Background & Rationale:
Chronic Kidney Disease (CKD) is associated with significant alterations in gut
microbiota, leading to the production and accumulation of uremic toxins such as indoxyl
sulfate (IS) and p-cresyl sulfate (PCS). These toxins contribute to systemic
inflammation, oxidative stress, and accelerated kidney disease progression, ultimately
increasing cardiovascular mortality. The disruption of gut barrier function and dysbiosis
are major contributing factors in CKD pathophysiology.
Probiotic supplementation has been proposed as an adjuvant therapy to modulate gut
microbiota, enhance intestinal barrier integrity, and reduce systemic inflammation.
Probiotics, particularly Lactobacillus species, have been shown to ferment dietary fiber,
produce beneficial metabolites, and competitively inhibit harmful bacteria. Despite some
promising findings, prior clinical trials have reported inconsistent results,
necessitating further investigation into the efficacy of probiotics in slowing CKD
progression.
This randomized, double-blind, placebo-controlled clinical trial aims to assess the
impact of probiotic supplementation on renal function, systemic inflammation, and
gut-derived uremic toxins in patients with moderate to severe CKD (Stages III-IV).
Study Design & Methodology This trial is a parallel-group, double-blind, randomized
controlled study with a 1:1 allocation ratio. Participants will be recruited from the
Urology and Nephrology Center, Mansoura University, and randomized into either the
probiotic intervention group or the placebo control group.
Intervention Details:
Study Group: Participants will receive probiotic supplementation (Lactogemikan; Pescado
Pharmaceuticals, Egypt), containing 10 billion CFU of Lactobacillus plantarum per tablet.
The dose will be one tablet daily for 6 months.
Control Group: Participants will receive an identical placebo tablet for 6 months.
Both groups will be followed up for an additional 6 months after treatment cessation to
evaluate any persistent effects of probiotic supplementation.
Primary & Secondary Outcomes:
The trial will measure:
Primary Outcomes:
Changes in serum creatinine, estimated glomerular filtration rate (eGFR), and urinary
protein levels over 12 months.
Secondary Outcomes:
Changes in systemic inflammatory markers (C-reactive protein, ferritin, total
cholesterol, albumin).
Alterations in gut microbiota composition, assessed by urinary indican (indoxyl sulfate)
levels before and after treatment.
Evaluation of safety and tolerability of probiotic supplementation in CKD patients.
Randomization & Blinding:
Randomization: Conducted via a computerized random sequence generator.
Blinding:
Double-blinded (both participants and investigators are blinded to group assignments).
The probiotic and placebo tablets are identical in appearance, taste, and packaging.
Follow-Up & Monitoring:
Participants will be evaluated at three time points:
Baseline assessment (before treatment initiation) 6-month follow-up (after completing
treatment) 12-month follow-up (6 months post-treatment cessation) At each visit,
clinical, biochemical, and microbiota assessments will be conducted. Any adverse events
will be documented.
Statistical Analysis Plan Data will be analyzed using R statistical software (R Core
Team, 2023).
Descriptive statistics will summarize baseline characteristics. Continuous variables will
be assessed using the Shapiro-Wilk test for normality.
Depending on normality:
Welch's t-test (normally distributed variables) Mann-Whitney U test (non-normally
distributed variables) Categorical variables will be analyzed using the Chi-square test.
A p-value < 0.05 will be considered statistically significant. Ethical Considerations &
Regulatory Compliance Ethical Approval: The study has been approved by the Institutional
Review Board (IRB) of Mansoura Faculty of Medicine, Mansoura University (IRB Code:
MD.24.06.864).
Informed Consent: All participants will provide written informed consent before
enrollment.
Adverse Events Reporting: Any serious adverse events (SAEs) will be immediately reported
to the IRB and Ethics Committee.
Confidentiality: Participant data will be anonymized and stored securely. Significance of
the Study This study aims to provide new insights into the therapeutic role of probiotics
in CKD patients. If effective, probiotic supplementation may offer a low-cost,
non-invasive adjunct therapy to slow kidney disease progression, reduce inflammation, and
improve metabolic health.
By investigating the mechanistic role of probiotics in modulating gut-derived toxins,
this trial may contribute to developing novel microbiome-targeted interventions in
nephrology practice.