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Abstract Early peritoneal dialysis (PD)-related infection is a severe complication. This study investigated the relationship between patient–doctor contact (PDC) duration and early PD-related infection. In the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) Korea, incident dialysis patients receiving PD were divided into two groups based on PDC duration (

Abstract Background There is a lack of contemporary data describing global variations in vascular access for hemodialysis (HD). We used the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) to highlight differences in funding and availability of hemodialysis accesses used for initiating HD across world regions. Methods Survey questions were directed at understanding the funding modules for obtaining vascular access and types of accesses used to initiate dialysis. An electronic survey was sent to national and regional key stakeholders affiliated with the ISN between June and September 2022. Countries that participated in the survey were categorized based on World Bank Income Classification (low-, lower-middle, upper-middle, and high-income) and by their regional affiliation with the ISN. Results Data on types of vascular access were available from 160 countries. Respondents from 35 countries (22% of surveyed countries) reported that > 50% of patients started HD with an arteriovenous fistula or graft (AVF or AVG). These rates were higher in Western Europe (n = 14; 64%), North & East Asia (n = 4; 67%), and among high-income countries (n = 24; 38%). The rates of > 50% of patients starting HD with a tunneled dialysis catheter were highest in North America & Caribbean region (n = 7; 58%) and lowest in South Asia and Newly Independent States and Russia (n = 0 in both regions). Respondents from 50% (n = 9) of low-income countries reported that > 75% of patients started HD using a temporary catheter, with the highest rates in Africa (n = 30; 75%) and Latin America (n = 14; 67%). Funding for the creation of vascular access was often through public funding and free at the point of delivery in high-income countries (n = 42; 67% for AVF/AVG, n = 44; 70% for central venous catheters). In low-income countries, private and out of pocket funding was reported as being more common (n = 8; 40% for AVF/AVG, n = 5; 25% for central venous catheters). Conclusions High income countries exhibit variation in the use of AVF/AVG and tunneled catheters. In low-income countries, there is a higher use of temporary dialysis catheters and private funding models for access creation.

Key features of chronic kidney disease (CKD) include tubulointerstitial inflammation and fibrosis. Protease activated receptor-2 (PAR2), a G-protein coupled receptor (GPCR) expressed by the kidney proximal tubular cells, induces potent proinflammatory responses in these cells. The hypothesis tested here was that PAR2 signalling can contribute to both inflammation and fibrosis in the kidney by transactivating known disease associated pathways. Using a primary cell culture model of human kidney tubular epithelial cells (HTEC), PAR2 activation induced a concentration dependent, PAR2 antagonist sensitive, secretion of TNF, CSF2, MMP-9, PAI-1 and CTGF. Transcription factors activated by the PAR2 agonist 2F, including NFκB, AP1 and Smad2, were critical for production of these cytokines. A TGF-β receptor-1 (TGF-βRI) kinase inhibitor, SB431542, and an EGFR kinase inhibitor, AG1478, ameliorated 2F induced secretion of TNF, CSF2, MMP-9, and PAI-1. Whilst an EGFR blocking antibody, cetuximab, blocked PAR2 induced EGFR and ERK phosphorylation, a TGF-βRII blocking antibody failed to influence PAR2 induced secretion of PAI-1. Notably simultaneous activation of TGF-βRII (TGF-β1) and PAR2 (2F) synergistically enhanced secretion of TNF (2.2-fold), CSF2 (4.4-fold), MMP-9 (15-fold), and PAI-1 (2.5-fold). In summary PAR2 activates critical inflammatory and fibrotic signalling pathways in human kidney tubular epithelial cells. Biased antagonists of PAR2 should be explored as a potential therapy for CKD.

Abstract Background Goals generated by Goal Attainment Scaling (GAS) can be used as an outcome measure to promote person-centred research and care. There are no training packages which support its use outside of the rehabilitation discipline. This paper describes the development and evaluation of a training package to support the implementation of GAS as an outcome measure in healthcare research. The training package consisted of classroom teaching, a training manual for self-directed learning, one-on-one simulation and hot reviews. It was developed for the GOAL Trial, a randomised controlled trial assessing a Comprehensive Geriatric Assessment’s effectiveness in enabling frail older people living with chronic kidney disease to attain their goals. Training participants were invited to complete pre- and post-training online evaluation surveys. Results Forty-two healthcare professionals attended an initial online classroom teaching, with 27 proceeding to administer GAS to GOAL Trial patients. Response rates for the online pre- and post-training surveys were 95% and 72%, respectively. Prior to training, only 15% of participants reported being able to appropriately scale and troubleshoot GAS goals. Post-training this was 92%. There was 100% participant satisfaction for the training manual, one-on-one simulation, and hot reviews. Conclusions This training package helps ensure healthcare professionals administering GAS have adequate knowledge and skills. It has the potential for adoption as a guide to support the implementation of GAS by other researchers seeking to embrace persont-centred principles in their work.

Abstract Background Peritoneal dialysis (PD)-related infections, such as peritonitis, exit site, and tunnel infections, substantially impair the sustainability of PD. Accordingly, PD-related infection is the top-priority research outcome for patients and caregivers. While PD nurse trainers teach patients to perform their own PD, PD training curricula are not standardized or informed by an evidentiary base and may offer a potential approach to prevent PD infections. The Targeted Education ApproaCH to improve Peritoneal Dialysis outcomes (TEACH-PD) trial evaluates whether a standardized training curriculum for PD nurse trainers and incident PD patients based on the International Society for Peritoneal Dialysis (ISPD) guidelines reduces PD-related infections compared to usual training practices. Methods The TEACH-PD trial is a registry-based, pragmatic, open-label, multi-center, binational, cluster-randomized controlled trial. TEACH-PD will recruit adults aged 18 years or older who have not previously undergone PD training at 42 PD treatment units (clusters) in Australia and New Zealand (ANZ) between July 2019 and June 2023. Clusters will be randomized 1:1 to standardized TEACH-PD training curriculum or usual training practice. The primary trial outcome is the time to the first occurrence of any PD-related infection (exit site infection, tunnel infection, or peritonitis). The secondary trial outcomes are the individual components of the primary outcome, infection-associated catheter removal, transfer to hemodialysis (greater than 30 days and 180 days), quality of life, hospitalization, all-cause death, a composite of transfer to hemodialysis or all-cause death, and cost-effectiveness. Participants are followed for a minimum of 12 months with a targeted average follow-up period of 2 years. Participant and outcome data are collected from the ANZ Dialysis and Transplant Registry (ANZDATA) and the New Zealand Peritoneal Dialysis (NZPD) Registry. This protocol follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. Discussion TEACH-PD is a registry-based, cluster-randomized pragmatic trial that aims to provide high-certainty evidence about whether an ISPD guideline-informed standardized PD training curriculum for PD nurse trainers and adult patients prevents PD-related infections. Trial registration ClinicalTrials.gov NCT03816111. Registered on 24 January 2019.

Abstract Background Implementing Patient-reported Outcome Measures (PROMs) and Patient-reported Experience Measures (PREMs) is an effective way to deliver patient- and family-centered care (PFCC). Although Alberta Health Services (AHS) is Canada's largest and fully integrated health system, PROMs and PREMs are yet to be routinely integrated into the pediatric healthcare system. This study addresses this gap by investigating the current uptake, barriers, and enablers for integrating PROMs and PREMs in Alberta's pediatric healthcare system. Methods Pediatric clinicians and academic researchers with experience using PROMs and PREMs were invited to complete a quantitative survey. Additionally, key stakeholders were qualitatively interviewed to understand current challenges in implementing pediatric PROMs and PREMs within AHS. Quantitative data gathered from 22 participants were descriptively analyzed, and qualitative data from 14 participants were thematically analyzed. Results Participants identified 33 PROMs and 6 PREMs showing diversity in the types of pediatric PROMs and PREMs currently being used in Alberta and their mode of administration. The qualitatively identified challenges were associated with patients, family caregivers, and clinicians. The absence of system-level support, such as integration within electronic medical records, is considered a significant system-level challenge. Conclusions The significant variation in the types of PROMs and PREMs used, the rationale for their use, and their mode of administration demonstrate the diverse and sporadic use of these measures in Alberta. These findings highlight the need for province-wide uniform implementation of pediatric PROMs and PREMs in Alberta. Our results could benefit healthcare organizations in developing evidence-based PROM and PREM implementation strategies in pediatrics.

