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Abstract Background Physical inactivity is common among older adults and is associated with poor health outcomes. Medical fitness facilities provide a medically focused approach to physical fitness and can improve physical activity in their communities. This study aimed to assess the relationship between membership in the medical fitness model and all-cause mortality, health care utilization, and major adverse cardiac events in older adults. Methods A propensity weighted retrospective cohort study linked individuals that attended medical fitness facilities to provincial health administrative databases. Older adults who had at least 1 year of health coverage from their index date between January 1st, 2005 to December 31st 2015 were included. Controls were assigned a pseudo-index date at random based on the frequency distribution of index dates in members. Members were stratified into low frequency attenders ( 1 Weekly Visits). Time to event models estimated the hazard ratios (HRs) for risk of all-cause mortality and major adverse cardiac event. Negative binomial models estimated the risk ratios (RRs) for risk of hospitalizations, outpatient primary care visits and emergency department visits. Results Among 3,029 older adult members and 91,734 controls, members had a 45% lower risk of all-cause mortality (HR: 0.55, 95% CI: 0.50 – 0.61), 20% lower risk of hospitalizations (RR: 0.80, 95% CI: 0.75 – 0.84), and a 27% (HR: 0.72, 95% CI: 0.66 – 0.77), lower risk of a major adverse cardiovascular event. A dose–response effect with larger risk reductions was associated with more frequent attendance as regular frequency attenders were 4% more likely to visit a general practitioner for a routine healthcare visit (RR: 1.04, 95% CI: 1.01 – 1.07), but 23% less likely to visit the emergency department (RR: 0.87, 95% CI: 0.82 – 0.92). Conclusions Membership at a medical fitness facility was associated with a decreased risk of mortality, health care utilization and cardiovascular events. The medical fitness model may be an alternative approach for public health strategies to promote positive health behaviors in older adult populations.

Background. Modern organ allocation systems are tasked with equitably maximizing the utility of transplanted organs. Increasing the use of deceased donor organs at risk of discard may be a cost-effective strategy to improve overall transplant benefit. We determined the survival implications and cost utility of increasing the use of marginal kidneys in an older adult Canadian population of patients with end-stage kidney disease. Methods. We constructed a cost-utility model with microsimulation from the perspective of the Canadian single-payer health system for incident transplant waitlisted patients aged 60 y and older. A kidney donor profile index score of ≥86 was considered a marginal kidney. Donor- and recipient-level characteristics encompassed in the kidney donor profile index and estimated posttransplant survival scores were used to derive survival posttransplant. Patients were followed up for 10 y from the date of waitlist initiation. Our analysis compared the routine use of marginal kidneys (marginal kidney scenario) with the current practice of limited use (status quo scenario). Results. The 10-y mean cost and quality-adjusted life-years per patient in the marginal kidney scenario were estimated at $379 485.33 (SD: $156 872.49) and 4.77 (SD: 1.87). In the status quo scenario, the mean cost and quality-adjusted life-years per patient were $402 937.68 (SD: $168 508.85) and 4.37 (SD: 1.87); thus, the intervention was considered dominant. At 10 y, 62.8% and 57.0% of the respective cohorts in the marginal kidney and status quo scenarios remained alive. Conclusions. Increasing the use of marginal kidneys in patients with end-stage kidney disease aged 60 y and older may offer cost savings, improved quality of life, and greater patient survival in comparison with usual care.

Purpose of Review: Chronic kidney disease (CKD)-associated pruritus is a common, persistent, and distressing itch experienced by patients across the CKD spectrum. Although the disorder is associated with adverse outcomes and poor health-related quality of life, it remains underdiagnosed and undertreated. The purpose of this narrative review is to offer health care providers guidance on how to effectively identify, assess, and treat patients with CKD-associated pruritus, with the goal of reducing symptom burden and improving patient-important outcomes, such as quality of life (QoL). Sources of Information: A panel of nephrologists and researchers from across Canada and the United States was assembled to develop this narrative review based on the best available data, current treatment guidelines, and their clinical experiences. Methods: A panel of nephrologists who actively care for patients with pruritus receiving dialysis from across Canada was assembled. Two researchers from the United States were also included based on their expertise in the diagnosis and management of CKD-associated pruritus. Throughout Spring 2023, the panel met to discuss key topics in the identification, assessment, and management of CKD-associated pruritus. Panel members subsequently developed summaries of the pertinent information based on the best available data, current treatment guidelines, and added information on their own clinical experiences. In all cases, approval of the article was sought and achieved through discussion. Key Findings: This narrative review provides pragmatic guidance addressing: (1) methods for screening CKD-associated pruritus, (2) assessing severity, (3) management of CKD-associated pruritus, and (4) suggested areas for future research. The panel developed a 3-pillar framework for proactive assessment and severity scoring in CKD-aP: systematic screening for CKD-associated pruritus (pillar 1), assessment of pruritus intensity (pillar 2), and understanding the impact of CKD-associated pruritus on the patient’s QoL (pillar 3). Management of CKD-associated pruritus can include ensuring optimization of dialysis adequacy, achieving mineral metabolism targets (ie, calcium, phosphate, and parathyroid hormone). However, treatment of CKD-associated pruritus usually requires additional interventions. Patients, regardless of CKD-associated pruritus severity, should be counseled on adequate skin hydration and other non-pharmacological strategies to reduce pruritus. Antihistamines should be avoided in favor of evidence-based treatments, such as difelikefalin and gabapentin. Limitations: A formal systematic review (SR) of the literature was not undertaken, although published SRs were reviewed. The possibility for bias based on the experts’ own clinical experiences may have occurred. Key takeaways are based on the current available evidence, of which head-to-head clinical trials are lacking. Funding: This work was funded by an arm’s length grant from Otsuka Canada Pharmaceutical Inc. (the importer and distributer of difelikefalin in Canada). LiV Medical Education Agency Inc. provided logistical and editorial support.

Background: People receiving hemodialysis experience high symptom burden that contributes to low functional status and poor health-related quality of life. Management of symptoms is a priority for individuals receiving hemodialysis but limited effective treatments exist. There is emerging evidence that exercise programming can improve several common dialysis-related symptoms. Objective: The primary aim of this study is to evaluate the effect of an exercise rehabilitation program on symptom burden in individuals receiving maintenance hemodialysis. Design: Multicenter, randomized controlled, 1:1 parallel, open label, prospective blinded end point trial. Setting: Three facility-based hemodialysis units in Winnipeg, Manitoba, Canada. Participants: Adults aged 18 years or older with end-stage kidney disease receiving facility-based maintenance hemodialysis for more than 3 months, with at least 1 dialysis-related symptom as indicated by the Dialysis Symptom Index (DSI) severity score >0 (n = 150). Intervention: Supervised 26-week exercise rehabilitation program and 60 minutes of cycling during hemodialysis thrice weekly. Exercise intensity and duration were supervised and individualized by the kinesiologist as per participant baseline physical function with gradual progression over the course of the intervention. Control: Usual hemodialysis care (no exercise program). Measurements: Our primary outcome is change in symptom burden at 12 weeks as measured by the DSI severity score. Secondary outcomes include change in modified DSI severity score (includes 10 symptoms most plausible to improve with exercise), change in DSI severity score at 26 and 52 weeks; time to recover post-hemodialysis; health-related quality of life measured using EuroQol (EQ)-5D-5L; physical activity behavior measured by self-report (Godin-Shepherd questionnaire) and triaxial accelerometry; exercise capacity (shuttle walk test); frailty (Fried); self-efficacy for exercise; and 1-year hospitalization and mortality. Methods: Change in primary outcome will be compared between groups by independent 2-tailed t test or Mann-Whitney U test depending on data distribution and using generalized linear mixed models, with study time point as a random effect and adjusted for baseline DSI score. Similarly, change in secondary outcomes will be compared between groups over time using appropriate parametric and nonparametric statistical tests depending on data type and distribution. Limitations: The COVID-19 pandemic restrictions on clinical research at our institution delayed completion of target recruitment and prevented collection of accelerometry and physical function outcome data for 15 months until restrictions were lifted. Conclusions: The application of an exercise rehabilitation program to improve symptom burden in individuals on hemodialysis may ameliorate common symptoms observed in individuals on hemodialysis and result in improved quality of life and reduced disability and morbidity over the long term. Importantly, this pragmatic study, with a standardized exercise intervention that is adaptable to baseline physical function, addresses an important gap in both clinical care of hemodialysis patients and our current knowledge.

Background Cardiovascular disease remains the leading cause of disease burden and death in the world. The medical fitness model may be an alternative public health strategy to address cardiovascular risk factors with medical integrated programming. Methods and Results We performed a retrospective cohort study between January 1, 2005, and December 31, 2015. Adults (aged ≥18 years) who did not have a prior major adverse cardiovascular event were included. Controls were assigned a pseudo‐index date at random on the basis of the frequency distribution of start dates in the medical fitness facility group. Multivariate Cox proportional hazards regression models were adjusted for age, sex, socioeconomic status, comorbidities, and year of index date. We stratified the medical fitness facility group into low‐frequency attenders (≤1 weekly visit) and regular‐frequency attenders (>1 weekly visit). Our primary outcome was a hospitalization for nonfatal myocardial infarction and stroke, heart failure, or cardiovascular death. We included 11 319 medical fitness facility members and 507 400 controls in our study. Compared with controls, members had a lower hazard risk of a major adverse cardiovascular event‐plus (hazard ratio [HR], 0.88 [95% CI, 0.81–0.96]). Higher weekly attendance was associated with a lower hazard risk of a major adverse cardiovascular event‐plus compared with controls, but the effect was not significant for lower weekly attendance (low‐frequency attenders: HR, 0.94 [95% CI, 0.85–1.04]; regular‐frequency attenders: HR, 0.77 [95% CI, 0.67–0.89]). Conclusions Medical fitness facility membership and attendance at least once per week may lower the risk of a major adverse cardiovascular event‐plus. The medical fitness model should be considered as a public health intervention, especially for individuals at risk for cardiovascular disease.

Introduction: Intradialytic cycling is often performed during the first half of hemodialysis because of concerns regarding increased frequency of intradialytic hypotension (IDH) late in hemodialysis. This increases exercise program resource needs and limits utility of intradialytic cycling to treat dialysis-related symptoms. Methods: This multicenter, randomized, crossover trial compared IDH rate when cycling during the first half versus the second half of hemodialysis in 98 adults on maintenance hemodialysis. Group A cycled during the first half of hemodialysis for 2 weeks and subsequently during the second half for 2 weeks. In group B, the cycling schedule was reversed. Blood pressure (BP) was measured every 15 minutes throughout hemodialysis. Primary outcome was IDH rate (systolic BP [SBP] decrease of >20 mm Hg or SBP

Background: During the 30-day period prior to initiating dialysis, there is a 10-fold rise in emergency department visits and hospitalizations related to kidney failure. Objective: The Virtual Ward Incorporating Electronic Wearables (VIEWER) trial implemented a home telemonitoring system to track changes in patients’ vitals and assess their adherence and the acceptability of telemonitoring in a chronic kidney disease (CKD) population. Design: A pilot prospective clinical trial using a mixed methods approach was performed. Setting: The research was conducted in Winnipeg, Manitoba. Participants: There were 2 phases: Phase 1 was a 2-week-long pilot trial consisting of 10 participants. Phase 2 was a 3-month-long trial with a total of 26 participants. Patients with an estimated glomerular filtration rate 40% risk of beginning dialysis in the next 2 years according to the kidney failure risk equation were eligible to participate in the study. Methods: The primary quantitative outcome was adherence, defined as the proportion of daily self-assessments completed using VIEWER over the follow-up period. The usability and acceptability of VIEWER was assessed qualitatively at the end of the trial through structured questionnaires and focus groups. Results: Phase 1 participants (n = 10) had a median adherence of 77.17% for the 2-week observation period. Phase 2 participants (n = 26) showed a lower median adherence of 36% for the 3-month period. Focus group participants (n = 11) identified many positive aspects of VIEWER, including increased awareness and empowerment over health, simplicity of the data platform, and the ability to show clinical staff their health trends. Some challenges identified with VIEWER were connectivity issues with the Bluetooth, perceived inconvenience, and negative thoughts toward their health Limitations: Limitations of the study include a small sample size, which limited our ability to measure quantitative outcomes. In addition, patients agreeing to participate in any trial are generally more highly motivated and engaged in their care than those declining participation. Therefore, our results may not be generalizable to individuals who are not interested in self-management of their health. Conclusion: Our results suggest that home telemonitoring in patients with advanced CKD is feasible using a CKD-specific platform like VIEWER. We anticipate that improved functionality with incorporation of feedback from this study will result in greater long-term adherence. A future randomized clinical trial is planned.

Background: Fabry disease is a rare disorder caused by the deficient activity of α-galactosidase A (GLA) that often leads to organ damage. Fabry disease can be treated with enzyme replacement or pharmacological therapy, but due to its rarity and nonspecific manifestations, it often goes undiagnosed. Mass screening for Fabry disease is impractical; however, a targeted screening program for high-risk individuals may uncover previously unknown cases. Objective: Our objective was to use population-level administrative health databases to identify patients at high risk of Fabry disease. Design: Retrospective cohort study. Setting: Population-level health administrative databases housed at the Manitoba Centre for Health Policy. Patients: All residents of Manitoba, Canada, between 1998 and 2018. Measurements: We ascertained the evidence of GLA testing in a cohort of patients at high risk of Fabry disease. Methods: Individuals without a hospitalization or prescription indicative of Fabry disease were included if they had evidence of 1 of 4 high-risk conditions for Fabry disease: (1) ischemic stroke

