The Gut Microbiome and Symptom Burden After Kidney Transplantation: An Overview and Research Opportunities.

Many kidney transplant recipients continue to experience high symptom burden despite restoration of kidney function. High symptom burden is a significant driver of quality of life. In the post-transplant setting, high symptom burden has been linked to negative outcomes including medication non-adherence, allograft rejection, graft loss, and even mortality. Symbiotic bacteria (microbiota) in the human gastrointestinal tract critically interact with the immune, endocrine, and neurological systems to maintain homeostasis of the host. The gut microbiome has been proposed as an underlying mechanism mediating symptoms in several chronic medical conditions including irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, and psychoneurological disorders via the gut-brain-microbiota axis, a bidirectional signaling pathway between the enteric and central nervous system. Post-transplant exposure to antibiotics, antivirals, and immunosuppressant medications results in significant alterations in gut microbiota community composition and function, which in turn alter these commensal microorganisms' protective effects. This overview will discuss the current state of the science on the effects of the gut microbiome on symptom burden in kidney transplantation and future directions to guide this field of study.

Explainable AI: A Neurally-Inspired Decision Stack Framework.

European law now requires AI to be explainable in the context of adverse decisions affecting the European Union (EU) citizens. At the same time, we expect increasing instances of AI failure as it operates on imperfect data. This paper puts forward a neurally inspired theoretical framework called "decision stacks" that can provide a way forward in research to develop Explainable Artificial Intelligence (X-AI). By leveraging findings from the finest memory systems in biological brains, the decision stack framework operationalizes the definition of explainability. It then proposes a test that can potentially reveal how a given AI decision was made.

Preemptive renal transplant: too early is not always better-a national cohort study.

BACKGROUND: Preemptive renal transplants (PRT) confer better outcomes than renal transplants performed after initiation of hemodialysis. PRTs are occurring at progressively higher residual recipient renal function. METHODS: We evaluated donor, recipient, and transplant characteristics of 26,384 preemptive transplants between 2010 and 2019 using the United Network of Organ Sharing (UNOS) database. Recipients of PRTs were divided into four distinct groups depending upon the glomerular filtration rate (GFR) (GFR [Formula: see text] 10, 10 < GFR [Formula: see text] 15, 15 < GFR [Formula: see text] 19 and > 19, ml/min/1.73 m2) at the time of transplant. We followed graft and patient survival for five years and assessed donor, recipient, and transplant characteristics such as race, gender, and type of insurance. RESULTS: PRTs occurring at GFR > 19 ml/min (early preemptive renal transplants, ePRT) from live and deceased donors were not associated with improved graft nor patient survival compared to the other preemptive transplants. PRTs occurring at GFR range of 10-15 ml/min conferred the best graft survival. Black donor-recipient pairs were 54% less likely to be involved in ePRT, while non-Hispanic White donor-recipient pairs were 20% more likely to receive ePRT. CONCLUSION: ePRT represents misallocation of valuable organ resources and a waste of native renal function. There is no evidence that ePRT is associated with superior graft or patient survival compared to the other preemptive transplants. Conversely, ePRT produces poorer graft and patient survival outcomes compared to the other PRTs. GFR range of 10-15 ml/min is optimal and associated with superior outcomes.

Risk factors for delayed graft function and their impact on graft outcomes in live donor kidney transplantation.

BACKGROUND: Delayed graft function (DGF) is a manifestation of acute kidney injury uniquely framed within the transplant process and a predictor of poor long-term graft function1. It is less common in the setting of living donor (LD) kidney transplantation. However, the detrimental impact of DGF on graft survival is more pronounced in LD2. PURPOSE: To study the effects of DGF in the setting of LD kidney transplantation. METHODS: We performed a retrospective analysis of LD kidney transplantations performed between 2010 and 2018 in the UNOS/OPTN database for DGF and its effect on graft survival. RESULTS: A total of 42,736 LD recipients were identified, of whom 1115 (2.6%) developed DGF. Recipient dialysis status, male gender, diabetes, end-stage renal disease, donor age, right donor nephrectomy, panel reactive antibodies, HLA mismatch, and cold ischemia time were independent predictors of DGF. Three-year graft survival in patients with and without DGF was 89% and 95%, respectively. DGF was the greatest predictor of graft failure at three years (hazard ratio = 1.766, 95% CI: 1.514-2.059, P = 0.001) and was associated with higher rates of rejection (9% vs. 6.28%, P = 0.0003). Among patients with DGF, the graft survival rates with and without rejection were not different. CONCLUSION: DGF is a major determinant of poor graft functional outcomes, independent of rejection.