Introduction Chronic kidney disease (CKD) is increasingly recognised as a growing global public health problem. Early detection and management can significantly reduce the loss of kidney function. The proposed trial aims to evaluate the impact of a community pharmacy-led intervention combining CKD screening and medication review on CKD detection and quality use of medicines (QUM) for patients with CKD. We hypothesise that the proposed intervention will enhance detection of newly diagnosed CKD cases and reduce potentially inappropriate medications use by people at risk of or living with CKD.Methods and analysis This study is a multicentre, pragmatic, two-level cluster randomised controlled trial which will be conducted across different regions in Australia. Clusters of community pharmacies from geographical groups of co-located postcodes will be randomised. The project will be conducted in 122 community pharmacies distributed across metropolitan and rural areas. The trial consists of two arms: (1) Control Group: a risk assessment using the QKidney CKD risk assessment tool, and (2) Intervention Group: a risk assessment using the QKidney CKD plus Point-of-Care Testing for kidney function markers (serum creatinine and estimated glomerular filtration rate), followed by a QUM service. The primary outcomes of the study are the proportion of patients newly diagnosed with CKD at the end of the study period (12 months); and rates of changes in the number of medications considered problematic in kidney disease (number of medications prescribed at inappropriate doses based on kidney function and/or number of nephrotoxic medications) over the same period. Secondary outcomes include proportion of people on potentially inappropriate medications, types of recommendations provided by the pharmacist (and acceptance rate by general practitioners), proportion of people who were screened, referred, and took up the referral to visit their general practitioners, and economic and other patient-centred outcomes.Ethics and dissemination The trial protocol has been approved by the Human Research Ethics Committee at the University of Sydney (2022/044) and the findings of the study will be presented at scientific conferences and published in peer-reviewed journal(s).Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12622000329763).

Abstract. Introduction:. Individual genetic variation may influence clinical effects for pain medications. Effects of CYP2C9, CYP3A4, and CYP2D6 polymorphisms on clinical effectiveness and safety for ibuprofen and oxycodone were studied. Objective:. Primary objectives were to AU2 evaluate if allelic variations would affect clinical effectiveness and adverse events (AEs) occurrence. Methods:. This pragmatic prospective, observational cohort included children aged 4 to 16 years who were seen in a pediatric emergency department with an acute fracture and prescribed ibuprofen or oxycodone for at-home pain management. Saliva samples were obtained for genotyping of allelic variants, and daily telephone follow-up was conducted for 3 days. Pain was measured using the Faces Pain Scale-Revised. Results:. We included 210 children (n = 140 ibuprofen and n = 70 oxycodone); mean age was 11.1 (±SD 3.5) years, 33.8% were female. Median pain reduction on day 1 was similar between groups [ibuprofen 4 (IQR 2,4) and oxycodone 4 (IQR 2,6), P = 0.69]. Over the 3 days, the oxycodone group experienced more AE than the ibuprofen group (78.3% vs 53.2%, P < 0.001). Those with a CYP2C9*2 reduced function allele experienced less adverse events with ibuprofen compared with those with a normal functioning allele CYP2C9*1 (P = 0.003). Neither CYP3A4 variants nor CYP2D6 phenotype classification affected clinical effect or AE. Conclusion:. Although pain relief was similar, children receiving oxycodone experienced more AE, overall, than those receiving ibuprofen. For children receiving ibuprofen or oxycodone, pain relief was not affected by genetic variations in CYP2C9 or CYP3A4/CYP2D6, respectively. For children receiving ibuprofen, the presence of CYP2C9*2 was associated with less adverse events.

Abstract Background Neonatal Abstinence Syndrome (NAS), a problem common in newborns exposed to substances in-utero, is an emerging health concern. In traditional models of care, infants with NAS are routinely separated from their mothers and admitted to the Neonatal Intensive Care Unit (NICU) with long, expensive length of stay (LOS). Research shows a rooming-in approach (keeping mothers and infants together in hospital) with referral support is a safe and effective model of care in managing NAS. The model’s key components are facilitating 24-h care by mothers on post-partum or pediatric units with support for breastfeeding, transition home, and access to Opioid Dependency Programs (ODP). This study will implement the rooming-in approach at eight hospitals across one Canadian Province; support practice and culture shift; identify and test the essential elements for effective implementation; and assess the implementation’s impact/outcomes. Methods A stepped wedge cluster randomized trial will be used to evaluate the implementation of an evidence-based rooming-in approach in the postpartum period for infants born to mothers who report opioid use during pregnancy. Baseline data will be collected and compared to post-implementation data. Six-month assessment of maternal and child health and an economic evaluation of cost savings will be conducted. Additionally, barriers and facilitators of the rooming-in model of care within the unique context of each site and across sites will be explored pre-, during, and post-implementation using theory-informed surveys, interviews, and focus groups with care teams and parents. A formative evaluation will examine the complex contextual factors and conditions that influence readiness and sustainability and inform the design of tailored interventions to facilitate capacity building for effective implementation. Discussion The primary expected outcome is reduced NICU LOS. Secondary expected outcomes include decreased rates of pharmacological management of NAS and child apprehension, increased maternal ODP participation, and improved 6-month outcomes for mothers and infants. Moreover, the NASCENT program will generate the detailed, multi-site evidence needed to accelerate the uptake, scale, and spread of this evidence-based intervention throughout Alberta, leading to more appropriate and effective care and use of healthcare resources. Trial registration ClinicalTrials.gov, NCT0522662. Registered February 4th, 2022.

Cancer transmission from deceased donors is an exceedingly rare but potentially fatal complication in transplant recipients. We aimed to quantify the likelihood of non-utilization of kidneys for transplantation from donors with a prior cancer history. We included all intended and actual deceased donors in Australia and New Zealand between 1989 and 2017. Association between prior cancer history and non-utilization of donor kidneys was examined using adjusted logistic regression. Of 9,485 deceased donors, 345 (4%) had a prior cancer history. Of 345 donors with a prior cancer history, 197 (57%) were utilized for transplantation. Donor characteristics of age, sex and comorbidities were similar between utilized and non-utilized donors with prior cancer. The time from cancer to organ donation was similar between utilized and non-utilized donors, irrespective of cancer subtypes. Donors with a prior cancer history were less likely to be utilized [adjusted OR (95% CI) 2.29 (1.68–3.13)] than donors without prior cancer. Of all actual donors, the adjusted OR for non-utilization among those with prior cancer was 2.36 (1.58–3.53). Non-melanoma skin cancer was the most frequent prior cancer type for utilized and non-utilized potential donors. Donors with prior cancers were less likely to be utilized for transplantation, with no discernible differences in cancer characteristics between utilized and non-utilized donors.