Rationale & Objective: To what degree and how patient navigators improve clinical outcomes for patients with chronic kidney disease (CKD) and kidney failure is uncertain. We performed a systematic review to summarize patient navigator program design, evidence, and implementation in kidney disease. Study Design: A search strategy was developed for randomized controlled trials and observational studies that evaluated the impact of navigators on outcomes in the setting of CKD and kidney failure. Articles were identified from various databases. Two reviewers independently screened the articles and identified those meeting the inclusion criteria. Setting & Participants: Patients with CKD or kidney failure (in-center hemodialysis, peritoneal dialysis, home hemodialysis, or kidney transplantation). Selection Criteria for Studies: Studies that compared patient navigators with a control, without limits on size, duration, setting, or language. Studies focusing solely on patient education were excluded. Data Extraction: Data were abstracted from full texts and risk of bias was assessed. Analytical Approach: No meta-analysis was performed. Results: Of 3,371 citations, 17 articles met the inclusion criteria including 14 original studies. Navigators came from various healthcare backgrounds including nursing (n=6), social worker (n=2), medical interpreter (n=1), research (n=1), and also included kidney transplant recipients (n=2) and non-medical individuals (n=2). Navigators focused mostly on education (n=9) and support (n = 6). Navigators were used for patients with CKD (n=5), peritoneal dialysis (n=2), in-center hemodialysis (n=4), kidney transplantation (n=2), but not home hemodialysis. Navigators improved transplant workup and listing, peritoneal dialysis utilization, and patient knowledge. Limitations: Many studies did not show benefits across other outcomes, were at a high risk of bias, and none reported cost-effectiveness or patient-reported experience measures. Conclusions: Navigators improve some health outcomes for CKD but there was heterogeneity in their structure and function. High-quality randomized controlled trials are needed to evaluate navigator program efficacy and cost-effectiveness.

Peer review aims to select articles for publication and to improve articles before publication. We believe that this process can be infused by kindness without losing rigor. In 2014, the founding editorial team of the Canadian Journal of Kidney Health and Disease (CJKHD) made an explicit commitment to treat authors as we would wish to be treated ourselves. This broader group of authors reaffirms this principle, for which we suggest the terminology “supportive review.”

Objective: Lower limb complications are major adverse events in patients with peripheral artery disease (PAD) and chronic kidney disease (CKD). These complications can lead to morbidity, disability, reduced quality of life, and higher health care costs. We sought to determine how interim lower limb complications modify the subsequent risk of progression to kidney failure, all-cause mortality before kidney failure, and cardiovascular (CV) events in a cohort of patients with CKD stages G3 to G5. Methods: We performed a retrospective cohort study using patient-level data obtained by linking several administrative databases from Manitoba, Canada. We used Fine and Gray regression models for the primary outcomes of (1) kidney failure adjusted for the competing risk of all-cause mortality, (2) death before kidney failure, and (3) cardiovascular-related hospitalization with the competing risk of non-CV death. Results: A total of 92,618 patients were included in the final cohort, with a median follow-up time of 2.56 years. Compared with patients who did not experience an interim lower limb complication, there was a higher risk of kidney failure (adjusted hazard ratio [HR] 2.51, 95% confidence interval [CI] 2.10–3.00), all-cause mortality before kidney failure (adjusted HR 2.73, 95% CI 2.55–2.92), and CV events (adjusted HR 2.12, 95% CI 1.90–2.38). Conclusions: Interim lower limb complications are associated with an increased risk of kidney failure, all-cause mortality before kidney failure, and cardiovascular-related hospitalization. Clinical trials of screening and treatment strategies for patients with CKD at risk for lower limb complications may help determine optimal strategies to manage this risk.

Background: Home-based peritoneal dialysis (PD) is an alternative to facility-based hemodialysis and has lower costs and greater freedom for patients with kidney failure. For a patient to undergo PD, a safe and reliable method of accessing the peritoneum is needed. However, different catheter insertion techniques may affect patient health outcomes. Objective: To compare the risk of infectious and mechanical complications between surgical (open and laparoscopic) PD catheter insertion and percutaneous catheter insertion. Design: Systematic review and meta-analysis. Setting: We searched for observational studies and randomized controlled trials (RCTs) in CENTRAL, EMBASE, MEDLINE, PubMed, and SCOPUS from inception until June 2018. Data were extracted by 2 independent reviewers based on a preformed template. Patients: Adult (aged 18+) patients with kidney failure who underwent a PD catheter insertion procedure. Measurements: We analyzed leak, malfunction, and bleed as early complications (occurring within 1 month of catheter insertion). Infectious complications (exit-site infections, tunnel infections, and peritonitis) were presented as both early complications and with the longest duration of follow-up. Methods: Random effects meta-analyses with the generic inverse variance method to estimate pooled rate ratios and 95% confidence intervals. We quantified heterogeneity by using the I2 statistic for inconsistency and assessed heterogeneity using the χ 2 test. Sensitivity analysis was performed by removing studies at high risk of bias as measured with the Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool. Results: Twenty-four studies (22 observational, 2 RCTs) with 3108 patients and 3777 catheter insertions were selected. Data from 2 studies were unable to be extracted and were qualitatively assessed. In the remaining 22 studies, percutaneous insertion was associated with a lower risk of both exit-site infections (risk ratio [RR] = 0.36, 95% confidence interval [CI] = 0.24-0.53, I 2 = 0%) and peritonitis (RR = 0.52, 95% CI = 0.36-0.77, I 2 = 3%) within 1 month of the procedure. There was no difference in mechanical complication rates between the 2 techniques. Limitations: Lack of consistency in the time periods for the various outcomes reported, risk of bias concerns with respect to population comparability, and the inability to analyze individual component causes of primary nonfunction (catheter obstruction, catheter migration, and leak). Conclusions: Our meta-analysis suggests differences in early infectious complications in favor of percutaneous insertion and no significant differences in mechanical complications compared with surgical insertion. These findings have implications on the direction of PD programs in terms of maximizing operating room resources.

Rationale & Objective: The prevalence of kidney failure is increasing globally. Most of these patients will require life-sustaining dialysis at a substantial cost to the health care system. Assisted peritoneal dialysis (PD) and assisted home hemodialysis (HD) are potential alternatives to in-center HD and have demonstrated equivalent outcomes with respect to mortality and morbidity. We aim to describe the costs associated with assisted continuous cycling PD (CCPD) and assisted home HD. Study Design: Cost minimization model. Setting & Population: Adult incident maintenance dialysis patients in Manitoba, Canada. Intervention: Full- and partial-assist home HD and CCPD. Full-assist modalities were defined as nurse-assisted dialysis setup and takedown performed by a health care aide, whereas partial-assist modalities only included nurse-assisted setup. Additionally, full-assist home HD was evaluated under a complete care scenario with the inclusion of a health care aide remaining with the patient throughout the duration of treatment. Outcomes: Annual per-patient maintenance and training costs related to assisted and self-care home HD and CCPD, presented in 2019 Canadian dollars. Model, Perspective, & Time Frame: This model took the perspective of the Canadian public health payer using a 1-year time frame. Results: Annual total per-patient maintenance (and training) costs by modality were the following: full-assist CCPD, $75.717 (initial training costs, $301); partial-assist CCPD, $67,765 ($4,385); full-assist home HD, $47,862 ($301); partial-assist home HD, $44,650 ($14,813); and full-assist home HD (complete care), $64,659 ($301). Limitations: This model did not account for costs taken from the societal perspective or costs related to PD failure and modality switching. Additionally, this analysis reflects only costs experienced by a single center. Conclusions: Assisted home-based dialysis modalities are viable treatment options for patients from a cost perspective. Future studies to consider graduation rates to full self-care from assisted dialysis and the cost implications of respite care are needed.

