Optimizing the Use of Deceased Donor Kidneys at Risk of Discard: A Clinical Practice Guideline.

Underutilization of deceased donor organs has worsened the gap in the number of kidneys available for transplantation. The purpose of this clinical practice guideline is to provide recommendations on the utilization of donor kidneys at risk of discard. Six conditional recommendations were made all with very low certainty of evidence: 1) We suggest utilizing extended criteria donor (ECD) kidneys for transplantation rather than remaining on the wait list and continuing with dialysis; 2) We suggest utilizing kidneys from ECD versus non-ECD in selected transplant candidates; 3) We suggest that organs from older kidney donors can be used in selected transplant candidates who may derive benefit from them; 4) We suggest that kidneys from deceased donors with acute kidney injury can be used for transplantation based on clinician assessment and donor factors; 5) We suggest that donor kidneys with acute kidney injury from either ECD or non-ECD be used for kidney transplantation; 6) We suggest using kidneys from donors after death determination by circulatory criteria for transplantation.

Endothelial extracellular vesicle miR-423-5p regulates microvascular homeostasis and renal function after ischemia-reperfusion injury.

Microvascular rarefaction substantially contributes to renal dysfunction following ischemia-reperfusion injury (IRI). We characterized the microRNA signature of extracellular vesicles (EVs) released during endothelial apoptosis to identify biomarkers and regulators of microvascular rarefaction and renal dysfunction. Using in vitro models and RNA-Seq, we found miR-423-5p, let-7b-5p, and let-7c-5p enriched in small EVs from apoptotic endothelial cells.

Patient and Caregiver Perceptions on the Allocation Process and Waitlist, and Accepting a Less-Than-Ideal Kidney: A Canadian Survey.

Background: Transplanting less-than-ideal (LTI) kidneys could help optimize organ utilization, but little is known about how patients and caregivers perceive the allocation process, waitlist, or LTI kidneys.

Objective: To explore the perspectives of patients and caregivers on the Canadian kidney transplant allocation process, waitlist, and LTI kidneys.

Design: Electronic survey.

Clinical Urinary Tract Infections in Kidney Transplant Recipients With Initially Asymptomatic Bacteriuria: A Single-Center Retrospective Cohort Study.

Rationale & Objective: Management of asymptomatic bacteriuria in kidney transplant recipients remains uncertain. Our main objective was to evaluate whether patient- or episode-related factors could help identify episodes of asymptomatic bacteriuria associated with a higher risk of being followed by a symptomatic urinary tract infection.

Study Design: A single-center, retrospective cohort study.

Exposure to renin-angiotensin system inhibitors before kidney transplantation is associated with a decreased risk of delayed graft function.

Introduction: Animal models suggest a protective role of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor blockers (ARBs) in reducing renal and cardiac ischemia-reperfusion injury. Our aim was to determine the association between pre-transplant ACEi/ARBs use and the occurrence of delayed graft function (DGF) in patients who received a kidney transplantation from a deceased donor.

Methods: Consecutive recipients between 2008 and 2021 in 2 Canadian university-affiliated centers were included in this retrospective cohort study.

The Use of Kidneys With Lower Longevity From Deceased Donors to Improve Access to Preemptive Renal Transplantation for Elderly Patients: A Qualitative Study.

Background: There is a gap between the number of patients waiting for a transplant and the number of kidneys available. Some deceased donor kidneys are currently nonutilized, as medical teams fear that they will experience suboptimal graft survival. However, these organs could provide an acceptable therapeutic option if they were allocated for preemptive kidney transplantation in elderly candidates.

The Strategies Used to Balance Health and Work Across the Solid Organ Transplantation Trajectory.

Workers who undergo solid organ transplantation report frequent conflicts between the unpredictable demands of their health condition and the rigid requirements of their employer and of health services. The present study aimed to describe the self-management strategies adopted by workers while staying at work before transplantation and during sustainable return-to-work posttransplantation. Fifteen employed kidney, liver, and lung transplant recipients were recruited from 2 large urban university health centers in Montreal, Canada.

A Multinational Cohort Study Examining Sex Differences in Excess Risk of Death With Graft Function After Kidney Transplant.

Background: Kidney transplant recipients show sex differences in excess overall mortality risk that vary by donor sex and recipient age. However, whether the excess risk of death with graft function (DWGF) differs by recipient sex is unknown.

Methods: In this study, we combined data from 3 of the largest transplant registries worldwide (Scientific Registry of Transplant Recipient, Australia and New Zealand Dialysis and Transplant Registry, and Collaborative Transplant Study) using individual patient data meta-analysis to compare the excess risk of DWGF between male and female recipients of a first deceased donor kidney transplant (1988-2019), conditional on donor sex and recipient age.

NephroCAGE-German-Canadian Consortium on AI for Improved Kidney Transplantation Outcome: Protocol for an Algorithm Development and Validation Study.

Background: Recent advances in hardware and software enabled the use of artificial intelligence (AI) algorithms for analysis of complex data in a wide range of daily-life use cases. We aim to explore the benefits of applying AI to a specific use case in transplant nephrology: risk prediction for severe posttransplant events. For the first time, we combine multinational real-world transplant data, which require specific legal and technical protection measures.

Calcineurin Inhibition in Deceased Organ Donors: A Systematic Review and Meta-analysis of Preclinical Studies.

Background: Preconditioning deceased organ donors with calcineurin inhibitors (CNIs) may reduce ischemia-reperfusion injury to improve transplant outcomes.