Rationale & Objective: The development of new therapies for autosomal dominant polycystic kidney disease requires clinical trials to be conducted efficiently. In this study, the factors affecting the recruitment and retention of participants enrolled in a 3-year randomized controlled trial in autosomal dominant polycystic kidney disease were investigated. Study Design: Qualitative study. Setting & Participants: All participants (N=187) were invited to complete a 16-item questionnaire at the final study visit of the primary trial. Participants were recruited to complete a semistructured interview using purposeful sampling according to age, self-reported gender, and randomization group. Analytical Approach: Descriptive statistics were used for demographic data and questionnaires. The interview transcripts underwent inductive thematic coding. Results: One hundred and forty-six of the 187 randomized participants (79%) completed the post-trial questionnaire, and 31 of the 187 participants (21%) completed the interview. Most participants (94%) rated their global satisfaction with the trial as high (a score of 8 or more out of 10). Altruism, knowledge gain, and access to new treatments were the main motivators for recruitment. The main reasons for considering leaving the study were concerns about the risk of intervention and family or work issues. Strategies that favored retention included flexibility in attending different study sites, schedule flexibility, staff interactions, and practical support with parking and reminders. The main burden was time away from work with lost wages, and burden associated with magnetic resonance imaging scans and 24-hour urine output collections. Limitations: The study population was restricted to participants in a single nondrug clinical trial, and the results could be influenced by selection and possible social desirability bias. Conclusions: Participants reported high levels of satisfaction that occurred as a function of the trial meeting participants’ expectations. Furthermore, retention was a balance between the perceived benefits and burden of participation. Consideration of these perspectives in the design of future clinical trials will improve their efficiency and conduct. Plain-Language Summary: Advances in the clinical practice of autosomal dominant polycystic kidney disease (ADPKD) require affected individuals to voluntarily participate in long-term multicenter randomized controlled trials (RCTs). In this qualitative post hoc study of a 3-year RCT of increased water intake in ADPKD, altruism, knowledge gain, and access to a nondrug treatment positively influenced the decision to volunteer. Ongoing participation was enabled by building flexibility into the study protocol and staff prioritizing a participant’s needs during study visits. Although participants completed the required tests, most were considered burdensome. This study highlights the importance of incorporating protocol flexibility into trial design; the preference for interventions with a low risk of adverse effects; and the urgent requirement for robust surrogate noninvasive biomarkers to enable shorter RCTs in ADPKD.

Abstract Background Modulating the microbiota in the large intestine of kidney transplant recipients through prebiotic supplementation may prevent infectious complications from occurring. To date, there have been no interventional trials which have investigated this novel treatment in kidney transplantation. The aim of PREBIOTIC is to assess the feasibility of performing a randomised controlled trial of prebiotics in reducing infections and gastrointestinal symptoms in kidney transplant recipients. Methods Sixty kidney transplant patients will be recruited to a double-blind, placebo-controlled, randomised feasibility trial. Patients will be provided with prebiotic therapy or placebo for 4 to 6 weeks. Outcomes will include recruitment, adherence, tolerance, retention, laboratory parameters (including serum indoxyl sulphate, ρ-cresyl sulphate and stool collection), patients’ self-assessed quality of life, gastrointestinal symptoms and clinical outcomes. Discussion This trial will assess the feasibility of prebiotic supplementation in kidney transplant recipients. Prebiotics not only may alter the gut microbiota and their inherent metabolism and production of uraemic toxins but also may prevent infections from occurring in kidney transplant recipients. Trial registration Australian New Zealand Clinical Trials Registry number ACTRN12618001057279p. The date of registration was 25th June 2018, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375370&isReview=true .

Abstract Background A functioning vascular access (VA) is crucial to providing adequate hemodialysis (HD) and considered a critically important outcome by patients and healthcare professionals. A validated, patient-important outcome measure for VA function that can be easily measured in research and practice to harvest reliable and relevant evidence for informing patient-centered HD care is lacking. Vascular Access outcome measure for function: a vaLidation study In hemoDialysis (VALID) aims to assess the accuracy and feasibility of measuring a core outcome for VA function established by the international Standardized Outcomes in Nephrology (SONG) initiative. Methods VALID is a prospective, multi-center, multinational validation study that will assess the accuracy and feasibility of measuring VA function, defined as the need for interventions to enable and maintain the use of a VA for HD. The primary objective is to determine whether VA function can be measured accurately by clinical staff as part of routine clinical practice (Assessor 1) compared to the reference standard of documented VA procedures collected by a VA expert (Assessor 2) during a 6-month follow-up period. Secondary outcomes include feasibility and acceptability of measuring VA function and the time to, rate of, and type of VA interventions. An estimated 612 participants will be recruited from approximately 10 dialysis units of different size, type (home-, in-center and satellite), governance (private versus public), and location (rural versus urban) across Australia, Canada, Europe, and Malaysia. Validity will be measured by the sensitivity and specificity of the data acquisition process. The sensitivity corresponds to the proportion of correctly identified interventions by Assessor 1, among the interventions identified by Assessor 2 (reference standard). The feasibility of measuring VA function will be assessed by the average data collection time, data completeness, feasibility questionnaires and semi-structured interviews on key feasibility aspects with the assessors. Discussion Accuracy, acceptability, and feasibility of measuring VA function as part of routine clinical practice are required to facilitate global implementation of this core outcome across all HD trials. Global use of a standardized, patient-centered outcome measure for VA function in HD research will enhance the consistency and relevance of trial evidence to guide patient-centered care. Trial registration Clinicaltrials.gov: NCT03969225. Registered on 31st May 2019.

Abstract Background This update summarises key changes made to the protocol since the publication of the original protocol for the NAVKIDS2 trial of patient navigators for children with chronic kidney disease (CKD) experiencing social disadvantage and provides the statistical analysis plan (SAP) which has not previously been published. Methods/design The original protocol was published in BMC Nephrology ( https://doi.org/10.1186/s12882-019-1325-y ) prior to the commencement of trial recruitment. During the course of the trial, some key methodological changes needed to be made including changes to eligibility criteria (addition of patients with CKD stages 1–2, broadening of financial status eligibility criterion, addition of patients living in rural/remote areas, modification of age eligibility to 0–16 years, addition of limits related to the language spoken by family, guidance regarding families with multiple eligible children), changes to sites, reduction of sample size, addition of virtual options for consent and study procedures in response to the COVID-19 pandemic, removal of staggered recruitment across sites, addition of outcomes, and changes to the timing and number of assessments. This update summarises the changes made and their rationale and provides the detailed plan for statistical analysis of the trial. These changes have been finalised prior to the completion of study follow-up and the commencement of data analysis. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618001152213 . Prospectively registered on 12 July 2018

Acute kidney injury (AKI) is one of the most common and consequential complications among hospitalized patients. Timely AKI risk prediction may allow simple interventions that can minimize or avoid the harm associated with its development. Given the multifactorial and complex etiology of AKI, machine learning (ML) models may be best placed to process the available health data to generate accurate and timely predictions. Accordingly, we searched the literature for externally validated ML models developed from general hospital populations using the current definition of AKI. Of 889 studies screened, only three were retrieved that fit these criteria. While most models performed well and had a sound methodological approach, the main concerns relate to their development and validation in populations with limited diversity, comparable digital ecosystems, use of a vast number of predictor variables and over-reliance on an easily accessible biomarker of kidney injury. These are potentially critical limitations to their applicability in diverse socioeconomic and cultural settings, prompting a need for simpler, more transportable prediction models which can offer a competitive advantage over the current tools used to predict and diagnose AKI.

