Probiotic and Prebiotic Supplementation in Peritoneal Dialysis Patients

This is a randomized, controlled, double-blind clinical trial designed to evaluate the clinical and biochemical impact of synbiotic supplementation in patients with chronic kidney disease undergoing peritoneal dialysis at the Regional Center for Kidney Diseases. Eligible participants will be randomly assigned in a 1:1 ratio into one of two parallel groups for a 6-month period:

1. Synbiotic Group: Participants will receive one oral capsule daily in the morning before meals, containing prebiotic fibers (chicory inulin root and tapioca starch) and probiotic strains (Bifidobacterium longum, Lactobacillus acidophilus, and Streptococcus thermophilus) at a concentration of 7.5 x 10\^12 CFU/100g.
2. Placebo Group: Participants will receive one identical, inactive oral capsule daily.

Clinical and biochemical evaluations will be conducted at three distinct time points: Baseline (Visit 1), 3 months (Visit 2), and 6 months (Visit 3). At each visit, blood samples will be drawn to measure primary pro-inflammatory and uremic toxin markers, specifically p-cresol and indoxyl sulfate, alongside high-sensitivity C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Additionally, nutritional status will be evaluated using the Malnutrition-Inflammation Score (MIS). Secondary clinical outcomes, including the incidence of peritonitis episodes, will be documented throughout the entire 6-month study duration. To ensure protocol compliance, participant adherence will be tracked using two methods: Pill-counts conducted during each scheduled follow-up visit and periodic telephone calls between visits to provide reminders and monitor supplement intake.

• Synbiotic (Dietary supplement): Oral administration of an active nutritional supplement consisting of one capsule daily taken in the morning before meals for 6 months. Each capsule contains a specific synbiotic formulation composed of probiotic strains (Bifidobacterium longum, Lactobacillus acidophilus, and Streptococcus thermophilus at 7.5 x 10\^12 CFU/100g) combined with prebiotic soluble fibers (chicory inulin root and tapioca starch) designed to modulate the gut microbiota.
• Placebo (Dietary supplement): Oral administration of one identical, inactive oral capsule daily taken in the morning before meals for a period of 6 months. The placebo capsule looks, tastes, and smells exactly like the intervention supplement but contains no active ingredients.

Primary outcomes

• Change from baseline in serum high-sensitivity C-reactive protein (hs-CRP) at 3 and 6 months. [Baseline (Month 0), Month 3, and Month 6.]: Serum hs-CRP levels will be measured to evaluate systemic inflammation. The change will be assessed by comparing values at 3 and 6 months against the baseline values.
• Change from baseline in Erythrocyte Sedimentation Rate (ESR) at 3 and 6 months. [Baseline (Month 0), Month 3, and Month 6.]: Erythrocyte Sedimentation Rate (ESR) will be measured to evaluate systemic inflammation. The change will be assessed by comparing values at 3 and 6 months against the baseline values.
• Change from baseline in serum p-Cresyl Sulfate (pCS) levels at 3 and 6 months. [Baseline (Month 0), Month 3, and Month 6.]: Serum levels of the microbiota-derived uremic toxin p-Cresyl Sulfate will be quantified to evaluate the effect of the synbiotic intervention over time. The change will be assessed by comparing values at 3 and 6 months against the baseline values.
• Change from baseline in serum Indoxyl Sulfate (IS) levels at 3 and 6 months. [Baseline (Month 0), Month 3, and Month 6.]: Serum levels of Indoxyl Sulfate will be quantified as a key protein-bound uremic toxin to determine if the synbiotic intervention decreases its accumulation. The change will be assessed by comparing values at 3 and 6 months against the baseline values.

Secondary outcomes

• Change from baseline in Malnutrition-Inflammation Score (MIS) at 3 and 6 months. [Baseline (Month 0), Month 3, and Month 6.]: The Malnutrition-Inflammation Score (MIS) will be used to assess the nutritional and inflammatory status of the patients. The score ranges from 0 (normal) to 30 (severe malnutrition and inflammation), where a higher score indicates a more severe degree of malnutrition. The change will be assessed by comparing values at 3 and 6 months against the baseline values.
• Number of peritonitis episodes during the 6-month follow-up period. [Up to 6 months.]: The total number of confirmed peritonitis episodes per patient will be recorded throughout the study to evaluate if the synbiotic intervention reduces the incidence of infectious complications compared to the placebo group.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Patients aged 18 years or older.
* Patients diagnosed with kidney disease who have been receiving peritoneal dialysis at home for at least 1 month.

Exclusion Criteria:

* Patients who are unable to eat or receive food through a feeding tube.
* Patients who have taken prebiotics or probiotics (supplements that support gut health) in the month before the study starts.
* Patients who used antibiotics in the month before the study starts.
* Patients who cannot attend the scheduled follow-up visits (missing the second follow-up appointment will result in being removed from the study).
* Note on non-adherence and withdrawal: Patients who are unable to take their assigned capsules regularly (taking less than 80% of the total capsules will result in being removed from the study).

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• Elisa María Guadalupe Guerrero González, MD, Principal investigator, Hospital Universitario. Dr. José Eleuterio González