Longitudinal Characterisation of the Host Microbiota After Kidney Donation and Transplantation
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- Change in gastrointestinal and urinary microbiota composition and diversity
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All adult (≥18 years old) undergoing living donor nephrectomy or kidney transplantation. Patients willing to provide samples including Urine, Blood, Faecal samples.
- •Participant able to give Informed Consent
- •All patients will be at least 18 years old
- •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.
- •Patients attending hospital clinics at participating centre for routine clinical follow -up.
- •Patients willing to comply with study procedures and willing to provide blood, faecal and urine samples.
排除标准
- •Patients under the age of 18 years
- •Patients unable to give informed consent
- •Patients not able to comply with study procedures or follow-up visits
- •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.
结局指标
主要结局
Change in gastrointestinal and urinary microbiota composition and diversity
时间窗: 1 year
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.
Correlation of change in gastrointestinal and urinary microbiota diversity with post-transplantation outcomes.
时间窗: 1 year
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.
次要结局
- Incidence of renal graft dysfunction as determined by the MDRD-derived estimated Glomerular Filtration Rate (eGFR).(1 year)
- Incidence of biopsy proven acute or chronic cellular or humoral rejection up to 5 years after transplantation as per Banff classification(5 years)
- The proportion of patients reaching a defined CKD stage at up to 5 years after transplantation.(5 years)
- Patient and graft survival rates up to 5 years after transplantation.(5 years)
- Change in microbial-associated metabolite profile and correlation with clinical outcomes and/or microbial diversity changes(1 year)
- Change in frequency of conventional and regulatory immune phenotypes and correlation with clinical outcome and microbial diversity changes(1 year)
- Incidence of post-donation and post-transplant bacterial or viral infections up to 5 years after surgery(5 years)