Background. Kidney transplants from small pediatric donors are considered marginal and often transplanted as dual grafts. This study aimed to compare long-term outcomes between recipients of single kidney transplants (SKTs) and dual en bloc kidney transplants (EBKTs) from small pediatric donors. Methods. Data were obtained from the Australia and New Zealand Dialysis and Transplant Registry. All adult recipients of kidney transplants from donors aged ≤5 y were identified. The primary outcome of interest was death-censored graft survival by donor type. The secondary outcomes were early graft loss, delayed graft function, serum creatinine posttransplantation, acute rejection, and patient survival. Results. There were 183 adult recipients of kidney transplants from donors aged ≤5 y old. Of these, 60 patients had EBKT grafts, 79 patients had SKT grafts, and 44 patients had grafts of unknown type. Compared with SKT donors, EBKT donors had lower mean age (P < 0.001) and body weight (P < 0.001). There was no significant difference in death-censored graft survival between the groups, with median survival of 23.8 y (interquartile range 21.2–25) in the EBKT cohort and 21.8 y (11.6–26.8) in the SKT cohort (hazard ratio 1.3; 95% confidence interval, 0.59-2.64; P = 0.56). EBKT grafts had lower acute rejection rates than SKT grafts (P = 0.014). There was no significant difference observed between groups with respect to early graft loss, delayed graft function, posttransplantation serum creatinine posttransplantation, or patient survival. Conclusions. EBKT and SKTs from small pediatric donors are associated with excellent long-term graft survival rates.

Potassium dysregulation can be life-threatening. Dietary potassium modification is a management strategy for hyperkalaemia. However, a 2017 review for clinical guidelines found no trials evaluating dietary restriction for managing hyperkalaemia in chronic kidney disease (CKD). Evidence regarding dietary hyperkalaemia management was reviewed and practice recommendations disseminated. A literature search using terms for potassium, hyperkalaemia, and CKD was undertaken from 2018 to October 2022. Researchers extracted data, discussed findings, and formulated practice recommendations. A consumer resource, a clinician education webinar, and workplace education sessions were developed. Eighteen studies were included. Observational studies found no association between dietary and serum potassium in CKD populations. In two studies, 40–60 mmol increases in dietary/supplemental potassium increased serum potassium by 0.2–0.4 mmol/L. No studies examined lowering dietary potassium as a therapeutic treatment for hyperkalaemia. Healthy dietary patterns were associated with improved outcomes and may predict lower serum potassium, as dietary co-factors may support potassium shifts intracellularly, and increase excretion through the bowel. The resource recommended limiting potassium additives, large servings of meat and milk, and including high-fibre foods: wholegrains, fruits, and vegetables. In seven months, the resource received > 3300 views and the webinar > 290 views. This review highlights the need for prompt review of consumer resources, hospital diets, and health professionals’ knowledge.

Abstract Background Patient-reported outcome measures (PROMs) play an important role in promoting and supporting patient and family-centered care. Implementing interventions like PROMs in routine clinical care require key stakeholders to change their behavior. The aim of this study was to utilize the Theoretical Domains Framework (TDF) to identify barriers and enablers to the implementation of PROMs in pediatric outpatient asthma clinics from healthcare providers’ perspective. Methods This TDF-guided qualitative descriptive study is part of a larger multi-phase project to develop the KidsPRO program, an electronic platform to administer, collect, and use PROMs in pediatrics. Semi-structured qualitative interviews were conducted with 17 participants, which included pediatricians, nurses, allied health professionals and administrative staff from outpatient asthma clinics. All the interviews were transcribed, deductively coded, inductively grouped in themes, and categorized into barriers and enablers. Results We identified 33 themes within 14 TDF domains, which were further categorized and tabulated into 16 barriers and 17 enablers to implementing PROMs in asthma clinics. Barriers to behavioral change were attributed to personal, clinical, non-clinical, and other system-level factors; they ranged from limited awareness of PROMs to language barriers and patient’s complex family background. Enablers ranged from a personal commitment to providing patient and family-centered care to administering PROMs electronically. Conclusion This implementation of science-based systematic inquiry captured the complexity of PROMs implementation in pediatric outpatient clinical care for asthma. Considering the consistency in barriers and enablers to implementing PROMs across patient populations and care settings, many findings of this study will be directly applicable to other pediatric healthcare settings.

Incremental peritoneal dialysis (PD), defined as less than “standard dose” PD prescription, has a number of possible benefits, including better preservation of residual kidney function (RKF), reduced risk of peritonitis, lower peritoneal glucose exposure, lesser environmental impact, and reduced costs. Patients commencing PD are often new to kidney replacement therapy and possess substantial RKF, which may allow safe delivery of an incremental prescription, often in the form of lower frequency or duration of PD. This has the potential to help improve quality of life (QOL) and life participation through reducing time requirements and burden of treatment. Alternatively, incremental PD could potentially contribute to reduced small solute clearance, fluid overload, or patient reluctance to increase dialysis prescription when later needed. This review discusses the definition, rationale, uptake, potential advantages and disadvantages, and clinical trial evidence pertaining to the use of incremental PD.

Abstract Background Delayed graft function, or the requirement for dialysis due to poor kidney function, is a frequent complication of deceased donor kidney transplantation that is associated with inferior outcomes. Intravenous fluids with a high chloride content, such as isotonic sodium chloride (0.9% saline), are widely used in transplantation but may increase the risk of poor kidney function. The primary objective of the BEST-Fluids trial is to compare the effect of a balanced low-chloride crystalloid, Plasma-Lyte 148 (Plasmalyte), versus 0.9% saline on the incidence of DGF in deceased donor kidney transplant recipients. This article describes the statistical analysis plan for the trial. Methods and design BEST-Fluids is an investigator-initiated, pragmatic, registry-based, multi-centre, double-blind, randomised controlled trial. Eight hundred patients (adults and children) in Australia and New Zealand with end-stage kidney disease admitted for a deceased donor kidney transplant were randomised to intravenous fluid therapy with Plasmalyte or 0.9% saline in a 1:1 ratio using minimization. The primary outcome is delayed graft function (dialysis within seven days post-transplant), which will be modelled using a log-binomial generalised linear mixed model with fixed effects for treatment group, minimization variables, and ischaemic time and a random intercept for study centre. Secondary outcomes including early kidney transplant function (a ranked composite of dialysis duration and the rate of graft function recovery), treatment for hyperkalaemia, and graft survival and will be analysed using a similar modelling approach appropriate for the type of outcome. Discussion BEST-Fluids will determine whether Plasmalyte reduces the incidence of DGF and has a beneficial effect on early kidney transplant outcomes relative to 0.9% saline and will inform clinical guidelines on intravenous fluids for deceased donor kidney transplantation. The statistical analysis plan describes the analyses to be undertaken and specified before completion of follow-up and locking the trial databases. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12617000358347 . Prospectively registered on 8 March 2017 ClinicalTrials.gov identifier NCT03829488 . Registered on 4 February 2019

National strategies for addressing chronic kidney disease (CKD) are crucial to improving kidney health. We sought to describe country-level variations in non-communicable disease (NCD) strategies and CKD-specific policies across different regions and income levels worldwide. The International Society of Nephrology Global Kidney Health Atlas (GKHA) was a multinational cross-sectional survey conducted between July and October 2018. Responses from key opinion leaders in each country regarding national NCD strategies, the presence and scope of CKD-specific policies, and government recognition of CKD as a health priority were described overall and according to region and income level. 160 countries participated in the GKHA survey, comprising 97.8% of the world’s population. Seventy-four (47%) countries had an established national NCD strategy, and 53 (34%) countries reported the existence of CKD-specific policies, with substantial variation across regions and income levels. Where CKD-specific policies existed, non-dialysis CKD care was variably addressed. 79 (51%) countries identified government recognition of CKD as a health priority. Low- and low-middle income countries were less likely to have strategies and policies for addressing CKD and have governments which recognise it as a health priority. The existence of CKD-specific policies, and a national NCD strategy more broadly, varied substantially across different regions around the world but was overall suboptimal, with major discrepancies between the burden of CKD in many countries and governmental recognition of CKD as a health priority. Greater recognition of CKD within national health policy is critical to improving kidney healthcare globally.