Purpose of program: Access to health care services remains a significant barrier for many Indigenous people’s living in rural and remote regions of Canada. Driven by geographical isolation and compounded by socioeconomic and environmental disparities, individuals living under these circumstances face disproportionately poor health outcomes. Kidney Check is a comprehensive screening, triage, and treatment initiative working to bring culturally safe preventive care to rural and remote Indigenous communities across Manitoba, Ontario, BC, Alberta, and Saskatchewan. The project’s patient-oriented approach addresses concerns raised by kidney patients and their caregivers using culturally safe practices. Using the various expertise of their multidisciplinary team, Kidney Check seeks to further collaborative efforts to improve access to preventive health care for these groups. Meaningful engagement with patients, communities, and local health care stakeholders ensures Indigenous voices are heard and incorporated into the project in a way that promotes shared decision-making and sustainability. Sources of information: As an affiliate program of the Can-SOLVE CKD Network, Kidney Check’s guiding priorities were developed over 3 years of patient consultation and finalized during 2 workshops held with more than 30 patients, caregivers, Indigenous peoples, researchers, and policy makers using a modified Delphi process. Today, patients continue to participate in project development via 2 governing bodies: The Patient Governance Circle and the Indigenous Peoples Engagement and Research Council (IPERC). Methods: Modeled after the Indigenous-led 2015 FINISHED project in Manitoba, Kidney Check employs point-of-care testing to identify diabetes, hypertension, and chronic kidney disease (CKD) in individuals, ages 10 and above, regardless of pre-existing risk factors. The Kidney Check team consists of 4 working groups: project leadership, provincial management, local community partners, and patient partners. By using and building on existing relationships between local and provincial health care stakeholders and various Indigenous communities, the program furthers collaborative efforts to bridge gaps in health equity. Key findings: The Kidney Check program has established an infrastructure that integrates patient engagement at all stages of the program from priority setting to deployment and dissemination strategies. Limitations: While we encourage and offer screening services to all, many still choose not to attend for a variety of reasons which may introduce selection bias. Kidney Check uses patient engagement as a foundational component of the program; however, there is currently a limited amount of research documenting the benefits of patient engagement in health care settings. More formal qualitative evaluations of these activities are needed. In addition, as the COVID-19 pandemic has halted screening procedures in most communities, we currently do not have quantitative data to support the efficacy of the Kidney Check program. Implications: For many Indigenous people, lack of accessibility to health care services is compounded by sociopolitical barriers that disrupt relationships between patients and providers. Meaningful engagement presents one opportunity to ensure the voices and perspectives of Indigenous patients and communities are incorporated into health services. In addition, this screening paradigm has shown to be cost effective as shown by analyses done on the FINISHED screening program.

Rationale & Objective: The kidney failure population is growing, necessitating the expansion of dialysis programs. These programs are costly and require a substantial amount of health care resources. Tools that accurately forecast resource use can aid efficient allocation. The objective of this study is to describe the development of an economic simulation model that incorporates treatment history and detailed modality transitions for patients with kidney disease using real-world data to estimate associated costs, utility, and survival by initiating modality. Study Design: Cost-utility model with microsimulation. Setting & Population: Adult incident maintenance dialysis patients in Canada who initiated facility-based hemodialysis (HD) or home peritoneal dialysis (PD) between 2004 and 2013. Intervention: HD and PD. Outcomes: Costs (related to dialysis, transplantation, infections, and hospitalizations), survival, utility, and dialysis modality mix over time. Model, Perspective, & Timeframe: The model took the perspective of the health care payer. Patients were followed up for 10 years from initiation of dialysis. Our cost-utility analysis compared the intervention with receiving no treatment. Results: During a 10-year time horizon, the cost-utility ratio for all patients initiating dialysis was $103,779 per quality-adjusted life-year (QALY) in comparison to no treatment. Patients who initiated with facility-based HD were treated at a cost-utility ratio of $104,880/QALY and patients who initiated with home PD were treated at a cost-utility ratio of $83,762/QALY. During this time horizon, the total mean cost and QALYs per patient were estimated at $350,774 ± $204,704 and 3.38 ± 2.05) QALYs respectively. Limitations: The results do not include costs from the societal perspective. Rare patient trajectories were unable to be assessed. Conclusions: This model demonstrates that patients who initiated dialysis with PD were treated more cost-effectively than those who initiated with HD during a 10-year time horizon.

BackgroundReadmission following hospital discharge is common and is a major financial burden on healthcare systems.ObjectivesOur objectives were to 1) identify studies describing post-discharge interventions and their efficacy with respect to reducing risk of mortality and rate of hospital readmission; and 2) identify intervention characteristics associated with efficacy.MethodsA systematic review of the literature was performed. We searched MEDLINE, PubMed, Cochrane, EMBASE and CINAHL. Our selection criteria included randomized controlled trials comparing post-discharge interventions with usual care on rates of hospital readmission and mortality in high-risk chronic disease patient populations. We used random effects meta-analyses to estimate pooled risk ratios for all-cause and cause-specific mortality as well as all-cause and cause-specific hospitalization.ResultsWe included 31 randomized controlled trials encompassing 9654 patients (24 studies in CHF, 4 in COPD, 1 in both CHF and COPD, 1 in CKD and 1 in an undifferentiated population). Meta-analysis showed post-discharge interventions reduced cause-specific (RR = 0.71, 95% CI = 0.63-0.80) and all cause (RR = 0.90, 95% CI = 0.81-0.99) hospitalization, all-cause (RR = 0.73, 95% CI = 0.65-0.83) and cause-specific mortality (RR = 0.68, 95% CI = 0.54-0.84) in CHF studies, and all-cause hospitalization (RR = 0.52, 95% CI = 0.32-0.83) in COPD studies. The inclusion of a cardiac nurse in the multidisciplinary team was associated with greater efficacy in reducing all-cause mortality among patients discharged after heart failure admission (HR = 0.64, 95% CI = 0.54-0.75 vs. HR = 0.87, 95% CI = 0.73-1.03).ConclusionsPost-discharge interventions reduced all-cause mortality, cause-specific mortality, and cause-specific hospitalization in CHF patients and all-cause hospitalization in COPD patients. The presence of a cardiac nurse was associated with greater efficacy in included studies. Additional research is needed on the impact of post-discharge intervention strategies in COPD and CKD patients.

Introduction: Rural and remote indigenous individuals have a high burden of chronic kidney disease (CKD) when compared to the general population. However, it has not been previously explored how these rates compare to urban-dwelling indigenous populations. Methods: In a recent cross-sectional screening study, 1346 adults 18 to 80 years of age were screened for CKD and diabetes across 11 communities in rural and remote areas in Manitoba, Canada, as part of the First Nations Community Based Screening to Improve Kidney Health and Prevent Dialysis (FINISHED) program. An additional 284 Indigenous adults who resided in low-income areas in the city of Winnipeg, Manitoba, Canada were screened as part of the NorWest Mobile Diabetes and Kidney Disease Screening and Intervention Project. Results: Our findings indicate that a gradient of CKD and diabetes prevalence exists for Indigenous individuals living in different geographic areas. Compared to urban-dwelling Indigenous individuals, rural-dwelling individuals had more than a 2-fold (2.1, 95% CI = 1.4−3.1) increase in diabetes whereas remote-dwelling individuals had a 4-fold (4.1, 95% CI = 2.8−6.0) increase, and more than a 3-fold (3.1, 95% CI = 2.2−4.5) increase in CKD prevalence. Conclusion: Although these results highlight the relative importance of geography in determining the prevalence of diabetes and CKD in Indigenous Canadians, geography is but an important surrogate of other determinants, such as poverty and access to care. Keywords: chronic kidney disease, Indigenous Canadians, remoteness, rurality, screening, social determinants of health

