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

Texas A&M University

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

SUPPORTIVE_CARE

Masking

NONE

Conditions

Chronic Kidney Failure

Eligibility

Sex: ALLMin age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Net whole-body protein synthesis

Change in whole-body protein synthesis rate after intake of meal

Time frame: 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal

Secondary Outcomes

Citrulline Rate of appearance

Plasma enrichment of citrulline

Time frame: Postabsorptive state during 3 hours

Glucose absorption

Recovery of 3-O-Methyl-D-glucose in the urine.

Time frame: 7 hours

Gut permeability

Recovery of rhamnose/lactulose in urine

Time frame: 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.

Time frame: 1 day

Cognitive function

Outcome of neuro-psychological tests in heart failure patients and healthy controls in relation to the tryptophan metabolism

Time frame: 1 day

Fatty acid digestion after feeding

Enrichment in palmitic acid and tripalmitin fatty acids in plasma

Time frame: 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

Time frame: 0,15,30,45,60,75,90,105,120,150,180,210, min post-meal

Arginine turnover rate

Arginine enrichment in plasma

Time frame: Postabsorptive state during 3 hours

Whole body collagen breakdown rate

Hydroxyproline enrichment in plasma

Time frame: Postabsorptive state during 3 hours

Tryptophan turnover rate

Tryptophan enrichment in plasma

Time frame: Postabsorptive state during 3 hours

Insulin response to feeding

Acute change from postabsorptive state after intake of meal

Time frame: During 3 hours after feeding

Fat-free mass

Characteristics of study subjects

Time frame: Postabsorptive state during 15 min

Myofibrillar protein breakdown rate

3-Methylhistidine enrichment in plasma

Time frame: 0,15,30,45,60,75,90,105,120,150,180,210 min post-meal

Glycine rate of appearance

Glycine enrichment in plasma

Time frame: Postabsorptive state during 3 hours

Taurine turnover rate

Enrichment of taurine in plasma

Time frame: Postabsorptive state during 3 hours

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes