Seven Oaks General Hospital

IMPORTANCE: Identifying patients at risk of chronic kidney disease (CKD) progression may facilitate more optimal nephrology care. Kidney failure risk equations, including such factors as age, sex, estimated glomerular filtration rate, and calcium and phosphate concentrations, were previously developed and validated in 2 Canadian cohorts. Validation in other regions and in CKD populations not under the care of a nephrologist is needed. OBJECTIVE: To evaluate the accuracy of the risk equations across different geographic regions and patient populations through individual participant data meta-analysis. DATA SOURCES: Thirty-one cohorts, including 721,357 participants with CKD stages 3 to 5 in more than 30 countries spanning 4 continents, were studied. These cohorts collected data from 1982 through 2014. STUDY SELECTION: Cohorts participating in the CKD Prognosis Consortium with data on end-stage renal disease. DATA EXTRACTION AND SYNTHESIS: Data were obtained and statistical analyses were performed between July 2012 and June 2015. Using the risk factors from the original risk equations, cohort-specific hazard ratios were estimated and combined using random-effects meta-analysis to form new pooled kidney failure risk equations. Original and pooled kidney failure risk equation performance was compared, and the need for regional calibration factors was assessed. MAIN OUTCOMES AND MEASURES: Kidney failure (treatment by dialysis or kidney transplant). RESULTS: During a median follow-up of 4 years of 721,357 participants with CKD, 23,829 cases kidney failure were observed. The original risk equations achieved excellent discrimination (ability to differentiate those who developed kidney failure from those who did not) across all cohorts (overall C statistic, 0.90; 95% CI, 0.89-0.92 at 2 years; C statistic at 5 years, 0.88; 95% CI, 0.86-0.90); discrimination in subgroups by age, race, and diabetes status was similar. There was no improvement with the pooled equations. Calibration (the difference between observed and predicted risk) was adequate in North American cohorts, but the original risk equations overestimated risk in some non-North American cohorts. Addition of a calibration factor that lowered the baseline risk by 32.9% at 2 years and 16.5% at 5 years improved the calibration in 12 of 15 and 10 of 13 non-North American cohorts at 2 and 5 years, respectively (P = .04 and P = .02). CONCLUSIONS AND RELEVANCE: Kidney failure risk equations developed in a Canadian population showed high discrimination and adequate calibration when validated in 31 multinational cohorts. However, in some regions the addition of a calibration factor may be necessary.

PURPOSE OF REVIEW: Glomerular filtration rate (GFR) is rarely measured in clinical practice because of the complexity of the measurement. As such, kidney function is typically estimated using validated study equations, which use readily available data including age, sex, race, and serum creatinine as filtration marker. Contemporary research suggests that cystatin C may be an improved alternative to creatinine for inclusion in GFR estimating equations. The purpose of this article is to evaluate the benefits and limitations of using cystatin C as a biomarker of filtration. RECENT FINDINGS: Cystatin C has fewer non-GFR determinants, when compared with serum creatinine. Use of serum cystatin C avoids the limitations related to both diet and muscle mass that affect serum creatinine. Cystatin C may be more accurate than serum creatinine in estimating GFR, and is more strongly associated with all-cause mortality and cardiovascular events. SUMMARY: Cystatin C has some advantages over serum creatinine in estimating GFR. The use of cystatin C as a confirmatory biomarker in deciding medication dosages or as a confirmatory test in patients with an uncertain diagnosis of chronic kidney disease may be beneficial.

