End-stage Renal Disease (ESRD), Kidney Transplantation
Conditions
Keywords
gut microbiota, urinary microbiota, kidney transplantation, immunosuppression, tacrolimus, mycophenolate mofetil, dysbiosis, rejection, infection
Brief 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.
Interventions
OTHERFecal 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)
OTHERUrinary sample
Urinary sample collected via indwelling catheter at V3 (day of transplantation).
OTHERBlood 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.
OTHERSimplified 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.
Sponsors
Hospices Civils de Lyon
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patient (18 years of age or older) * Living-donor kidney transplantation * Initial triple immunosuppressive maintenance therapy: calcineurin inhibitor (tacrolimus) + purine synthesis inhibitor (mycophenolate mofetil) + steroids * Women of childbearing age: effective contraception required (required by the transplantation procedure and -immunosuppressive treatment, not by the study protocol itself) * Able to understand study objectives and risks and to provide dated signed written informed consent
Exclusion criteria
* Pregnant, parturient, or breastfeeding women * Persons deprived of liberty by judicial or administrative decision * Persons receiving psychiatric care or under legal protection (guardianship, curatorship) * Persons not affiliated with a social security scheme or equivalent * ABO-incompatible kidney transplantation * Ongoing immunosuppressive treatment or discontinued less than 3 months ago (conventional treatments) or less than 6 months ago (immunosuppressive immunotherapy) * Antibiotic therapy within 3 weeks before inclusion * History of bariatric surgery or gastrointestinal tract resection (excluding appendectomy or cholecystectomy performed more than 12 months prior) * Chronic inflammatory bowel disease * Currently participating in another interventional study with an exclusion period still in effect and potentially interfering with the present study, per investigator judgment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
France
Contacts
CONTACTDr Xavier CHARMETANT
PRINCIPAL_INVESTIGATORXavier CHARMETANT, MD, PhD
Hospices Civils de Lyon
Outcome results
None listed