Methods: We searched MEDLINE, EMBASE, Cochrane Library, and conference proceedings for animal models of organ donation and transplantation, comparing donor treatment with CNIs with either placebo or no intervention, and evaluating outcomes for organ transplantation. Reviewers independently screened and selected studies, abstracted data, and assessed the risk of bias and clinical relevance of included studies.

Predicting Time to and Average Quality of Future Offers for Kidney Transplant Candidates Declining a Current Deceased Donor Kidney Offer: A Retrospective Cohort Study.

Background: At the time a kidney offer is made by an organ donation organization (ODO), transplant physicians must inform candidates on the and of accepting or declining the offer. Although physicians have a general idea of expected wait time to kidney transplantation by blood group in their ODO, there are no tools that provide quantitative estimates based on the allocation score used and donor/candidate characteristics. This limits the shared decision-making process at the time of kidney offer as (1) the consequences of declining an offer in terms of wait-time prolongation cannot be provided and (2) the quality of the current offer cannot be compared with that of offers that could be made to the specific candidate in the future.

Automated screening of potential organ donors using a temporal machine learning model.

Organ donation is not meeting demand, and yet 30-60% of potential donors are potentially not identified. Current systems rely on manual identification and referral to an Organ Donation Organization (ODO). We hypothesized that developing an automated screening system based on machine learning could reduce the proportion of missed potentially eligible organ donors.

Immunogenicity, Safety, and Breakthrough Severe Acute Respiratory Syndrome Coronavirus 2 Infections After Coronavirus Disease 2019 Vaccination in Organ Transplant Recipients: A Prospective Multicenter Canadian Study.

Background: Solid organ transplant (SOT) recipients are at risk for severe coronavirus disease 2019 (COVID-19), despite vaccination. Our study aimed to elucidate COVID-19 vaccine immunogenicity and evaluate adverse events such as hospitalization, rejection, and breakthrough infection in a SOT cohort.

Methods: We performed a prospective, observational study on 539 adult SOT recipients (age ≥18 years old) recruited from 7 Canadian transplant centers.

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.

Hypothermic Perfusion Modifies the Association Between Anti-LG3 Antibodies and Delayed Graft Function in Kidney Recipients.

We previously reported associations between autoantibodies to the LG3 fragment of perlecan, anti-LG3, and a higher risk of delayed graft function (DGF) in kidney transplant recipients. Here, we aimed to determine whether some factors that modulate ischemia-reperfusion injury (IRI) can modify this association. We performed a retrospective cohort study in kidney transplant recipients in 2 university-affiliated centers.

A multinational cohort study uncovered sex differences in excess mortality after kidney transplant.

Worldwide and at all ages, males have a higher mortality risk than females. This mortality bias should be preserved in kidney transplant recipients unless there are sex differences in the effects of transplantation. Here we compared the excess risk of mortality (risk above the general population) in female versus male recipients of all ages recorded in three large transplant databases.

Double Pretransplant Positivity for Autoantibodies to LG3 and Angiotensin II Type 1 Receptor Is Associated With Alloimmune Vascular Injury in Kidney Transplant Recipients.

Unlabelled: Both angiotensin II receptor autoantibodies (ATRabs) and autoantibodies to LG3 have been linked to kidney graft rejection with alloimmune vascular injury (AVI). We aimed to examine whether positivity for both anti-LG3 and ATRabs is associated with rejection with AVI in kidney transplant recipients.

Methods: We performed a retrospective cohort study including consecutive kidney transplant recipients between 2013 and 2017 at a single center.

Natural Antibodies Are Associated With Rejection and Long-term Renal Allograft Loss in a Multicenter International Cohort.

Background: Potentially harmful nonhuman leukocyte antigen antibodies have been identified in renal transplantation, including natural immunoglobulin G antibodies (Nabs) reactive to varied antigenic structures, including apoptotic cells.

Methods: In this retrospective, multicenter study, we assessed Nabs by reactivity to apoptotic cells in sera collected from 980 kidney transplant recipients across 4 centers to determine their association with graft outcomes.

Results: Elevated pretransplant Nabs were associated with graft loss (hazard ratio [HR] 2.

Severity of COVID-19 among solid organ transplant recipients in Canada, 2020-2021: a prospective, multicentre cohort study.

Background: Severe COVID-19 appears to disproportionately affect people who are immunocompromised, although Canadian data in this context are limited. We sought to determine factors associated with severe COVID-19 outcomes among recipients of organ transplants across Canada.

Methods: We performed a multicentre, prospective cohort study of all recipients of solid organ transplants from 9 transplant programs in Canada who received a diagnosis of COVID-19 from March 2020 to November 2021.

Factors Associated With the Use of Hypothermic Machine Perfusion in Kidney Transplant Recipients: A Multicenter Retrospective Cohort Study.

Background: Delayed graft function (DGF) is associated with an increased risk of graft loss. The use of cold hypothermic machine perfusion (HMP) has been shown to reduce the incidence of DGF in kidney transplant recipients (KTRs), especially when extended-criteria donors (ECDs) are used. HMP can also improve graft survival.

Humoral immune responses against SARS-CoV-2 Spike variants after mRNA vaccination in solid organ transplant recipients.

Although SARS-CoV-2 mRNA vaccination has been shown to be safe and effective in the general population, immunocompromised solid organ transplant recipients (SOTRs) were reported to have impaired immune responses after one or two doses of vaccine. In this study, we examined humoral responses induced after the second and the third dose of mRNA vaccine in different SOTR (kidney, liver, lung, and heart). Compared to a cohort of SARS-CoV-2 naïve immunocompetent health care workers (HCWs), the second dose induced weak humoral responses in SOTRs, except for the liver recipients.