OBJECTIVES: We performed a systematic review and meta-analysis to understand the role of flow-mediated dilatation (FMD) of the brachial artery (BA) and peripheral arterial tonometry (PAT) in predicting adverse events, including cardiovascular (CV) events and all-cause mortality. BACKGROUND: FMD of the BA and PAT are non-invasive measures of endothelial function. Impairment of endothelial function is associated with increased CV events. While FMD is the more widely used and studied technique, PAT offers several advantages. The purpose of this systematic review and meta-analysis is to determine whether brachial FMD and PAT are independent risk factors for future CV events and mortality. METHODS: Multiple electronic databases were searched for articles relating FMD or PAT to CV events. Data were extracted on study characteristics, study quality, and study outcomes. Relative risks (RRs) from individual studies were combined and a pooled multivariate RR was calculated. RESULTS: Thirty-six studies for FMD were included in the systematic review, of which 32 studies consisting of 15, 191 individuals were meta-analysed. The pooled RR of CV events and all-cause mortality per 1% increase in brachial FMD, adjusting for potential confounders, was 0.90 (0.88-0.92). In contrast, only three studies evaluated the prognostic value of PAT for CV events, and the pooled RR per 0.1 increase in reactive hyperaemia index was 0.85 (0.78-0.93). CONCLUSION: Brachial FMD and PAT are independent predictors of CV events and all-cause mortality. Further research to evaluate the prognostic utility of PAT is necessary to compare it with FMD as a non-invasive endothelial function test in clinical practice.

Various types of chronic diseases (CD) are the leading causes of disability and death worldwide. While those diseases are chronic in nature, accurate and timely clinical decision making is critically required. Current diagnosis procedures are often lengthy and costly, which present a major bottleneck for effective CD healthcare. Rapid, reliable and low-cost diagnostic tools at point-of-care (PoC) are therefore on high demand. Owing to miniaturization, lab-on-chip (LoC) technology has high potential to enable improved biomedical applications in terms of low-cost, high-throughput, ease-of-operation and analysis. In this direction, research toward developing new LoC-based PoC systems for CD diagnosis is fast growing into an emerging area. Some studies in this area began to incorporate digital and mobile technologies. Here we review the recent developments of this area with the focus on chronic respiratory diseases (CRD), diabetes, and chronic kidney diseases (CKD). We conclude by discussing the challenges, opportunities and future perspectives of this field.

BACKGROUND: There is little certainty as to the prevalence of frailty in Canadians in younger adulthood. This study examines and compares the prevalence of frailty in Canadians 18-79 years old using the Accumulation of Deficits and Fried models of frailty. METHODS: The Canadian Health Measures Study data were used to estimate the prevalence of frailty in adults 18-79 years old. A 23-item Frailty Index using the Accumulation of Deficits Model (cycles 1-3; n = 10,995) was developed; frailty was defined as having the presence of 25% or more indices, including symptoms, chronic conditions, and laboratory variables. Fried frailty (cycles 1-2; n = 7,353) included the presence of ≥3 criteria: exhaustion, physical inactivity, poor mobility, unintentional weight loss, and poor grip strength. RESULTS: The prevalence of frailty was 8.6 and 6.6% with the Accumulation of Deficits and the Fried Model. Comparing the Fried vs. the Accumulation of Deficits Model, the prevalence of frailty was 5.3% vs. 1.8% in the 18-34 age group, 5.7% vs. 4.3% in the 35-49 age group, 6.9% vs. 11.6% in the 50-64 age group, and 7.8% vs. 20.2% in the 65+ age group. Some indices were higher in the younger age groups, including persistent cough, poor health compared to a year ago, and asthma for the accumulation of deficits model, and exhaustion, unintentional weight loss, and weak grip strength for the Fried model, compared to the older age groups. CONCLUSIONS: These data show that frailty is prevalent in younger adults, but varies depending on which frailty tool is used. Further research is needed to determine the health impact of frailty in younger adults.

