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Introduction: Acute kidney injury (AKI) is common in the perioperative setting and associated with poor outcomes. Whether clinical decision support improves early management and outcomes of AKI on surgical units is uncertain., Methods: In this cluster-randomized, stepped-wedge trial, 8 surgical units in Alberta, Canada were randomized to various start dates to receive an education and clinical decision support intervention for recognition and early management of AKI. Eligible patients were aged ≥18 years, receiving care on a surgical unit, not already receiving dialysis, and with AKI., Results: There were 2135 admissions of 2038 patients who met the inclusion criteria; mean (SD) age was 64.3 (16.2) years, and 885 (41.4%) were females. The proportion of patients who experienced the composite primary outcome of progression of AKI to a higher stage, receipt of dialysis, or death was 16.0% (178 events/1113 admissions) in the intervention group; and 17.5% (179 events/1022 admissions) in the control group (time-adjusted odds ratio, 0.76; 95% confidence interval [CI], 0.53-1.08; P  = 0.12). There were no significant differences between groups in process of care outcomes within 48 hours of AKI onset, including administration of i.v. fluids, or withdrawal of medications affecting kidney function. Both groups experienced similar lengths of stay in hospital after AKI and change in estimated glomerular filtration rate (eGFR) at 3 months., Conclusion: An education and clinical decision support intervention did not significantly improve processes of care or reduce progression of AKI, length of hospital stays, or recovery of kidney function in patients with AKI on surgical units., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Evidence supports the benefit of managing atrial fibrillation (AF) specific risk factors in secondary prevention of AF. However, a comprehensive summary of the effect of multifactorial risk factor interventions on outcomes of patients with AF over long-term is lacking. We searched MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL databases from inception to October 2021 for both randomized controlled trials (RCT) and observational studies comparing multifactorial risk factor interventions to usual care in patients with AF. Fifteen studies (10 RCT, 5 observational) with 3786 patients were included (mean age 63.8 years, 64.0% males). Follow-up ranged from 3 to 42 months. We found no significant effects of multifactorial risk factor interventions on AF recurrence [pooled relative risk (RR): 0.93, 95% CI: 0.74-1.16, P = 0.51, I 2  = 54%], AF-related rehospitalization at 12 months (RR: 0.69, 95% CI: 0.43-1.11, P= 0.13, I 2  = 0%), cardiovascular rehospitalization at 12 months (RR: 0.76, 95% CI: 0.53-1.09, P= 0.13, I 2  = 53%), or AF-related adverse events at 12 and 15 months. However, multifactorial interventions were associated with reduced AF-related symptoms and improved health-related quality of life (HRQoL) at all studied time points. Current evidence does not support consistent associations between multifactorial risk factor interventions and AF recurrence after rhythm control therapy or AF-related or cardiovascular hospitalization in patients with AF. However, these interventions are associated with clinically relevant improvement in AF-related symptoms and HRQoL. Additional randomized studies are required to evaluate the impact of multifactorial risk factor interventions on patient-centered health outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Patients with coronary artery disease (CAD) are at risk for developing atrial fibrillation (AF). Whether attending a cardiac rehabilitation (CR) program can attenuate this risk is unclear., Methods: This retrospective cohort study included patients who were free of pre-existing AF and referred to CR after coronary revascularization between April 2004 and March 2015 in Calgary, Canada. Patients with incident AF were identified using administrative data and the local electrocardiogram repository. Exposure variables and covariates were extracted from electronic medical records of a CR program and a clinical registry., Results: The study included 11,662 patients (mean age [standard deviation], 60.9 [10.9] years; male, 80.6%). In a median follow-up of 4.8 years, the cumulative incidence rate of AF was 1.04 per 100 person-years. There was no association between completion of CR and the risk of incident AF after adjusting for baseline characteristics (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.83-1.15). However, each higher metabolic equivalent (MET) of baseline cardiorespiratory fitness (CRF) and each MET gain in CRF following CR were independently associated with a 12% (95% CI, 6%-18%) and 18% (95% CI, 6%-28%) lower relative risk of incident AF, respectively. The risk of incident AF declined progressively, with the baseline CRF increasing up to 9.0 peak METs and with the 12-week CRF increasing up to 10.3 peak METs; beyond these peak MET levels, benefits plateaued., Conclusions: Completion of CR alone was not associated with a lower risk of incident AF. However, higher baseline CRF and greater CRF improvement had dose-dependent protective effects., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

There is substantial variability in the reported incidence and outcomes of acute kidney injury (AKI). The extent to which this is attributable to differences in source populations versus methodological differences between studies is uncertain. We used 4 population-based datasets from Canada, Denmark, and the United Kingdom to measure the annual incidence and prognosis of AKI and acute kidney disease (AKD), using a homogenous analytical approach that incorporated KDIGO creatinine-based definitions and subsets of the AKI/AKD criteria. The cohorts included 7 million adults ≥18 years of age between 2011 and 2014; median age 59-68 years, 51.9-54.4% female sex. Age- and sex-standardised incidence rates for AKI or AKD were similar between regions and years; range 134.3-162.4 events/10,000 person years. Among patients who met either KDIGO 48-hour or 7-day AKI creatinine criteria, the standardised 1-year mortality was similar (30.4%-38.5%) across the cohorts, which was comparable to standardised 1-year mortality among patients who met AKI/AKD criteria using a baseline creatinine within 8-90 days prior (32.0%-37.4%). Standardised 1-year mortality was lower (21.0%-25.5% across cohorts) among patients with AKI/AKD ascertained using a baseline creatinine >90 days prior. These findings illustrate that the incidence and prognosis of AKI and AKD based on KDIGO criteria are consistent across 3 high-income countries when capture of laboratory tests is complete, creatinine-based definitions are implemented consistently within but not beyond a 90-day period, and adjustment is made for population age and sex. These approaches should be consistently applied to improve the generalizability and comparability of AKI research and clinical reporting., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Magnetic resonance imaging (MRI) is often considered the gold-standard test for characterizing cardiac as well as noncardiac structure and function. However, many patients with cardiac implantable electronic devices (CIEDs) and/or severe renal dysfunction are unable to undergo this test because of safety concerns. In the past 10 years, newer-generation CIEDs and gadolinium-based contrast agents (GBCAs) as well as coordinated care between imaging and heart rhythm device teams have mitigated risk to patients and improved access to MRI at many hospitals. The purpose of this statement is to review published data on safety of MRI in patients with conditional and nonconditional CIEDs in addition to patient risks from older and newer GBCAs. This statement was developed through multidisciplinary collaboration of pan-Canadian experts after a relevant and independent literature search by the Canadian Agency for Drugs and Technologies in Health. All recommendations align with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Key recommendations include: (1) the development of standardized protocols for patients with a CIED undergoing MRI; (2) patients with MRI nonconditional pacemakers and pacemaker dependency should be programmed to asynchronous mode and those with MRI nonconditional transvenous defibrillators should have tachycardia therapies turned off during the scan; and (3) macrocyclic or newer linear GBCAs should be used in preference to older GBCAs because of their better safety profile in patients at higher risk of nephrogenic systemic fibrosis., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Cardiac rehabilitation (CR) is a proven therapy for reducing cardiovascular death and hospitalization. Whether CR participation is associated with improved outcomes in patients with chronic kidney disease (CKD) is unknown., Methods: We obtained data on all adult patients in Calgary, Alberta, Canada with angiographically proven coronary artery disease from 1996 to 2016 referred to CR from The Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease and TotalCardiology Rehabilitation. An estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m 2 or kidney replacement therapy defined CKD. Predictors of CR use were estimated with multinomial logistic regression. The association between starting versus not starting and completion versus noncompletion of CR and clinical outcomes were estimated using multivariable Cox proportional hazards models., Results: Of 23,215 patients referred to CR, 12,084 were eligible for inclusion. Participants with CKD (N = 1322) were older, had more comorbidity, lower exercise capacity on graded treadmill testing, and took longer to be referred and to start CR than those without CKD. CKD predicted not starting CR: odds ratio 0.73 (95% confidence interval [CI] 0.64-0.83). Over a median 1 year follow-up, there were 146 deaths, 40 (0.3%) from CKD and 106 (1.0%) not from CKD. Similar to those without CKD, the risk of death was lower in CR completers (hazard ratio [HR] 0.24 [95% CI 0.06-0.91) and starters (HR 0.56 [95% CI 0.29- 1.10]) with CKD., Conclusion: CR participation was associated with comparable benefits in people with moderate CKD as those without who survived to CR. Lower