AXOS and Microbial Metabolites in CKD

Study Overview
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Brief Summary
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Chronic kidney disease is associated with the accumulation of various metabolites, i.e., uremic retention solutes. Evidence is mounting that the colonic microbiota 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, overall mortality and chronic kidney disease progression. The most important regulator of colonic bacterial metabolism is nutrient availability and especially the ratio of available fermentable carbohydrate to nitrogen, which can be modified by intake of so-called prebiotics (non-digestible food ingredients). Arabinoxylan oligosaccharides (AXOS) are a recently developed group of prebiotics, and already demonstrated a decreasing effect on intestinal generation of p-cresol in healthy individuals. Whether prebiotics in general, and AXOS more specifically, can influence intestinal generation of microbial metabolites in predialysis patients has not been studied to date. An interventional study with AXOS will therefore be initiated to test the hypothesis that AXOS can decrease intestinal generation and serum concentrations of microbial metabolites in patients with CKD not yet on dialysis.

Official Title
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The Effect of Arabinoxylan-oligosaccharides (AXOS) on Intestinal Generation of Microbial Metabolites in Chronic Kidney Disease

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Dietary Supplement: Arabinoxylan-oligosaccharides
* Dietary Supplement: Maltodextrine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 and ≤ 85 years Chronic kidney disease stage 3b-4, i.e., with estimated glomerular filtration rate (CKD-epi) between 45 - 15 ml/min/m² 29 Written informed consent Exclusion Criteria: History of organic gastro-intestinal disease (e.g., inflammatory bowel disease, malignancy) History of colonic surgery Recipient of a renal or other solid organ transplant Use of pre-/pro-/syn- or antibiotics in preceding 4 weeks

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arabinoxylan-oligosaccharides<br>Arabinoxylan-oligosaccharides 10g BID | Dietary Supplement: Arabinoxylan-oligosaccharides<br> <br> * Other names: AXOS;|
| Placebo Comparator: Maltodextrine<br>Maltodextrine BID | Dietary Supplement: Maltodextrine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum levels of p-cresol and indole derivatives |  | After 4 weeks of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary excretion rates of p-cresol and indole derivatives |  | After 4 weeks of intervention | 
| Insuline resistance | Insuline resistance, measured by HOMA index | After 4 weeks of intervention |