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.

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