BackgroundConcussion is a common injury in children and adolescents. Current best practice guidelines indicate that recovery should be supervised through recurrent follow-up visits. A more detailed understanding of the system-level and individual factors that are associated with follow-up care is a critical step towards increasing evidence-based practice. The objective of this study was to identify predisposing, enabling, and need-based factors associated with follow-up care after pediatric concussion.Materials and methodsA retrospective population-based cohort study was conducted using linked, province-wide administrative health data for all patients

Background. Cardiovascular disease is a major cause of morbidity and mortality in kidney transplant recipients. Trial evidence to improve cardiovascular outcomes is limited by inconsistent reporting of outcomes, which may also lack patient-relevance. This study aimed to assess the range and consistency of cardiovascular outcomes reported by contemporary trials in kidney transplant recipients. Methods. A systematic review of all randomized controlled trials involving adult kidney transplant recipients that reported at least 1 cardiovascular outcome from January 2012 to December 2019 was performed, including Embase, MEDLINE, Cochrane, and ClinicalTrials.gov electronic databases. Trial characteristics were extracted and all levels of specification of the cardiovascular outcome measures reported were analyzed (the measure definition, metric‚ and method of aggregation). Measures assessing a similar aspect of cardiovascular disease were categorized into outcomes. Results. From 93 eligible trials involving 27 609 participants, 490 outcome measures were identified. The outcome measures were grouped into 38 outcomes. A cardiovascular composite was the most common outcome reported (40 trials, 43%) followed by cardiovascular mortality (42%) and acute coronary syndrome (31%). Cardiovascular composite was also the most heterogeneous outcome with 77 measures reported followed by cardiovascular mortality (n = 58) and inflammatory biomarkers (n = 51). The most common cardiovascular composite outcome components reported were major cardiovascular events (18 trials), stroke unspecified (11 trials), and myocardial infarction unspecified (10 trials). Conclusions. There is substantial heterogeneity in cardiovascular outcome reporting in kidney transplant trials.

Abstract Background Cardiovascular disease is a leading cause of mortality in kidney failure (KF). Patients with KF from atheroembolic disease are at higher risk of cardiovascular disease than other causes of KF. This study aimed to determine survival on dialysis for patients with KF from atheroembolic disease compared with other causes of KF. Methods All adults (≥ 18 years) with KF initiating dialysis as the first kidney replacement therapy between 1 January 1990 and 31 December 2017 according to the Australia and New Zealand Dialysis and Transplant registry were included. Patients were grouped into either: KF from atheroembolic disease and all other causes of KF. Survival outcomes were assessed by the Kaplan-Meier method and Cox regression analysis adjusted for patient-related characteristics. Results Among 65,266 people on dialysis during the study period, 334 (0.5%) patients had KF from atheroembolic disease. A decreasing annual incidence of KF from atheroembolic disease was observed from 2008 onwards. Individuals with KF from atheroembolic disease demonstrated worse survival on dialysis compared to those with other causes of KF (HR 1.80, 95% confidence interval [CI] 1.61–2.03). The respective one- and five-year survival rates were 77 and 23% for KF from atheroembolic disease and 88 and 47% for other causes of KF. After adjustment for patient characteristics, KF from atheroembolic disease was not associated with increased patient mortality (adjusted HR 0.93 95% CI 0.82–1.05). Conclusions Survival outcomes on dialysis are worse for individuals with KF from atheroembolic disease compared to those with other causes of KF, probably due to patient demographics and higher comorbidity.

Background. Delayed graft function (DGF) is a major complication of deceased donor kidney transplantation. Saline (0.9% sodium chloride) is a commonly used intravenous fluid in transplantation but may increase the risk of DGF because of its high chloride content. Better Evidence for Selecting Transplant Fluids (BEST-Fluids), a pragmatic, registry-based, double-blind, randomized trial, sought to determine whether using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce DGF. We sought to evaluate the generalizability of the trial cohort by reporting the baseline characteristics and representativeness of the trial participants in detail. Methods. We compared the characteristics of BEST-Fluids participants with those of a contemporary cohort of deceased donor kidney transplant recipients in Australia and New Zealand using data from the Australia and New Zealand Dialysis and Transplant Registry. To explore potential international differences, we compared trial participants with a cohort of transplant recipients in the United States using data from the Scientific Registry of Transplant Recipients. Results. During the trial recruitment period, 2373 deceased donor kidney transplants were performed in Australia and New Zealand; 2178 were eligible‚ and 808 were enrolled in BEST-Fluids. Overall, trial participants and nonparticipants were similar at baseline. Trial participants had more coronary artery disease (standardized difference [d] = 0.09; P = 0.03), longer dialysis duration (d = 0.18, P < 0.001), and fewer hypertensive (d = −0.11, P = 0.03) and circulatory death (d = −0.14, P < 0.01) donors than nonparticipants. Most key characteristics were similar between trial participants and US recipients, with moderate differences (|d| ≥ 0.2; all P < 0.001) in kidney failure cause, diabetes, dialysis duration, ischemic time, and several donor risk predictors, likely reflecting underlying population differences. Conclusions. BEST-Fluids participants had more comorbidities and received slightly fewer high-risk deceased donor kidneys but were otherwise representative of Australian and New Zealand transplant recipients and were generally similar to US recipients. The trial results should be broadly applicable to deceased donor kidney transplantation practice worldwide.

Abstract To examine if skin autofluorescence (sAF) differed in early adulthood between individuals with type 1 diabetes and age-matched controls and to ascertain if sAF aligned with risk for kidney disease. Young adults with type 1 diabetes (N = 100; 20.0 ± 2.8 years; M:F 54:46; FBG-11.6 ± 4.9 mmol/mol; diabetes duration 10.7 ± 5.2 years; BMI 24.5(5.3) kg/m2) and healthy controls (N = 299; 20.3 ± 1.8 years; M:F-83:116; FBG 5.2 ± 0.8 mmol/L; BMI 22.5(3.3) kg/m2) were recruited. Skin autofluorescence (sAF) and circulating AGEs were measured. In a subset of both groups, kidney function was estimated by GFRCKD-EPI CysC and uACR, and DKD risk defined by uACR tertiles. Youth with type 1 diabetes had higher sAF and BMI, and were taller than controls. For sAF, 13.6% of variance was explained by diabetes duration, height and BMI (P model = 1.5 × 10–12). In the sub-set examining kidney function, eGFR and sAF were higher in type 1 diabetes versus controls. eGFR and sAF predicted 24.5% of variance in DKD risk (P model = 2.2 × 10–9), which increased with diabetes duration (51%; P model

Introduction: This describes variations in facility peritoneal dialysis (PD) effluent (PDE) culture techniques and local microbiology laboratory practices, competencies, and quality assurance associated with peritonitis, with a specific emphasis on factors associated with culture-negative peritonitis (CNP). Methods: Peritonitis data were prospectively collected from 22 Thai PD centers between May 2016 and October 2017 as part of the Peritoneal Dialysis Outcomes and Practice Patterns Study. The first cloudy PD bags from PD participants with suspected peritonitis were sent to local and central laboratories for comparison of pathogen identification. The associations between these characteristics and CNP were evaluated. Results: CNP was significantly more frequent in local laboratories (38%) compared with paired PDE samples sent to the central laboratory (12%, P < 0.05). Marked variations were observed in PD center practices, particularly with respect to specimen collection and processing, which often deviated from International Society for Peritoneal Dialysis Guideline recommendations, and laboratory capacities, capabilities, and certification. Lower rates of CNP were associated with PD nurse specimen collection, centrifugation of PDE, immediate transfer of samples to the laboratory, larger hospital size, larger PD unit size, availability of an on-site nephrologist, higher laboratory capacity, and laboratory ability to perform aerobic cultures, undertake standard operating procedures in antimicrobial susceptibilities, and obtain local accreditation. Conclusion: There were large variations in PD center and laboratory capacities, capabilities, and practices, which in turn were associated with the likelihood of culturing and correctly identifying organisms responsible for causing PD-associated peritonitis. Deviations in practice from International Society for Peritoneal Dialysis guideline recommendations were associated with higher CNP rates.

