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Key Points: Question: Do normotensive living kidney donors, compared with nondonors, have a higher risk of hypertension in the first 7 years following donation? Findings: In this 17-center prospective cohort study that included 924 living kidney donors and 396 nondonors, there were no significant between-group differences in the risk of hypertension and no significant between-group differences in mean blood pressure or the change in blood pressure during a median follow-up of 7.3 years. Meaning: After accounting for differences in baseline risk, living donors had a similar risk of hypertension as nondonors in the 7 years following donation and no significant difference in mean blood pressure. Importance: Recent guidelines call for better evidence on health outcomes after living kidney donation. Objective: To determine the risk of hypertension in normotensive adults who donated a kidney compared with nondonors of similar baseline health. Their rates of estimated glomerular filtration rate (eGFR) decline and risk of albuminuria were also compared. Design, Setting, and Participants: Prospective cohort study of 924 standard-criteria living kidney donors enrolled before surgery and a concurrent sample of 396 nondonors. Recruitment occurred from 2004 to 2014 from 17 transplant centers (12 in Canada and 5 in Australia); follow-up occurred until November 2021. Donors and nondonors had the same annual schedule of follow-up assessments. Inverse probability of treatment weighting on a propensity score was used to balance donors and nondonors on baseline characteristics. Exposure: Living kidney donation. Main Outcomes and Measures: Hypertension (systolic blood pressure [SBP] ≥140 mm Hg, diastolic blood pressure [DBP] ≥90 mm Hg, or antihypertensive medication), annualized change in eGFR (starting 12 months after donation/simulated donation date in nondonors), and albuminuria (albumin to creatinine ratio ≥3 mg/mmol [≥30 mg/g]). Results: Among the 924 donors, 66% were female; they had a mean age of 47 years and a mean eGFR of 100 mL/min/1.73 m2. Donors were more likely than nondonors to have a family history of kidney failure (464/922 [50%] vs 89/394 [23%], respectively). After statistical weighting, the sample of nondonors increased to 928 and baseline characteristics were similar between the 2 groups. During a median follow-up of 7.3 years (IQR, 6.0-9.0), in weighted analysis, hypertension occurred in 161 of 924 donors (17%) and 158 of 928 nondonors (17%) (weighted hazard ratio, 1.11 [95% CI, 0.75-1.66]). The longitudinal change in mean blood pressure was similar in donors and nondonors. After the initial drop in donors' eGFR after nephrectomy (mean, 32 mL/min/1.73 m2), donors had a 1.4-mL/min/1.73 m2 (95% CI, 1.2-1.5) per year lesser decline in eGFR than nondonors. However, more donors than nondonors had an eGFR between 30 and 60 mL/min/1.73 m2 at least once in follow-up (438/924 [47%] vs 49/928 [5%]). Albuminuria occurred in 132 of 905 donors (15%) and 95 of 904 nondonors (11%) (weighted hazard ratio, 1.46 [95% CI, 0.97-2.21]); the weighted between-group difference in the albumin to creatinine ratio was 1.02 (95% CI, 0.88-1.19). Conclusions and Relevance: In this cohort study of living kidney donors and nondonors with the same follow-up schedule, the risks of hypertension and albuminuria were not significantly different. After the initial drop in eGFR from nephrectomy, donors had a slower mean rate of eGFR decline than nondonors but were more likely to have an eGFR between 30 and 60 mL/min/1.73 m2 at least once in follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT00936078 This cohort study aims to determine the risk of hypertension in normotensive adults who donated a kidney compared with nondonors of similar baseline health. [ABSTRACT FROM AUTHOR]

Background: Non-valvular atrial fibrillation (AF) is a common heart arrhythmia in the elderly population. AF patients are at high-risk of ischemic strokes, but oral anticoagulant (OAC) therapy reduces such risks. Warfarin had been the standard OAC for AF patients, however its effectiveness is highly variable and dependent on close monitoring of the anticoagulant response. Newer OACs such as rivaroxaban and apixaban address these drawbacks but are more costly. It is uncertain which OAC therapy for AF is cost-saving from the healthcare system perspective. Methods: We followed a cohort of patients in Ontario, Canada, aged ≥ 66 who were newly diagnosed with AF and prescribed OACs between 2012 and 2017. We used a two-stage estimation procedure. First, we account for the patient selection into OACs using a multinomial logit regression model and estimated propensity scores. Second, we used an inverse probability weighted regression adjustment approach to determine cost-saving OAC options. We also examined component-specific costs (i.e., drug, hospitalization, emergency department and physician) to understand the drivers of cost-saving OACs. Results: We found that compared to warfarin, rivaroxaban and apixaban treatments were cost-saving options, with per-patient 1-year healthcare cost savings at $2436 and $1764, respectively. These savings were driven by cost-savings in hospitalization, emergency department visits, and physician visits, outweighing higher drug costs. These results were robust to alternative model specifications and estimation procedures. Conclusions: Treating AF patients with rivaroxaban and apixaban than warfarin reduces healthcare costs. OAC reimbursement policies for AF patients should consider rivaroxaban or apixaban over warfarin as the first-line treatment. [ABSTRACT FROM AUTHOR]

Background: The shortage of available organs for life-saving transplants persists worldwide. While a majority support donating their organs or tissue when they die, many have not registered their wish to do so. When registered, next of kin are much more likely to follow-through with the decision to donate. In many countries, most people visit their family physician office each year and this setting is a promising, yet underused, site where more people could register for deceased organ donation. Our primary aim was to evaluate the effectiveness of an intervention to promote organ donation registration in family physician's offices.Methods: We developed an intervention to address barriers and enablers to organ donation registration that involved physician office reception staff inviting patients to register on a tablet in the waiting room while they waited for their appointment. We conducted a cross-sectional stepped-wedge cluster randomized controlled registry trial to evaluate the intervention. We recruited six family physician offices in Canada. All offices began with usual care and then every two weeks, one office (randomly assigned) started the intervention until all offices delivered the intervention. The primary outcome was registration for deceased organ donation in the provincial organ registration registry, assessed within the 7 days of the physician visit. At the end of the trial, we also conducted interviews with clinic staff to assess any barriers and enablers to delivering the intervention.Results: The trial involved 24,616 patient visits by 13,562 unique patients: 12,484 visits in the intervention period and 12,132 in the control period. There was no statistically significant difference in the percentage of patients registered for deceased organ donation in the intervention versus control period (48.0% vs 46.2%; absolute difference after accounting for the secular trend: 0.12%; 95% CI: - 2.30, 2.54; p=0.92). Interviews with clinic staff indicated location of the tablet within a waiting room, patient rapport, existing registration, confidence and motivation to deliver the intervention and competing priorities as barriers and enablers to delivery.Conclusions: Our intervention did not increase donor registration. Nonetheless, family physician offices may still remain a promising setting to develop and evaluate better interventions to increase organ donation registration.Trial Registration: NCT03213171. [ABSTRACT FROM AUTHOR]

Background concurrent declines in gait speed and cognition have been associated with future dementia. However, the clinical profile of 'dual decliners', those with concomitant decline in both gait speed and cognition, has not been yet described. We aimed to describe the phenotype and the risk for incident dementia of those who present with dual decline in comparison with non-dual decliners. Methods prospective cohort of community-dwelling older adults free of dementia at baseline. We evaluated participants' gait speed, cognition, medical status, functionality, incidence of adverse events and dementia, biannually over 7 years. Gait speed was assessed with a 6-m electronic walkway and global cognition using the MoCA test. We compared characteristics between dual decliners and non-dual decliners using t -test, chi-square and hierarchical regression models. We estimated incident dementia using Cox models. Results among 144 participants (mean age 74.23 ± 6.72 years, 54% women), 17% progressed to dementia. Dual decliners had a 3-fold risk (HR: 3.12, 95%CI: 1.23–7.93, P  = 0.017) of progression to dementia compared with non-dual decliners. Dual decliners were significantly older with a higher prevalence of hypertension and dyslipidemia (P  = 0.002). Hierarchical regression models show that age and sex alone explained 3% of the variation in the dual decliners group. Adding hypertension and dyslipidemia increased the explained variation by 8 and 10%, respectively. The risk of becoming a dual decliner was 4-fold higher if hypertension was present. Conclusion older adults with a concurrent decline in gait speed and cognition represent a group at the highest risk of progression to dementia. Older adults with dual decline have a distinct phenotype with a higher prevalence of hypertension, a treatable condition. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing treatment for cancer are at increased risk of acute kidney injury (AKI). There are few data on AKI incidence and risk factors in the current era of cancer treatment.Methods: We conducted a population-based study of all patients initiating systemic therapy (chemotherapy or targeted agents) for a new cancer diagnosis in Ontario, Canada (2007-2014). The primary outcome was hospitalization with AKI or acute dialysis. We estimated the cumulative incidence of AKI and fitted Fine and Gray models, adjusting for demographics, cancer characteristics, comorbidities, and coprescriptions. We modeled exposure to systemic therapy (the 90-day period following treatments) as a time-varying covariate. We also assessed temporal trends in annual AKI incidence.Results: We identified 163 071 patients initiating systemic therapy of whom 10 880 experienced AKI. The rate of AKI was 27 per 1000 person-years, with overall cumulative incidence of 9.3% (95% CI = 9.1% to 9.6%). Malignancies with the highest 5-year AKI incidence were myeloma (26.0%, 95% CI = 24.4% to 27.7%), bladder (19.0%, 95% CI = 17.6% to 20.5%), and leukemia (15.4%, 95% CI = 14.3% to 16.5%). Advanced cancer stage, chronic kidney disease, and diabetes were associated with increased risk of AKI (adjusted hazard ratios [aHR] = 1.41, 95% CI = 1.28 to 1.54; 1.80, 95% CI = 1.67 to 1.93; and 1.43, 95% CI = 1.37 to 1.50, respectively). In patients aged 66 years or older with universal drug benefits, diuretic, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker coprescription was associated with higher AKI risk (aHR = 1.20, 95% CI = 1.14 to 1.28; 1.30, 95% CI = 1.23 to 1.38). AKI risk was further accentuated during the 90-day period following systemic therapy (aHR = 2.34, 95% CI = 2.24 to 2.45). The annual incidence of AKI increased from 18 to 52 per 1000 person-years between 2007 and 2014.Conclusion: Cancer-related AKI is common and associated with advanced stage, chronic kidney disease, diabetes, and concomitant receipt of diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Risk is heightened in the 90 days after systemic therapy. Preventive strategies are needed to address the increasing burden of AKI in this population. [ABSTRACT FROM AUTHOR]

