Metabolic and Inflammatory Responses to Hemodialysis and the Effect of a Meal

Study Overview
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Brief Summary
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The objective of this study is to characterize the hormonal and inflammatory responses to hemodialysis, and to determine the effect of a meal versus fast on the metabolic changes in the post-dialytic phase.

Detailed Description
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Studies show that hemodialysis (HD) is a protein catabolic event per se and probably contributes to the high prevalence of protein-energy wasting among HD patients. The muscle catabolic effect of HD is probably caused by loss of amino acids (10-12 grams per dialysis session) and by exacerbation of the inflammatory and hormonal disorders already present. Activation of the immune system during HD has been linked to the contact of blood cells with the dialyzer membrane and to bacterial-derived DNA fragments in the dialysis fluid. An intradialytic increase in interleukin-6 (IL-6) has been shown to correlate with muscle protein catabolism, and because IL-6 continues to increase for 2 hours after HD has ended, there might be a considerable carry-over effect to the post-dialytic period. Moreover, HD induces significant changes in the insulin/insulin-like growth factor I (IGF-I) signaling pathways. Plasma insulin is cleared by HD, and the bioactivity of IGF-I is reduced by 50% during a 4-hr maintenance HD due to an up-regulation of IGF-binding protein 1 (IGFBP-1), the only acutely regulated IGFBP.

Official Title
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Metabolic and Inflammatory Responses to Hemodialysis and the Effect of a Meal

Conditions
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Kidney Failure, Chronic

Intervention / Treatment
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* Dietary Supplement: Double meal


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: > 18 years stable maintenance hemodialysis for at least 3 months well-functioning arteriovenous shunts with recirculation less than 5% informed consent Exclusion criteria: diabetes mellitus body mass index below 18.5 or above 30.0 kg/m2 malnutrition (global assessment score C) active malignant disease immunosuppressive treatment (including glucocorticoid treatment) evidence of an ongoing inflammatory disease (including infection and autoimmune disorders) pregnancy Exclusion criteria during the study: myocardial infarction or arrythmia with hemodynamic derangements permanent thrombosis in the arteriovenous (AV) shunt severe infectious disease renal transplantation

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Double meal on a HD day<br>A standardized meal is served 1 h after start of HD and 1 h after end of HD | Dietary Supplement: Double meal<br>* A standardized meal is served 1 h after start of HD and 1 h after end of HD.<br>|
| No Intervention: Single meal on a HD day<br>A standardized meal is served 1 h after start of HD. After the meal participants fast for 9 h (6 h after end of HD). | |
| No Intervention: Single meal on a non-HD day<br>A standardized meal is served 1 h after study start. After the meal participants fast for 9 h. | |
| No Intervention: Single meal (healthy controls)<br>A standardized meal is served 1 h after study start. After the meal participants fast for 9 h. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in serum Bioactive IGF-I and IGFBP-1 levels during and after hemodialysis |  | At 1, 2, 3, 5, 6, 7, 9, and 10 hours after start of hemodialysis | 
| Changes in plasma Interleukin-6 and serum hsCRP levels during and after hemodialysis |  | At 1, 2, 3, 5, 6, 7, 9, and 10 hours after start of hemodialysis | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulse wave analysis (augmentation index (AIx)) during and after hemodialysis |  | At 1, 2, 3, ,4, 5, 6, 7, 8, 9, and 10 hours after start of hemodialysis | 
| Mineral metabolism (including calcium, phosphate, PTH, and FGF-23 levels) during and after hemodialysis |  | At 1, 2, 3, 5, 6, 7, 9, and 10 hours after start of hemodialysis | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dialysis, Protein-energy wasting, Insulin-Like Growth Factor I, Insulin-Like Growth Factor Binding Protein 1, Inflammation