Abstract The unprecedented demand placed on healthcare systems from the COVID-19 pandemic has forced a reassessment of clinical trial conduct and feasibility. Consequently, the Australasian Kidney Trials Network (AKTN), an established collaborative research group known for conducting investigator-initiated global clinical trials, had to efficiently respond and adapt to the changing landscape during COVID-19. Key priorities included ensuring patient and staff safety, trial integrity and network sustainability for the kidney care community. New resources have been developed to enable a structured review and contingency plan of trial activities during the pandemic and beyond.

Introduction: Hypokalemia, including normal range values

Abstract Background Reliable estimates of the absolute and relative risks of postoperative complications in kidney transplant recipients undergoing elective surgery are needed to inform clinical practice. This systematic review and meta-analysis aimed to estimate the odds of both fatal and non-fatal postoperative outcomes in kidney transplant recipients following elective surgery compared to non-transplanted patients. Methods Systematic searches were performed through Embase and MEDLINE databases to identify relevant studies from inception to January 2020. Risk of bias was assessed by the Newcastle Ottawa Scale and quality of evidence was summarised in accordance with GRADE methodology (grading of recommendations, assessment, development and evaluation). Random effects meta-analysis was performed to derive summary risk estimates of outcomes. Meta-regression and sensitivity analyses were performed to explore heterogeneity. Results Fourteen studies involving 14,427 kidney transplant patients were eligible for inclusion. Kidney transplant recipients had increased odds of postoperative mortality; cardiac surgery (OR 2.2, 95%CI 1.9–2.5), general surgery (OR 2.2, 95% CI 1.3–4.0) compared to non-transplanted patients. The magnitude of the mortality odds was increased in the presence of diabetes mellitus. Acute kidney injury was the most frequently reported non-fatal complication whereby kidney transplant recipients had increased odds compared to their non-transplanted counterparts. The odds for acute kidney injury was highest following orthopaedic surgery (OR 15.3, 95% CI 3.9–59.4). However, there was no difference in the odds of stroke and pneumonia. Conclusion Kidney transplant recipients are at increased odds for postoperative mortality and acute kidney injury following elective surgery. This review also highlights the urgent need for further studies to better inform perioperative risk assessment to assist in planning perioperative care.

Abstract Background Delayed graft function, the requirement for dialysis due to poor kidney function post-transplant, is a frequent complication of deceased donor kidney transplantation and is associated with inferior outcomes and higher costs. Intravenous fluids given during and after transplantation may affect the risk of poor kidney function after transplant. The most commonly used fluid, isotonic sodium chloride (0.9% saline), contains a high chloride concentration, which may be associated with acute kidney injury, and could increase the risk of delayed graft function. Whether using a balanced, low-chloride fluid instead of 0.9% saline is safe and improves kidney function after deceased donor kidney transplantation is unknown. Methods BEST-Fluids is an investigator-initiated, pragmatic, registry-based, multi-center, double-blind, randomized controlled trial. The primary objective is to compare the effect of intravenous Plasma-Lyte 148 (Plasmalyte), a balanced, low-chloride solution, with the effect of 0.9% saline on the incidence of delayed graft function in deceased donor kidney transplant recipients. From January 2018 onwards, 800 participants admitted for deceased donor kidney transplantation will be recruited over 3 years in Australia and New Zealand. Participants are randomized 1:1 to either intravenous Plasmalyte or 0.9% saline peri-operatively and until 48 h post-transplant, or until fluid is no longer required; whichever comes first. Follow up is for 1 year. The primary outcome is the incidence of delayed graft function, defined as dialysis in the first 7 days post-transplant. Secondary outcomes include early kidney transplant function (composite of dialysis duration and rate of improvement in graft function when dialysis is not required), hyperkalemia, mortality, graft survival, graft function, quality of life, healthcare resource use, and cost-effectiveness. Participants are enrolled, randomized, and followed up using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Discussion If using Plasmalyte instead of 0.9% saline is effective at reducing delayed graft function and improves other clinical outcomes in deceased donor kidney transplantation, this simple, inexpensive change to using a balanced low-chloride intravenous fluid at the time of transplantation could be easily implemented in the vast majority of transplant settings worldwide. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12617000358347 . Registered on 8 March 2017. ClinicalTrials.gov: NCT03829488 . Registered on 4 February 2019.

Background. Expanded criteria donor (ECD) kidneys are associated with higher graft loss rates than standard criteria donor kidneys. We sought to determine factors associated with early graft loss and their discrimination ability for this outcome compared with kidney donor risk index. Methods. Data were extracted from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) for ECD transplants between 1997 and 2014. The primary outcome was early graft loss (all-cause graft loss within 3 y of transplantation). Death-censored graft loss was substituted as a sensitivity analysis. Era-adjusted odds ratios were calculated by multivariable logistic regression for donor, recipient, and transplant factors available at transplantation. Discrimination was assessed by c-statistic, with 95% confidence intervals (CIs) calculated by bootstrapping. Results. Of 2152 ECD kidney transplants, early graft loss occurred in 406 (19%) and was associated with recipient diabetes, smoking, First Nations recipients, and oliguria. Of factors defining ECD (age, elevated terminal creatinine, hypertension, death from cerebrovascular accident), all but mode of death were associated with early graft loss. The multivariable model, including known donor, recipient, and transplant factors, was moderately good at predicting early graft loss (c-statistic 0.65; 95% CI, 0.62-0.68). Recipient factors (c-statistic 0.62; 95% CI, 0.59-0.65) performed equally well compared with donor factors (c-statistic 0.60; 95% CI, 0.57-0.64) or the kidney donor risk index (c-statistic 0.60; 95% CI, 0.56-0.63). Conclusions. Early graft loss occurs in approximately one-fifth of ECD kidney transplants. The discriminatory value of commonly used recipient, donor, and transplant factors are approximately comparable and limited.

Abstract Background Vitamin D deficiency has been shown to be closely associated with peritoneal dialysis (PD)-related peritonitis. The aim of this study is to examine the feasibility of conducting a large, powered randomized controlled trial to determine the effects of vitamin D supplementation on the risk of PD-related peritonitis in patients who have already experienced an episode of peritonitis. Methods This prospective, open-label randomized controlled pilot trial with blinded end-points aims to determine the feasibility of oral vitamin D supplementation and to explore its effects on the risk of subsequent PD-related peritonitis among PD patients who have recovered from a recent episode of peritonitis. Eligible patients will be randomized 1:1 to either oral vitamin D supplementation (2000 IU per day; intervention group) or no vitamin D supplementation (control group) in addition to usual care according to International Society for Peritoneal Dialysis guidelines. The sample size will be 30 patients for both groups. All participants will be followed for 12 months. The primary outcome is the assessment of feasibility (recruitment success, retention, adherence, safety) and fidelity (change in serum 25-hydroxyvitamin D level during follow-up) for a large, powered randomized controlled trial to determine the effects of vitamin D on the risk of PD-related peritonitis in the future. Secondary outcomes include time to peritonitis occurrence, recovery of peritonitis, peritonitis-related transition to hemodialysis, and peritonitis-related death (defined as death within 30 days of peritonitis onset). Discussion This is the first randomized controlled trail investigating the effects of vitamin D supplementation on the risk of subsequent PD-related peritonitis among patients on PD. The findings for this pilot study will determine the feasibility of conducting a full-scale randomized controlled trail, which may provide a new strategy for preventing PD-related peritonitis among PD patients. Trial registration Clinicaltrails.gov, NCT03264625. Registered on 29 August 2017.

