Pretransplant, Th17 dominant alloreactivity in highly sensitized kidney transplant candidates.

Introduction: Sensitization to donor human leukocyte antigen (HLA) molecules prior to transplantation is a significant risk factor for delayed access to transplantation and to long-term outcomes. Memory T cells and their cytokines play a pivotal role in shaping immune responses, thereby increasing the risk of allograft rejection among highly sensitized patients. This study aims to elucidate the precise contribution of different CD4 memory T cell subsets to alloreactivity in highly sensitized (HS) kidney transplant recipients.

RORγt inverse agonist TF-S14 inhibits Th17 cytokines and prolongs skin allograft survival in sensitized mice.

Chronic antibody mediated rejection (AMR) is the major cause of solid organ graft rejection. Th17 contributes to AMR through the secretion of IL17A, IL21 and IL22. These cytokines promote neutrophilic infiltration, B cell proliferation and donor specific antibodies (DSAs) production.

Policies and practice of solid organ donation amongst people living with HIV in Canada: time for education and re-evaluation.

The numbers of organ donors in Canada and the USA fall short of increasing demand, resulting in increased morbidity, poor health outcomes, higher medical costs and death of many individuals waitlisted for transplantation. In the US, since 2013 when the US HIV Organ Policy Equity (HOPE) Act lifted the ban on organ donation between people living with HIV, the option of using organs from People with HIV became a reality. In Canada, HIV diagnosis was an exclusion criterion to organ donation until 2017, when permission was granted if requirements for 'exceptional distribution' could be met.

Predicting Long-term Outcomes in Deceased Donor Kidney Transplant Recipients Using Three Short-term Graft Characteristics.

Key Points: Delayed graft function is not an ideal measure of graft function, yet is used to assess risk in kidney transplantation. We propose a model that combines it with two other measures of 90-day graft function to identify recipients at incremental risk of inferior long-term outcomes.

Background: Delayed graft function (DGF) in kidney transplant recipients is used to determine graft prognosis, make organ utilization decisions, and as an important end point in clinical trials.

Discovery, Synthesis, and In Vitro Characterization of 2,3 Derivatives of 4,5,6,7-Tetrahydro-Benzothiophene as Potent Modulators of Retinoic Acid Receptor-Related Orphan Receptor γt.

Retinoic acid receptor-related orphan receptor γt (RORγt) is a nuclear receptor that is expressed in a variety of tissues and is a potential drug target for the treatment of inflammatory and auto-immune diseases, metabolic diseases, and resistant cancer types. We herein report the discovery of 2,3 derivatives of 4,5,6,7-tetrahydro-benzothiophene modulators of RORγt. We also report the solubility in acidic/neutral pH, mouse/human/dog/rat microsomal stability, Caco-2, and MDR1-MDCKII permeabilities of a set of these derivatives.

Outcomes of kidney transplant recipients who underwent pre-transplant bariatric surgery for severe obesity: a long-term follow-up study.

Background: Kidney transplantation (KT) is the preferred therapy for end-stage renal disease (ESRD). While a major cause for ESRD, obesity is also a key obstacle to candidacy for KT. Bariatric surgery, particularly sleeve gastrectomy (SG), is increasingly used to improve access to KT in patients with obesity, but the literature especially on outcomes post-KT remains lacking.

TFNR2 in Ischemia-Reperfusion Injury, Rejection, and Tolerance in Transplantation.

Tumor necrosis factor receptor 2 (TNFR2) has been shown to play a crucial role in CD4+ T regulatory cells (CD4+Tregs) expansion and suppressive function. Increasing evidence has also demonstrated its role in a variety of immune regulatory cell subtypes such as CD8+ T regulatory cells (CD8+ Tregs), B regulatory cells (Bregs), and myeloid-derived suppressor cells (MDSCs). In solid organ transplantation, regulatory immune cells have been associated with decreased ischemia-reperfusion injury (IRI), improved graft survival, and improved overall outcomes.

Extracellular Vesicles From Kidney Allografts Express miR-218-5p and Alter Th17/Treg Ratios.

Delayed graft function (DGF) in kidney transplantation is associated with ischemic injury and carries long term functional and immunological risks. Extracellular vesicles (EV) released from allografts may signal a degree of ischemic stress, and are thought to play an important role in the development of anti-donor immunity. Here, we show that kidney perfusate-derived extracellular vesicles (KP-EV) express donor-specific human leukocyte antigen.

Relative decrease in hemoglobin and outcomes in patients undergoing kidney transplantation surgery: A retrospective cohort study.

Background: Recent surgical literature suggests that a relative decrease in hemoglobin (ΔHb) is predictive of adverse outcomes regardless of the absolute level. We aimed to examine the association between perioperative ΔHb and kidney transplantation (KT) outcomes.

Methods: This was a retrospective cohort study of transplant recipients, where ΔHb = [Hb0- Hb1Hb0]x 100 (Hb = hemoglobin pre-KT and Hb = lowest hemoglobin 24-h post-KT).

Successful surgical weight loss with laparoscopic sleeve gastrectomy for morbid obesity prior to kidney transplantation.

Morbid obesity in kidney transplant (KT) candidates is associated with increased complications and graft failure. Multiple series have demonstrated rapid and significant weight loss after laparoscopic sleeve gastrectomy (LSG) in this population. Long-term and post-transplant weight evolutions are still largely unknown.

Predicting Clinical Outcome in Expanded Criteria Donor Kidney Transplantation: A Retrospective Cohort Study.

Background: The gaps in organ supply and demand necessitate the use of expanded criteria donor (ECD) kidneys.

Objective: To identify which pre-transplant and post-transplant predictors are most informative regarding short- and long-term ECD transplant outcomes.

