Preferences in treating polyomavirus infection in kidney transplant recipients: A discrete choice experiment with patients, caregivers, and clinicians.

Background: Treatment strategies for BK polyomavirus (BKPyV) infection in kidney transplant recipients are heterogeneous among clinicians. We aimed to identify the treatment preferences of key stakeholders for BKPyV infection and measure the trade-offs between treatment outcomes.

Methods: Adult kidney transplant recipients, caregivers, and clinicians were eligible to participate in a discrete choice experiment between February 2021 and June 2022.

Patients' Perspectives, Factors, and Patterns of eHealth Use in Kidney Transplant Recipients.

Introduction: eHealth supports the delivery of relevant health information and management of chronic disease. However, little is known about patients' perspectives and the determinants of eHealth use among kidney transplant recipients.

Methods: Kidney transplant recipients aged 18 years and older from 3 transplant units in Australia and the Better Evidence and Translation in Chronic Kidney Disease consumer network completed a survey with free-text responses relating to eHealth uptake.

The first Australian uterus transplantation procedure: A result of a long-term Australian-Swedish research collaboration.

Aims: The aim is to report the results of Australia's first uterus transplantation (UTx).

Methods: Following long-standing collaboration between the Swedish and Australian teams, Human Research Ethics approval was obtained to perform six UTx procedures in a collaborative multi-site research study (Western Sydney Local District Health 2019/ETH13038), including Royal Hospital for Women, Prince of Wales Hospital, and Westmead Hospital in New Souh Wales. Surgeries were approved in both the live donor (LD) and deceased donor models in collaboration with the inaugural Swedish UTx team.

Membranous nephropathy: Clearer pathology and mechanisms identify potential strategies for treatment.

Primary membranous nephropathy (PMN) is one of the common causes of adult-onset nephrotic syndrome and is characterized by autoantibodies against podocyte antigens causing immune complex deposition. Much of our understanding of the disease mechanisms underpinning this kidney-limited autoimmune disease originally came from studies of Heymann nephritis, a rat model of PMN, where autoantibodies against megalin produced a similar disease phenotype though megalin is not implicated in human disease. In PMN, the major target antigen was identified to be M-type phospholipase A2 receptor 1 (PLA2R) in 2009.

Predictive Models for Recurrent Membranous Nephropathy After Kidney Transplantation.

Unlabelled: Recurrent membranous nephropathy (MN) posttransplantation affects 35% to 50% of kidney transplant recipients (KTRs) and accounts for 50% allograft loss 5 y after diagnosis. Predictive factors for recurrent MN may include HLA-D risk alleles, but other factors have not been explored with certainty.

Methods: The Australian and New Zealand Dialysis and Transplant registry was used to develop 3 prediction models for recurrent MN (Group Least Absolute Shrinkage and Selection Operator [LASSO], penalized Cox regression, and random forest), which were tuned using tenfold cross-validation in a derivation cohort with complete HLA data.

Deep learning identified pathological abnormalities predictive of graft loss in kidney transplant biopsies.

Interstitial fibrosis, tubular atrophy, and inflammation are major contributors to kidney allograft failure. Here we sought an objective, quantitative pathological assessment of these lesions to improve predictive utility and constructed a deep-learning-based pipeline recognizing normal vs. abnormal kidney tissue compartments and mononuclear leukocyte infiltrates.

Key driver genes as potential therapeutic targets in renal allograft rejection.

Acute rejection (AR) in renal transplantation is an established risk factor for reduced allograft survival. Molecules with regulatory control among immune pathways of AR that are inadequately suppressed, despite standard-of-care immunosuppression, could serve as important targets for therapeutic manipulation to prevent rejection. Here, an integrative, network-based computational strategy incorporating gene expression and genotype data of human renal allograft biopsy tissue was applied, to identify the master regulators - the key driver genes (KDGs) - within dysregulated AR pathways.

Low-Dose Interleukin-2 Combined With Rapamycin Led to an Expansion of CD4CD25FOXP3 Regulatory T Cells and Prolonged Human Islet Allograft Survival in Humanized Mice.

Islet transplantation is an emerging therapy for type 1 diabetes and hypoglycemic unawareness. However, a key challenge for islet transplantation is cellular rejection and the requirement for long-term immunosuppression. In this study, we established a diabetic humanized NOD-scidIL2Rγ (NSG) mouse model of T-cell-mediated human islet allograft rejection and developed a therapeutic regimen of low-dose recombinant human interleukin-2 (IL-2) combined with low-dose rapamycin to prolong graft survival.

Brief Normothermic Machine Perfusion Rejuvenates Discarded Human Kidneys.

Unlabelled: Normothermic machine perfusion (NMP) may allow resuscitation and improved assessment of kidneys before transplantation. Using discarded human kidneys, we investigated the mechanistic basis and translational potential of NMP compared with cold static storage (CS).