Abstract Background Membranoproliferative glomerulonephritis (MPGN) is an uncommon cause of end stage kidney disease (ESKD) and the clinical outcomes of patients with MPGN who commence kidney replacement therapy have not been comprehensively studied. Methods All adult patients with ESKD due to glomerulonephritis commencing kidney replacement therapy in Australia and New Zealand from January 1, 1996 to December 31, 2016 were reviewed. Patients with ESKD due to MPGN were compared to patients with other forms of glomerulonephritis. Patient survival on dialysis and following kidney transplantation, kidney recovery on dialysis, time to transplantation, allograft survival, death-censored allograft survival and disease recurrence post-transplant were compared between the two groups using Kaplan Meier survival curves and Cox proportional hazards regression. Results Of 56,481 patients included, 456 (0.8%) had MPGN and 12,660 (22.4%) had another form of glomerulonephritis. Five-year patient survival on dialysis and following kidney transplantation were similar between patients with ESKD from MPGN and other forms of glomerulonephritis (Dialysis: 59% vs. 62% p = 0.61; Transplant: 93% vs. 93%, p = 0.49). Compared to patients with other forms of glomerulonephritis, patients with MPGN had significantly poorer 5-year allograft survival (70% vs. 81% respectively, p = 0.02) and death censored allograft survival (74% vs. 87%, respectively; p

Abstract Background Patient-reported measures are increasingly recognized as important predictors of clinical outcomes in peritoneal dialysis (PD). We sought to understand associations between patient-reported perceptions of the advantages and disadvantages of PD and clinical outcomes. Methods In this cohort study, 2760 PD patients in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) completed a questionnaire on their PD experience, between 2014 and 2017. In this questionnaire, PDOPPS patients rated 17 aspects of their PD experience on a 5-category ordinal scale, with responses scored from − 2 (major disadvantage) to + 2 (major advantage). An advantage/disadvantage score (ADS) was computed for each patient by averaging their response scores. The ADS, along with each of these 17 aspects, were used as exposures. Outcomes included mortality, transition to hemodialysis (HD), patient-reported quality of life (QOL), and depression. Cox regression was used to estimate associations between ADS and mortality, transition to HD, and a composite of the two. Logistic regression with generalized estimating equations was used to estimate cross-sectional associations of ADS with QOL and depression. Results While 7% of PD patients had an ADS

Abstract Background Over-occupancy at the two tertiary pediatric care hospitals in Alberta, Canada is steadily increasing with simultaneous decline in occupancy of pediatric beds at regional hospitals. Over-occupancy negatively impacts timeliness and potentially, the safety of patient care provided at these two tertiary hospitals. In contrast, underutilization of pediatric beds at regional hospitals poses the risk of losing beds provincially, dilution of regional pediatric expertise and potential erosion of confidence by regional providers. One approach to the current situation in provincial pediatric care capacity is development of telemedicine based innovative models of care that increase the population of patients cared for in regional pediatric beds. A Telemedicine Rounding and Consultation (TRAC) model involves discussing patient care or aspects of their care using telemedicine by employing visual displays, audio and information sharing between tertiary and regional hospitals. To facilitate implementation of a TRAC model, it is essential to understand the perceived barriers among its potential users in local context. The current study utilizes qualitative methodologies to assess these perceived clinician barriers to inform a future pilot and evaluation of this innovative virtual pediatric tertiary-regional collaborative care model in Alberta. Methods We will use a qualitative descriptive design guided by the Theoretical Domain Framework (TDF) to systematically identify the tertiary and regional clinical stakeholder’s perceived barriers and enablers to the implementation of proposed TRAC model of inpatient pediatric care. Semi-structured interviews and focus groups with pediatricians, nurses and allied health professionals, administrators, and family members will be conducted to identify key barriers and enablers to implementation of the TRAC model using TDF. Appropriate behaviour change techniques will be identified to develop potential intervention strategies to overcome identified barriers. These intervention strategies will facilitate implementation of the TRAC model during the pilot phase. Discussion The proposed TRAC model has the potential to address the imbalance between utilization of regional and tertiary inpatient pediatric facilities in Alberta. Knowledge generated regarding barriers and enablers to the TRAC model and the process outlined in this study could be used by health services researchers to develop similar telemedicine-based interventions in Canada and other parts of the world.

Coagulation abnormalities and increased risk of atherothrombosis are common in patients with chronic kidney diseases (CKD). Mechanisms that alter renal hemostasis and lead to thrombotic events are not fully understood. Here we show that activation of protease activated receptor-2 (PAR2) on human kidney tubular epithelial cells (HTECs), induces tissue factor (TF) synthesis and secretion that enhances blood clotting. PAR-activating coagulation-associated protease (thrombin), as well as specific PAR2 activators (matriptase, trypsin, or synthetic agonist 2f-LIGRLO-NH2 (2F), induced TF synthesis and secretion that were potently inhibited by PAR2 antagonist, I-191. Thrombin-induced TF was also inhibited by a PAR1 antagonist, Vorapaxar. Peptide activators of PAR1, PAR3, and PAR4 failed to induce TF synthesis. Differential centrifugation of the 2F-conditoned medium sedimented the secreted TF, together with the exosome marker ALG-2 interacting protein X (ALIX), indicating that secreted TF was associated with extracellular vesicles. 2F-treated HTEC conditioned medium significantly enhanced blood clotting, which was prevented by pre-incubating this medium with an antibody for TF. In summary, activation of PAR2 on HTEC stimulates synthesis and secretion of TF that induces blood clotting, and this is attenuated by PAR2 antagonism. Thrombin-induced TF synthesis is at least partly mediated by PAR1 transactivation of PAR2. These findings reveal how underlying hemostatic imbalances might increase thrombosis risk and subsequent chronic fibrin deposition in the kidneys of patients with CKD and suggest PAR2 antagonism as a potential therapeutic strategy for intervening in CKD progression.

En este artículo presentaré y desarrollaré el concepto de 風土 fūdo, o clima geocultural, una idea que se halla en el trabajo del filósofo japonés Watsuji Tetsurō. Mi tesis es que este concepto puede ayudarnos en dos sentidos. Primero, puede ayudarnos a comprender mejor la relación desconcertante entre la naturaleza y el artificio, es decir, la naturaleza y la cultura, y segundo, puede ayudarnos a repensar el concepto de naturaleza de una manera que ofrezca la posibilidad de un mundo natural reencantado.

Abstract The norms of dispute resolution began their development alongside human communication, literally thousands of years before the internet. Mediation emerged as a social system possessed of culture-specific norms and rules that express themselves to this day, in how this mediation operates as a profoundly human system of meaning. This article asks whether these thoroughly time-tested and -refined norms specific to mediation will port over, relatively intact, into virtual space. To be sure, the answer will be seen in how designers build and implement the virtual spaces and attendant automation technology. To do that optimally, however, designers first must identify, understand and respect the values, ethics and purpose embedded in these inter-generational norms.

Synbiotics have emerged as a therapeutic strategy for modulating the gut microbiome and targeting novel cardiovascular risk factors, including uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (PCS). This study aims to evaluate the feasibility of a trial of long-term synbiotic supplementation in adults with stage 3–4 chronic kidney disease (CKD). Adult participants with CKD and estimated glomerular filtration rate (eGFR) of 15–60 mL/min/1.73 m2) were recruited between April 2017 and August 2018 to a feasibility, double-blind, placebo-controlled, randomized trial of synbiotic therapy or matched identical placebo for 12 months. The primary outcomes were recruitment and retention rates as well as acceptability of the intervention. Secondary outcomes were treatment adherence and dietary intake. Exploratory outcomes were evaluation of the cardiovascular structure and function, serum IS and PCS, stool microbiota profile, kidney function, blood pressure, and lipid profile. Of 166 potentially eligible patients, 68 (41%) were recruited into the trial (synbiotic n = 35, placebo n = 33). Synbiotic and placebo groups had acceptable and comparable 12-month retention rates (80% versus 85%, respectively, p = 0.60). Synbiotic supplementation altered the stool microbiome with an enrichment of Bifidobacterium and Blautia spp., resulting in a 3.14 mL/min/1.73 m2 (95% confidence interval (CI), −6.23 to −0.06 mL/min/1.73 m2, p < 0.01) reduction in eGFR and a 20.8 µmol/L (95% CI, 2.97 to 38.5 µmol/L, p < 0.01) increase in serum creatinine concentration. No between-group differences were observed in any of the other secondary or exploratory outcomes. Long-term synbiotic supplementation was feasible and acceptable to patients with CKD, and it modified the gastrointestinal microbiome. However, the reduction in kidney function with synbiotics warrants further investigation.