Background: In prior studies, higher mortality was observed among patients who had elective surgery on a Friday rather than earlier in the week. We investigated whether mortality after elective surgery was associated with day of the week of surgery in a Canadian population and whether the association was influenced by surgeon experience and volume.Methods: We conducted a population-based retrospective cohort study in the province of Ontario, Canada. We included adults who underwent 1 of 12 elective daytime surgical procedures from Apr. 1, 2002, to Dec. 31, 2012. The primary outcome was 30-day mortality. We used generalized estimating equations to compare outcomes for surgeries performed on different days of the week, adjusting for patient and surgeon factors.Results: A total of 402 899 procedures performed by 1691 surgeons met our inclusion criteria. The median length of hospital stay was 6 (interquartile range 5-8) days. Surgeon experience varied significantly by day of week (p < 0.001), with surgeons operating on Fridays having the least experience. Nearly all of the patients who had their procedure on a Friday had postoperative care on the weekend, as compared with 49.1% of those whose surgery was on a Monday (p < 0.001). We found no difference in the 30-day mortality between procedures performed on Fridays and those performed on Mondays (adjusted odds ratio 1.08, 95% confidence interval 0.97-1.21).Interpretation: Although surgeon experience differed across days of the week, the risk of 30-day mortality after elective surgery was similar regardless of which day of the week the procedure took place. [ABSTRACT FROM AUTHOR]

Background: Canada has low rates of deceased organ and tissue donation. Immigrants to Canada may differ in their registered support for deceased organ donation based on their country of origin. Methods: We used linked administrative databases in Ontario (about 11 million residents aged ≥ 16 yr) to study the proportion of immigrants and long-term residents registered for deceased organ and tissue donation as of October 2013. We used modified Poisson regression to identify and quantify predictors of donor registration. Results: Compared with long-term residents (n = 9 244 570), immigrants (n = 1 947 646) were much less likely to register for deceased organ and tissue donation (11.9% v. 26.5%). Immigrants from the United States, Australia and New Zealand had the highest registration rate (40.0%), whereas immigrants with the lowest registration rates were from Eastern Europe and Central Asia (9.4%), East Asia and Pacific (8.4%) and sub-Saharan Africa (7.9%). The largest numbers of unregistered immigrants were from India (n = 202 548), China (n = 186 678) and the Philippines (n = 125 686). Characteristics among the immigrant population associated with a higher likelihood of registration included economic immigrant status, living in a rural area (population < 10 000), living in an area with a lower ethnic concentration, less material deprivation, a higher education, ability to speak English and French, and more years residing in Canada. Interpretation: Immigrants in Ontario were less likely to register for deceased organ and tissue donation than long-term residents. There is a need to better understand reasons for lower registration rates among Canadian immigrants and to create culture-sensitive materials to build support for deceased organ and tissue donation. [ABSTRACT FROM AUTHOR]

Objective: For various reasons, people of Chinese (China, Hong Kong or Taiwan) and South Asian (Indian subcontinent) ancestry (the two largest ethnic minority groups in Ontario, Canada) may be less likely to register for deceased organ donation than the general public, and their families may be less likely to consent for deceased organ donation at the time of death. Methods: We conducted two population-based studies: (1) a cross-sectional study of deceased organ donor registration as of May 2013, and (2) a cohort study of the steps in proceeding with deceased organ donation for patients who died in hospital from October 2008 to December 2012. Results: A total of 49 938 of 559 714 Chinese individuals (8.9%) and 47 774 of 374 291 South Asians (12.8%) were registered for deceased organ donation, proportions lower than the general public (2 676 260 of 10 548 249 (25.4%). Among the 168 703 Ontarians who died in a hospital, the families of 33 of 81 Chinese (40.1%; 95% CI: 30.7%-51.6%) and 39 of 72 South Asian individuals (54.2%; 95% CI: 42.7-65.2%) consented for deceased organ donation, proportions lower than the general public (68.3%; 95% CI: 66.4%-70.0%). Conclusions: In Ontario, Canada Chinese and South Asian individuals are less likely to register and their families are less likely to consent to deceased organ donation compared to the remaining general public. There is an opportunity to build support for organ and tissue donation in these two large ethnic communities in Canada. [ABSTRACT FROM AUTHOR]

Background. Beta-blockers may be cardioprotective in patients receiving chronic dialysis. We examined cardiovascular outcomes among incident dialysis patients receiving beta-blocker therapy.Methods. We conducted a retrospective cohort study employing linked healthcare databases in Ontario, Canada. We studied all consecutive chronic dialysis patients aged ≥66 years who initiated dialysis between 1 July 1991 and 31 July 2007. Patients were divided into three groups according to new medication use after the initiation of chronic dialysis. The three groups were patients initiated on beta-blockers, calcium channel blockers and statins only. Patients in the beta-blocker and calcium channel blocker groups could also be concurrently receiving a statin. The primary outcome was time to a composite endpoint of death, myocardial infarction, stroke or coronary revascularization.Results. There were a total of 1836 patients (504 beta-blocker, 570 calcium channel blocker and 762 statin-only users). Compared to statin-only use, beta-blocker use was not associated with improved cardiovascular outcomes [adjusted hazard ratio (aHR) 1.07, 95% confidence interval (CI) 0.92–1.23]. As expected, calcium channel blocker use was also not associated with improved cardiovascular outcomes (aHR 0.91, 95% CI 0.79–1.06). Among all subgroup analyses by beta-blocker attributes, only high-dose beta-blocker therapy was associated with better cardiovascular outcomes as compared to low-dose beta-blockers (aHR 0.50, 95% CI 0.29–0.88).Conclusions. We observed no beneficial effect of beta-blocker use among patients receiving chronic dialysis relative to our comparator groups. Given current uncertainty around the cardioprotective benefits of beta-blockers in patients receiving dialysis, a large randomized clinical trial is warranted. [ABSTRACT FROM PUBLISHER]

Background: Physicians face challenges when searching PubMed for research evidence, and they may miss relevant articles while retrieving too many nonrelevant articles. We investigated whether the use of search filters in PubMed improves searching by physicians. Methods: We asked a random sample of Canadian nephrologists to answer unique clinical questions derived from 100 systematic reviews of renal therapy. Physicians provided the search terms that they would type into PubMed to locate articles to answer these questions. We entered the physician-provided search terms into PubMed and applied two types of search filters alone or in combination: a methods-based filter designed to identify high-quality studies about treatment (clinical queries "therapy") and a topic-based filter designed to identify studies with renal content. We evaluated the comprehensiveness (proportion of relevant articles found) and efficiency (ratio of relevant to nonrelevant articles) of the filtered and non-filtered searches. Primary studies included in the systematic reviews served as the reference standard for relevant articles. Results: The average physician-provided search terms retrieved 46% of the relevant articles, while 6% of the retrieved articles were nonrelevant (the ratio of relevant to nonrelevant articles was 1:16). The use of both filters together produced a marked improvement in efficiency, resulting in a ratio of relevant to nonrelevant articles of 1:5 (16 percentage point improvement; 99% confidence interval 9% to 22%; p < 0.003) with no substantive change in comprehensiveness (44% of relevant articles found; p = 0.55). Interpretation: The use of PubMed search filters improves the efficiency of physician searches. Improved search performance may enhance the transfer of research into practice and improve patient care. [ABSTRACT FROM AUTHOR]

The article examines population-level data from two provinces in Canada that have experienced the largest increases in rates of deceased organ donation to explore the correlation between annual rates of overdose mortality and deceased organ donation.

The article offers information on the Major Outcomes with Personalized Dialysate Temperature (MyTEMP) clinical trial which aims to determine whether patients cared for in hemodialysis centres and randomly assigned to personalized reduced-temperature hemodialysis have better outcomes than patients cared for in hemodialysis centres using a standard dialysate temperature. It mentions that several patients receiving hemodialysis have poor quality of life and life expectancy.

Presents an opinion on the economic disincentives facing living organ donors in Canada. Frequency and magnitude of living organ donation costs; Overview of the need for a national unified reimbursement policy for living organ donors; Factors that may influence the creation and implementation of a donor reimbursement policy.