Abstract Neutrophil trafficking in tissues critically regulates the body’s immune response. Neutrophil migration can either play a protective role in host defense or cause health problems. Fibroblast growth factor 23 (FGF23) is a known biomarker for chronic kidney disease (CKD) and was recently shown to impair neutrophil arrest on endothelium and transendothelial migration. In the present study, we further examined the effect of FGF23 on human blood neutrophil chemotaxis using two new microfluidic devices. Our results showed that chemotaxis of FGF23 pre-treated neutrophils to a fMLP gradient, in the presence or absence of a uniform FGF23 background, is quantitatively lower compared to the control cells. This effect is accompanied with a stronger drifting of FGF23 pre-treated cells along the flow. However, without the FGF23 pre-treatment, the FGF23 background only reduces chemotaxis of transmigrated cells through the thin barrier channel to the fMLP gradient. The effect of FGF23 on neutrophil migration and the correlation between multiple cell migration parameters are further revealed by chemotactic entropy and principle component analysis. Collectively, these results revealed the effect of FGF23 on weakening neutrophil chemotaxis, which shed light on FGF23 mediated neutrophil migration with direct disease relevance such as CKD.

Acute kidney injury (AKI) is a potentially fatal complication of cardiac surgery. The inability to predict cardiac surgery-associated AKI is a major barrier to prevention and early treatment. Current clinical risk models for the prediction of cardiac surgery-associated AKI are insufficient, particularly in patients with preexisting kidney dysfunction. Methods: To identify intraoperative variables that might improve the performance of a validated clinical risk score (Cleveland Clinic Score, CCS) for the prediction of cardiac surgery-associated AKI, we conducted a prospective cohort study in 289 consecutive elective cardiac surgery patients at a tertiary care center. We compared the area under the receiver operator characteristic curve (AUC) of a base model including only the CCS with models containing additional selected intraoperative variables including mean arterial pressure, hematocrit, duration of procedure, blood transfusions, and fluid balance. AKI was defined by the Kidney Disease Improving Global Outcomes 2012 criteria. Results: The CCS alone gave an AUC of 0.72 (95% confidence interval, 0.62–0.82) for postoperative AKI. Nadir intraoperative hematocrit was the only variable that improved AUC for postoperative AKI when added to the CCS (AUC = 0.78; 95% confidence interval, 0.70–0.87; P = 0.002). In the subcohort of patients without preexisting chronic kidney disease (n = 214), where the CCS underperformed (AUC, 0.60 [0.43–0.76]), the improvement with the addition of nadir hematocrit was more marked (AUC, 0.74 [0.62–0.86]). Other variables did not improve discrimination. Discussion: Nadir intraoperative hematocrit is useful in improving discrimination of clinical risk scores for AKI, and may provide a target for intervention.

Background: A risk-based model of care for managing patients with chronic kidney disease (CKD) using the Kidney Failure Risk Equation (KFRE) has been successfully integrated into nephrology care pathways in several jurisdictions. However, as most patients with CKD can be managed in primary care, the next pertinent steps would be to integrate the KFRE into primary care pathways. Objective: Using a risk-based approach for guiding CKD care in the primary care setting, the objective of the study is to develop, implement, and evaluate tools that can be used by patients and providers. Design: This study is a multicenter cluster randomized control trial. Setting: Thirty-two primary care clinics belonging to the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) across Manitoba and Alberta. Patients: All patients at least 18 years old or older with CKD categories G3-G5 attending the participating clinics; we estimate each clinic will have an average of 185 patients with CKD. Methods: Thirty-two primary care clinics will be randomized to receive either an active knowledge translation intervention or no intervention. The intervention involves the addition of the KFRE and decision aids to clinics’ Data Presentation Tool (DPT), as well as patient-facing visual aids, a medical detailing visit, and sentinel feedback reports. Control clinics will only be exposed to current guidelines for CKD management, without active dissemination. Measurements: Data from the CPCSSN repository will be used to assess whether a risk-based care approach affected management of CKD. Primary outcomes are as follows: the proportion of patients with measured urine albumin-to-creatinine ratio, and the proportion of patients being appropriately treated with angiotensin-converting enzyme inhibitor or angiotensin receptor blockers. Secondary outcomes are as follows: the optimal management of diabetes (hemoglobin A1C

Background: Nonvalvular atrial fibrillation (NVAF) is an independent risk factor for ischemic stroke and is common in chronic kidney disease (CKD) and dialysis patients. The use of oral anticoagulation to prevent stroke and systemic embolism in the setting of kidney disease is controversial. Novel alternatives to vitamin K antagonists include left atrial appendage occlusion devices (LAAOD) and apixaban. Objective: We sought to elicit Canadian nephrologist views regarding stroke and systemic embolism prevention therapies in CKD and dialysis patients with NVAF. Design: Survey. Setting: Online via https://www.surveymonkey.com . Participants: Canadian Society of Nephrology members actively treating adult dialysis patients with NVAF. Measurements: Management questions were asked with response options consisting of a Likert scale ranging from 1 to 8 (with 1 being definitely would not and 8 being definitely would ). Methods: We randomly allocated each respondent to 2 of 4 cases that varied by stroke and bleeding risks (using varying CHADS2 and HASBLED scores, respectively). Results: There were 91 responses (36.3% response rate) from mostly university (83.5%) and also community with university affiliation (12.1%) and community (4.4%) nephrologists. Warfarin was more likely to be recommended in individuals at high stroke risk and low bleeding risk (mean = 5.47, 95% confidence interval = 4.87-6.07) and less likely to be recommended in individuals at moderate stroke risk and high bleeding risk (mean = 2.89, 95% confidence interval = 2.37-3.41). The likelihood of recommending LAAOD did not vary by stroke or bleeding risks (means ranging from 3.92-4.90). Apixaban was not likely to be recommended in any case (means ranging from 2.60-3.50). However, nephrologists felt there was equipoise regarding anticoagulation strategies allowing participation in appropriate randomized controlled trials (RCTs). Limitations: The survey only involved nephrologists and only 4 cases with dichotomized risk categories were presented instead of complete range of stroke and bleeding risk combinations. As with any survey, there was the potential for responder bias and treatment decisions are not anchored directly to patient management. Conclusions: Nephrologists caring for patients with kidney disease appear willing to include patients in clinical trials examining alternatives to warfarin for stroke and systemic embolism prevention for NVAF in the setting of kidney disease.

