Intestinal Transport of Microbial Metabolites in Chronic Kidney Disease

The Influence of Chronic Kidney Disease on Intestinal Transport of Gut Microbial Metabolites

Chronic kidney disease is associated with the accumulation of various metabolites, i.e., uremic retention solutes. Evidence is mounting that the colonic microbiome contributes substantially to these uremic retention solutes. Indoxyl sulfate and p-cresyl sulfate are among the most extensively studied gut microbial metabolites, and are associated with cardiovascular disease, chronic kidney disease progression and overall mortality. Mechanisms governing their intestinal uptake and metabolism, however, are currently unknown. The investigators aim to explore these transport characteristics in depth. Therefore, colonic biopsies will be sampled of patients with chronic kidney disease, analyzed and compared to available data of healthy controls. Insights in the mechanisms controlling intestinal transport and metabolism of indoxyl sulfate and p-cresyl sulfate is certainly relevant as it might lead to novel therapeutic targets in the treatment of chronic kidney disease.

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Disease

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Sander Derjongh; Phone Number: + 32 16 342352; Email: sander.dejongh@kuleuven.be
• Study Contact Backup: Name: Bjorn Meijers, MD, PhD; Phone Number: +32 16 344 580; Email: bjorn.meijers@uzleuven.be

Study Locations

• Belgium
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
      • Recruiting
      • University Hospitals Leuven
      • Principal Investigator: Ruben Poesen, MD
      • Principal Investigator: Björn Meijers, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited from the nephrology outpatient clinic and dialysis center at University Hospital Leuven, Belgium.

Description

Inclusion Criteria:

• Age ≥ 18 and ≤ 85 years
• Chronic kidney disease ≤ stage III (KDOQI), i.e., estimated glomerular filtration rate (MDRD) < 60 ml/min/m² or need of dialysis therapy 27
• Scheduled colonoscopy for diagnostic purposes
• Written informed consent

Exclusion Criteria:

• History of gastro-intestinal disease (e.g., inflammatory bowel disease)
• History of colon surgery
• Recipient of a renal or other solid organ transplant
• Exposure to antibiotics or drug therapy with a known influence on intestinal transporters (e.g., P-gp) or enzymes during 2 weeks before colonoscopy

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change in number of intestinal drug transporters and enzymes	Influence of chronic kidney disease on intestinal drug transporters and enzymes responsible for uptake and metabolism of microbial metabolites	4 years

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Bjorn Meijers, MD, PhD, UZ Leuven; Principal Investigator: Sander Dejongh, KU Leuven

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): December 31, 2021
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: December 11, 2012
• First Submitted That Met QC Criteria: December 18, 2012
• First Posted (Estimated): December 19, 2012

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: July 2, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: S54909