Characterization Of the Intestinal Microbiome Evolution After Kidney Transplant Donation or Receipt

The emergence of multidrug resistant organisms (MDROs) is a growing threat to global public
health and is associated with high morbidity and mortality in both the general and solid
organ transplant population. Intestinal microbiota diversity can provide functional and
spatial barriers to bacterial and fungal MDRO colonization, and loss of diversity is
associated with increased MDRO colonization. Dysbiosis is a state of loss of microbiota
diversity and a single antibiotic treatment course can cause significant disruption in
microbiota diversity, even in otherwise healthy individuals. This disruption can promote the
growth of pathogenic and multidrug-resistant bacteria and fungi. Transplant patients, in
particular, are at increased risk of colonization and infection with MDRO because of
immunomodulatory therapies, healthcare exposure, increased antibiotic exposure and surgical
manipulation of mucosa. Furthermore, chronic kidney disease and dialysis therapy leading up
to transplant has been shown to be associated with alterations in both the intestinal and
periodontal microbiome. Understanding the evolution of the disruption in the intestinal
microbiome in both kidney transplant recipients and healthy kidney transplant donors during
the time of transplant surgical prophylaxis will give valuable insight into further avenues
for research and possible interventions that may mitigate the risk of MDRO colonization.

This is a prospective, observational, and non-interventional pilot study which aims to enroll
100 adult renal transplant recipients and 100 adult renal transplant donors. Participants
will provide stool samples and anal swab samples, and will complete dietary questionnaires.
Participants may also choose to take part in an optional sub-study which involves banking
leftover stool for future research use.

The diversity change of the intestinal microbiota over time will be assessed at the screening
visit, Post-Operative Day 2; Post-Discharge Day 15 and Post-Discharge Day 30. Participants
will be followed by way of medical record review for 24 weeks post-surgery.

This study is designed to understand the intestinal microbiota diversity in the setting of
renal transplant surgery and the clinical significance of antibiotic use and the associated
resistome (collection of all antibiotic resistance genes and precursors within a sample).
Information learned from this study will be used to guide the design of future clinical
trials.

Inclusion Criteria:

- Ability to understand and the willingness to sign a written informed consent document.

- Ability and willingness to comply with study protocol requirements.

- Completed Verbal Screening Form

- Planned kidney donation or planned receipt of a living donor kidney transplant within
28 days from time of written informed consent.

- If performance status is known, a score of any of the following:

- American Society of Anesthesia (ASA) classification of I (a normal healthy
patient), II (a patient with mild systemic disease) or III (a patient with severe
systemic disease)

- Eastern Cooperative Oncology Group (ECOG) Status Scale grade of 0 (normal
activity), 1 (symptoms, but ambulatory) or 2 (in bed <50% of the time)

- Karnofsky Performance Scale (KPS) of 50% (requires considerable assistance and
frequent medical care) to 100% (normal, no complaints, no evidence of disease)

- English speaking.

Exclusion Criteria:

- Any condition that, in the opinion of the investigator, might interfere with study
objectives or limit compliance with study requirements, including but not limited to:

- Known active intravenous drug or alcohol abuse

- Psychiatric illness

- Social situation

- Planned or actual receipt of a deceased donor kidney transplant.

- Prior kidney transplant that still requires active immunosuppressive treatment or
intervention.

- Presence of diverting ileostomy or colostomy.