Importance: Sodium polystyrene sulfonate is commonly prescribed for the treatment of hyperkalemia. Case reports of intestinal injury after administration of sodium polystyrene sulfonate with sorbitol resulted in a US Food and Drug Administration warning and discontinuation of combined 70% sorbitol-sodium polystyrene sulfonate formulations. There are ongoing concerns about the gastrointestinal (GI) safety of sodium polystyrene sulfonate use. Objective: To assess the risk of hospitalization for adverse GI events associated with sodium polystyrene sulfonate use in patients of advanced age. Design, Setting, and Participants: Population-based, retrospective matched cohort study of eligible adults of advanced age (≥66 years) dispensed sodium polystyrene sulfonate from April 1, 2003, to September 30, 2015, in Ontario, Canada, with maximum follow-up to March 31, 2016. Initial data analysis was conducted from August 1, 2018, to October 3, 2018; revision analysis was conducted from February 25, 2019, to April 2, 2019. Cox proportional hazards regression models were used to examine the association of sodium polystyrene sulfonate use with a composite of GI adverse events compared with nonuse that was matched via a high-dimensional propensity score. Additional analyses were limited to a subpopulation with baseline laboratory values of estimated glomerular filtration rate and serum potassium level. Exposure: Dispensed sodium polystyrene sulfonate in an outpatient setting. Main Outcomes and Measures: The primary outcome was a composite of adverse GI events (hospitalization or emergency department visit with intestinal ischemia/thrombosis, GI ulceration/perforation, or resection/ostomy) within 30 days of initial sodium polystyrene sulfonate prescription. Results: From a total of 1 853 866 eligible adults, 27 704 individuals were dispensed sodium polystyrene sulfonate (mean [SD] age, 78.5 [7.7] years; 54.7% male), and 20 020 sodium polystyrene sulfonate users were matched to 20 020 nonusers. Sodium polystyrene sulfonate use compared with nonuse was associated with a higher risk of an adverse GI event over the following 30 days (37 events [0.2%]; incidence rate, 22.97 per 1000 person-years vs 18 events [0.1%]; incidence rate, 11.01 per 1000 person-years) (hazard ratio, 1.94; 95% CI, 1.10-3.41). Results were consistent in additional analyses, including the subpopulation with baseline laboratory values (hazard ratio, 2.91; 95% CI, 1.38-6.12), and intestinal ischemia/thrombosis was the most common type of GI injury. Conclusions and Relevance: The use of sodium polystyrene sulfonate is associated with a higher risk of hospitalization for serious adverse GI events. These findings require confirmation and suggest caution with the ongoing use of sodium polystyrene sulfonate.

BACKGROUND: The utility of acupuncture in managing osteoarthritis symptoms is uncertain. Trial results are conflicting and previous systematic reviews may have overestimated the benefits of acupuncture. METHODS: Two reviewers independently identified randomized controlled trials (up to May 2014) from multiple electronic sources (including PubMed/Medline, EMBASE, and CENTRAL) and reference lists of relevant articles, extracted data and assessed risk of bias (Cochrane's Risk of Bias tool). Pooled data are expressed as mean differences (MD), with 95% confidence intervals (CI) (random-effects model). RESULTS: We included 12 trials (1763 participants) comparing acupuncture to sham acupuncture, no treatment or usual care. We adjudicated most trials to be unclear (64%) or high (9%) risk of bias. Acupuncture use was associated with significant reductions in pain intensity (MD -0.29, 95% CI -0.55 to -0.02, I2 0%, 10 trials, 1699 participants), functional mobility (standardized MD -0.34, 95% CI -0.55 to -0.14, I2 70%, 9 trials, 1543 participants), health-related quality of life (standardized MD -0.36, 95% CI -0.58 to -0.14, I2 50%, 3 trials, 958 participants). Subgroup analysis of pain intensity by intervention duration suggested greater pain intensity reduction with intervention periods greater than 4 weeks (MD -0.38, 95% CI -0.69 to -0.06, I2 0%, 6 trials, 1239 participants). CONCLUSIONS: The use of acupuncture is associated with significant reductions in pain intensity, improvement in functional mobility and quality of life. While the differences are not as great as shown by other reviews, current evidence supports the use of acupuncture as an alternative for traditional analgesics in patients with osteoarthritis. SYSTEMATIC REVIEW REGISTRATION: CRD42013005405.

