Microbiota Changes Related to Outcomes in Kidney Transplantation

Condition(s) studied

Investigational drug(s) / intervention(s)

Fecal samples: Fecal samples collected by patient at home or in hospital using standardized kits at 3 timepoints: V1 (14 days before transplantation, before immunosuppression), V2 (day before transplantation, after 4 days of immunosuppression), and V4 (3 months post-transplantation)

Urinary sample: Urinary sample collected via indwelling catheter at V3 (day of transplantation).

Blood samples: Blood samples (serum 4 mL, plasma 8 mL, PBMCs 24 mL) collected at V1, V2, and V4 for immunological and metabolomic analyses. Microbiota analyzed by shotgun metagenomic sequencing.

Simplified dietary questionnaire: Simplified dietary questionnaire administered at V1 (14 days before transplantation), V4 (3-month follow-up visit), and V5 (6-month follow-up visit) to assess major food categories and evaluate their Spearman correlation with fecal microbiota composition and evolution after kidney transplantation.

Study summary

Chronic kidney disease affects approximately 10% of the world population. End-stage renal disease (ESRD) is associated with immune dysregulation, chronic inflammation, and alteration of the gut and urinary microbiota. Kidney transplantation is the reference treatment for ESRD, but required immunosuppressive therapy further aggravates immune dysregulation and is associated with cardiovascular, metabolic and infectious complications. The gut microbiota plays a central role in modulating systemic immunity. In ESRD, microbiota composition is strongly altered. A recent study showed an association between gut dysbiosis and all-cause mortality in over 1,300 kidney transplant recipients. However, the mechanisms underlying deleterious microbiota modifications in transplant recipients remain poorly understood, particularly the respective roles of immunosuppressive treatment and renal function recovery. The MICRO-KT study hypothesizes that the programmed introduction of immunosuppressive therapy followed by partial or complete correction of ESRD after living-donor kidney transplantation induces quantitative and qualitative modifications of the fecal microbiota, and that specific microbial signatures are associated with clinical and immunological transplant outcomes. This prospective, single-center, longitudinal, interventional, single-arm cohort study will evaluate microbiota dynamics in 30 adult patients before and after living-donor kidney transplantation. Fecal samples are collected at 14 days before transplantation (before immunosuppression), the day before transplantation (after 4 days of immunosuppression), and 3 months post-transplantation. Urinary samples are collected at transplantation. Blood samples (serum, plasma, PBMCs) are collected at 3 timepoints for immunological and metabolomic analyses. The primary endpoint is to describe fecal microbiota beta-diversity dynamics (Bray-Curtis and Jaccard indices at genus level) across three timepoints. Secondary objectives evaluate associations between microbiota composition and clinical outcomes (rejection, infection, survival), immunosuppressant tolerance, drug levels, PBMC immunological profiles, metabolomic signatures, and dietary patterns.

Eligibility

Primary outcome measure(s)

• Change in Fecal Microbiota Beta-Diversity (Bray-Curtis and Jaccard Indices) at the Genus Taxonomic Level — From V1 (14 days before transplantation, before immunosuppression) to V2 (day before transplantation, after 4 days of immunosuppression)
  Comparative analysis of fecal microbiota composition using beta-diversity indices (Bray-Curtis and Jaccard) at the genus taxonomic level, determined by shotgun metagenomic sequencing (Illumina NovaSeq). Statistical comparison performed by PERMANOVA (999 permutations). Alpha-diversity indices (Chao1, Shannon) assessed by Wilcoxon test. Differential taxon analysis performed using Maaslin3 (R software).
• Change in Fecal Microbiota Beta-Diversity (Bray-Curtis and Jaccard Indices) at the Genus Taxonomic Level — From V2 (day before transplantation, after 4 days of immunosuppression) to V4 (3 months post-transplantation)
  Comparative analysis of fecal microbiota composition using beta-diversity indices (Bray-Curtis and Jaccard) at the genus taxonomic level, determined by shotgun metagenomic sequencing (Illumina NovaSeq). Statistical comparison performed by PERMANOVA (999 permutations). Alpha-diversity indices (Chao1, Shannon) assessed by Wilcoxon test. Differential taxon analysis performed using Maaslin3 (R software).
• Change in Fecal Microbiota Beta-Diversity (Bray-Curtis and Jaccard Indices) at the Genus Taxonomic Level — From V1 (14 days before transplantation, before immunosuppression) to V4 (3 months post-transplantation)
  Comparative analysis of fecal microbiota composition using beta-diversity indices (Bray-Curtis and Jaccard) at the genus taxonomic level, determined by shotgun metagenomic sequencing (Illumina NovaSeq). Statistical comparison performed by PERMANOVA (999 permutations). Alpha-diversity indices (Chao1, Shannon) assessed by Wilcoxon test. Differential taxon analysis performed using Maaslin3 (R software).

Trial sites (1)

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