Protein and Exercise Training in Chronic KIDNEY Disease

Study Overview
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Brief Summary
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When patients progress to the final stage of chronic kidney disease (CKD) and require hemodialysis treatment, they typically have lost so much muscle function that they are no longer physically independent. However, due to disease- and hemodialysis-related muscle catabolism, dietary protein and exercise interventions are only capable to attenuate the decline in physical function of patients on hemodialysis treatment. Therefore, lifestyle interventions to increase muscle function should be implemented before hemodialysis is required. However, it is still a matter of debate whether muscle protein synthesis rates of patients with advanced CKD can be increased with a patient-tailored dietary protein and exercise intervention.Therefore, the current study will assess MPS rates during habitual lifestyle and during an interventional program including dietary protein and exercise in patients with advanced CKD. In addition, we will compare MPS rates during free-living conditions between patients with advanced CKD and healthy controls.

Official Title
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Protein Supplementation and Exercise Training to Increase Muscle Protein Synthesis Rates in Patients With Advanced Chronic Kidney Disease

Conditions
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Kidney Diseases, Muscle Loss

Intervention / Treatment
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* Dietary Supplement: Whey protein


Participation Criteria
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Eligibility Criteria
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In order to be eligible to participate in this study, a patient with CKD must meet all of the following criteria: (e)glomerular filtration rate (GFR) <45 ml/min/1.73m2 Age: 18 - 80 y Able to provide written informed consent In order to be eligible to participate in this study, a healthy subject must meet all of the following criteria: (e)GFR >60 ml/min/1.73m2 without albuminuria Age: 18 - 80 y Able to provide written informed consent 1. A potential subject with CKD who meets any of the following criteria will be excluded from participation in this study: Insulin-dependent diabetes mellitus or two or more oral glucose lowering medications Active inflammatory disease / malignancies Uncontrolled hypertension (>160/100mm Hg), unstable angina pectoris, or arrhythmia Pulmonary disease restricting exercise performance (e.g. COPD) A history of neuromuscular problems Cognitive Impairment Diagnosed GI tract diseases / dysphagia Allergies to milk proteins / Lactose intolerance Pregnancy Hospitalization <1 months prior to study period Participation in any structured exercise program Any medications known to affect protein metabolism (i.e. corticosteroids or prescription strength acne medications). Use of DOAC, vitamin-K-antagonist, or multiple anticoagulants. Dialysis treatment or previous kidney transplantation 2. A potential healthy subject who meets any of the following criteria will be excluded from participation in this study: Insulin-dependent diabetes mellitus or two or more oral glucose lowering medications Active inflammatory disease / malignancies Uncontrolled hypertension (>160/100mm Hg), unstable angina pectoris, or arrhythmia Pulmonary disease restricting exercise performance (e.g. COPD) A history of neuromuscular problems Cognitive Impairment Diagnosed GI tract diseases / dysphagia Allergies to milk proteins / Lactose intolerance Pregnancy Hospitalization <1 months prior to study period Participation in any structured exercise program Any medications known to affect protein metabolism (i.e. corticosteroids or prescription strength acne medications). Use of DOAC, vitamin-K-antagonist, or multiple anticoagulants.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized crossover study (1-week intervention vs. 1-week habitual lifestyle) for both patients with advanced CKD and healthy controls
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Habitual lifestyle period<br>All participants will be encouraged to keep their diet and physical activity similar to before the study period. Subjects will be asked to record their food intake and wear an Actical physical activity monitor for 3 days throughout the habitual lifestyle period (2 week days and 1 weekend day). All participants will be asked to ingest 20 mL deuterated water and take a saliva sample daily | |
| Experimental: Exercise training period<br>All participants will be encouraged to keep their diet and physical activity similar to before the study period. Subjects will be asked to record their food intake and wear an Actical physical activity monitor for 3 days throughout the exercise training period (2 week days and 1 weekend day). Participants will be asked to ingest 20 mL deuterated water and take a saliva sample daily Participants will visit the University three times with 2-day intervals (e.g. Monday-Wednesday-Friday) for an exercise training session as described in 5.6. Following the training sessions, participants will be provided with a protein supplement as described in 5.7. Before and after ingestion of the protein supplement, participants will be asked to fill in a gastrointestinal tolerance and palatability survey. | Dietary Supplement: Whey protein<br>* Throughout 1 week (either in week 1 or 2), all participants will perform a 1-week resistance type exercise-training program, consisting of two different exercises. Leg press and leg extension exercise will be performed on regular weightlifting machines (Technogym, Rotterdam) at 3 days during the 1-week period (e.g. Monday-Wednesday-Friday). During the resistance exercise training protocol, participants will continue their habitual diet as usual. However, patients with CKD will be provided with a protein supplement following the exercise sessions.<br>* Other names: Resistance exercise;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle protein synthesis rates | Muscle protein synthesis rates as measured by the deuterated water method | 1-week period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical activity levels | as measured by accelerometry | 1-week period | 
| Dietary intake (energy/macronutrient) | as measured by dietary diaries | 1-week period | 
| Leg fat free mass | as measured by DEXA | Baseline | 
| Body composition | as measured by BIA | Baseline | 
| Type I and II skeletal muscle fiber size | of muscle biopsy of vastus lateralis | Baseline | 
| Skeletal muscle mitochondrial bioenergetics | of muscle biopsy of vastus lateralis | Baseline | 
| Muscle strength | 1-RM max testing of leg press and leg extension | Baseline | 
| Aerobic capacity | VO2-peak test on ergometer | Baseline |