There is a spectrum of acute illness for individuals who ingest toxigenic Escherichia coli , ranging from no symptoms to self-limited gastroenteritis, to full acute hemolytic uremic syndrome. Knowledge of the long-term prognosis of acute toxigenic E. coli ingestion, based on the presentation of acute illness, is important for patient counseling and follow-up. Here, we consider subsequent 5-year renal outcomes for groups of individuals who presented across a spectrum of acute illness during a municipal water outbreak of E. coli O157:H7 in Walkerton, Canada. [ABSTRACT FROM AUTHOR]

Background: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively., Objective: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery., Design: Partial factorial randomized trial of 2 perioperative blood pressure management strategies (reported here) and tranexamic acid versus placebo. (ClinicalTrials.gov: NCT03505723)., Setting: 110 hospitals in 22 countries., Patients: 7490 patients having noncardiac surgery who were at risk for vascular complications and were receiving 1 or more long-term antihypertensive medications., Intervention: In the hypotension-avoidance strategy group, the intraoperative mean arterial pressure target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld and the other long-term antihypertensive medications were administered only for systolic blood pressures 130 mm Hg or greater, following an algorithm. In the hypertension-avoidance strategy group, the intraoperative mean arterial pressure target was 60 mm Hg or greater; all antihypertensive medications were continued before and after surgery., Measurements: The primary outcome was a composite of vascular death and nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest at 30 days. Outcome adjudicators were masked to treatment assignment., Results: The primary outcome occurred in 520 of 3742 patients (13.9%) in the hypotension-avoidance group and in 524 of 3748 patients (14.0%) in the hypertension-avoidance group (hazard ratio, 0.99 [95% CI, 0.88 to 1.12]; P  = 0.92). Results were consistent for patients who used 1 or more than 1 antihypertensive medication in the long term., Limitation: Adherence to the assigned strategies was suboptimal; however, results were consistent across different adherence levels., Conclusion: In patients having noncardiac surgery, our hypotension-avoidance and hypertension-avoidance strategies resulted in a similar incidence of major vascular complications., Primary Funding Source: Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and Research Grant Council of Hong Kong., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-3157.

Background: Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding., Methods: We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025., Results: A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, -2.6 percentage points; 95% CI, -3.8 to -1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, -1.1 to 1.7; one-sided P = 0.04 for noninferiority)., Conclusions: Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. (Funded by the Canadian Institutes of Health Research and others; POISE-3 ClinicalTrials.gov number, NCT03505723.)., (Copyright © 2022 Massachusetts Medical Society.)

Background and Objectives: Home dialysis therapies (peritoneal and home hemodialysis) are less expensive and provide similar outcomes to in-center hemodialysis, but they are underutilized in most health systems. Given this, we designed a multifaceted intervention to increase the use of home dialysis. In this study, our objective was to evaluate the effect of this intervention on home dialysis use in CKD clinics across Canada., Design, Setting, Participants, & Measurements: We conducted a cluster randomized controlled trial in 55 CKD clinic clusters in nine provinces in Canada between October 2014 and November 2015. Participants included all adult patients who initiated dialysis in the year following the intervention. We evaluated the implementation of a four-component intervention, which included phone surveys from a knowledge translation broker, a 1-year center-specific audit/feedback on home dialysis use, delivery of an educational package (including tools aimed at both providers and patients), and an academic detailing visit. The primary outcome was the proportion of patients using home dialysis at 180 days after dialysis initiation., Results: A total of 55 clinics were randomized (27 in the intervention and 28 in the control), with 5312 patients initiating dialysis in the 1-year follow-up period. In the primary analysis, there was no difference in the use of home dialysis at 180 days in the intervention and control clusters (absolute risk difference, 4%; 95% confidence interval, -2% to 10%). Using a difference-in-difference comparison, the use of home dialysis at 180 days was similar before and after implementation of the intervention (difference of 0% in intervention clinics; 95% confidence interval, -2% to 3%; difference of 0.8% in control clinics; 95% confidence interval, -1% to 3%; P =0.84)., Conclusions: A multifaceted intervention did not increase the use of home dialysis in adults initiating dialysis., Clinical Trial Registry Name and Registration Number: A Cluster Randomized Trial to Assess the Impact of Patient and Provider Education on Use of Home Dialysis, NCT02202018., (Copyright © 2022 by the American Society of Nephrology.)

Background: Living kidney donors incur donation-related expenses, but how these expenses impact postdonation mental health is unknown., Methods: In this prospective cohort study, the association between mental health and donor-incurred expenses (both out-of-pocket costs and lost wages) was examined in 821 people who donated a kidney at one of the 12 transplant centers in Canada between 2009 and 2014. Mental health was measured by the RAND Short Form-36 Health Survey along with Beck Anxiety Inventory and Beck Depression Inventory., Results: A total of 209 donors (25%) reported expenses of >5500 Canadian dollars. Compared with donors who incurred lower expenses, those who incurred higher expenses demonstrated significantly worse mental health-related quality of life 3 months after donation, with a trend towards worse anxiety and depression, after controlling for predonation mental health-related quality of life and other risk factors for psychological distress. Between-group differences for donors with lower and higher expenses on these measures were no longer significant 12 months after donation., Conclusions: Living kidney donor transplant programs should ensure that adequate psychosocial support is available to all donors who need it, based on known and unknown risk factors. Efforts to minimize donor-incurred expenses and to better support the mental well-being of donors need to continue. Further research is needed to investigate the effect of donor reimbursement programs, which mitigate donor expenses, on postdonation mental health., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Patients undergoing cardiac surgery are placed under intense physiologic stress. Blood and urine biomarkers measured peri-operatively may help identify patients at higher risk for adverse long-term kidney outcomes.We sought to determine independent associations of various biomarkers with development or progression of chronic kidney disease (CKD) following cardiac surgery. In this sub-study of the prospective cohort -TRIBE-AKI Study, we evaluated 613 adult patients undergoing cardiac surgery in Canada in our primary analysis and tested the association of 40 blood and urinary biomarkers with the primary composite outcome of CKD incidence or progression. In those with baseline estimated glomerular filtration rate (eGFR) over 60 mL/min/1.73m 2 , we defined CKD incidence as a 25% reduction in eGFR and an eGFR under 60. In those with baseline eGFR under 60 mL/min/1.73m 2 , we defined CKD progression as a 50% reduction in eGFR or eGFR under 15. Results were evaluated in a replication cohort of 310 patients from one study site in the United States. Over a median follow-up of 5.6 years, 172 patients developed the primary outcome. Each log increase in basic fibroblast growth factor (adjusted hazard ratio 1.52 [95% confidence interval 1.19, 1.93]), Kidney Injury Molecule-1 (1.51 [0.98, 2.32]), N-terminal pro-B-type natriuretic peptide (1.19 [1.01, 1.41]), and tumor necrosis factor receptor 1 (1.75 [1.18, 2.59]) were associated with outcome after adjustment for demographic factors, serum creatinine, and albuminuria. Similar results were noted in the replication cohort. Although there was no interaction by acute kidney injury in continuous analysis, mortality was higher in the no acute kidney injury group by biomarker tertile. Thus, elevated post-operative levels of blood biomarkers following cardiac surgery were independently associated with the development of CKD. These biomarkers can provide additional value in evaluating CKD incidence and progression after cardiac surgery., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Older adults with chronic kidney disease (CKD) are at heightened risk for polypharmacy. We examined potentially inappropriate prescribing in this population and whether introducing pharmacists into the ambulatory kidney care model was associated with improved prescribing practices., Methods: Retrospective cohort study using linked administrative databases. We included patients with an eGFR ≤30 mL/min/1.73 m2 ≥66 years of age followed in multidisciplinary kidney clinics in Ontario, Canada (n = 25,016 from 28 centres). The primary outcome was the absence of a statin prescription or the receipt of a potentially inappropriate prescription defined by the American Geriatric Society Beers Criteria® and a modified Delphi panel that identified key drugs of concern in CKD. We calculated the crude cumulative incidence and incidence rate for the primary outcome and used change-point regression to determine if a change occurred following pharmacist introduction., Results: There were 6,007 (24%) and 16,497 patients (66%) not prescribed a statin and with ≥1 potentially inappropriate prescription, respectively. The rate of potentially inappropriate prescribing was 125.6 per 100 person-years and was higher in more recent years. The change-point regression analysis included 2,275 patients from two centres. No immediate change was detected at pharmacist introduction, but potentially inappropriate prescribing was increasing pre-pharmacist introduction, and this rising trend was reversed post-pharmacist introduction. The incidence of potentially inappropriate prescribing still remained high post-pharmacist introduction., Conclusions: Potentially inappropriate prescribing practices were common. Incorporating pharmacists into the kidney care model may improve prescribing practices. The role of pharmacists in the ambulatory kidney care team warrants further investigation in a randomized controlled trial., Competing Interests: Manish M. Sood has received grant funding from Otsuka and speaker fees from Astrazeneca unrelated to this study. All other authors have no conflicts to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The incidence of infective endocarditis related to injection drug use is increasing. On the basis of clinical practice and epidemiological and in-vitro data, we postulated that exposure to controlled-release hydromorphone is associated with an increased risk of infective endocarditis among people who inject drugs., Methods: We used linked health administrative databases in Ontario, Canada, to assemble a retrospective cohort of adults (aged 18-55 years) who inject drugs for the period of April 1, 2006, to Sept 30, 2015. Cases of infective endocarditis among this cohort were identified using International Classification of Diseases 10 codes. We estimated exposure to hydromorphone and risk of infective endocarditis among this cohort in two ways. First, in a population-level analysis, we identified patients living in regions with high (≥25%) and low (≤15%) hydromorphone prescription rates and, after matching 1:1 on various baseline characteristics, compared their frequency of infective endocarditis. Second, in a patient-level analysis including only those with prescription drug data, we identified those who had filled prescriptions (ie, received the drug from the pharmacy) for controlled-release or immediate-release hydromorphone and, after matching 1:1 on various baseline characteristics, compared their frequency of infective endocarditis with that of patients who had filled prescriptions for other opioids., Results: Between April 1, 2006, and Sept 30, 2015, 60 529 patients had evidence of injection drug use, 733 (1·2%, 95% CI 1·1-1·3) of whom had infective endocarditis. In the population-level analysis of 32 576 matched patients, we identified 254 (1·6%) admissions with infective endocarditis in regions with high hydromorphone use and 113 (0·7%) admissions in regions with low use (adjusted odds ratio [OR] 2·2, 95% CI 1·8-2·8, p<0·0001). In the patient-level analysis of 3884 matched patients, the frequency of infective endocarditis was higher among patients who filled prescriptions for hydromorphone than among those who filled prescriptions for non-hydromorphone opioids (2·8% [109 patients] vs 1·1% [41 patients]; adjusted OR 2·5, 95% CI 1·8-3·7, p<0·0001). This significant association was seen for controlled-release hydromorphone (3·9% [73 of 1895 patients] vs 1·1% [20 of 1895]; adjusted OR 3·3, 95% CI 2·1-5·6, p<0·0001), but not for immediate-release hydromorphone (1·8% [36 of 1989] vs 1·1% [21 of 1989]; 1·7, 0·9-3·6, p=0·072., Interpretation: Among people who inject drugs, the risk of infective endocarditis is significantly higher for those exposed to controlled-release hydromorphone than to other opioids. This association might be mediated by the controlled-release mechanism and should be the subject of further investigation., Funding: Ontario Ministry of Health and Long-Term Care, Academic Medical Organization of Southwestern Ontario, Schulich School of Medicine and Dentistry (Western University), and Lawson Health Research Institute., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Alpha-blockers (ABs) are commonly prescribed as part of a multidrug regimen in the management of hypertension. We set out to assess the risk of hypotension and related adverse events with AB use compared with other blood pressure (BP) lowering drugs using a population-based, retrospective cohort study of women (≥66 years) between 1995 and 2015 in Ontario, Canada. Cox proportional hazards examined the association of AB use and hypotension and related events (syncope, fall, and fracture) compared with other BP lowering drugs matched via a high dimensional propensity score. The primary outcome was a composite of hospitalizations for hypotension and related events (syncope, fractures, and falls) within 1 year. From 734 907 eligible women, 14 106 were dispensed an AB (mean age, 75.7; standard deviation 6.9 years, median follow-up 1 year) and matched to 14 106 dispensed other BP lowering agents. The crude incidence rate of hypotension and related events was 95.7 (95% CI [confidence interval], 90.4-101.1, events 1214 [8.6%]) with AB and 79.8 (95% CI, 74.9-84.7 per 1000 person-years, events 1025 [7.3%]) with other BP lowering medications (incident rate ratio, 1.20; 95% CI, 1.10-1.30). The risk was higher for hypotension (hazard ratio, 1.71; 95% CI, 1.33-2.20) and syncope (hazard ratio, 1.44; 95% CI, 1.18-1.75) with no difference in falls, fractures, adverse cardiac events, or all-cause mortality. Treatment of hypertension in women with ABs is associated with a higher risk of hypotension and hypotension-related events compared with other BP lowering agents. Our findings suggest that ABs should be used with caution, even as add on therapy for hypertension.