BACKGROUND: Frailty is a condition characterized by a decline in physical function and functional capacity. Common symptoms of frailty, such as weakness and exhaustion, are prevalent in patients with chronic kidney disease (CKD). The increased vulnerability of frail patients with coexisting CKD may place them at a heightened risk of encountering additional health complications. The purpose of this systematic review was to explore the link between frailty, CKD and clinical outcomes. METHODS: We searched for cross sectional and prospective studies in the general population and in the CKD population indexed in EMBASE, Pubmed, Web of Science, CINAHL, Cochrane and Ageline examining the association between frailty and CKD and those relating frailty in patients with CKD to clinical outcomes. RESULTS: We screened 5,066 abstracts and retrieved 108 studies for full text review. We identified 7 studies associating frailty or physical function to CKD. From the 7 studies, we identified only two studies that related frailty in patients with CKD to a clinical outcome. CKD was consistently associated with increasing frailty or reduced physical function [odds ratios (OR) 1.30 to 3.12]. In patients with CKD, frailty was associated with a greater than two-fold higher risk of dialysis and/or death [OR from 2.0 to 5.88]. CONCLUSIONS: CKD is associated with a higher risk of frailty or diminished physical function. Furthermore, the presence of frailty in patients with CKD may lead to a higher risk of mortality. Further research must be conducted to understand the mechanisms of frailty in CKD and to confirm its association with clinical outcomes.

Hemodialysis vascular access recommendations promote arteriovenous (AV) fistulas first; however, it may not be the best approach for all hemodialysis patients, because likelihood of successful fistula placement, procedure-related and subsequent costs, and patient survival modify the optimal access choice. We performed a decision analysis evaluating AV fistula, AV graft, and central venous catheter (CVC) strategies for patients initiating hemodialysis with a CVC, a scenario occurring in over 70% of United States dialysis patients. A decision tree model was constructed to reflect progression from hemodialysis initiation. Patients were classified into one of three vascular access choices: maintain CVC, attempt fistula, or attempt graft. We explicitly modeled probabilities of primary and secondary patency for each access type, with success modified by age, sex, and diabetes. Access-specific mortality was incorporated using preexisting cohort data, including terms for age, sex, and diabetes. Costs were ascertained from the 2010 USRDS report and Medicare for procedure costs. An AV fistula attempt strategy was found to be superior to AV grafts and CVCs in regard to mortality and cost for the majority of patient characteristic combinations, especially younger men without diabetes. Women with diabetes and elderly men with diabetes had similar outcomes, regardless of access type. Overall, the advantages of an AV fistula attempt strategy lessened considerably among older patients, particularly women with diabetes, reflecting the effect of lower AV fistula success rates and lower life expectancy. These results suggest that vascular access-related outcomes may be optimized by considering individual patient characteristics.

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 <3% over 5 years were returned to primary care with recommendations based on diabetes and hypertension guidelines. The average wait time and number of consults seen between the pretriage (January 1, 2011, to December 31, 2011) and posttriage period (January 1, 2013, to December 31, 2013) were compared using a general linear model. RESULTS: In the pretriage period, the median number of referrals was 68/month (range: 44-76); this increased to 94/month (range: 61-147) in the posttriage period. In the posttriage period, 35% of referrals were booked as urgent, 31% as nonurgent, and 34% of referrals were not booked. The median wait times improved from 230 days (range: 126-355) in the pretriage period to 58 days (range: 48-69) in the posttriage period. LIMITATIONS: We do not have long-term follow-up on patients triaged as low risk. Our study may not be applicable to nephrology teams operating under capacity without wait lists. We did not collect detailed information on all referrals in the pretriage period, so any differences in our pretriage and posttriage patient groups may be unaccounted for. CONCLUSIONS: Our risk-based triage scheme is an effective health policy tool that led to improved wait times and access to care for patients at highest risk of progression to kidney failure.

