Clinical trial NCT04388930: The Microbiota in Kidney Donation and Transplantation
Official title: Longitudinal Characterisation of the Host Microbiota After Kidney Donation and Transplantation
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Kidney Diseases
Kidney Transplant Failure and Rejection
Urinary Tract Infections
Lead sponsor: Royal Free Hospital NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: University College, London
First posted: 2020-05-14
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Renal transplant live-donors and recipients of live-donor and cadaveric renal transplants

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.


Eligibility criteria: Inclusion Criteria:

* All adult (≥18 years old) undergoing living donor nephrectomy or kidney transplantation. Patients willing to provide samples including Urine, Blood, Faecal samples.

  1. Participant able to give Informed Consent
  2. All patients will be at least 18 years old
  3. Patients will either be a live renal transplant donor or a renal transplant recipient on the waiting list to have or will have had an ABO-blood group compatible renal transplant.
  4. Patients attending hospital clinics at participating centre for routine clinical follow -up.
  5. Patients willing to comply with study procedures and willing to provide blood, faecal and urine samples.

Exclusion Criteria:

1. Patients under the age of 18 years
2. Patients unable to give informed consent
3. Patients not able to comply with study procedures or follow-up visits
4. Patients that are not a live renal donor or that are not on the waiting list to have or have not had an ABO blood group compatible renal transplant and are not attending hospital outpatient clinics at participating study centres for routine clinical follow-up.

Primary outcomes:
measure: Change in gastrointestinal and urinary microbiota composition and diversity
timeFrame: 1 year
measure: Correlation of change in gastrointestinal and urinary microbiota diversity with post-transplantation outcomes.
timeFrame: 1 year
Secondary outcomes:
measure: Change in frequency of conventional and regulatory immune phenotypes and correlation with clinical outcome and microbial diversity changes
timeFrame: 1 year
measure: Change in microbial-associated metabolite profile and correlation with clinical outcomes and/or microbial diversity changes
timeFrame: 1 year
measure: Incidence of renal graft dysfunction as determined by the MDRD-derived estimated Glomerular Filtration Rate (eGFR).
timeFrame: 1 year
measure: The proportion of patients reaching a defined CKD stage at up to 5 years after transplantation.
timeFrame: 5 years
measure: Incidence of biopsy proven acute or chronic cellular or humoral rejection up to 5 years after transplantation as per Banff classification
timeFrame: 5 years
measure: Incidence of post-donation and post-transplant bacterial or viral infections up to 5 years after surgery
timeFrame: 5 years
measure: Patient and graft survival rates up to 5 years after transplantation.
timeFrame: 5 years
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal Free London NHS Trust
Study officials:
affiliation: Sponsor GmbH
name: Research and Development Manager
role: STUDY_CHAIR
References: