Effects of High Dietary Fiber Supplementation in Diabetic Chronic Kidney Disease

Effects of High Dietary Fiber Supplementation on Uremic Retention Molecules and Inflammation in Diabetic Chronic Kidney Disease (CKD)

Loss of kidney function results in accumulation in the blood of molecules that are either excreted or metabolized by the kidney. Collectively, these molecules are termed Uremic Retention Molecules (URMs) or toxins. It is increasingly recognized that colonic bacterial metabolites like p-cresyl sulfate and indoxyl sulfate that are absorbed from the colon and excreted by the kidney may contribute to the pool of compounds implied in uremic toxicity. Indeed, these URMs have been linked to increased levels of inflammation markers, chronic kidney disease (CKD) progression, cardiovascular disease and overall mortality in CKD and/ or hemodialysis patients. Therefore, interventions that target the production or absorption of URMs from the gut might decrease inflammation and oxidative stress that are commonly seen in the uremic milieu. The National Health and Nutrition Examination Survey III (NHANES III) data show that high dietary fiber intake is associated with decreased serum levels of C-reactive protein (CRP) in those with and without CKD and these associations are much stronger in the CKD population. A possible explanation of this effect is that a high fiber diet in CKD patients modulates the bacterial production, intestinal absorption and finally the serum levels of URMs like p-cresyl sulfate and indoxyl sulfate, which in turn results in decrease in inflammation.

OBJECTIVES:

Hypothesis:

1. Higher serum levels of markers of inflammation such as high sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6) and tumor necrosis factor (TNF) -α seen in stage 4 CKD (estimated Glomerular Filtration Rate 15-29 ml/min/1.73 m2) compared to stage 2 CKD (estimated Glomerular Filtration Rate 60-89 ml/min/1.73 m2) is partly explained by the higher circulating levels of URMs (p-cresyl sulfate and indoxyl sulfate) in stage 4 CKD, and
2. Dietary supplementation in stage 4 CKD with 30g/d of a soluble fiber Psyllium (brand name-Metamucil TM) will decrease circulating URMs levels and thereby, decrease serum levels of inflammation markers and urinary levels of transforming growth factor (TGF)-β, a marker of kidney fibrosis.

Study Overview

• Status: Completed
• Conditions: Kidney Disease
• Intervention / Treatment: Dietary supplement: psyllium

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah nephrology clinics, the internal medicine and endocrinology clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with or without diabetes and Stage 1 or 2 CKD (estimated Glomerular Filtration Rate > 60 mL/min/1.73 m2) with urine dipstick positive for protein or urinary albumin/ creatinine > 30 mg/g of creatinine; or
• Stage 3 or 4 CKD (estimated Glomerular Filtration Rate < 60 to 15 mL/min/1.73 m2).

Exclusion Criteria:

• Pregnant women
• Prisoners
• Bowel obstruction
• Enrolled in other interventional studies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chronic Kidney Disease Stage 3-4; Study participants with stage 3 or 4 CKD will receive 15 grams/day of soluble fiber psyllium for the first week, followed by 30 grams/day of a soluble fiber psyllium for 4 months.	Dietary supplement: psyllium; 15 grams/day for 1 week, followed by 30 grams/day for 4 months; Other Names: Metamucil
No Intervention: Chronic Kidney Disease Stage 1-2; Study participants with stage 1 or 2 CKD will not receive study treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
p-cresyl sulfate serum concentration	Comparison of serum p-cresyl sulfate concentration between Stage 3-4 CKD subjects (following treatment with soluble fiber psyllium) and Stage 1-2 CKD subjects (having received no study treatment)	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Indoxyl sulfate serum concentration	Comparison of serum indoxyl sulfate concentration between Stage 3-4 CKD subjects (following treatment with soluble fiber psyllium) and Stage 1-2 CKD subjects (having received no study treatment)	4 months
Interleukin-6 (IL-6) serum concentration	Comparison of serum IL-6 concentration between Stage 3-4 CKD subjects (following treatment with soluble fiber psyllium) and Stage 1-2 CKD subjects (having received no study treatment)	4 months

Collaborators and Investigators

• Sponsor: University of Utah
• Investigators: Principal Investigator: Nestor Almeida, MD, University of Utah

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: January 30, 2013
• First Submitted That Met QC Criteria: April 23, 2013
• First Posted (Estimate): April 24, 2013

Study Record Updates

• Last Update Posted (Estimate): August 11, 2016
• Last Update Submitted That Met QC Criteria: August 9, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Fiber; Kidney Disease; Dietary Intervention
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Gastrointestinal Agents; Cathartics; Psyllium
• Other Study ID Numbers: IRB_00052609

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No