Background: Patients undergoing treatment for cancer are at increased risk of acute kidney injury (AKI). There are few data on AKI incidence and risk factors in the current era of cancer treatment., Methods: We conducted a population-based study of all patients initiating systemic therapy (chemotherapy or targeted agents) for a new cancer diagnosis in Ontario, Canada (2007-2014). The primary outcome was hospitalization with AKI or acute dialysis. We estimated the cumulative incidence of AKI and fitted Fine and Gray models, adjusting for demographics, cancer characteristics, comorbidities, and coprescriptions. We modeled exposure to systemic therapy (the 90-day period following treatments) as a time-varying covariate. We also assessed temporal trends in annual AKI incidence., Results: We identified 163 071 patients initiating systemic therapy of whom 10 880 experienced AKI. The rate of AKI was 27 per 1000 person-years, with overall cumulative incidence of 9.3% (95% CI = 9.1% to 9.6%). Malignancies with the highest 5-year AKI incidence were myeloma (26.0%, 95% CI = 24.4% to 27.7%), bladder (19.0%, 95% CI = 17.6% to 20.5%), and leukemia (15.4%, 95% CI = 14.3% to 16.5%). Advanced cancer stage, chronic kidney disease, and diabetes were associated with increased risk of AKI (adjusted hazard ratios [aHR] = 1.41, 95% CI = 1.28 to 1.54; 1.80, 95% CI = 1.67 to 1.93; and 1.43, 95% CI = 1.37 to 1.50, respectively). In patients aged 66 years or older with universal drug benefits, diuretic, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker coprescription was associated with higher AKI risk (aHR = 1.20, 95% CI = 1.14 to 1.28; 1.30, 95% CI = 1.23 to 1.38). AKI risk was further accentuated during the 90-day period following systemic therapy (aHR = 2.34, 95% CI = 2.24 to 2.45). The annual incidence of AKI increased from 18 to 52 per 1000 person-years between 2007 and 2014., Conclusion: Cancer-related AKI is common and associated with advanced stage, chronic kidney disease, diabetes, and concomitant receipt of diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Risk is heightened in the 90 days after systemic therapy. Preventive strategies are needed to address the increasing burden of AKI in this population., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Importance: Published in 2010, the Initiating Dialysis Early and Late (IDEAL) randomized clinical trial, which randomized patients with an estimated glomerular filtration rate (GFR) between 10 and 15 mL/min/1.73 m2 to planned initiation of dialysis with an estimated GFR between 10 and 14 mL/min/1.73 m2 (early start) or an estimated GFR between 5 and 7 mL/min/1.73 m2 (late start), concluded that early initiation was not associated with improved survival or clinical outcomes., Objective: To assess the association between the IDEAL trial results and the proportion of early dialysis starts over time., Design, Setting, and Participants: This interrupted time series analysis used data from the Canadian Organ Replacement Register to study adult (≥18 years of age) patients with incident chronic dialysis between January 1, 2006, and December 31, 2015, in Canada, which has a universal health care system. Patients from the province of Quebec were excluded because its privacy laws preclude submission of deidentified data without first-person consent. The patients included in the study (n = 28 468) had at least 90 days of nephrologist care before starting dialysis and a recorded estimated GFR at dialysis initiation. Data analyses were performed from November 2016 to January 2019., Main Outcomes and Measures: The primary outcome was the proportion of early dialysis starts (estimated GFR >10.5 mL/min/1.73 m2), and the secondary outcomes included the proportions of acute inpatient dialysis starts, patients who started dialysis using a home modality, and patients receiving hemodialysis who started with an arteriovenous access. Measures included the trend prior to the IDEAL trial publication, the change in this trend after publication, and the immediate consequence of publication., Results: The final cohort comprised 28 468 patients, of whom 17 342 (60.9%) were male and the mean (SD) age was 64.8 (14.6) years. Before the IDEAL trial, a statistically significant increasing trend was observed in the monthly proportion of early dialysis starts (adjusted rate ratio, 1.002; 95% CI, 1.001-1.004; P = .004). After the IDEAL trial, an immediate decrease was observed in the proportion of early dialysis starts (rate ratio, 0.874; 95% CI, 0.818-0.933; P < .001), along with a statistically significant change in trend between the pretrial and posttrial periods (rate ratio, 0.994; 95% CI, 0.992-0.996; P < .001). No statistically significant differences were found in acute inpatient dialysis initiations, the proportion of patients receiving home dialysis as the initial modality, or the proportion of arteriovenous access creation at hemodialysis initiation after the IDEAL trial publication., Conclusions and Relevance: The publication of the IDEAL trial appeared to be associated with an immediate and meaningful change in the timing of dialysis initiation in Canada.