Design: Retrospective cohort study.

Renal actinomycosis presenting as uro-cutaneous fistula.

Renal actinomycosis is a rare clinical entity. Diagnosis is usually made after resection. A 36-year-old male presented with uro-cutaneous fistula and left xanthogranulomatous pyelonephritis.

Safety and efficacy of the sleeve gastrectomy as a strategy towards kidney transplantation.

Background: Obese individuals suffering from advanced chronic kidney disease (CKD) may be precluded from accessing kidney transplantation. Bariatric surgery is an effective treatment for obesity and related conditions but its use in those with severe CKD remains limited due to morbidity concerns. We aimed to evaluate the safety and efficacy of sleeve gastrectomy (SG) in patients with severe CKD as a bridging strategy towards kidney transplant candidacy.

Immune Response to Extracellular Vesicles From Human Islets of Langerhans in Patients With Type 1 Diabetes.

The autoimmune response that characterizes type 1 diabetes (T1D) has no clear cause. Extracellular vesicles (EVs) play an important role in triggering the immune response in other contexts. Here, we propose a model by which EVs isolated from human islets stimulate proinflammatory immune responses and lead to peripheral blood mononuclear cell (PBMC) activation.

Renal resistance thresholds during hypothermic machine perfusion and transplantation outcomes - a retrospective cohort study.

Renal resistance (RR), of allografts undergoing hypothermic machine perfusion (HMP), is considered a measure of organ quality. We conducted a retrospective cohort study of adult deceased donor kidney transplant (KT) recipients whose grafts underwent HMP. Our aim was to evaluate whether RR is predictive of death-censored graft failure (DCGF).

Impact of acute kidney injury following liver transplantation on long-term outcomes.

Background: The incidence of acute kidney injury (AKI) after liver transplantation (LTx) ranges from 17% to 94%. AKI is associated with prolonged hospitalization and increased early mortality. In our cohort study, we examined the impact of AKI on long-term patient survival and on the incidence of stage 4-5 chronic kidney disease (CKD).

Early renal function recovery and long-term graft survival in kidney transplantation.

Following kidney transplantation (KTx), renal function improves gradually until a baseline eGFR is achieved. Whether or not a recipient achieves the best-predicted eGFR after KTx may have important implications for immediate patient management, as well as for long-term graft survival. The aim of this cohort study was to calculate the renal function recovery (RFR) based on recipient and donor eGFR and to evaluate the association between RFR and long-term death-censored graft failure (DCGF).

Pretransplant Recipient Circulating CD4+CD127lo/- Tumor Necrosis Factor Receptor 2+ Regulatory T Cells: A Surrogate of Regulatory T Cell-Suppressive Function and Predictor of Delayed and Slow Graft Function After Kidney Transplantation.

Background: Delayed graft function (DGF) and slow graft function (SGF) are ischemia-reperfusion-associated acute kidney injuries (AKI) that decrease long-term graft survival after kidney transplantation. Regulatory T (Treg) cells are protective in murine AKI, and their suppressive function predictive of AKI in kidney transplantation. The conventional Treg cell function coculture assay is however time-consuming and labor intensive.

Post-transplant liver function score as an early surrogate marker of long-term outcome.

Background: Currently, there is no universally accepted method to evaluate liver function post-orthotopic liver transplant (OLTx) and there are no early surrogate function markers to assess the impact of perioperative interventions in trial settings.

Material And Methods: In total, 495 patients were included in the study. On multivariate analysis, PTLF score, defined as normal (score <4) or dysfunctional (score ≥ 4), was the only significant variable for determining significant complications (P=0.

Pretransplantation recipient regulatory T cell suppressive function predicts delayed and slow graft function after kidney transplantation.

Background: Delayed graft function (DGF) and slow graft function (SGF) are a continuous spectrum of ischemia-reperfusion-related acute kidney injury (AKI) that increases the risk for acute rejection and graft loss after kidney transplantation. Regulatory T cells (Tregs) are critical in transplant tolerance and attenuate murine AKI. In this prospective observational cohort study, we evaluated whether pretransplantation peripheral blood recipient Treg frequency and suppressive function are predictors of DGF and SGF after kidney transplantation.

Impact of early graft function on 10-year graft survival in recipients of kidneys from standard- or expanded-criteria donors.

Background: The use of kidneys from expanded-criteria donors (ECD) is regarded with caution.

Methods: We compared 279 kidney transplant recipients (KTxR) from standard-criteria donors (SCD) and 237 from ECD, transplanted between January 1990 and December 2006. We evaluated the impact of immediate graft function (IGF), slow graft function (SGF), and delayed graft function (DGF) and the drop in estimated glomerular filtration rate (ΔeGFR) ≤ 30% or > 30% during the first year after transplantation on long-term patient and death-censored graft survival (DCGS).

Postoperative delirium in the intensive care unit predicts worse outcomes in liver transplant recipients.

Background: Delirium is common in intensive care unit patients and is associated with worse outcome.

Objective: To identify early risk factors for delirium in patients admitted to the intensive care unit following orthotopic liver transplantation (OLT).

Methods: An observational study of patients admitted to the intensive care unit from January 2000 to May 2010 for elective or semi-elective OLT was conducted.

Hepatitis C infection and hepatocellular carcinoma in liver transplantation: a 20-year experience.

Background: Hepatitis C infection (HCV) and hepatocellular carcinoma (HCC), the two main causes of liver transplantation (LT), have reduced survival post-LT. The impact of HCV, HCC and their coexistence on post-LT survival were assessed.

Methodology: All 601 LT patients from 1992 to 2011 were reviewed.