Background: Individuals with chronic kidney disease (CKD) have low levels of physical activity and physical function. Although guidelines endorse exercise counseling for individuals with CKD, it is not yet part of routine care. Objective: We investigated the effect of attending a real-life exercise counseling clinic (ECC) on physical function in individuals with CKD. Design: Retrospective analysis of prospectively collected observational data with quasi-experimental design. Setting and Participants: Patients with all stages of CKD registered in a large provincial renal program were eligible. The exposed cohort who attended the ECC between January 1, 2011, and March 15, 2014, included 214 individuals. The control cohort included 292 individuals enrolled in an observational study investigating longitudinal change in frailty during the same time period. Predictor/Factor: Attendance at an ECC. Outcomes and Measurements: Change in physical function as measured by Short Physical Performance Battery (SPPB) score, physical activity level (Human Activity Profile [HAP]/Physical Activity Scale for the Elderly [PASE]), and health-related quality of life (HRQOL; EQ5D/VAS) over 1 year. Results: Eighty-seven individuals in the ECC cohort and 125 participants in the control cohort completed 1-year follow-up. Baseline median SPPB score was 10 (interquartile range [IQR]: 9-12) and 9 (IQR: 7-11) in the ECC and control cohorts, respectively ( P < .01). At 1 year, SPPB scores were 10 (IQR: 8-12) and 9 (IQR: 6-11) in the ECC and control cohorts, respectively ( P = .04). Mean change in SPPB over 1 year was not significantly different between groups: −0.33 (95% confidence interval [CI]: −0.81 to 0.15) in ECC and −0.22 (95% CI: −0.61 to 0.17) in control ( P = .72). There was no significant difference in the proportion of individuals in each cohort with an increase/decrease in SPPB score over time. There was no significant change in physical activity or HRQOL over time between groups. Limitations: Quasi-experimental design, low rate of follow-up attendance. Conclusions: In this pragmatic study, exercise counseling had no significant effect on change in SPPB score, suggesting that a single exercise counseling session alone is inadequate to improve physical function in CKD.

Background: Acute kidney injury (AKI) following cardiac surgery leads to increased morbidity and mortality. Characterization and validation of early biomarkers of AKI may ultimately facilitate early therapeutic intervention. We have previously identified that elevated urinary hepcidin-25 is inversely and independently associated with the development of AKI in adult cardiac surgery patients. Hepcidin-25 is an antimicrobial peptide that sequesters iron intracellularly, and its elevation following human ischemia reperfusion injury may represent a renoprotective response to minimize renal injury. Objective: Our goal was to validate urinary hepcidin-25 as a non-invasive biomarker in an independent cardiac surgery cohort, within the context of clinical AKI predictors. Design: Prospective observational cohort study. Setting: Adult cardiac surgery program at St. Boniface Hospital, Winnipeg, Manitoba, Canada. Patients: Adult cardiac surgery patients undergoing cardiopulmonary bypass (CPB), n = 306. Measurements: Urine hepcidin-25, measured on post-operative day (POD) 1. Methods: A prospective, observational cohort of adult CPB patients (n = 306) was collected with serial perioperative urine samples. Urine hepcidin-25 at POD 1 was measured by competitive ELISA. Its diagnostic performance was evaluated in conjunction with clinical parameters and the Thakar clinical prediction score, using multivariate logistic regression. Results: Urinary hepcidin-25 is elevated following cardiac surgery in AKI and non-AKI patients. Elevated urinary hepcidin-25 concentration was inversely associated with AKI on both univariate (odds ratio [OR]: 0.61, 95% confidence interval [CI]: 0.45-0.83, P = .002) and multivariate analysis (OR: 0.67, 95% CI: 0.50-0.95, P = .02). A combined model with clinical risk factors demonstrated that baseline estimated glomerular filtration rate (eGFR), diabetes mellitus, and urinary hepcidin-25 concentration had an overall area under the curve (AUC) of 0.82 (0.75-0.88) for predicting subsequent AKI development, which was superior to clinical prediction alone as determined by the Thakar score. Limitations: (1) A single-center observational study. (2) Polyclonal antibody–based competitive ELISA. Conclusion: Hepcidin-25 is inversely associated with AKI in a multivariate model when combined with eGFR and diabetes mellitus, with an overall AUC of 0.82. Notably, urinary hepcidin-25 improves on clinical AKI prediction compared to the Thakar score alone.

Patients on dialysis are often elderly and frail, with multiple comorbid conditions, and are heavy users of Emergency Department (ED) services. However, objective data on the frequency and pattern of ED utilization by dialysis patients are sparse. Such data could identify periods of highest risk for ED visits and inform health systems interventions to mitigate these risks and improve outcomes.To describe the pattern and frequency of presentation to ER by dialysis patients.Retrospective cohort study using administrative data collected over ten years (2000-2009) in the Province of Manitoba, Canada.Patients presenting to any of 9 ED's in Winnipeg and Brandon Manitoba. These departments serve >90% of the population of Manitoba, Canada (population 1.2 million).All patients presenting to an ED in any of 9 emergency departments in Manitoba, Canada.Dialysis status.Presentation to the ED.Over 2.1 million ED visits by more than 1.2 million non-dialysis patients and 17,782 ED visits by 3257 dialysis patients were included. Dialysis patients presented 8.5 times more frequently to the ED than the general population (age and sex adjusted, p

Unplanned hospital admissions in high-risk patients are common and costly in an increasingly frail chronic disease population. Virtual Wards (VW) are an emerging concept to improve outcomes in these patients.To evaluate the effect of post-discharge VWs, as an alternative to usual community based care, on hospital readmissions and mortality among heart failure and non-heart failure populations.Ovid MEDLINE, EMBASE, PubMed, the Cochrane Database of Systematic Reviews, SCOPUS and CINAHL, from inception through to Jan 31, 2017; unpublished data, prior systematic reviews; reference lists.Randomized trials of post-discharge VW versus community based, usual care that reported all-cause hospital readmission and mortality outcomes.Data were reviewed for inclusion and independently extracted by two reviewers. Risk of bias was assessed using the Cochrane Collaboration risk of bias tool.In patients with heart failure, a post-discharge VW reduced risk of mortality (six trials, n = 1634; RR 0.59, 95% CI = 0.44-0.78). Heart failure related readmissions were reduced (RR 0.61, 95% CI = 0.49-0.76), although all-cause readmission was not. In contrast, a post-discharge VW did not reduce death or hospital readmissions for patients with undifferentiated high-risk chronic diseases (four trials, n = .3186).Heterogeneity with respect to intervention and comparator, lacking consistent descriptions and utilization of standardized nomenclature for VW. Some trials had methodologic shortcomings and relatively small study populations.A post-discharge VW can provide added benefits to usual community based care to reduce all-cause mortality and heart failure-related hospital admissions among patients with heart failure. Further research is needed to evaluate the utility of VWs in other chronic disease settings.

Background: In some jurisdictions, routine reporting of the estimated glomerular filtration rate (eGFR) has led to an increase in nephrology referrals and wait times. Objective: We describe the use of the Kidney Failure Risk Equation (KFRE) as part of a triage process for new nephrology referrals for patients with chronic kidney disease stages 3 to 5 in a Canadian province. Design: A quasi-experimental study design was used. Setting: This study took place in Manitoba, Canada. Measurements: Demographics, laboratory values, referral numbers, and wait times were compared between periods. Methods: In 2012, we adopted a risk-based cutoff of 3% over 5 years using the KFRE as a threshold for triage of new referrals. Referrals who did not meet other prespecified criteria (such as pregnancy, suspected glomerulonephritis, etc) and had a kidney failure risk of

Background: Patients with chronic kidney disease (CKD) are at risk to progress to kidney failure. We previously developed the Kidney Failure Risk Equation (KFRE) to predict progression to kidney failure in patients referred to nephrologists. Objective: The objective of this study was to determine the ability of the KFRE to discriminate which patients will progress to kidney failure in an unreferred population. Design: A retrospective cohort study was conducted using administrative databases. Setting: This study took place in Manitoba, Canada. Measurements: Age, sex, estimated glomerular filtration rate (eGFR), and urine albumin-to-creatinine ratio (ACR) were measured. Methods: We included patients from the Diagnostic Services of Manitoba database with an eGFR

Myocardial infarction (MI) is associated with high morbidity and mortality, particularly in the first 12 months post-event. Interventions such as dual antiplatelet therapy can reduce the risk of major adverse cardiovascular events (MACE), but the duration of the high-risk time interval and the optimal prescription time frame for these interventions remains unknown.We performed a retrospective cohort study using data from medical services and hospitalizations in Manitoba, Canada for patients admitted with a MI between April 2006 and March 2010, and followed until Nov 30, 2014. We used survival analysis to determine the cumulative incidence of death, subsequent MI, or stroke, and used Cox proportional hazards models to assess factors associated with these endpoints.There were 8,493 patients in Manitoba admitted to hospital for a MI during the study period. Of those, 6,749 (79.5%) survived for at least 1 year without a recurrent MI or stroke. In the following year, this population remained at high risk, with 372 (5.5%) of the remaining patients dying in the next twelve months (48.1% cardiovascular deaths), 244 (3.6%) having a recurrent MI, and 74 (1.1%) having a stroke. Older age, male sex, diabetes, prior stroke, prior heart failure, prior unstable angina, and absence of revascularization were associated with worse long-term prognosis.The risk of MACE remains elevated among post-MI patients after the first year. Interventions to more intensively monitor, evaluate, and treat these patients should be considered beyond the first year following myocardial infarction.

Background: Reactivation of latent Mycobacterium tuberculosis infection (LTBI) is a health concern for patients on dialysis or receiving a kidney transplant, as these patients are often immunosuppressed. The most frequently used test for LTBI screening in this population is the tuberculin skin test (TST). The diagnostic accuracy (sensitivity and specificity) of the TST in a contemporary North American or Western European dialysis population is unknown. Objectives: Our objective was to determine the diagnostic accuracy and clinical utility of the two-step TST in patients receiving dialysis. Design: This is a retrospective cohort study. Setting: This study is set at four tertiary dialysis units across Winnipeg, Manitoba. Patients: There are 483 chronic hemodialysis and peritoneal dialysis patients in the study. Measurements: The measurements are sensitivity and specificity of the TST with respect to abnormal chest X-ray. Methods: All patients received a two-step TST and assessment of risk factors for prior tuberculosis (TB) infection between February 2008 and December 2008. This cohort was retrospectively linked to our tuberculosis registry to ascertain if prophylaxis was received for LTBI. Results: At an induration cutoff of 5 mm, 62 (13 %) patients had a positive two-step TST. Patients with a known Bacillus Calmette-Guérin (BCG) vaccination were more likely to test positive (50 % of those with a positive TST had a BCG versus 34 % with a negative TST, p = 0.05). Using a diagnostic gold standard of an abnormal chest X-ray as a proxy for LTBI, the sensitivity of the TST was only 14 % and the specificity was 88 %. Only 8 of 62 patients with a positive TST (13 %) received prophylaxis for LTBI. None of the patients who tested negative were treated. Limitations: There is a lack of a truly accurate gold standard for LTBI. Conclusions: The TST has limited diagnostic and clinical utility for LTBI screening in patients on dialysis. Further research into the diagnostic accuracy of interferon-gamma release assays and a revision of LTBI screening guidelines in patients on dialysis should be considered.

Background: Predicting the clinical trajectories of chronic kidney disease (CKD) to discern personalized care remains a complex challenge in nephrology. Understanding the appropriate risk thresholds and time frame associated with predicting risks of key outcomes (kidney failure, cardiovascular (CV) events, and death) is critical in facilitating decision-making. As part of an exploratory research and practice support needs assessment, we aimed to determine the importance of the time frames for predicting key outcomes, and to assess the perceived demand for risk prediction tools among Canadian nephrologists. Methods: A web-based survey was developed by a pan-Canadian expert panel of practitioners. Upon pre-test for clarity and ease of completion, the final survey was nationally deployed to Canadian nephrologists. Anonymous responses were gathered over a 4-month period. The results were analyzed using descriptive statistics. Results: One hundred eleven nephrologists responded to our survey. The majority of the respondents described prediction of events over time frames of 1–5 years as being “extremely important” or “very important” to decision-making on a 5-point Likert scale. To plan for arteriovenous fistula referral, the respondents deemed thresholds which would predict probability of kidney failure between >30 and >50 % at 1 year, as useful, while many commented that the rate of progression should be included for decision-making. Over 80 % of the respondents were not satisfied with their current ability to predict the progression to kidney failure, CV events, and death. Most of them indicated that they would value and use validated risk scores for decision-making. Conclusions: Our national survey of nephrologists shows that the risk prediction for major adverse clinical outcomes is valuable in CKD at multiple time frames and risk thresholds. Further research is required in developing relevant and meaningful risk prediction models for clinical decision-making in patient-centered CKD care.

Knowledge generation through randomized controlled trials (RCTs) is critical to advance the medical evidence base, inform decision-making, and improve care and outcomes. Unfortunately, nephrology has typically lagged behind other medical specialties in this regard. The establishment of formal clinical trial networks can facilitate the successful conduct of RCTs and has significantly increased the number of RCTs performed worldwide in other medical specialties. No such formal network of nephrology trialists exists in Canada. On April 24, 2014, the Canadian Kidney Knowledge Translation and Generation Network (CANN-NET) Clinical Trials Committee held a stakeholder engagement meeting to address this gap and improve the nephrology clinical trial landscape in Canada. The meeting was held in Vancouver in association with the 2014 Canadian Society of Nephrology Annual General Meeting and was co-sponsored by the Kidney Foundation of Canada and CANN-NET. Attendees included nephrologists from university- and non-university-affiliated nephrology practices, administrators, and representatives from the Kidney Foundation of Canada. Through structured presentations and facilitated group discussions, the group explored the extent to which nephrology trials are currently happening in Canada, barriers to leading or participating in larger investigator-initiated trials, and strategies to improve clinical trial output in nephrology in Canada. The themes and action items arising from this meeting are discussed.

Cardiovascular disease (CVD) and cancer are two leading causes of death worldwide. CVD and cancer share risk factors such as obesity and diabetes mellitus and have common diagnostic biomarkers such as interleukin-6 and C-reactive protein. Thus, timely and accurate diagnosis of these two correlated diseases is of high interest to both the research and healthcare communities. Most conventional methods for CVD and cancer biomarker detection such as microwell plate-based immunoassay and polymerase chain reaction often suffer from high costs, low test speeds, and complicated procedures. Recently, lab-on-a-chip (LoC)-based platforms have been increasingly developed for CVD and cancer biomarker sensing and analysis using various molecular and cell-based diagnostic biomarkers. These new platforms not only enable better sample preparation, chemical manipulation and reaction, high-throughput and portability, but also provide attractive features such as label-free detection and improved sensitivity due to the integration of various novel detection techniques. These features effectively improve the diagnostic test speed and simplify the detection procedure. In addition, microfluidic cell assays and organ-on-chip models offer new potential approaches for CVD and cancer diagnosis. Here we provide a mini-review focusing on recent development of LoC-based methods for CVD and cancer diagnostic biomarker measurements, and our perspectives of the challenges, opportunities and future directions.

