Chronic Kidney Disease in Relation to Alterations in Protein and Amino Acid Metabolism and Function

Study Overview
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Brief Summary
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Weight loss commonly occurs in patients with chronic kidney disease (CKD), negatively influencing their quality of life, treatment response and survival. Loss of muscle protein is generally a central component of weight loss in CKD patients but patients also have reductions in fat mass and bone density, independent of the severity of the disease state. Attempts to reverse weight and muscle loss in CKD and improve nutritional status by nutritional supplementation have been unsuccessful and there are currently no approved therapies. Purpose of this study is to provide detailed insight in disease related gut function by obtaining information on gut permeability, digestion and absorption of glucose, fat and protein in CKD patients compared to matched healthy controls. Additionally, to examine whether protein and amino acid metabolism is disturbed in CKD patients compared to healthy controls. This will provide required information that will lead to implement new strategies to develop optimal nutritional regimen in order to enhance nutritional status, quality of life and survival in relation to kidney disease.

Detailed Description
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This study involves one test day of approximately 7-8 hours. On this test day subjects will ingest a sugar drink to assess gut permeability and gut function, and a protein meal to measure digestion/absorption and the anabolic response to food intake. Subjects will also receive a mixture of amino acids that are made a little heavier than normal, called stable isotopes. This stable isotopes is used to investigate protein behavior in the body (protein kinetics). Blood (100-120 ml in total) and urine samples will be collected over 7.5 hours.

Official Title
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Chronic Kidney Disease in Relation to Alterations in Protein and Amino Acid Metabolism and Function

Conditions
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Chronic Kidney Failure

Intervention / Treatment
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* Dietary Supplement: Boost High Protein


Participation Criteria
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Eligibility Criteria
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Inclusion criteria CKD subjects Ability to walk, sit down and stand up independently Age 55 years or older Ability to lie in supine or elevated position for 7 hours Diagnosis of kidney disease; undergoing hemodialysis Clinically stable condition; no hospitalization 4 weeks preceding first study day Willingness and ability to comply with the protocol Inclusion criteria healthy subjects: Healthy male or female according to the investigator's or appointed staff's judgment Ability to walk, sit down and stand up independently Age 55 years or older (older control group) Ability to lay in supine or elevated position for 7 hours No diagnosis of CKD Willingness and ability to comply with the protocol Exclusion Criteria all subjects: Any condition that may interfere with the definition 'healthy subject' according to the investigator's judgment (healthy subjects only) Established diagnosis of malignancy Established diagnosis of Insulin Dependent Diabetes Mellitus History of untreated metabolic diseases including hepatic disorder Presence of acute illness or metabolically unstable chronic illness Presence of fever within the last 3 days Body mass index >40 kg/m2 (healthy subjects only) Any other condition that would interfere with the study or safety of the patient (according to the PI or nurse) Use of protein or amino acid containing nutritional supplements within 5 days of first study day Use of long-term oral corticosteroids or short course of oral corticosteroids within 4 weeks preceding first study day Failure to give informed consent or Investigator's uncertainty about the willingness or ability of the subject to comply with the protocol requirements (Possible) pregnancy

Ages Eligible for Study
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Minimum Age: 55 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: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Boost High Protein<br>Boost high protein with added spirulina | Dietary Supplement: Boost High Protein<br>* Subjects will receive stable amino acid isotopes IV and will receive Boost High Protein with added isotopes to measure anabolic response to a meal.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Net whole-body protein synthesis | Change in whole-body protein synthesis rate after intake of meal | 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Citrulline Rate of appearance | Plasma enrichment of citrulline | Postabsorptive state during 3 hours | 
| Glucose absorption | Recovery of 3-O-Methyl-D-glucose in the urine. | 7 hours | 
| Gut permeability | Recovery of rhamnose/lactulose in urine | 7 hours | 
| Skeletal and respiratory muscle strength | Difference in leg strength and fatigue, handgrip strength and fatigue, and inspiratory and expiratory pressure between heart failure patients and healthy controls. | 1 day | 
| Cognitive function | Outcome of neuro-psychological tests in heart failure patients and healthy controls in relation to the tryptophan metabolism | 1 day | 
| Fatty acid digestion after feeding | Enrichment in palmitic acid and tripalmitin fatty acids in plasma | 0,15,30,45,60,75,90,105,120,150,180,210 min post-meal | 
| Protein digestion after feeding | Ratio enrichment free phenylalanine vs phenylalanine from protein spirulina | 0,15,30,45,60,75,90,105,120,150,180,210, min post-meal | 
| Arginine turnover rate | Arginine enrichment in plasma | Postabsorptive state during 3 hours | 
| Whole body collagen breakdown rate | Hydroxyproline enrichment in plasma | Postabsorptive state during 3 hours | 
| Tryptophan turnover rate | Tryptophan enrichment in plasma | Postabsorptive state during 3 hours | 
| Insulin response to feeding | Acute change from postabsorptive state after intake of meal | During 3 hours after feeding | 
| Fat-free mass | Characteristics of study subjects | Postabsorptive state during 15 min | 
| Myofibrillar protein breakdown rate | 3-Methylhistidine enrichment in plasma | 0,15,30,45,60,75,90,105,120,150,180,210 min post-meal | 
| Glycine rate of appearance | Glycine enrichment in plasma | Postabsorptive state during 3 hours | 
| Taurine turnover rate | Enrichment of taurine in plasma | Postabsorptive state during 3 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CKD, Hemodialysis, Protein Digestion, Fat Digestion, Gut Function, Glucose Absorption, Muscle Function