
available to answer any questions or discuss any concerns that patients may have.   
 
The patient may experience mild anxiety or discomfort in providing information about 
their health and well-being. The patient may also have a potential to feel anxiety when 
being video recorded (if applicable). 
 
Risks associated with the exercise program 
The likely risks and discomforts expected in this study are those that largely involve 
being engaged in an exercise program after a prolonged period of inactivity. Such risks 
include: strains, sprains, and muscle soreness.  Serious physical injury is considered 
unlikely given the screening for inclusion and physician approval. We will attempt to 
reduce risks of injury and harm by promoting gradual increases in exercise across time 
throughout the 3 month period and having exercise be instructed and supervised by 
trained professional fitness personnel.  
 
Risks associated with the blood draw: 
The risks associated with a blood draw include: mild pain, bleeding or bruising at the site 
of the draw.  In general, any bruising should completely disappear within several days.  
There are minimal risks of fainting or hypotension (low blood pressure) during or after 
the blood draw. 
 
Risks associated with the Maximal Aerobic Capacity Test (VO2 Test) and the 6 minute 
walk test include: 
The risks associated with the treadmill max test and 6 minute walk test include: fatigue, 
being out of breath, muscle soreness, heart rhythm irregularities, dizziness, loss of 
consciousness and death.  However, serious adverse events (side effects) are very rare 
and by careful screening and monitoring during the test, the risk of such events are 
minimized. Further risks include slips, trips, ankle sprains and falls.  These risks will be 
minimized by having a research assistant within arm’s reach for stability. All personnel 
assisting in testing are trained in CPR and emergency lab procedure (including calling 
911 and the principal researcher) as outlined by the Department of Kinesiology and 
Nutrition’s procedures and policies.  
 
Risks associated with Vascular Function and Vascular Stiffness measures: 
There are no known risks associated with the ultrasound tests used to measure artery 
stiffness and heart function..  Because we will need to place 3 electrodes on the skin to 
measure heart rate during these procedures, we may need to shave the area on males 
where these will be placed which may cause some discomfort and/or redness. Some 

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adhesive may remain once electrodes are removed which may cause redness. This should 
wear off within 1-8 hours. For the assessment of endothelial function (FMD), the act of 
inflating a blood pressure cuff around the arm for five minutes before deflation may 
cause some discomfort, temporary numbness, or tingling. These discomforts, however 
generally last for a minimal amount of time post deflation. 
 
Risks associated with the Biodex include 
Risks associated with the measure of muscular strength (Biodex) testing include strains, 
sprains, and muscle soreness, as with an exercise program.   
 
 
Measures of Physical Activity: 
There are no risks associated with the accelerometer. Some other risks include shortness 
of breath, fatigue and rarely heart attack or stroke, and very rarely dealth.  
 
 
Radiation Exposure from the DEXA  scan:The duration of the scan will be less than 10 
min. The participant will be exposed to a radiation dose of less than or equal to 0.3 mrem 
based upon manufacturer’s specifications and pre-determined calculations.  This amount 
of radiation exposure is minimal given the estimated effective equivalent dose is below 
100 mrem per year, a limit set by the Nuclear Regulatory Commission for “general 
public” exposure. 
 
 
Risks of Muscle Biopsy and lidocaine use 
Risks of a muscle tissue biopsy include bleeding, bruising, and infection at the procedure 
site. A subfascial hematoma (a pocket of blood that forms beneath the fatty layer of the 
skin next to the muscle) may occur. Medical conditions or use of medications or 
supplements that causes excessive bleeding creates a higher risk of bleeding from the 
procedure site. Risk associated with any surgical procedure include infection. Due to the 
immunosuppressant drugs these patients are on as part of standard care, this risk may be 
increased, however the procedure will be done in a sterile environment with a minimal 
incision to protect against infection. Less common risks include muscle contracture 
(shortening of the muscle) and nerve damage leading to loss of feeling at or around the 
procedure site. Arm may be tender or sore for 2 to 3 days post biopsy. Common side 
effects of lidocaine include injection site pain, feeling lightheaded, shaking, low blood 
pressure, drowsiness, confusion, weakness, blurry or double vision, and dizziness. 
Serious reactions such as seizures, abnormal heart beats, slow heart beat, heart block, 
severe allergic reactions, respiratory arrest, and coma have occurred.  
 
 
Benefits 
This study is not being done to improve the subject’s health.   We anticipate that the 
results of this study will contribute to our understanding of exercise training effects on 
persons who have had a kidney transplant. It is hopeful that the knowledge gained from 
this research will benefit others who undergo kidney transplant in the future. 

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The patients in the supervised physical therapy and GH arms will have the benefit of 
increased supervision of their physical activity and nutrition compared to what is 
normally provided per standard of care. In order to assure safety, a medical doctor within 
the department of surgery who is not affiliated with this research will be appointed to 
review patient outcomes and monitor the research.   
 
REFERENCES 
 
1. Porrini E, Delgado P, Bigo C, Alvarez A, Cobo M, Checa MD, et al. Impact of 
metabolic syndrome on graft function and survival after cadaveric renal 
transplantation. Am J Kidney Dis 2006;48(1):134–42.  
2. Honda H, Qureshi AR, Axelsson J, Heimburger O, Suliman ME, Barany P, 
Stenvinkel P, Lindholm B. Obese sarcopenia in patients with end-stage renal disease 
is associated with inflammation and increased mortality. Am J Clin Nutr. 2007 
Sep;86(3):633-8. 
3. Ikizler TA, Wingard RL, Harvell J, Shyr Y, Hakim RM. Association of morbidity 
with markers of nutrition and inflammation in chronic hemodialysis patients: a 
prospective study. Kidney Int. 1999 May;55(5):1945-51. 
4. Bosma RJ, Kwakernaak AJ, van der Heide JJ, de Jong PE, Navis GJ. Body mass 
index and glomerular hyperfiltration in renal transplant recipients: cross-sectional 
analysis and long-term impact. Am J Transplant. 2007;7(3):645–52. 
5. Stengel B, Tarver-Carr ME, Powe NR, Eberhardt MS, Brancati FL. Lifestyle factors, 
obesity and the risk of chronic kidney disease. Epidemiology. 2003;14(4):479–87. 
6. Khan IH, Catto GR, Edward N, Fleming LW, Henderson IS, MacLeod AM. Influence 
of coexisting disease on survival on renal-replacement therapy. Lancet. 1993 Feb 
13;341(8842):415-8. 
7. Wright RS, Reeder GS, Herzog CA, Albright RC, Williams BA, Dvorak DL, Miller 
WL, Murphy JG, Kopecky SL, Jaffe AS. Acute myocardial infarction and renal 
dysfunction: a high-risk combination. Ann Intern Med. 2002 Oct 1;137(7):563-70. 
8. Painter PL, Hector L, Ray K, et al. A rancdomized trial of exercise training after renal 
transplantation. Transplantation 2002;74:42-8. 
9. Dubowitz V., Sewry CA, and Oldfors, A. Muscle biopsy: A practical approach. 4th 
ed.  2013 : 2-3. 

Physical Activity in KT 
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Baseline 
6 months 
12 months 
Screening & 
consent 
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X 
BMI 
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X 
X 
DEXA 
X 
X 
X 
Biodex 
X 
X 
X 
6 minute walk test 
X 
X 
X 
7 day accelerometer 
X 
X 
X 
Vascular function 
and stiffness  
X 
X 
X 
Blood draw 
X 
X 
X 
Questionnaires 
X 
X 
X 
Muscle Biopsy 
 
 
X