Methods: Discarded deceased donor kidneys (n = 15) underwent 1-hour NMP following CS.

A Peripheral Blood Gene Expression Signature to Diagnose Subclinical Acute Rejection.

Background: In kidney transplant recipients, surveillance biopsies can reveal, despite stable graft function, histologic features of acute rejection and borderline changes that are associated with undesirable graft outcomes. Noninvasive biomarkers of subclinical acute rejection are needed to avoid the risks and costs associated with repeated biopsies.

Methods: We examined subclinical histologic and functional changes in kidney transplant recipients from the prospective Genomics of Chronic Allograft Rejection (GoCAR) study who underwent surveillance biopsies over 2 years, identifying those with subclinical or borderline acute cellular rejection (ACR) at 3 months (ACR-3) post-transplant.

Pretransplant transcriptomic signature in peripheral blood predicts early acute rejection.

Commonly available clinical parameters fail to predict early acute cellular rejection (EAR, occurring within 6 months after transplant), a major risk factor for graft loss after kidney transplantation. We performed whole-blood RNA sequencing at the time of transplant in 235 kidney transplant recipients enrolled in a prospective cohort study (Genomics of Chronic Allograft Rejection [GoCAR]) and evaluated the relationship of pretransplant transcriptomic profiles with EAR. EAR was associated with downregulation of NK and CD8+ T cell gene signatures in pretransplant blood.

Standardisation of flow cytometry for whole blood immunophenotyping of islet transplant and transplant clinical trial recipients.

Understanding the immunological phenotype of transplant recipients is important to improve outcomes and develop new therapies. Immunophenotyping of whole peripheral blood (WPB) by flow cytometry is a rapid method to obtain large amounts of data relating to the outcomes of different transplant treatments with limited patient impact. Healthy individuals and patients with type 1 diabetes (T1D) enrolled in islet transplantation were recruited and WPB was collected.

SHROOM3-FYN Interaction Regulates Nephrin Phosphorylation and Affects Albuminuria in Allografts.

Background: We previously showed that the presence of a CKD-associated locus in SHROOM3 in a donor kidney results in increased expression of SHROOM3 (an F-actin-binding protein important for epithelial morphogenesis, via rho-kinase [ROCK] binding); this facilitates TGF-b signaling and allograft fibrosis. However, other evidence suggests Shroom3 may have a protective role in glomerular development.

Methods: We used human data, Shroom3 knockdown podocytes, and inducible shRNA-mediated knockdown mice to study the role of Shroom3 in adult glomeruli.

The causes, significance and consequences of inflammatory fibrosis in kidney transplantation: The Banff i-IFTA lesion.

Inflammation within areas of interstitial fibrosis and tubular atrophy (i-IFTA) is associated with adverse outcomes in kidney transplantation. We evaluated i-IFTA in 429 indication- and 2052 protocol-driven biopsy samples from a longitudinal cohort of 362 kidney-pancreas recipients to determine its prevalence, time course, and relationships with T cell-mediated rejection (TCMR), immunosuppression, and outcome. Sequential histology demonstrated that i-IFTA was preceded by cellular interstitial inflammation and followed by IF/TA.

Genomic Analysis of Kidney Allograft Injury Identifies Hematopoietic Cell Kinase as a Key Driver of Renal Fibrosis.

Renal fibrosis is the common pathway of progression for patients with CKD and chronic renal allograft injury (CAI), but the underlying mechanisms remain obscure. We performed a meta-analysis in human kidney biopsy specimens with CAI, incorporating data available publicly and from our Genomics of Chronic Renal Allograft Rejection study. We identified an family tyrosine kinase, hematopoietic cell kinase (), as upregulated in allografts in CAI.

Biopsy transcriptome expression profiling to identify kidney transplants at risk of chronic injury: a multicentre, prospective study.

Background: Chronic injury in kidney transplants remains a major cause of allograft loss. The aim of this study was to identify a gene set capable of predicting renal allografts at risk of progressive injury due to fibrosis.

Methods: This Genomics of Chronic Allograft Rejection (GoCAR) study is a prospective, multicentre study.

The Use of Genomics and Pathway Analysis in Our Understanding and Prediction of Clinical Renal Transplant Injury.

The development and application of high-throughput molecular profiling have transformed the study of human diseases. The problem of handling large, complex data sets has been facilitated by advances in complex computational analysis. In this review, the recent literature regarding the application of transcriptional genomic information to renal transplantation, with specific reference to acute rejection, acute kidney injury in allografts, chronic allograft injury, and tolerance is discussed, as is the current published data regarding other "omics" strategies-proteomics, metabolomics, and the microRNA transcriptome.