BACKGROUND: Hemodialysis is associated with a high symptom burden that impairs health-related quality of life and functional status. Effective symptom management is a priority for individuals receiving hemodialysis. Aerobic exercise may be an effective, nonpharmacologic treatment for specific hemodialysis-related symptoms. This systematic review investigated the effect of aerobic exercise on hemodialysis-related symptoms in adults with kidney failure undergoing maintenance hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We searched MEDLINE, PubMed, Cochrane CENTRAL, CINAHL, PsycINFO, SPORTDiscus, EMBASE, PEDro, and Scopus databases from 1960 or inception until April 15, 2020 for randomized controlled trials investigating the effect of aerobic exercise on hemodialysis-related symptoms, identified as prespecified primary or secondary outcomes, as compared with controls in adults on maintenance hemodialysis. We identified restless legs syndrome as the primary outcome. RESULTS: Of 3048 studies identified, 15 randomized controlled trials met the eligibility criteria. These studies investigated the effect of aerobic exercise on restless legs syndrome (two studies), sleep disturbance (four studies), anxiety (four studies), depression (nine studies), muscle cramping (one study), and fatigue (one study). Exercise interventions were intradialytic in ten studies and outside of hemodialysis in five studies. Heterogenous interventions and outcomes and moderate to high risk of bias precluded meta-analysis for most symptoms. Aerobic exercise demonstrated improvement in symptoms of restless legs syndrome, muscle cramping, and fatigue, as compared with nonexercise controls. Meta-analysis of depressive symptoms in studies using the Beck Depression Inventory demonstrated a greater reduction in Beck Depression Inventory score with exercise as compared with control (mean difference -7.57; 95% confidence interval, -8.25 to -6.89). CONCLUSIONS: Our review suggests that in adults on maintenance hemodialysis, aerobic exercise improves several hemodialysis-related symptoms, including restless legs syndrome, symptoms of depression, muscle cramping, and fatigue. However, the use of validated outcome measures with demonstrated reliability and responsiveness in more diverse hemodialysis populations is required to fully characterize the effect of this intervention. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: PROSPERO #CRD42017056658.

Importance: The burden of chronic kidney disease (CKD) is expected to increase worldwide as the global population ages, potentially increasing the demand for nephrology services. Understanding whether CKD inevitably progresses or may regress can inform clinical decision-making and health policy. Objective: To study CKD progression and regression by age in adults with CKD. Design, Setting, and Participants: This population-based cohort study used linked administrative and laboratory data to assess adults in the province of Alberta, Canada, with incident mild, moderate, or severe CKD, defined by estimated glomerular filtration rate (eGFR) of 45 to 59, 30 to 44, or 15 to 29 mL/min/1.73 m2 for longer than 3 months, from April 1, 2009, to March 31, 2015. Data were analyzed from July 20 to November 30, 2020. Exposures: Age. Main Outcomes and Measures: Time to the earliest of CKD regression or progression (defined as sustained increase or drop in eGFR category for >3 months, respectively, and a ≥25% increase or decrease in eGFR from baseline, respectively), kidney failure (the earlier of kidney replacement initiation or eGFR <15 mL/min/1.73 m2 for >3 months), death, or censoring (outmigration, 5 years of follow-up, or end of study on March 31, 2017). Results: Study participants with CKD (55.2% women and 44.8% men) included 81 320 with mild CKD (mean [SD] age, 72.4 [11.3] years), 35 929 with moderate CKD (mean [SD] age, 77.1 [11.5] years), and 12 237 with severe CKD (mean [SD] age, 76.6 [13.8] years). The annual incidence of CKD increased with advancing age, from 180 per 100 000 population younger than 65 years to 7250 per 100 000 in those 85 years or older. After cohort entry, the 5-year probability of regression was similar to that of progression or kidney failure in mild (14.3% vs 14.6%), moderate (18.9% vs 16.5%), and severe (19.3% vs 20.4%) CKD. As mortality at 5 years increased with advancing age in moderate (from 9.6% for age <65 years to 48.4% for age ≥85 years) and severe (from 10.8% for age <65 years to 60.2% for age ≥85 years) CKD, the risk of progression or kidney failure decreased substantially (for moderate CKD, from 32.3% for <65 years to 9.4% for ≥85 years; for severe CKD, from 55.2% for <65 years to 4.7% for ≥85 years), whereas the probabilities of regression varied to a lesser extent (for moderate CKD, from 22.5% for <65 years to 15.4% for ≥85 years; for severe CKD, from 13.9% for <65 years to 18.7% for ≥85 years). Conclusions and Relevance: This cohort study found that with advancing age, CKD regression and death were more likely than CKD progression or kidney failure. These findings have important implications for patient care and for assessing the potential effect of population aging on the burden of CKD.