Rationale & Objective: The mortality rate is high among dialysis patients, but how this compares with other diseases such as cancer is poorly understood. We compared the survival of maintenance dialysis patients with that for patients with common cancers to enhance the understanding of the burden of end-stage kidney disease., Study Design: Population-based cohort study., Setting & Participants: 33,500 incident maintenance dialysis patients in Ontario, Canada, and 532,452 incident patients with cancer (women: breast, colorectal, lung, or pancreas; men: prostate, colorectal, lung, or pancreas) from 1997 to 2015 using administrative health care databases., Exposure: Incident kidney failure treated with maintenance dialysis versus incident diagnoses of cancer., Outcome: All-cause mortality., Analytical Approach: Kaplan-Meier product limit estimator was used to describe the survival of subgroups of study participants. Extended Cox regression with a Heaviside function was used to compare survival between patients with incident kidney failure treated with maintenance dialysis and individual diagnoses of various incident cancers., Results: In men, dialysis had worse unadjusted 5-year survival (50.8%; 95% CI, 50.1%-51.6%) compared with prostate (83.3%; 95% CI, 83.1%-83.5%) and colorectal (56.1%; 95% CI, 55.7%-56.5%) cancer, but better survival than lung (14.0%; 95% CI, 13.7%-14.3%) and pancreas (9.1%; 95% CI, 8.5%-9.7%) cancer. In women, dialysis had worse unadjusted 5-year survival (49.8%; 95% CI, 48.9%-50.7%) compared with breast (82.1%; 95% CI, 81.9%-82.4%) and colorectal (56.8%; 95% CI, 56.3%-57.2%) cancer, but better survival than lung (19.7%; 95% CI, 19.4%-20.1%) and pancreas (9.4%; 95% CI, 8.9%-10.0%) cancer. After adjusting for clinical characteristics, similar results were found except when examining men and women with lung and pancreas cancer, for which dialysis patients had a higher rate of death 4 or more years after diagnosis. Women and men 70 years and older with incident kidney failure treated with maintenance dialysis had unadjusted 10-year survival probabilities that were comparable to pancreas and lung cancer., Limitations: Cancer stage could be obtained for only a subpopulation., Conclusions: Survival in incident dialysis patients was lower than in patients with several different solid-organ cancers. These results highlight the need to develop interventions to improve survival on dialysis therapy and can be used to aid advance care planning for elderly patients beginning treatment with maintenance dialysis., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Approximately 40% of the kidneys for transplant worldwide come from living donors. Despite advantages of living donor transplants, rates have stagnated in recent years. One possible barrier may be costs related to the transplant process that potential willing donors may incur for travel, parking, accommodation, and lost productivity., Methods: To better understand and quantify the financial costs incurred by living kidney donors, we conducted a prospective cohort study, recruiting 912 living kidney donors from 12 transplant centers across Canada between 2009 and 2014; 821 of them completed all or a portion of the costing survey. We report microcosted total, out-of-pocket, and lost productivity costs (in 2016 Canadian dollars) for living kidney donors from donor evaluation start to 3 months after donation. We examined costs according to ( 1 ) the donor's relationship with their recipient, including spousal (donation to a partner), emotionally related nonspousal (friend, step-parent, in law), or genetically related; and ( 2 ) donation type (directed, paired kidney, or nondirected)., Results: Living kidney donors incurred a median (75th percentile) of $1254 ($2589) in out-of-pocket costs and $0 ($1908) in lost productivity costs. On average, total costs were $2226 higher in spousal compared with emotionally related nonspousal donors ( P =0.02) and $1664 higher in directed donors compared with nondirected donors ( P <0.001). Total costs (out-of-pocket and lost productivity) exceeded $5500 for 205 (25%) donors., Conclusions: Our results can be used to inform strategies to minimize the financial burden of living donation, which may help improve the donation experience and increase the number of living donor kidney transplants., (Copyright © 2018 by the American Society of Nephrology.)

Competing Interests: Competing interests: The authors declare Dialysis Clinic Inc. provided partnership and financial support for the MyTEMP trial with no commercial interest.

Background: A prolonged living kidney donor evaluation may result in worse outcomes for transplant recipients. Better knowledge of the duration of this process may help inform future donors and identify opportunities for improvement., Study Design: 1 prospective and 1 retrospective cohort study., Setting & Participants: At 16 Canadian and Australian transplantation centers (prospective cohort) and 5 Ontario transplantation centers (retrospective cohort), we assessed the duration of living kidney donor evaluation and explored donor, recipient, and transplantation factors associated with longer evaluation times. Data were obtained from 2 sources: donor medical records using chart abstraction and health care administrative databases., Predictors: Donor and recipient demographics, direct versus paired donation, center-level variables., Outcomes: Duration of living donor evaluation., Results: The median total duration of transplantation evaluation (time from when the candidate started the evaluation until donation) was 10.3 (IQR, 6.5-16.7) months. The median duration from evaluation start until approval to donate was 7.9 (IQR, 4.6-14.1) months, and from approval until donation was 0.7 (IQR, 0.3-2.4) months, respectively. The median time between the first and last consultation among donors who completed a nephrology, surgery, and psychosocial assessment in the prospective cohort was 3.0 (IQR, 1.0-6.3) months, and between computed tomography angiography and donation was 4.8 (IQR, 2.6-9.2) months. After adjustment, the total duration of transplantation evaluation was longer if the donor participated in paired donation (6.6 [95% CI, 1.6-9.7] months) and if the recipient was referred later relative to the donor's evaluation start date (0.9 [95% CI, 0.8-1.0] months [per month of delayed referral]). Results depended on whether the recipient was receiving dialysis., Limitations: Living donor candidates who did not donate were not included and proxy measures were used for some dates in the donor evaluation process., Conclusions: The duration of kidney transplant donor evaluation is variable and can be lengthy. Better understanding of the reasons for a prolonged evaluation may inform quality improvement initiatives to reduce unnecessary delays., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The healthcare costs to evaluate, perform surgery, and follow a living kidney donor for the year after donation are poorly described., Methods: We obtained information on the healthcare costs of 1099 living kidney donors between April 1, 2004, and March 31, 2014, from Ontario, Canada, using comprehensive healthcare administrative databases. We estimated the cost of 3 periods of the living donation process: the predonation evaluation period (start of evaluation until the day before donation), perioperative period (day of donation until 30-days postdonation), and 1 year of follow-up period (after perioperative period until 1 year postdonation). We analyzed data for donors and healthy matched nondonor controls using regression-based methods to estimate the incremental cost of living donation. Costs are presented from the perspective of the Canadian healthcare payer (2017 CAD $)., Results: The incremental healthcare costs (compared with controls) for the evaluation, perioperative, and follow-up periods were CAD $3596 (95% confidence interval [CI], CAD $3350-$3842), CAD $11 694 (95% CI, CAD $11 415-CAD $11 973), and $1011 (95% CI, CAD $793-CAD $1230), respectively, totalling CAD $16 290 (95% CI, CAD $15 814-CAD $16 767). The evaluation cost was higher if the intended recipient started dialysis partway through the donor evaluation (CAD $886; 95% CI, CAD $19, CAD $1752). The perioperative cost varied across transplant centers (P < 0.0001)., Conclusions: Although substantial costs of living donor care are related to the nephrectomy procedure, comprehensive assessment of costs must also include the evaluation and follow-up periods. These estimates are informative for planning future work to support and expand living donation and transplantation, and directing efforts to improve the cost efficiency of living donor care.

Background: Contemporary data on venous thromboembolism (VTE) risk in dialysis patients are limited. Our objective was to determine the risk and complications of VTE among incident maintenance dialysis patients., Methods: We performed a retrospective cohort study using administrative databases. We included adult incident dialysis patients from 2004 to 2010 (n = 13 315). Dialysis patients were age- and sex-matched to individuals of the general population using a 1:4 ratio (n = 53 260). We determined the 3-year cumulative incidence and incidence rate (IR) of VTE, pulmonary embolism (PE) and deep venous thrombosis (DVT). We examined outcomes of bleeding and all-cause mortality following a VTE event among matched dialysis patients who did and did not experience a VTE. We used Cox proportional hazards regression models, stratified on matched sets, to calculate the hazard ratios (HRs) for all outcomes of interest., Results: VTE occurred in 1114 (8.4%) dialysis patients compared with 1233 (2.3%) individuals in the general population {IR 37.1 versus 8.1 per 1000 person-years; HR 4.5 [95% confidence interval (CI) 4.1-4.9]; adjusted HR 2.9 (95% CI 2.6-3.4)}. Both components of VTE [PE and DVT; adjusted HR 4.0 (95% CI 2.9-5.6) and HR 2.8 (95% CI 2.4-3.2), respectively] occurred more frequently in dialysis patients. Compared with dialysis patients without a VTE, those with a VTE had a higher risk of bleeding [adjusted HR 2.0 (95% CI 1.3-2.9)] and all-cause mortality [adjusted HR 2.4 (95% CI 2.0-2.8)]., Conclusions: VTE is common in dialysis patients and confers a high risk of major bleeding and all-cause mortality. Thromboprophylaxis and VTE treatment studies in dialysis patients are needed.

