Updates in Kidney Transplantation From the 2022 Banff-Canadian Society of Transplantation Joint Meeting: Conference Report.

Purpose Of The Conference: The 2022 Banff-Canadian Society of Transplantation Meeting in Banff, Alberta, brought together transplant professionals to review new developments across various aspects of solid organ transplantation (SOT) in Canada.

Sources Of Information: Presentations included consensus recommendations from expert-led forums; experiences with new procedures and legislation; reports from public health data repositories; original clinical and laboratory research; and industry updates regarding novel technologies. Speakers referenced articles and reports published in peer-reviewed journals and online, and unpublished data and preliminary findings.

Multicenter Validation of a Urine CXCL10 Assay for Noninvasive Monitoring of Renal Transplants.

Background: Urine CXCL10 (C-X-C motif chemokine ligand 10, interferon gamma-induced protein 10 [IP10]) outperforms standard-of-care monitoring for detecting subclinical and early clinical T-cell-mediated rejection (TCMR) and may advance TCMR therapy development through biomarker-enriched trials. The goal was to perform an international multicenter validation of a CXCL10 bead-based immunoassay (Luminex) for transplant surveillance and compare with an electrochemiluminescence-based (Meso Scale Discovery [MSD]) assay used in transplant trials.

Methods: Four laboratories participated in the Luminex assay development and evaluation.

A RAND-Modified Delphi on Key Indicators to Measure the Efficiency of Living Kidney Donor Candidate Evaluations.

Background And Objectives: Many patients, providers, and potential living donors perceive the living kidney donor evaluation process to be lengthy and difficult to navigate.

Design, Setting, Participants, & Measurements: We sought consensus on key terms and process and outcome indicators that can be used to measure how efficiently a transplant center evaluates persons interested in becoming a living kidney donor. Using a RAND-modified Delphi method, 77 participants (kidney transplant recipients or recipient candidates, living kidney donors or donor candidates, health care providers, and health care administrators) completed an online survey to define the terms and indicators.

Rictor deficiency in dendritic cells exacerbates acute kidney injury.

Dendritic cells (DCs) are critical initiators of innate immunity in the kidney and orchestrate inflammation following ischemia-reperfusion injury. The role of the mammalian/mechanistic target of rapamycin (mTOR) in the pathophysiology of renal ischemia-reperfusion injury has been characterized. However, the influence of DC-based alterations in mTOR signaling is unknown.

Influence of the Novel ATP-Competitive Dual mTORC1/2 Inhibitor AZD2014 on Immune Cell Populations and Heart Allograft Rejection.

Background: Little is known about how new-generation adenosine triphosphate-competitive mechanistic target of rapamycin (mTOR) kinase inhibitors affect immunity and allograft rejection.

Methods: mTOR complex (C) 1 and 2 signaling in dendritic cells and T cells was analyzed by Western blotting, whereas immune cell populations in normal and heart allograft recipient mice were analyzed by flow cytometry. Alloreactive T cell proliferation was quantified in mixed leukocyte reaction; intracellular cytokine production and serum antidonor IgG levels were determined by flow analysis and immunofluorescence staining used to detect IgG in allografts.

Roles of mTOR complexes in the kidney: implications for renal disease and transplantation.

The mTOR pathway has a central role in the regulation of cell metabolism, growth and proliferation. Studies involving selective gene targeting of mTOR complexes (mTORC1 and mTORC2) in renal cell populations and/or pharmacologic mTOR inhibition have revealed important roles of mTOR in podocyte homeostasis and tubular transport. Important advances have also been made in understanding the role of mTOR in renal injury, polycystic kidney disease and glomerular diseases, including diabetic nephropathy.

New perspectives on mTOR inhibitors (rapamycin, rapalogs and TORKinibs) in transplantation.

The macrolide rapamycin and its analogues (rapalogs) constitute the first generation of mammalian target of rapamycin (mTOR) inhibitors. Since the introduction of rapamycin as an immunosuppressant, there has been extensive progress in understanding its complex mechanisms of action. New insights into the function of mTOR in different immune cell types, vascular endothelial cells and neoplastic cells have opened new opportunities and challenges regarding mTOR as a pharmacological target.

Aortic calcification: Novel insights from familial hypercholesterolemia and potential role for the low-density lipoprotein receptor.

Once thought to be a passive process of calcium accrual in arterial vascular beds, vascular calcification is considered to be a tightly regulated process mediated by osteoblast-like cells under the dys-regulated interplay of shear stress, metabolites, cytokines and transcription factors. Unfortunately, without effective medical interventions to prevent or regress vascular calcification, this process directly contributes to cardiovascular morbidity and mortality. We have previously shown that patients with familial hypercholesterolemia (FH) have severe, premature aortic calcification and calcific aortic stenosis.

Injury in First Nations communities in Ontario.

Background: High and variable rates of injury have been reported in Aboriginal communities in Canada. This has not been well studied for specific injury types. We sought to compare the rate and categories of injuries leading to hospital admission among those in First Nations communities relative to those living in small northern and southern communities in Ontario.

General RNA-binding proteins have a function in poly(A)-binding protein-dependent translation.

The interaction between the poly(A)-binding protein (PABP) and eukaryotic translational initiation factor 4G (eIF4G), which brings about circularization of the mRNA, stimulates translation. General RNA-binding proteins affect translation, but their role in mRNA circularization has not been studied before. Here, we demonstrate that the major mRNA ribonucleoprotein YB-1 has a pivotal function in the regulation of eIF4F activity by PABP.

Structural basis of ligand recognition by PABC, a highly specific peptide-binding domain found in poly(A)-binding protein and a HECT ubiquitin ligase.

The C-terminal domain of poly(A)-binding protein (PABC) is a peptide-binding domain found in poly(A)-binding proteins (PABPs) and a HECT (homologous to E6-AP C-terminus) family E3 ubiquitin ligase. In protein synthesis, the PABC domain of PABP functions to recruit several translation factors possessing the PABP-interacting motif 2 (PAM2) to the mRNA poly(A) tail. We have determined the solution structure of the human PABC domain in complex with two peptides from PABP-interacting protein-1 (Paip1) and Paip2.