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: The efficacy of erythropoietin-stimulating agents (ESAs) for improving health-related quality of life (HRQOL) in anemia of chronic kidney disease (CKD) is unclear. PURPOSE: To determine the effect of ESAs on HRQOL at different hemoglobin targets in adults with CKD who were receiving or not receiving dialysis. DATA SOURCES: Searches of PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov from inception to 1 November 2015, supplemented with manual screening. STUDY SELECTION: Randomized, controlled trials that evaluated the treatment of anemia with ESAs, including erythropoietin and darbepoetin, targeted higher versus lower hemoglobin levels, and used validated HRQOL metrics. DATA EXTRACTION: Study characteristics, quality, and data were assessed independently by 2 reviewers. Outcome measures were scores on the Short Form-36 Health Survey (SF-36), Kidney Dialysis Questionnaire (KDQ), and other tools. DATA SYNTHESIS: Of 17 eligible studies, 13 reported SF-36 outcomes and 4 reported KDQ outcomes. Study populations consisted of patients not undergoing dialysis (n = 12), those undergoing dialysis (n = 4), or a mixed sample (n = 1). Only 4 studies had low risk of bias. Pooled analyses showed that higher hemoglobin targets resulted in no statistically or clinically significant differences in SF-36 or KDQ domains. Differences in HRQOL were further attenuated in studies at low risk of bias and in subgroups of dialysis recipients. LIMITATION: Statistically significant heterogeneity among studies, few good-quality studies, and possible publication bias. CONCLUSION: ESA treatment of anemia to obtain higher hemoglobin targets does not result in important differences in HRQOL in patients with CKD. PRIMARY FUNDING SOURCE: KRESCENT and Manitoba Health Research Council Establishment.

BACKGROUND AND OBJECTIVES: The prevalence of ESKD is increasing worldwide. Treating ESKD is disproportionately costly in comparison with its prevalence, mostly due to the direct cost of dialysis therapy. Here, we aim to provide a contemporary cost description of dialysis modalities, including facility-based hemodialysis, peritoneal dialysis, and home hemodialysis, provided with conventional dialysis machines and the NxStage System One. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We constructed a cost-minimization model from the perspective of the Canadian single-payer health care system including all costs related to dialysis care. The labor component of costs consisted of a breakdown of activity-based per patient direct labor requirements. Other costs were taken from statements of operations for the kidney program at Seven Oaks General Hospital (Winnipeg, Canada). All costs are reported in Canadian dollars. RESULTS: Annual maintenance expenses were estimated as $64,214 for in-center facility hemodialysis, $43,816 for home hemodialysis with the NxStage System One, $39,236 for home hemodialysis with conventional dialysis machines, and $38,658 for peritoneal dialysis. Training costs for in-center facility hemodialysis, home hemodialysis with the NxStage System One, home hemodialysis with conventional dialysis machines, and peritoneal dialysis are estimated as $0, $16,143, $24,379, and $7157, respectively. The threshold point to achieve cost neutrality was determined to be 9.7 months from in-center hemodialysis to home hemodialysis with the NxStage System One, 12.6 months from in-center hemodialysis to home hemodialysis with conventional dialysis machines, and 3.2 months from in-center hemodialysis to peritoneal dialysis. CONCLUSIONS: Home modalities have lower maintenance costs, and beyond a short time horizon, they are most cost efficient when considering their incremental training expenses. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_07_18_CJASNPodcast_18_8_F.mp3.