Background: Although peritoneal dialysis (PD) costs less to the health care system compared to in-center hemodialysis (HD), it is an underused therapy. Neither modality has been consistently shown to confer a clear benefit to patient survival. A key limitation of prior research is that study patients were not restricted to those eligible for both therapies., Study Design: Retrospective cohort study., Setting & Participants: All adult patients developing end-stage renal disease from January 2004 to December 2013 at any of 7 regional dialysis centers in Ontario, Canada, who had received at least 1 outpatient dialysis treatment and had completed a multidisciplinary modality assessment., Predictor: HD or PD., Outcomes: Mortality from any cause., Results: Among all incident patients with end-stage renal disease (1,579 HD and 453 PD), PD was associated with lower risk for death among patients younger than 65 years. However, after excluding approximately one-third of all incident patients deemed to be ineligible for PD, the modalities were associated with similar survival regardless of age. This finding was also observed in analyses that were restricted to patients initiating dialysis therapy electively as outpatients. The impact of modality on survival did not vary over time., Limitations: The determination of PD eligibility was based on the judgment of the multidisciplinary team at each dialysis center., Conclusions: HD and PD are associated with similar mortality among incident dialysis patients who are eligible for both modalities. The effect of modality on survival does not appear to change over time. Future comparisons of dialysis modality should be restricted to individuals who are deemed eligible for both modalities to reflect the outcomes of patients who have the opportunity to choose between HD and PD in clinical practice., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: An association between high heat and acute kidney injury (AKI) has been reported in warm climates. However, whether this association generalizes to a northern climate, with more variable temperatures, is unknown., Study Design: Matched case-control study., Setting & Participants: Our study focused on older adults (mean age, 80 years) in the northern climate of Ontario, Canada. 52,913 case patients who had a hospital encounter with AKI in April through September 2005 to 2012 were matched with 174,222 controls for exact date, age, sex, rural residence, income, and history of chronic kidney disease., Predictor: Heat periods were defined as 3 consecutive days exceeding the 95th percentile of area-specific maximum temperature., Outcomes: Hospital encounter (inpatient admission or emergency department visit) with a diagnosis of AKI., Measurements: ORs (95% CIs) were used to assess the association between heat periods and AKI. To quantify the effect in absolute terms, we multiplied the population incidence rate of AKI in the absence of heat periods by our adjusted OR (an approximate of relative risk)., Results: Heat periods were significantly associated with higher risk for AKI (adjusted OR, 1.11; 95% CI, 1.00-1.23). Heat periods in absolute terms were associated with an additional 182 cases of AKI per 100,000 person-years during the warm season., Limitations: We did not know how long persons were outside or if they had access to air conditioning., Conclusions: In a northern climate, periods of higher environmental heat were associated with a modestly higher risk for hospital encounter with AKI among older adults., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The association of atrial fibrillation (AF), estimated glomerular filtration rate (eGFR), and adverse events remains unknown., Study Design: Population-based retrospective cohort study from Ontario, Canada., Setting & Participants: 1,422,978 adult residents with eGFRs < 90mL/min/1.73m 2 from April 1, 2006, through March 31, 2015., Factor: A diagnosis of AF at hospitalization., Outcomes: Congestive heart failure (CHF), myocardial infarction (MI), end-stage kidney disease, all-cause mortality., Results: All adverse events were more frequent in individuals with AF (93,414 propensity score matched) compared to no AF, and this difference was more pronounced within the first 6 months of the index date (CHF: 3.04% [AF] vs 0.28% [no AF], subdistribution HR [sHR] of 11.57 [95% CI, 10.26-13.05]; MI: 0.97% [AF] vs 0.21% [no AF], sHR of 4.76 [95% CI, 4.17-5.43]; end-stage kidney disease: 0.16% [AF] vs 0.03% [no AF], sHR of 5.84 [95% CI, 3.82-8.93]; and all-cause mortality: 6.11% [AF] vs 2.50% [no AF], HR of 2.62 [95% CI, 2.50-2.76]) than in the period more than 6 months after the index date (CHF: 6.87% [AF] vs 2.87% [no AF], sHR of 2.64 [95% CI, 2.55-2.74]; MI: 2.21% [AF] vs 1.81% [no AF], sHR of 1.24 [95% CI, 1.18-1.30]; end-stage kidney disease: 0.52% [AF] vs 0.32% [no AF], sHR of 1.75 [95% CI, 1.57-1.95]; and all-cause mortality: 15.55% [AF] vs 15.10% [no AF], HR of 1.07 [95% CI, 1.04-1.10]). The results accounted for the competing risk for mortality. eGFR level modified the effect of AF on CHF (P for interaction < 0.05)., Limitations: Observational study design does not permit determination of causality; only a single outpatient eGFR measure was used; medication data were not included., Conclusions: Incident AF is associated with a high risk for adverse outcomes in patients with eGFRs < 90mL/min/1.73m 2 . Because the risk is exceedingly high within the first 6 months after AF diagnosis, therapeutic interventions and monitoring may improve outcomes., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: Increased water intake may have a beneficial effect on the kidney through suppression of plasma vasopressin. We examined the effect of increased water intake on plasma copeptin (a marker of vasopressin) over 6 weeks in patients with chronic kidney disease., Design: Secondary analysis of a randomised controlled parallel-group pilot trial., Setting: Canada, 2012-2013., Participants: 28 patients with stage 3 chronic kidney disease randomised (2:1) to a hydration (n=17) or control group (n=11)., Intervention: The hydration group was coached to increase water intake by up to 1.5 L/day for 6 weeks. The control group was asked to maintain regular water intake., Measures and Outcomes: Participants provided blood and 24 h urine samples at baseline and 6 weeks. Change in plasma copeptin was compared within and between study groups., Results: Participants were 64% male with a mean age of 62 years and an estimated glomerular filtration rate of 40 mL/min/1.73 m(2). Between baseline and 6 weeks, 24 h urine volume increased by 0.7 L/day in the hydration group, rising from 2.3 to 3.0 L/day (p=0.01), while decreasing by 0.3 L/day among controls, from 2.0 to 1.7 L/day (p=0.07); between-group difference: 0.9 L/day (95% CI 0.37 to 1.46; p=0.002). In the hydration group, median copeptin decreased by 3.6 pmol/L, from 15.0 to 10.8 pmol/L (p=0.005), while remaining stable among controls at 19 pmol/L (p=0.76; p=0.19 for the between-group difference in median change); the between-group difference in mean change was 5.4 pmol/L (95% CI -1.2 to 12.0; p=0.11)., Conclusions: Adults with stage 3 chronic kidney disease can be successfully randomised to drink approximately 1 L more per day than controls. This increased water intake caused a significant decrease in plasma copeptin concentration. Our larger 12-month trial will examine whether increased water intake can slow renal decline in patients with chronic kidney disease., Trial Registration Number: NCT01753466., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

In patients with severe acute kidney injury (AKI) but no urgent indication for renal replacement therapy (RRT), the optimal time to initiate RRT remains controversial. While starting RRT preemptively may have benefits, this may expose patients to unnecessary RRT. To study this, we conducted a 12-center open-label pilot trial of critically ill adults with volume replete severe AKI. Patients were randomized to accelerated (12 h or less from eligibility) or standard RRT initiation. Outcomes were adherence to protocol-defined time windows for RRT initiation (primary), proportion of eligible patients enrolled, follow-up to 90 days, and safety in 101 fully eligible patients (57 with sepsis) with a mean age of 63 years. Median serum creatinine and urine output at enrollment were 268 micromoles/l and 356 ml per 24 h, respectively. In the accelerated arm, all patients commenced RRT and 45/48 did so within 12 h from eligibility (median 7.4 h). In the standard arm, 33 patients started RRT at a median of 31.6 h from eligibility, of which 19 did not receive RRT (6 died and 13 recovered kidney function). Clinical outcomes were available for all patients at 90 days following enrollment, with mortality 38% in the accelerated and 37% in the standard arm. Two surviving patients, both randomized to standard RRT initiation, were still RRT dependent at day 90. No safety signal was evident in either arm. Our findings can inform the design of a large-scale effectiveness randomized control trial.

Background: Children undergoing cardiac surgery may exhibit a pronounced inflammatory response to cardiopulmonary bypass (CPB). Inflammation is recognized as an important pathophysiologic process leading to acute kidney injury (AKI). The aim of this study was to evaluate the association of the inflammatory cytokines interleukin (IL)-6 and IL-10 with AKI and other adverse outcomes in children after CPB surgery., Methods: This is a sub-study of the Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI) cohort, including 106 children ranging in age from 1 month to 18 years undergoing CPB. Plasma IL-6 and IL-10 concentrations were measured preoperatively and postoperatively [day 1 (within 6 h after surgery) and day 3]., Results: Stage 2/3 AKI, defined by at least a doubling of the baseline serum creatinine concentration or dialysis, was diagnosed in 24 (23%) patients. The preoperative IL-6 concentration was significantly higher in patients with stage 2/3 AKI [median 2.6 pg/mL, interquartile range (IQR) 2.6 0.6-4.9 pg/mL] than in those without stage 2/3 AKI (median 0.6 pg/mL, IQR 0.6-2.2 pg/mL) (p = 0.03). After adjustment for clinical and demographic variables, the highest preoperative IL-6 tertile was associated with a sixfold increased risk for stage 2/3 AKI compared with the lowest tertile (adjusted odds ratio 6.41, 95 % confidence interval 1.16-35.35). IL-6 and IL-10 levels increased significantly after surgery, peaking postoperatively on day 1. First postoperative IL-6 and IL-10 measurements did not significantly differ between patients with stage 2/3 AKI and those without stage 2/3 AKI. The elevated IL-6 level on day 3 was associated with longer hospital stay (p = 0.0001)., Conclusions: Preoperative plasma IL-6 concentration is associated with the development of stage 2/3 AKI and may be prognostic of resource utilization.

The objective of this study was to determine the 30-day incidence of ischemic stroke following neck dissection compared to matched patients undergoing non-head and neck surgeries.A surgical dissection of the neck is a common procedure performed for many types of cancer. Whether such dissections increase the risk of ischemic stroke is uncertain.A retrospective cohort study using data from linked administrative and registry databases (1995-2012) in the province of Ontario, Canada was performed. Patients were matched 1-to-1 on age, sex, date of surgery, and comorbidities to patients undergoing non-head and neck surgeries. The primary outcome was ischemic stroke assessed in hospitalized patients using validated database codes.A total of 14,837 patients underwent surgical neck dissection. The 30-day incidence of ischemic stroke following the dissection was 0.7%. This incidence decreased in recent years (1.1% in 1995 to 2000; 0.8% in 2001 to 2006; 0.3% in 2007 to 2012; P for trend <0.0001). The 30-day incidence of ischemic stroke in patients undergoing neck dissection is similar to matched patients undergoing thoracic surgery (0.5%, P = 0.26) and colectomy (0.5%, P = 0.1). Factors independently associated with a higher risk of stroke in 30 days following neck dissection surgery were of age ≥75 years (odds ratio (OR) 1.63, 95% confidence interval (CI) 1.05-2.53), and a history of diabetes (OR 1.60, 95% CI 1.02-2.49), hypertension (OR 2.64, 95% CI 1.64-4.25), or prior stroke (OR 4.06, 95% CI 2.29-7.18).Less than 1% of patients undergoing surgical neck dissection will experience an ischemic stroke in the following 30 days. This incidence of stroke is similar to thoracic surgery and colectomy.

