Metabolomics for Identifying Biomarkers of Dietary Intake and Kidney Disease Progression

NCT03202914 | Completed

• 2 other identifiers: IRB00007383K01DK107782
• Study Type: interventional
• Target: 840
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Dietary Modification; Kidney Diseases, Chronic

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

Usual protein and phosphorus diet

ACTIVE COMPARATOR

protein: 1.3 g/kg/day, phosphorus: 16-20 mg/kg/day

Behavioral: Usual protein and phosphorus diet

Low protein and phosphorus diet

ACTIVE COMPARATOR

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

Very low protein and phosphorus

EXPERIMENTAL

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

Interventions

Usual protein and phosphorus diet BEHAVIORAL

Diet intervention

Usual protein and phosphorus diet

Low protein and phosphorus diet BEHAVIORAL

Diet intervention

Low protein and phosphorus diet

Very low protein and phosphorus BEHAVIORAL

Diet intervention

Very low protein and phosphorus

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Insulin-dependent diabetes
• Kidney transplant recipient

Sponsors & Collaborators

• Johns Hopkins Bloomberg School of Public Health: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Tufts Medical Center: collaborator

Study Sites (1)

Johns Hopkins Bloomberg School of Public Health

Baltimore, Maryland, 21287, United States

Location

Related Publications (3)

• 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.

  PMID: 8629624 RESULT

• 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.

  PMID: 8114857 RESULT

• 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.

  PMID: 30753252 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Diet, Protein-Restricted; Phosphorus

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Elements; Inorganic Chemicals

Study Officials

• Casey M. Rebholz, PhD, MPH, MS

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: During the original MDRD Study, clinical center personnel as well as study participants were masked to the results of the outcome assessment during the follow-up period.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 23, 2017
• First Posted: June 29, 2017
• Study Start: October 1, 1988
• Primary Completion: May 1, 1993
• Study Completion: January 1, 2016
• Last Updated: June 29, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)