BACKGROUND: Patients with chronic kidney disease stages 3 to 5 (glomerular filtration rate <60 mL/min/1.73m(2)) are at increased risk of cardiovascular (CV) disease when compared with patients with less severe chronic kidney disease. How CV events modify the subsequent risk of progression to end-stage-renal disease (ESRD) or all-cause mortality (ACM) before ESRD is not well known. METHODS AND RESULTS: This retrospective cohort study involved 2964 chronic kidney disease subjects referred between January 2001 and December 2008 to the nephrology clinic at Sunnybrook Health Sciences Center, Toronto, Ontario. Interim CV events (heart failure, myocardial infarction, and stroke), ESRD, and ACM were ascertained from administrative data. Over a median follow-up time of 2.76 years (interquartile range, 1.45-4.62), 447 (15%) subjects had a CV event. In the same time period, 318 (11%) developed ESRD, and 446 (15%) experienced ACM before ESRD (156 [5%] from a CV and 290 [10%] from a non-CV-related cause). When analyzed as a time-dependent variable, an interim CV event was associated with a higher risk of subsequent ESRD (hazard ratio, 5.33; 95% confidence interval, 3.74-7.58) and ACM before ESRD (hazard ratio, 4.15, hazard ratio, 3.30-5.23). The hazard ratio for CV-related death versus non-CV-related death before ESRD was 12.38 (95% confidence interval, 8.30-18.45) versus 2.13 (95% confidence interval, 1.57-2.87). CONCLUSIONS: CV events are common in patients with chronic kidney disease stages 3 to 5 and are associated with a substantial increase in the risk of ESRD and ACM before ESRD. Intensive primary and secondary prevention strategies may help attenuate this risk.

Background and objectives The safety of intravenous iron dosing in dialysis is uncertain. Higher-dose intravenous iron may be associated with a higher risk of infections, cardiovascular events, hospitalizations, and mortality. This systematic review aimed to determine the safety of higher-dose versus lower-dose intravenous iron, oral iron, or no iron supplementation in adult patients treated with dialysis. Design, setting, participants, &amp; measurements We searched Medline, EMBASE, Cochrane library, and CINAHL from inception to January 6, 2017 for randomized, controlled trials and observational studies comparing higher-dose intravenous iron with lower-dose intravenous iron, oral iron, or no iron in patients treated with dialysis that had all-cause mortality, infection, cardiovascular events, or hospitalizations as outcomes. Results Of the 2231 eligible studies, seven randomized, controlled trials and 15 observational studies met inclusion criteria. The randomized, controlled trials showed no association between higher-dose intravenous iron (&gt;400 mg/mo for most studies) and mortality (six studies; n =970; pooled relative risk, 0.93; 95% confidence interval, 0.47 to 1.84; follow-up ranging from 35 days to 26 months) or infection (four studies; n =743; relative risk, 1.02; 95% confidence interval, 0.74 to 1.41). The observational studies showed no association between higher-dose intravenous iron (&gt;200 mg/mo for most studies) and mortality (eight studies; n =241,408; hazard ratio, 1.09; 95% confidence interval, 0.98 to 1.21; follow-up ranging from 3 to 24 months), infection (eight studies; n =135,532; pooled hazard ratio, 1.13; 95% confidence interval, 0.99 to 1.28), cardiovascular events (seven studies; n =135,675; hazard ratio, 1.18; 95% confidence interval, 0.90 to 1.56), or hospitalizations (five studies; n =134,324; hazard ratio, 1.08; 95% confidence interval, 0.97 to 1.19). Conclusions Higher-dose intravenous iron does not seem to be associated with higher risk of mortality, infection, cardiovascular events, or hospitalizations in adult patients on dialysis. Strength of this finding is limited by small numbers of participants and events in the randomized, controlled trials and statistical heterogeneity in observational studies.

Introduction: Prediction of disease progression at all stages of chronic kidney disease (CKD) may help improve patient outcomes. As such, we aimed to develop and externally validate a random forest model to predict progression of CKD using demographics and laboratory data. Methods: and a urine albumin-to-creatinine ratio (ACR) available were included from Manitoba and 107,097 from Alberta. We considered >80 laboratory features, including analytes from complete blood cell counts, chemistry panels, liver enzymes, urine analysis, and quantification of urine albumin and protein. The primary outcome in our study was a 40% decline in eGFR or kidney failure. We assessed model discrimination using the area under the receiver operating characteristic curve (AUC) and calibration using plots of observed and predicted risks. Results: The final model achieved an AUC of 0.88 (95% CI 0.87-0.89) at 2 years and 0.84 (0.83-0.85) at 5 years in internal testing. Discrimination and calibration were preserved in the external validation data set with AUC scores of 0.87 (0.86-0.88) at 2 years and 0.84 (0.84-0.86) at 5 years. The top 30% of individuals predicted as high risk and intermediate risk represent 87% of CKD progression events in 2 years and 77% of progression events in 5 years. Conclusion: A machine learning model that leverages routinely collected laboratory data can predict eGFR decline or kidney failure with accuracy.