Background and Objectives: The Fracture Risk Assessment Tool (FRAX) is widely used to predict the 10-year probability of fracture; however, the clinical utility of FRAX in CKD is unknown. This study assessed the predictive ability of FRAX in individuals with reduced kidney function compared with individuals with normal kidney function., Design, Setting, Participants, & Measurements: The discrimination and calibration (defined as the agreement between observed and predicted values) of FRAX were examined using data from the Canadian Multicentre Osteoporosis Study (CaMos). This study included individuals aged ≥40 years with an eGFR value at year 10 of CaMos (defined as baseline). The cohort was stratified by kidney function at baseline (eGFR<60 ml/min per 1.73 m(2) [72.2% stage 3a, 23.8% stage 3b, and 4.0% stage 4/5] versus ≥60 ml/min per 1.73 m(2)) and followed individuals for a mean of 4.8 years for an incident major osteoporotic fracture (clinical spine, hip, forearm/wrist, or humerus)., Results: There were 320 individuals with an eGFR<60 ml/min per 1.73 m(2) and 1787 with an eGFR≥60 ml/min per 1.73 m(2). The mean age was 67±10 years and 71% were women. The 5-year observed major osteoporotic fracture risk was 5.3% (95% confidence interval [95% CI], 3.3% to 8.6%) in individuals with an eGFR<60 ml/min per 1.73 m(2), which was comparable to the FRAX-predicted fracture risk (6.4% with bone mineral density; 8.2% without bone mineral density). A statistically significant difference was not observed in the area under the curve values for FRAX in individuals with an eGFR<60 ml/min per 1.73 m(2) versus ≥60 ml/min per 1.73 m(2) (0.69 [95% CI, 0.54 to 0.83] versus 0.76 [95% CI, 0.70 to 0.82]; P=0.38)., Conclusions: This study showed that FRAX was able to predict major osteoporotic fractures in individuals with reduced kidney function; further study is needed before FRAX should be routinely used in individuals with reduced kidney function., (Copyright © 2015 by the American Society of Nephrology.)

Urinary biomarkers of AKI provide prognostic value for in-hospital outcomes, but little is known about their association with longer-term mortality after surgery. We sought to assess the association between kidney injury biomarkers and all-cause mortality in an international, multicenter, prospective long-term follow-up study from six clinical centers in the United States and Canada composed of 1199 adults who underwent cardiac surgery between 2007 and 2009 and were enrolled in the Translational Research in Biomarker Endpoints in AKI cohort. On postoperative days 1-3, we measured the following five urinary biomarkers: neutrophil gelatinase-associated lipocalin, IL-18, kidney injury molecule-1 (KIM-1), liver fatty acid binding protein, and albumin. During a median follow-up of 3.0 years (interquartile range, 2.2-3.6 years), 139 participants died (55 deaths per 1000 person-years). Among patients with clinical AKI, the highest tertiles of peak urinary neutrophil gelatinase-associated lipocalin, IL-18, KIM-1, liver fatty acid binding protein, and albumin associated independently with a 2.0- to 3.2-fold increased risk for mortality compared with the lowest tertiles. In patients without clinical AKI, the highest tertiles of peak IL-18 and KIM-1 also associated independently with long-term mortality (adjusted hazard ratios [95% confidence intervals] of 1.2 [1.0 to 1.5] and 1.8 [1.4 to 2.3] for IL-18 and KIM-1, respectively), and yielded continuous net reclassification improvements of 0.26 and 0.37, respectively, for the prediction of 3-year mortality. In conclusion, urinary biomarkers of kidney injury, particularly IL-18 and KIM-1, in the immediate postoperative period provide additional prognostic information for 3-year mortality risk in patients with and without clinical AKI., (Copyright © 2014 by the American Society of Nephrology.)

Introduction: Steroids In caRdiac Surgery trial (SIRS) is a large international randomised controlled trial of methylprednisolone or placebo in patients undergoing cardiac surgery with the use of a cardiopulmonary bypass pump. At the time of surgery, compared with placebo, methylprednisolone divided into two intravenous doses of 250 mg each may reduce the risk of postoperative acute kidney injury (AKI)., Methods and Analysis: With respect to the study schedule, over 7000 substudy eligible patients from 81 centres in 18 countries were randomised in December 2013. The authors will use a logistic regression to estimate the adjusted OR of methylprednisolone versus placebo on the primary outcome of AKI in the 14 days following surgery (a postoperative increase in serum creatinine of ≥50%, or ≥26.5 μmol/L, from the preoperative value). The stage of AKI will also be considered, as will the outcome of AKI in those with and without preoperative chronic kidney disease. After receipt of grant funding, the authors began to record additional perioperative serum creatinine measurements in consecutive patients enrolled at substudy participating centres, and patients were invited to enroll in a 6-month serum creatinine collection. In these trial subpopulations, the authors will consider the outcome of AKI defined in alternate ways, and the outcome of a 6-month change in kidney function from the preoperative value., Ethics and Dissemination: The authors were competitively awarded a grant from the Canadian Institutes of Health Research for this SIRS AKI substudy. Ethics approval was obtained for additional serum creatinine recordings in consecutive patients enrolled at participating centres. The additional kidney data collection first began for patients enrolled after 1 March 2012. In patients who provided consent, the last 6-month kidney outcome data will be collected in 2014. The results will be reported no later than 2015., Clinical Trial Registration: Number NCT00427388.

Introduction: Among critically ill patients with acute kidney injury (AKI) needing continuous renal replacement therapy (CRRT), the effect of convective (via continuous venovenous hemofiltration [CVVH]) versus diffusive (via continuous venovenous hemodialysis [CVVHD]) solute clearance on clinical outcomes is unclear. Our objective was to evaluate the feasibility of comparing these two modes in a randomized trial., Methods: This was a multicenter open-label parallel-group pilot randomized trial of CVVH versus CVVHD. Using concealed allocation, we randomized critically ill adults with AKI and hemodynamic instability to CVVH or CVVHD, with a prescribed small solute clearance of 35 mL/kg/hour in both arms. The primary outcome was trial feasibility, defined by randomization of >25% of eligible patients, delivery of >75% of the prescribed CRRT dose, and follow-up of >95% of patients to 60 days. A secondary analysis using a mixed-effects model examined the impact of therapy on illness severity, defined by sequential organ failure assessment (SOFA) score, over the first week., Results: We randomized 78 patients (mean age 61.5 years; 39% women; 23% with chronic kidney disease; 82% with sepsis). Baseline SOFA scores (mean 15.9, SD 3.2) were similar between groups. We recruited 55% of eligible patients, delivered >80% of the prescribed dose in each arm, and achieved 100% follow-up. SOFA tended to decline more over the first week in CVVH recipients (-0.8, 95% CI -2.1, +0.5) driven by a reduction in vasopressor requirements. Mortality (54% CVVH; 55% CVVHD) and dialysis dependence in survivors (24% CVVH; 19% CVVHD) at 60 days were similar., Conclusions: Our results suggest that a large trial comparing CVVH to CVVHD would be feasible. There is a trend toward improved vasopressor requirements among CVVH-treated patients over the first week of treatment., Trial Registration: ClinicalTrials.gov: NCT00675818.

Background: Acute kidney injury is a serious complication of elective major surgery. Acute dialysis is used to support life in the most severe cases. We examined whether rates and outcomes of acute dialysis after elective major surgery have changed over time., Methods: We used data from Ontario's universal health care databases to study all consecutive patients who had elective major surgery at 118 hospitals between 1995 and 2009. Our primary outcomes were acute dialysis within 14 days of surgery, death within 90 days of surgery and chronic dialysis for patients who did not recover kidney function., Results: A total of 552,672 patients underwent elective major surgery during the study period, 2231 of whom received acute dialysis. The incidence of acute dialysis increased steadily from 0.2% in 1995 (95% confidence interval [CI] 0.15-0.2) to 0.6% in 2009 (95% CI 0.6-0.7). This increase was primarily in cardiac and vascular surgeries. Among patients who received acute dialysis, 937 died within 90 days of surgery (42.0%, 95% CI 40.0-44.1), with no change in 90-day survival over time. Among the 1294 patients who received acute dialysis and survived beyond 90 days, 352 required chronic dialysis (27.2%, 95% CI 24.8-29.7), with no change over time., Interpretation: The use of acute dialysis after cardiac and vascular surgery has increased substantially since 1995. Studies focusing on interventions to better prevent and treat perioperative acute kidney injury are needed.