Disparities in DCD organ procurement policy from a national OPO survey: A call for standardization.

INTRODUCTION: Procurement practices across organ procurement organizations (OPOs) for donation after cardiac death (DCD) transplants have not been evaluated. METHODS: A national telephone survey of all 58 OPOs inquiring about their procurement practices of DCD organs was conducted. Policies concerning maximum donor body mass index (BMI), location of care withdrawal, pre-mortem heparin administration, vasodilator use, wait times after declaration of death before incisions, inclinations between rapid laparotomy and pre-mortem cannulation, and maximum time before aborting DCD procurement were queried. RESULTS: The survey revealed substantial differences across OPOs. Donor BMI restriction was considered by 36 of 58 OPOs, and 23 sites preferred OR for donor withdrawal of care. Pre-mortem heparin was utilized by 53 OPOs. Only 2 recommended vasodilators. Minimum wait time of 5-minutes was implemented by 41 OPOs. Rapid laparotomy was preferred by 57 organizations. 28 OPOs had a 90-minute limit before aborting DCD procurement. CONCLUSION: There are substantial variations across OPO protocols for procuring DCD organs. Current practices do not conform to ASTS guidelines for DCD procurement. Further investigations are needed to quantify the impact of OPO policies on transplant outcomes.

Improved outcomes after live donor renal transplantation for septuagenarians.

The average age of renal transplant recipients in the United States has increased over the past decade. The implications, however, have not been fully investigated. We explored predictors of success and demographic variables related to outcomes in elderly live donor transplantation. Retrospective analysis was performed using the UNOS database between 2001 and 2016. Donor characteristics and the graft failure rate of recipients above and below 70 years of age were compared across four eras: 2001-2004, 2005-2008, 2009-2012, and 2013-2016. There was a steady increase in average donor age from the first era to the fourth era (40-44) which was more evident among the septuagenarian patients (43-50) (P < .001). The 2-year graft survival rate improved from 92% in the first era to 96% in the fourth era (P < .001), and this was also more prominent in the >70 population (87%-93%) (P < .001). The >70 recipients were more likely to be non-Hispanic white (80.1% vs 65.1%, P < .001) and male (70.1% vs 61.0% P < .001), respectively. The donors were more likely to be non-Hispanic white and female in the >70 population. Live donation in the elderly is justified based on graft survival and patient survival. However, racial and gender differences exist in septuagenarian recipients and their donors.

Evaluation of Whether Kidney Paired Donations Improve Overall Transplant Center Performance.

OBJECTIVES: Increasing living-donor kidney transplant procedures via kidney paired donations could help combat organ shortages. We examined whether a higher volume of kidney paired donation transplants would lead to increased center performance. MATERIALS AND METHODS: Kidney paired donation, living-donor, and deceased-donor transplant data from 165 centers between 2012 and 2016 were obtained from the UNOS OPTN database. The fixed-effects model was used for panel analysis based on Durbin-Wu-Hausman tests (P < .001). Regression analyses tested associations between total transplant number and kidney paired donation-to-living donor kidney transplant ratio, incorporating up to 2-year lag terms. Regression analyses also tested associations between number of new wait list registrations and kidney paired donation transplant ratio. RESULTS: Mean and median number of kidney paired donor transplants equaled 3.59 and 1.2, respectively. Only 5 centers performed > 20 paired donation transplants annually. Mean and median ratios of paired donation transplants were 0.54 and 0.11. Total transplant number was not associated with paired donation transplant ratio of the same year (b= -.425, P = .662) or with that of 2 prior years (P = .830 and P = .629, respectively). Similarly, new wait list registrations were not correlated with paired donation transplant ratio of the same year (P= .501, P = .851) or that of 2 prior years (P = .792 and P = .816, respectively). When transplant centers were divided into those performing ≥ 10 paired donation trans-plants annually (18 transplant center, n = 90) versus those performing < 10 annually (147 transplant center, n = 735), no significant effects were shown (P > .10). CONCLUSIONS: Kidney paired donation transplant does not appear to affect transplant center performance. This may be due to the small volume of these transplants currently performed by centers, thereby limiting overall growth in the number of transplants and new registrations.