Metabolomics for Identifying Biomarkers of Dietary Intake and Kidney Disease Progression (MDRD)

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

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.

Study Overview

• Status: Completed
• Conditions: Dietary Modification; Kidney Diseases, Chronic
• Intervention / Treatment: Behavioral: Usual protein and phosphorus diet; Behavioral: Low protein and phosphorus diet; Behavioral: Very low protein and phosphorus

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 840
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Bloomberg School of Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Usual protein and phosphorus diet; protein: 1.3 g/kg/day, phosphorus: 16-20 mg/kg/day	Behavioral: Usual protein and phosphorus diet; Diet intervention
Active Comparator: Low protein and phosphorus diet; 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; Diet intervention
Experimental: Very low protein and phosphorus; 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; Diet intervention

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Johns Hopkins Bloomberg School of Public Health
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Tufts Medical Center
• Investigators: Principal Investigator: Casey M. Rebholz, PhD, MPH, MS, Johns Hopkins Bloomberg School of Public Health

Publications and helpful links

General Publications

• Levey AS, Adler S, Caggiula AW, England BK, Greene T, Hunsicker LG, Kusek JW, Rogers NL, Teschan PE. Effects of dietary protein restriction on the progression of advanced renal disease in the Modification of Diet in Renal Disease Study. Am J Kidney Dis. 1996 May;27(5):652-63. doi: 10.1016/s0272-6386(96)90099-2.
• Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek JW, Striker G. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group. N Engl J Med. 1994 Mar 31;330(13):877-84. doi: 10.1056/NEJM199403313301301.
• Rebholz CM, Zheng Z, Grams ME, Appel LJ, Sarnak MJ, Inker LA, Levey AS, Coresh J. Serum metabolites associated with dietary protein intake: results from the Modification of Diet in Renal Disease (MDRD) randomized clinical trial. Am J Clin Nutr. 2019 Mar 1;109(3):517-525. doi: 10.1093/ajcn/nqy202.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 1988
• Primary Completion (Actual): May 1, 1993
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: June 23, 2017
• First Submitted That Met QC Criteria: June 26, 2017
• First Posted (Actual): June 29, 2017

Study Record Updates

• Last Update Posted (Actual): June 29, 2017
• Last Update Submitted That Met QC Criteria: June 26, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Disease Progression; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: IRB00007383; K01DK107782 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No