Background: Frailty, a manifestation of unsuccessful aging, is highly prevalent in people with chronic kidney disease (CKD) and is associated with comorbid conditions in cross-sectional studies. Longitudinal studies investigating the progression of frailty in those with advanced non-dialysis CKD are lacking. Objectives: Can adian F railty Observation and I nterventions T rial (CanFIT). To determine the natural history, prevalence of perceived and measured frailty and its association with dialysis treatment choices and adverse outcomes in patients with advanced CKD. Design: Longitudinal observational study, designed to collect data from 600 participants over 2 years. Setting: Interprofessional non-dialysis CKD clinics at four tertiary health care centres in central Canada. Patients: People with CKD stage 4 and 5 (eGFR

Background: Screening the general population for Chronic Kidney Disease is not currently recommended. Rural and remote Canadian First Nations people suffer a disproportionate burden of Kidney Failure. The Fi rst N at i ons Community Based S creening to Improve Kidney He alth and Prevent D ialysis ( FINISHED ) project intends to test the hypothesis that a mobile, mass screening initiative available to all First Nations people 10 years of age and older residing in rural and/or remote communities, is feasible, will improve health outcomes and is cost effective. Objectives: The objective of this manuscript is to describe the key elements required to design, implement and evaluate such a program and describe key characteristics of our screened cohort. Design: Methods and cohort description. Setting: 11 First Nations communities within 2 Tribal Councils in Manitoba, Canada. Patients: All First Nations individuals between the ages of 10–80 living in the 11communities were eligible for the screening initiative. Measurements: Screening Rates achieved within communities. Methods: An interdisciplinary team partnership was established between the Diabetes Integration Project and the Manitoba Renal Program. Stakeholder consultation was obtained and protocols developed to mass screen community members using point of care testing equipment. All people screened were risk stratified, counselled and referred to nephrologists as required in real time, based on risk. Results: As of August 31, 2014, 1480 people in 11 communities over 2 Tribal Councils have been successfully screened. A mean screening rate of 21% of all community members eligible (aged 10–80) has been achieved. All patients at intermediate or high risk of kidney failure have been seen by nephrologists within 1 month of screening. Limitations: Long term outcomes of kidney failure rates not assessed for at least 5 years. Alternative public health initiatives to reduce kidney failure not investigated. Conclusions: Point of care mass screening, real time risk prediction and counselling of First Nations people at high risk of Kidney Failure is feasible in rural and remote communities. Further analysis of this cohort will describe theepidemiology of CKD in these communities, and test the cost effectiveness of this strategy.

Kidney Failure is epidemic in many remote communities in Canada. In-centre hemodialysis is provided within these settings in satellite hemodialysis units. The key cost drivers of this program have not been fully described. Such information is important in informing the design of programs aimed at optimizing efficiency in providing dialysis and preventative chronic kidney disease care in remote communities.We constructed a cost model based on data derived from 16 of Manitoba, Canada's remote satellite units. We included all costs for operation of the unit, transportation, treatment, and capital costs. All costs were presented in 2013 Canadian dollars.The annual per-patient cost of providing hemodialysis in the satellite units ranged from $80,372 to $215,918 per patient, per year. The median per patient, per year cost was $99,888 (IQR $89,057-$122,640). Primary cost drivers were capital costs related to construction, human resource expenses, and expenses for return to tertiary care centres for health care. Costs related to transport considerably increased estimates in units that required plane or helicopter transfers.Satellite hemodialysis units in remote areas are more expensive on a per-patient basis than hospital hemodialysis and satellite hemodialysis available in urban areas. In some rural, remote locations, better value for money may reside in local surveillance and prevention programs in addition support for home dialysis therapies over construction of new satellite hemodialysis units.

Background: Previous reports have demonstrated similar survival for men and women on hemodialysis, despite women's increased survival in the general population. Objectives: To examine the effect of age on mortality in women undergoing chronic hemodialysis. Design: A retrospective cohort study using an administrative data registry, the Canadian Organ Replacement Registry (CORR) from Jan. 2001 and Dec. 2009. Setting: Canada. Patients: 28,971 (Women 11,792 (40.7%), Men 17,179 (59.3%)) incident chronic hemodialysis patients who survived greater than 90 days on dialysis. Measurements: All-cause mortality. Methods: Cox proportional hazards and competing risks models were employed to determine the independent association between sex, age and likelihood of all-cause mortality with renal transplantation as the competing outcome. Results: During the study period, 6060 (51.4%) of women and 8650 (50.4%) of men initiating dialysis died. Younger women experienced higher mortality (Age < 45: Women 22.5%, Men 18.2%, hazard ratio (HR) 1.31 (1.12–1.52)) whereas elderly women experience lower mortality (Age 75–85: Women 65%, Men 67.3%, HR 0.94 95% CI 0.88–0.99, Age > 85: Women 66%, Men 70.2%, HR 0.83 95% CI 0.71–0.97) compared to men. This relationship persisted after accounting for the competing risk of transplantation. Limitations: The cause of death was unknown. Conclusions: Women's survival on chronic hemodialysis varies by age compared to men with a significantly higher mortality in women younger than 45 years old and lower mortality in woman older than 75 years of age.

Background: Chronic kidney disease screening using estimated glomerular filtration rate (eGFR) reporting is standard in many regions. With its implementation, many centres have had higher referral rates and increased wait times to see nephrologists. Objective: Manitoba began eGFR reporting in October 2010. We measured the effect of eGFR reporting on referral rates, wait times, and appropriateness of referrals after an educational intervention. Design: An interrupted time series design was used. Setting: This study took place in Manitoba, Canada. Patients: All referrals to the Manitoba Renal Program in the period prior to eGFR reporting between April 1, 2010 and September 30, 2010 were compared with a post period between January 1, 2011 and June 30, 2011. Measurements: Data on demographics, co-morbidities, referral numbers and wait times were compared between periods. Appropriateness of consults was also measured after eGFR implementation. Methods: Prior to eGFR reporting, primary care physicians underwent educational interventions on eGFR interpretation and referral guidelines. Referral rates and wait times were compared between periods using generalized linear models. Chart audits of a random sample of 232 patients in the pre period and 239 patients in the post period were performed. Results: The pre and post eGFR reporting referral rate was 116 and 152 referrals/month, respectively. Average wait times in the pre and post eGFR reporting was 113 and 115 days, respectively. Non-urgent referral wait times increased by 40 days immediately post reporting, while urgent median referral wait times had a more gradual increase. Despite our intervention, inappropriate consultations post eGFR reporting was 495/790 (62.7%). Limitations: Our study did not measure the intervention's success on primary care providers, which may have affected our appropriateness data. Our time series design was not powered to find a statistically significant difference in referral numbers. Residual confounding of our results was possible given the retrospective nature of our study. Conclusion: Despite our educational intervention, the inappropriate referrals remained high, and wait times increased. Other systemic interventions should be considered to attenuate the potential negative effects of eGFR reporting and ensure timely access for patients needing specialist consultation.