Brief Summary

The human gastrointestinal tract harbours \~40 trillion microbial cells, far outnumbering the cell number, and therefore the genetic content of its host. How this genetically diverse bacterial (collectively referred as 'microbiota') co-resident modulates host homeostasis is largely unknown. We are increasing gaining a better understanding how the microbes modulate mucosal and systemic metabolic/immune and organ systems including the kidney, heart and the brain. Therapeutic targeting of the gastrointestinal (GI) microbiota may help improve clinical outcomes in conditions as diverse as arthritis, cardiovascular disease, and cancer. In contrast to other organ systems, studies investigating the role of the microbiota in modulating clinical outcomes in renal transplantation lags behind. The aim of the study is to examine (a) how alterations in the urinary and GI microbiota and associated metabolites impact on host immunity after renal transplantation, and (b) whether such changes are correlated with post-transplant complications, such as rejection, development of de novo donor specific antibodies, metabolic complications (e.g post-transplant diabetes) and infections. Participants will be followed before and up to twelve months post-transplantation, and, longitudinal microbial data will be correlated with in-depth immune phenotyping and clinical end-points to define the impact that changes in urinary and GI microbial ecology have on kidney transplant outcomes.

Trial Health

At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date

Enrollment

130

participants targeted

Target at P50-P75 for all trials

Timeline

Completed

Started Mar 2020

Longer than P75 for all trials

Geographic Reach

1 country

1 active site

Status

unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

5.3 years study duration

Study Start

First participant enrolled

March 1, 2020

Completed

2 months until next milestone

First Submitted

Initial submission to the registry

May 12, 2020

Completed

2 days until next milestone

First Posted

Study publicly available on registry

May 14, 2020

Completed

5.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2025

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2025

Completed

Last Updated

December 14, 2023

Status Verified

December 1, 2023

Enrollment Period

5.3 years

First QC Date

May 12, 2020

Last Update Submit

December 13, 2023

Conditions

Kidney Diseases Kidney Transplant Failure and Rejection Urinary Tract Infections

Outcome Measures

Primary Outcomes (2)

Change in gastrointestinal and urinary microbiota composition and diversity
To understand the overall impact of transplantation on changes to the urinary and GI microbiota, the relative abundance of bacterial taxa will be evaluated using 16S rRNA gene sequencing methodologies. Alpha and Beta diversity indices will be determined from urine samples and faecal samples before and after live-donation and transplantation.
1 year
Correlation of change in gastrointestinal and urinary microbiota diversity with post-transplantation outcomes.
Incidence of renal graft dysfunction will be determined by the Modification of Diet in Renal Disease (MDRD)-derived estimated Glomerular Filtration Rate (eGFR) at 12 months. Graft survival time - date of transplantation to date of irreversible graft failure signified by return to dialysis (or re-transplantation, whichever is earlier) or the date of last follow-up during the period when the transplant was still functioning. In the event of death with a functioning graft, the follow-up period will be censored at the date of death.
1 year

Secondary Outcomes (7)

Change in frequency of conventional and regulatory immune phenotypes and correlation with clinical outcome and microbial diversity changes
1 year
Change in microbial-associated metabolite profile and correlation with clinical outcomes and/or microbial diversity changes
1 year
Incidence of renal graft dysfunction as determined by the MDRD-derived estimated Glomerular Filtration Rate (eGFR).
1 year
The proportion of patients reaching a defined CKD stage at up to 5 years after transplantation.
5 years
Incidence of biopsy proven acute or chronic cellular or humoral rejection up to 5 years after transplantation as per Banff classification
5 years
+2 more secondary outcomes

Study Arms (2)

Kidney transplant live-donor

Participants that will be a planned live renal transplant donor

Other: Pre-operative assessment - blood, urine, & faecal sampleOther: Post-operative day 3 assessment - blood, urine, & faecal sampleOther: Post-operative week 4-6 assessment - blood, urine, & faecal sampleOther: Post-operative 3 month assessment - blood, urine, & faecal sampleOther: Pre-operative 6 month assessment - blood, urine, & faecal sampleOther: Post-operative month 12 recipient assessment - blood, urine, & faecal sample

Kidney transplant recipient

Renal transplant recipient on the waiting list to have or will have had an ABO-blood group compatible live-donor or cadaveric transplant

Other: Pre-operative assessment - blood, urine, & faecal sampleOther: Post-operative week 4-6 assessment - blood, urine, & faecal sampleOther: Post-operative 3 month assessment - blood, urine, & faecal sampleOther: Pre-operative 6 month assessment - blood, urine, & faecal sampleOther: Post-operative month 12 recipient assessment - blood, urine, & faecal sample

Interventions

Pre-operative assessment - blood, urine, & faecal sampleOTHER

Blood sample for multi-parametric flow cytometry. Blood and urine samples for identifying microbial-associated metabolite signature. Urine and faecal samples for 16S rRNA gene sequencing