PURPOSE OF REVIEW: This article serves to describe the Can-SOLVE CKD network, a program of research projects and infrastructure that has excited patients and given them hope that we can truly transform the care they receive. ISSUE: Chronic kidney disease (CKD) is a complex disorder that affects more than 4 million Canadians and costs the Canadian health care system more than $40 billion per year. The evidence base for guiding care in CKD is small, and even in areas where evidence exists, uptake of evidence into clinical practice has been slow. Compounding these complexities are the variations in outcomes for patients with CKD and difficulties predicting who is most likely to develop complications over time. Clearly these gaps in our knowledge and understanding of CKD need to be filled, but the current state of CKD research is not where it needs to be. A culture of clinical trials and inquiry into the disease is lacking, and much of the existing evidence base addresses the concerns of the researchers but not necessarily those of the patients. PROGRAM OVERVIEW: The Canadian Institutes of Health Research (CIHR) has launched the national Strategy for Patient-Oriented Research (SPOR), a coalition of federal, provincial, and territorial partners dedicated to integrating research into care. Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD) is one of five pan-Canadian chronic kidney disease networks supported through the SPOR. The vision of Can-SOLVE CKD is that by 2020 every Canadian with or at high risk for CKD will receive the best recommended care, experience optimal outcomes, and have the opportunity to participate in studies with novel therapies, regardless of age, sex, gender, location, or ethnicity. PROGRAM OBJECTIVE: The overarching objective of Can-SOLVE CKD is to accelerate the translation of knowledge about CKD into clinical research and practice. By focusing on the patient's voice and implementing relevant findings in real time, Can-SOLVE CKD will transform the care that CKD patients receive, and will improve kidney health for future generations.

IntroductionHyperkalemia is a common, potentially life-threatening condition in patients with chronic kidney disease (CKD). We studied the association between hyperkalemia and mortality, cardiovascular events, hospitalizations, and intensive care unit (ICU) admissions.MethodsWe performed a retrospective cohort study using administrative databases in Manitoba, Canada. All adults (≥18 years of age) with potassium tests between January 2007 and December 2016 were included, with follow-up until March 31, 2017. Propensity score matching was performed among patients with de novo hyperkalemia (serum potassium ≥ 5.0 mmol/l) and patients who were nonhyperkalemic. The association between hyperkalemia and normokalemia and mortality was assessed using multivariate Cox proportional hazards regression models, adjusting for patient characteristics in a 1:1 propensity score–matched sample. Secondary outcomes included cardiovascular events, hospitalizations, and ICU admissions. A sensitivity analysis was performed with hyperkalemia defined as serum potassium ≥ 5.5 mmol/l.ResultsOf 93,667 patients with de novo hyperkalemia, 36% had diabetes mellitus (DM), 28% had CKD, and 21% had heart failure (HF). In the propensity score–matched sample of 177,082 individuals, hyperkalemia was associated with an increased risk for all-cause mortality (hazard ratio [HR] 1.15 [95% confidence interval {CI} 1.13–1.18], P < 0.001), cardiovascular events (HR 1.20 [95% CI 1.14–1.26], P < 0.001), short-term mortality (odds ratio [OR] 1.29 [95% CI 1.24–1.34], P < 0.001), hospitalizations (OR 1.71 [95% CI 1.68–1.74]), and ICU admissions (OR 3.48 [95% CI 3.34–3.62], P < 0.001). Findings were unchanged when a threshold of serum potassium ≥ 5.5 mmol/l was used.ConclusionHyperkalemia was an independent risk factor for all-cause mortality, cardiovascular events, hospitalizations, and ICU admissions. This finding expands our understanding of important clinical outcomes associated with hyperkalemia.