Low Protein Diet, Gut Microbiome and Chronic Kidney Disease

Exploring the Role of Low Protein Diet on the Gut Microbiome, Related Metabolites and Renal Function in Chronic Kidney Disease

Chronic kidney disease (CKD) is a worldwide public health dilemma because of close association with multiple comorbidities, demanding high cardiovascular events, mortality and expensive medical cost. Novel and effective therapeutic measures remain urgently needed to reduce burden and impact of disease. Advanced renal failure can profoundly alter the biochemical milieu of the gastrointestinal tract leading to a leak gut. Application of 16s rRNA gene analysis identified an increase of Clostridia, Actinobacteria, and Gammaproteobacteria in hemodialysis patients and decrease of Bifidobacterium and lactobacillus in peritoneal patients. This altered microbiome consequently affect production of indole or phenol derived uremic toxins leading to renal damage. Our preliminary results indicated reduced number and diversity of intestinal microbes CKD patients compared to normal. Different dietary nutrients can affect the gut microbiome and derive several deleterious metabolites leading to metabolic disarrangement. Clinically, low-protein diet should be prescribe to renal patients to preserve renal function and high fat content are usually recommended to avoid caloric malnutrition to dietary restriction. The changes of diet-microbiome-metabolite interaction are large unknown with this dietary manipulation. The aims of this study is to determine the renal progression-associated gene and taxonomic alterations bymetagenome-wide association studies and the functional characterization of gut microbiome in CKD patients receiving different low-protein or high-fat diets. The results of the study will provide insight on the exact role of dietary manipulation in CKD patients from gut-renal cross talk.

Study Overview

• Status: Unknown
• Conditions: Chronic Kidney Diseases
• Intervention / Treatment: Other: low protein diet

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Keelung, Taiwan, 204
    • Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. . Patients aged 30-90 years with diagnosis of CKD (defined as abovementioned).
2. . Sign the inform consent and agree to participate in this study.
3. . Compliant to low protein diet (defined as protein intake <0.8 g/Kg/day) for 4 weeks assessed by 24h urine urea estimates, before enrollment

Exclusion Criteria:

1. . History of any malignancy, liver cirrhosis, intestinal operation, irritable bowel syndrome, cardiovascular disease (defined as myocardial infarction, documented Q wave on EKG, unstable angina, coronary artery disease with stenosis > 75%, congestive heart failure with Ejection Fraction < 50% and cerebrovascular disease) in the past 3 months.
2. . History of or infection disease requiring admission in the past 3 months or, concomitant antibiotics use.
3. . Concomitant use of probiotics or prebiotics.
4. . Pregnancy.
5. . Renal transplant recipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: normal controls; subjects with normal renal function
Experimental: CKD_Low protein diet; CKD patient with low protein diet (<0.8g/kg/BW)	Other: low protein diet; Low protein diet (<0.8g/kg/BW/day)
Active Comparator: CKD_normal protein diet; CKD patient with normal protein diet	Other: low protein diet; Low protein diet (<0.8g/kg/BW/day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change of gut microbiota	change of relative abundance of microbes	3 months
change of host metabolite concentration	change of concentration of serum metabolomic profile	3 months
change of renal function	serum creatinine, estimated glomerular filtration rate or urine total protein	3 months

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Collaborators: Ministry of Science and Technology, Taiwan
• Investigators: Principal Investigator: I Wen Wu, Chang Gung Memorial Hospital

Publications and helpful links

General Publications

• Wu IW, Lee CC, Hsu HJ, Sun CY, Chen YC, Yang KJ, Yang CW, Chung WH, Lai HC, Chang LC, Su SC. Compositional and Functional Adaptations of Intestinal Microbiota and Related Metabolites in CKD Patients Receiving Dietary Protein Restriction. Nutrients. 2020 Sep 12;12(9):2799. doi: 10.3390/nu12092799.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Actual): July 31, 2020
• Study Completion (Anticipated): October 31, 2021

Study Registration Dates

• First Submitted: January 19, 2021
• First Submitted That Met QC Criteria: August 20, 2021
• First Posted (Actual): August 25, 2021

Study Record Updates

• Last Update Posted (Actual): August 25, 2021
• Last Update Submitted That Met QC Criteria: August 20, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: IWW-0008

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