Background: Acute kidney injury frequently arises within an acute care hospitalization. Outcomes among acute kidney injury survivors following hospital discharge are poorly documented., Methods: We conducted a population-based cohort study between 1996 and 2006 of all adult patients in Ontario with acute kidney injury who did not require in-hospital dialysis, and who survived free of dialysis ≥30 days after discharge. Those with acute kidney injury (n=41,327) were matched 1:1 to patients without acute kidney injury during their index hospitalization. Matching was by age (±1 year), sex, history of chronic kidney disease, receipt of mechanical ventilation during the index hospitalization, and a propensity score for developing acute kidney injury. The primary outcome was subsequent need for chronic dialysis. The secondary outcomes were all-cause mortality and rehospitalization., Results: Mean age was 70 years, and median follow-up was 2 years (maximum 10 years). The incidence of chronic dialysis was 1.78 per 100 person-years among those with acute kidney injury and 0.74 per 100 person-years among unaffected controls (adjusted hazard ratio [HR]; 2.70, 95% confidence interval [CI], 2.42-3.00). Rates also were higher for all-cause mortality (15.34 vs 14.51 per-100 person-years; adjusted HR 1.10; 95% CI, 1.07-1.13) and rehospitalization (44.93 vs 37.18 per 100 person-years; adjusted HR 1.21; 95% CI, 1.18-1.24)., Conclusion: Even when acute dialysis is not required, survivors of acute kidney injury remain at higher risk of receipt of chronic dialysis thereafter. The absolute risk of death was more than 8 times the rate of chronic dialysis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background and Objectives: The effect of increased fluid intake on kidney function is unclear. This study evaluates the relationship between urine volume and renal decline over 6 years in a large community-based cohort., Design, Setting, Participants, & Measurements: This prospective cohort study was undertaken in Canada from 2002 to 2008. We obtained 24-hour urine samples from adult participants with an estimated GFR (eGFR) ≥60 ml/min per 1.73 m(2) at study entry. Percentage annual change in eGFR from baseline was categorized as average decline <1% per year, between 1% and 4.9% (mild-to-moderate decline) or ≥5% (rapid decline)., Results: 2148 participants provided valid 24-hour urine samples, grouped as <1 L/d (14.5%); 1 to 1.9 L/d (51.5%); 2 to 2.9 L/d (26.3%); and ≥3 L/d (7.7%). Baseline eGFR for each category of urine volume was 90, 88, 84, and 87 ml/min per 1.73 m(2), respectively. Overall, eGFR declined by 1% per year, with 10% demonstrating rapid decline and 40% demonstrating mild-to-moderate decline. An inverse, graded relationship was evident between urine volume and eGFR decline: For each increasing category of 24-hour urine volume, percentage annual eGFR decline was progressively slower, from 1.3%, 1.0%, 0.8%, to 0.5%, respectively; P = 0.02. Compared with those with urine volume 1 to 1.9 L/d, those with urine volume ≥3 L/d were significantly less likely to demonstrate mild-to-moderate decline (adjusted odds ratio 0.66; 95% confidence interval 0.46 to 0.94) or rapid decline (adjusted odds ratio 0.46; 95% confidence interval 0.23 to 0.92); adjusted for age, gender, baseline eGFR, medication use for hypertension (including diuretics), proteinuria, diabetes, and cardiovascular disease., Conclusions: In this community-based cohort, decline in kidney function was significantly slower in those with higher versus lower urine volume.

Background and Objectives: Potential cost and effectiveness of a nephrologist/nurse-based multifaceted intervention for stage 3 to 4 chronic kidney disease are not known. This study examines the cost-effectiveness of a chronic disease management model for chronic kidney disease., Design, Setting, Participants, & Measurements: Cost and cost-effectiveness were prospectively gathered alongside a multicenter trial. The Canadian Prevention of Renal and Cardiovascular Endpoints Trial (CanPREVENT) randomized 236 patients to receive usual care (controls) and another 238 patients to multifaceted nurse/nephrologist-supported care that targeted factors associated with development of kidney and cardiovascular disease (intervention). Cost and outcomes over 2 years were examined to determine the incremental cost-effectiveness of the intervention. Base-case analysis included disease-related costs, and sensitivity analysis included all costs., Results: Consideration of all costs produced statistically significant differences. A lower number of days in hospital explained most of the cost difference. For both base-case and sensitivity analyses with all costs included, the intervention group required fewer resources and had higher quality of life. The direction of the results was unchanged to inclusion of various types of costs, consideration of payer or societal perspective, changes to the discount rate, and levels of GFR., Conclusions: The nephrologist/nurse-based multifaceted intervention represents good value for money because it reduces costs without reducing quality of life for patients with chronic kidney disease.

Background: Little evidence justifies the avoidance of glyburide in patients with impaired renal function. We aimed to determine if renal function modifies the risk of hypoglycaemia among patients using glyburide., Methods: We conducted a nested case-control study using administrative records and laboratory data from Ontario, Canada. We included outpatients 66 years of age and older with diabetes mellitus and prescriptions for glyburide, insulin or metformin. We ascertained hypoglycaemic events using administrative records and estimated glomerular filtration rates (eGFR) using serum creatinine concentrations., Results: From a cohort of 19,620 patients, we identified 204 cases whose eGFR was ≥ 60 mL/min/1.73 m(2) (normal renal function) and 354 cases whose eGFR was < 60 mL/min/1.73 m(2) (impaired renal function). Compared to metformin, glyburide is associated with a greater risk of hypoglycaemia in patients with both normal [adjusted odds ratio (OR) 9.0, 95% confidence interval (95% CI) 4.9-16.4] and impaired renal function (adjusted OR 6.0, 95% CI 3.8-9.5). We observed a similar relationship when comparing insulin to metformin; the risk was greater in patients with normal renal function (adjusted OR 18.7, 95% CI 10.5-33.5) compared to those with impaired renal function (adjusted OR 7.9, 95% CI 5.0-12.4). Tests of interaction showed that among glyburide users, renal function did not significantly modify the risk of hypoglycaemia, but among insulin users, impaired renal function is associated with a lower risk., Conclusions: In this population-based study, impaired renal function did not augment the risk of hypoglycaemia associated with glyburide use.

Background and Objectives: It is unclear how to optimally care for chronic kidney disease (CKD). This study compares a new coordinated model to usual care for CKD., Design, Setting, Participants, & Measurements: A randomized trial in nephrology clinics and the community included 474 patients with median estimated GFR (eGFR) 42 ml/min per 1.73 m(2) identified by laboratory-based case finding compared care coordinated by a general practitioner (controls) with care by a nurse-coordinated team including a nephrologist (intervention) for a median (interquartile range [IQR]) of 742 days. 32% were diabetic, 60% had cardiovascular disease, and proteinuria was minimal. Guided by protocols, the intervention team targeted risk factors for adverse kidney and cardiovascular outcomes. Serial eGFR and clinical events were tracked., Results: The average decline in eGFR over 20 months was -1.9 ml/min per 1.73 m(2). eGFR declined by ≥4 ml/min per 1.73 m(2) within 20 months in 28 (17%) intervention patients versus 23 (13.9%) control patients. Control of BP, LDL, and diabetes were comparable across groups. In the intervention group there was a trend to greater use of renin-angiotensin blockers and more use of statins in those with initial LDL >2.5 mmol/L. Treatment was rarely required for anemia, acidosis, or disordered mineral metabolism. Clinical events occurred in 5.2% per year., Conclusions: Patients with stage 3/4 CKD identified through community laboratories largely had nonprogressive kidney disease but had cardiovascular risk. Over a median of 24 months, the nurse-coordinated team did not affect rate of GFR decline or control of most risk factors compared with usual care.

Background and Objectives: Accurate and complete documentation of patient characteristics and comorbidities in renal registers is essential to control bias in the comparison of outcomes across groups of patients or dialysis facilities. The objectives of this study were to assess the quality of data collected in the Canadian Organ Replacement Register (CORR) compared with the patient's medical charts., Design, Setting, Participants, & Measurements: This cohort study of a representative sample of adult, incident patients registered in CORR in 2005 to 2006 examined the prevalence, sensitivity, specificity, positive and negative predictive values, and κ of comorbid conditions and agreement in coding of patient demographics and primary renal disease between CORR and the patient's medical record. The effect of coding variation on patient survival was evaluated., Results: Medical records on 1125 patients were reviewed. Agreement exceeded 97% for health card number, date of birth, and sex and 71% (range 46.6 to 89.1%) for the primary renal disease. Comorbid conditions were under-reported in CORR. Sensitivities ranged from 0.89 (95% confidence interval 0.80, 0.92) for hypertension to 0.47 (0.38, 0.55) for peripheral vascular disease. Specificity was >0.93 for all comorbidities except hypertension. Hazard ratios for death were similar whether calculated using data from CORR or the medical record., Conclusions: Comorbid conditions are under-reported in CORR; however, the associated risks of mortality were similar whether using the CORR data or the medical record data, suggesting that CORR data can be used in clinical research with minimal concern for bias., (© 2011 by the American Society of Nephrology)

Background: Information in health administrative databases increasingly guides renal care and policy., Study Design: Systematic review of observational studies., Setting & Population: Studies describing the validity of codes for acute kidney injury (AKI) and chronic kidney disease (CKD) in administrative databases operating in any jurisdiction., Selection Criteria: After searching 13 medical databases, we included observational studies published from database inception though June 2009 that validated renal diagnostic and procedural codes for AKI or CKD against a reference standard., Index Tests: Renal diagnostic or procedural administrative data codes., Reference Tests: Patient chart review, laboratory values, or data from a high-quality patient registry., Results: 25 studies of 13 databases in 4 countries were included. Validation of diagnostic and procedural codes for AKI was present in 9 studies, and validation for CKD was present in 19 studies. Sensitivity varied across studies and generally was poor (AKI median, 29%; range, 15%-81%; CKD median, 41%; range, 3%-88%). Positive predictive values often were reasonable, but results also were variable (AKI median, 67%; range, 15%-96%; CKD median, 78%; range, 29%-100%). Defining AKI and CKD by only the use of dialysis generally resulted in better code validity. The study characteristic associated with sensitivity in multivariable meta-regression was whether the reference standard used laboratory values (P < 0.001); sensitivity was 39% lower when laboratory values were used (95% CI, 23%-56%)., Limitations: Missing data in primary studies limited some of the analyses that could be done., Conclusions: Administrative database analyses have utility, but must be conducted and interpreted judiciously to avoid bias arising from poor code validity., (Copyright © 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)