Living kidney donation and reasons for denial: A report from a Brazilian single-center cross-sectional study

Chronic kidney disease is increasingly more prevalent worldwide, and kidney transplant remains the best option for patient survival. Living kidney transplants (LKT) pose advantages over deceased donor transplants, such as longer graft survival, lower ischemia time, and better HLA match. However, LKT is not always attainable for multiples reasons, with the absence of a suitable living donor being a significant barrier. Therefore, meticulous donor screening must be performed in order to guarantee donation safety. We examined medical appointments of living kidney donors evaluated at Hospital do Rim, São Paulo, between January and December 2020. Reasons for not proceeding with the donation were evaluated and were categorized as medical, surgical, immunological, psychosocial, or other. A total of 506 donor -receptor pairs were enrolled for evaluation during the study period. More than half of screened donor -receptor pairs (N=296, 58.5%) were not considered feasible for LKT. The primary cause for refusal was medical contraindication (32.1%), followed by immune (21.3%) and social (19.3%) causes. In addition, a considerable proportion of patients voluntarily withdrew themselves at variable time points during the evaluation process (N=79). In our center, most patients did not meet the criteria for kidney donation owing to medical reasons, similarly to other centers, and this reflects the importance of meticulous donor screening. In addition, the current Covid -19 pandemic affected the living transplant program, contributing to delayed complete donor and receptor evaluation.

An update of the contemporary donor screening tests used in fecal microbiota transplantation for its future developments: A systematic review

Review question / Objective: Western pacific and South-east Asian region have its own lifestyle and dietary habits, for an example, the prevalence of parasites and the MDR pathogens are different compared to the European region where most consensus documents have been disseminated. Hence, current investigation is being carried out in view of appraising contemporary methods that have been used internationally and to propose rigorous donor screening methods appropriate for the regional requirement. Information sources: EMBASE and MEDLINE through PubMed and WEB of SCIENCE. Additionally, we have reviewed all international consensus documents and local guidelines published in English.

Ethical Implications of the Fecal Microbiota Transplantation: Disclosure of a False-Positive HIV Test

Fecal microbiota transplantation (FMT) has gained popularity as an effective therapeutic option for Clostridioides difficile infection (CDI). Since its FDA recognition as a treatment modality for recurrent CDI in 2013, screening protocols for FMT donor stool have been in flux. However, extensive health questionnaires, in combination with serological and stool assays, have become mainstays in the donor screening process, although ethical implications are yet to be thoroughly considered. Herein, we present the case of a family member found to have a false-positive HIV test during the donor screening process and discuss potential ethical ramifications associated with FMT stool donation.

A comprehensive approach to stool donor screening for faecal microbiota transplantation in China

Background Faecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium difficile infections and chronic gastrointestional infections. However, the risks of FMT and the selection process of suitable donors remain insufficiently characterized. The eligibility rate for screening, underlying microbial basis, and core ethical issues of stool donors for FMT are yet to be elucidated in China. Results The potential stool donors were screened from December 2017 to December 2019 with the help of an online survey, clinical assessments, and stool and blood testing. Bioinformatics analyses were performed, and the composition and stability of gut microbiota in stool obtained from eligible donors were dynamically observed using metagenomics. Meanwhile, we build a donor microbial evaluation index (DoMEI) for stool donor screening. In the screening process, we also focused on ethical principles and requirements. Of the 2071 participants, 66 donors were selected via the screening process (3.19% success rate). Although there were significant differences in gut microbiota among donors, we found that the changes in the gut microbiota of the same donor were typically more stable than those between donors over time. Conclusions DoMEI provides a potential reference index for regular stool donor re-evaluation. In this retrospective study, we summarised the donor recruitment and screening procedure ensuring the safety and tolerability for FMT in China. Based on the latest advances in this field, we carried out rigorous recommendation and method which can assist stool bank and clinicians to screen eligible stool donor for FMT.

1035. Manufacturing Processes of SER-109, a Purified Investigational Microbiome Therapeutic, Reduce Risk of Transmission of Emerging and Undetected Infections in Donor Stool

Background Fecal microbiota transplantation (FMT) is vulnerable to emerging pathogens due to reliance on donor screening for risk mitigation. These concerns were highlighted by dual FDA safety alerts regarding FMT transmission of bacterial pathogens, which were recognized in hindsight only after hospitalizations and deaths. The FDA also warned of potential risk of SARS-CoV-2 transmission, leading to quarantine of FMT in March 2020, two months after COVID-19 was reported on US soil. Conversely, our development program for SER-109, an oral investigational microbiome therapeutic, was prospectively designed to inactivate organisms of concern, while purifying the hardy Firmicutes spores. We evaluated whether the manufacturing processes for SER-109 inactivate model organisms, including a coronavirus with gastrointestinal tropism, and a representative Gram-negative bacterium. Methods Model organisms were selected based on biologic suitability, detectability, and laboratory safety. Porcine Epidemic Diarrhea Virus (PEDV, a coronavirus) was selected to model SARS-CoV-2. Quantitation used a Vero cell tissue culture infectious dose (TCID50) assay. For E. coli, a rifampicin-tolerant Salmonella enterica was selected and quantified with MacConkey lactose agar plus rifampicin. Spiking experiments into representative fecal suspensions were completed to measure inactivation of model organisms. Log-reduction factors (LRF) were calculated based on the drop in organism titer during inactivation. Hold controls in non-ethanolic test matrices were used to confirm specificity of the ethanol inactivation. Results In 70% v/v ethanol, PEDV was inactivated by more than 4.2 log10 (to limit of detection, LOD) within 4 minutes (Fig1). In 50% v/v ethanol, S. enterica was inactivated by more than 6.5 log10 (to LOD) within 30 seconds (Fig2). Figure 1. Inactivation of Porcine Epidemic Diarrhea Virus (PEDV), log10 reduction factor (LRF) versus time Average of two experiments shown. Also shown is the maximum achievable inactivation based on the limit of detection (LOD). Figure 2. Inactivation of S. enterica, log10 reduction factor (LRF) versus time. Average of three experiments with error bars represent 95% CI. Also shown is the maximum achievable inactivation based on the limit of detection (LOD). Conclusion These experiments demonstrate substantial inactivation of the model organisms and support the potential benefit of SER-109 manufacturing process to mitigate risks of undetected or emerging pathogens for which reliable screening is limited. Ethanol exposure leads to a purified investigational product of beneficial Firmicutes spores while affording a safety net beyond donor screening alone. Disclosures Christopher McChalicher, n/a, Seres Therapeutics (Employee, Shareholder) Ahmad Abdulaziz, MS, Seres Therapeutics Inc. (Employee, Shareholder) Elizabeth Halvorsen, PhD, Seres Therapeutics (Employee, Shareholder) Mary-Jane Lombardo, PhD, Seres Therapeutics (Employee, Shareholder) Jonathan Winkler, PhD, Seres Therapeutics (Employee, Shareholder) Barbara McGovern, MD, Seres Therapeutics (Employee, Shareholder) Gregory McKenzie, PhD, Prolacta Bioscience (Employee) David Ege, PhD, Merck & Co., Inc. (Shareholder)Seres Therapeutics (Employee, Shareholder) John Aunins, PhD, Seres Therapeutics, Inc. (Employee)