Metabolomics for Identifying Biomarkers of Dietary Intake and Kidney Disease Progression

Study Overview
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Brief Summary
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The present record represents a secondary data analysis of the Modification of Diet in Renal Disease (MDRD) Study. For this analysis, the MDRD study data and specimens were retrieved from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repository. A global, untargeted, metabolomic profile was used to investigate biomarkers of dietary intake as well as biomarkers of kidney disease progression.

Detailed Description
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The present study was conducted in order to: 1) quantify the metabolomic expression of dietary intake; and 2) examine the relationship between metabolites that reflect dietary intake and kidney disease progression. This secondary data analysis leverages the completed Modification of Diet in Renal Disease (MDRD) study, a randomized clinical trial of dietary protein restriction (N=840).

Official Title
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Metabolomics for Identifying Biomarkers of Dietary Intake and Kidney Disease Progression: A Secondary Data Analysis of the Modification of Diet in Renal Disease (MDRD) Study

Conditions
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Dietary Modification, Kidney Diseases, Chronic

Intervention / Treatment
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* Behavioral: Usual protein and phosphorus diet
* Behavioral: Low protein and phosphorus diet
* Behavioral: Very low protein and phosphorus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-70 Evidence of chronic renal disease with increased serum creatinine (men: 1.4-7.0 mg/dL, women: 1.2-7.0 mg/dL) Mean arterial blood pressure less than or equal to 125 mmHg Exclusion Criteria: Insulin-dependent diabetes Kidney transplant recipient

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The present study consists of a secondary data analysis of the MDRD Study. Planned analyses will be limited to participants with available stored specimens. The original MDRD Study was a 2 x 2 factorial study design, in which individuals were randomized to amounts of protein and phosphorus intake and levels of blood pressure control. In this secondary data analysis, we will analyze metabolites according to level of protein intake and will adjust for the blood pressure intervention.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Usual protein and phosphorus diet<br>protein: 1.3 g/kg/day, phosphorus: 16-20 mg/kg/day | Behavioral: Usual protein and phosphorus diet<br>* Diet intervention<br>|
| Active Comparator: Low protein and phosphorus diet<br>protein: 0.58 g/kg/day with ≥0.35 g of protein high in amino acids, phosphorus: 5-10 mg/kg/day | Behavioral: Low protein and phosphorus diet<br>* Diet intervention<br>|
| Experimental: Very low protein and phosphorus<br>protein: 0.28 g/kg/day, phosphorus: 4-9 mg/kg/day; keto-acid and amino acid supplement (0.28 g/kg/day) | Behavioral: Very low protein and phosphorus<br>* Diet intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum metabolomic profile | Metabolites were measured using a global, untargeted, metabolomic platform in serum specimens collected at the 12 month follow-up visit in the MDRD Study. Reverse phase, untargeted ultra-performance liquid chromatography tandem mass spectrometry quantification was used to measure metabolites. Peaks were quantified by calculating the area under the curve. Data were normalized to account for day-to-day instrumental variation. Compounds were identified by comparison to a library of purified standards or recurrent unknown entities and matches were determined based on retention time, mass-to-charge ratio, and chromatographic data. | 12 month follow-up visit |