Coagulopathies common to patients with diabetes and chronic kidney disease (CKD) are not fully understood. Fibrin deposits in the kidney suggest the local presence of clotting factors including tissue factor (TF). In this study, we investigated the effect of glucose availability on the synthesis of TF by cultured human kidney tubular epithelial cells (HTECs) in response to activation of protease-activated receptor 2 (PAR2). PAR2 activation by peptide 2f-LIGRLO-NH2 (2F, 2 µM) enhanced the synthesis and secretion of active TF (~45 kDa) which was blocked by a PAR2 antagonist (I-191). Treatment with 2F also significantly increased the consumption of glucose from the cell medium and lactate secretion. Culturing HTECs in 25 mM glucose enhanced TF synthesis and secretion over 5 mM glucose, while addition of 5 mM 2-deoxyglucose (2DOG) significantly decreased TF synthesis and reduced its molecular weight (~40 kDa). Blocking glycosylation with tunicamycin also reduced 2F-induced TF synthesis while reducing its molecular weight (~36 kDa). In conclusion, PAR2-induced TF synthesis in HTECs is enhanced by culture in high concentrations of glucose and suppressed by inhibiting either PAR2 activation (I-191), glycolysis (2DOG) or glycosylation (tunicamycin). These results may help explain how elevated concentrations of glucose promote clotting abnormities in diabetic kidney disease. The application of PAR2 antagonists to treat CKD should be investigated further.

Abstract Background Arterial stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease (CKD). There are limited prospective data however on progression of arterial stiffness in CKD, including evaluating associations with bone mineral markers such as fibroblast growth factor 23 (FGF23) and soluble α-klotho (sKl). Methods In this prospective, single-center, observational study, arterial stiffness [measured by pulse wave velocity (PWV)] and hormones influencing mineral homeostasis, including serum FGF23 and sKl, were compared between non-dialysis CKD stages 4/5 and healthy controls at baseline and 12 months (12 m). Abdominal aortic calcification (AAC) was quantitated using lateral lumbar radiography at baseline. Results Forty patients with CKD [mean estimated glomerular filtration rate (eGFR) 19.5 ± 6.7 mL/min/1.73m2] and 42 controls (mean eGFR 88.6 ± 12.9 mL/min/1.73m2) completed follow-up. There were no differences in age, gender and body mass index between groups. A significant increase in FGF23 [240.6 (141.9–1129.8) to 396.8 (160.3–997.7) pg/mL, p = 0.001] was observed in the CKD group but serum phosphate, corrected calcium, parathyroid hormone and sKl did not change significantly over 12 m. At baseline, CKD subjects had higher AAC prevalence [83.8% versus (vs.) 43.6%, p = 0.002] and higher aortic PWV [9.7(7.6–11.7) vs. 8.1 (7.2–9.7) m/s, p = 0.047] compared to controls. At 12 m, aortic PWV increased by 1.3 m/s (95% confidence interval, 0.56 to 2.08, p 10 m/s). Serum FGF23 was associated with AAC, abnormal PWV and progression of PWV at 12 m. Conclusions Arterial stiffness and serum FGF23, both of which are associated with increased cardiovascular risk, increased over one year in individuals with CKD. Additionally, a significant association was found between serum FGF23 and arterial calcification and stiffness. Larger clinical studies and further experimental work are warranted to delineate the temporal relationship as well as the pathological mechanisms linking FGF23 and vascular disease.

Background. The transplantation of kidneys after cancer excision (restored kidney transplantation, RKT) warrants further evaluation as a source of kidneys for transplantation. We determined whether larger cancers can be safely transplanted, the risks of adverse events from RKT, and whether RKT confers a survival advantage for patients waiting for transplantation. Methods. In a retrospective cohort study, 23 dialysis patients awaiting transplant underwent RKT at John Hunter Hospital, Australia between 2008 and 2015. Patients were >60 years old and accepted onto the National Organ Matching Service. This RKT Group was divided into donor renal cancers ≤30 mm and >30–≤50 mm. Adverse event profiles for RKT recipients were compared with 22 standard live donor recipients using logistic regression analyses. Recipient and transplant survivals for RKT were compared with 2050 controls from Australian New Zealand Dialysis Transplant Registry using Cox regression models. To increase statistical power for survival analyses, data from 25 RKT recipients from Princess Alexandra Hospital, Brisbane were added, thus creating 48 RKT recipients. Results. There were no significant differences in mortality, transplant failure nor AEs between the 2 cancer Groups. RKT increased the risks of Adverse event profiles (odds ratio: 6.48 [2.92–15.44]; P < 0.001). RKT reduced mortality risk by 30% (hazard ratio [HR]: 0.70 [0.36–1.07]; P = 0.299) compared with those continuing on the transplant list who may or may not be transplanted. RKT significantly reduced mortality risk for those remaining on dialysis (HR: 2.86 [1.43–5.72]; P = 0.003). Transplant survival for RKT was reduced compared with control deceased donor (HR: 0.42 [0.21–0.83]; P = 0.013) and live donor transplants (HR: 0.33 [0.02–0.86]; P =0.023). Conclusions. The use of larger carefully selected cancer-resected kidneys for transplantation appears safe and effective. RKT confers a possible survival advantage compared with waiting for transplantation, an increased survival compared with those remaining on dialysis but reduced transplant survival.

Background: Chronic kidney disease (CKD) is a significant health problem in Canada. Understanding the capacity of the Canadian health-care system to deliver kidney care is important to provide optimal care. Objective: To compare Canada’s position in relation to countries of similar economic standing. Design: Cross-sectional electronic survey. Setting: Member countries of the Organisation for Economic Co-operation and Development (OECD) that participated in the survey. Participants: Nephrologists, other physicians, policymakers, and other professionals with relevant expertise in kidney care. Measurements: Not applicable. Methods: A survey administered by the International Society of Nephrology assessed the global capacity of kidney care delivery. Data from participating OECD countries were analyzed using descriptive statistics to compare Canada’s position. Results: Of the participating countries, most funded kidney care services (non-medication) by government (transplantation: 85%, dialysis: 81%, acute kidney injury (AKI): 77%). Most countries covered medication. Canada reported a public funding model for kidney services and a mix of public and private sources for medication. Nephrologists and nephrology trainee densities were lower in Canada compared to the median (15.33 vs. 25.82 and 1.74 vs. 3.94, respectively). CKD was recognized as a health priority in five countries, but not in Canada. Registries for CKD did not exist in most (24/26) countries. Canada followed a national strategy for noncommunicable diseases, but this was not specific to CKD care, dialysis, or transplantation. Limitations: Risks of recall bias or social desirability bias are present. Differences in a number of factors could influence discrepancies among countries and were not explored. Responses reflected the existence of practices, policies, and strategies, and may not necessarily describe action or impact. Capacity of care is not equal across all regions and provinces within Canada; however, the findings are reported on a national level and therefore may not appropriately address variability. Conclusions: This study describes the capacity for kidney care at a national level within the context of the Canadian health system. The Canadian health-care system is well funded by the government; however, there are areas that could be improved to increase the optimization of kidney care provided.