rates of CR attendance in this high-risk population suggest that strategies to increase CR utilization are needed., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Background: Infranodal conduction abnormalities, including right or left bundle branch block bifascicular block, and nonspecific intraventricular conduction block are common electrocardiogram (ECG) abnormalities with uncertain persistence and prognostic significance. We evaluated their trajectory and prognostic significance in patients undergoing coronary angiography., Methods: We linked an institutional ECG repository with the provincial coronary angiography registry and administrative databases. We included patients without severe left ventricular dysfunction who had an ECG within 180 days of angiography. Multivariable Cox models were used to assess associations between conduction abnormalities and a composite outcome, including all-cause mortality, heart failure hospitalizations, placement of a permanent pacemaker, and placement of an implantable cardiac defibrillator or cardiac resynchronization therapy defibrillator. Serial ECGs were used to model conduction disease as a time-dependent repeated measure., Results: We included 10,786 patients (mean age, 62.3 ± 12.4 years; 70.3% were male), of whom 2530 (23.4%) had baseline conduction abnormality. During a median follow-up of 3.5 years, conduction normalized in 885 patients (34.9%) and the composite outcome occurred in 1541 patients (14.3%). After multivariable adjustment, intraventricular conduction block (adjusted hazard ratio, 1.42; P = 0.001) and bifascicular block (adjusted hazard ratio, 1.59; P = 0.003) were associated with increased risk of the composite outcome. Left bundle branch block was not associated with the composite outcome., Conclusions: Regression of conduction abnormalities was frequent among patients undergoing coronary angiography, primarily for suspected acute coronary syndrome. After adjustment for important confounders including extent of coronary artery disease, infranodal conduction abnormalities were associated with a modest increase in cardiovascular risk., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac rehabilitation (CR) is a guideline-indicated modality for reducing residual cardiovascular risk among patients undergoing coronary artery bypass grafting (CABG) surgery. However, many referred patients do not initiate or complete a CR program; even more patients are never even referred., Methods: All post-CABG patients in Calgary, Alberta, Canada, from January 1, 1996, to March 31, 2016, were included. Data were obtained from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease and TotalCardiology Rehabilitation databases. Automated referral to CR at discharge after CABG was instituted on July 1, 2007. We used interrupted time series analysis to evaluate the impact of automated referral on CR referral and completion rates and studied the association of these CR process markers with mortality., Results: A total of 8,118 patients underwent CABG surgery during the study period: 5,103 before automation and 3,015 after automation. Automation increased referral rates from 39.5% to 75.0% (P < 0.001). Automated referral was associated with a 7.2% increase in CR completion in the overall population (33.3% vs 26.1%; P < 0.001). In adjusted models, CR referral alone was not associated with reduced mortality (hazard ratio [HR] 0.84, 95% CI 0.64-1.11), but CR completion was (HR 0.43, 95% CI 0.31-0.61)., Conclusion: Automated referral in post-CABG patients resulted in modest improvement in CR program completion. Therefore, even when CR referral is automated to include all eligible patients, additional strategies to support CR program enrollment and completion remain necessary to achieve the desired health benefits., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Contrast-induced acute kidney injury (CI-AKI) is a common and serious complication of invasive cardiac procedures. Quality improvement programs have been associated with a lower incidence of CI-AKI over time, but there is a lack of high-quality evidence on clinical decision support for prevention of CI-AKI and its impact on processes of care and clinical outcomes., Methods: The Contrast-Reducing Injury Sustained by Kidneys (Contrast RISK) study will implement an evidence-based multifaceted intervention designed to reduce the incidence of CI-AKI, encompassing automated identification of patients at increased risk for CI-AKI, point-of-care information on safe contrast volume targets, personalized recommendations for hemodynamic optimization of intravenous fluids, and follow-up information for patients at risk. Implementation will use cardiologist academic detailing, computerized clinical decision support, and audit and feedback. All 31 physicians practicing in all 3 of Alberta's cardiac catheterization laboratories will participate using a cluster-randomized stepped-wedge design. The order in which they are introduced to this intervention will be randomized within 8 clusters. The primary outcome is CI-AKI incidence, with secondary outcomes of CI-AKI avoidance strategies and downstream adverse major kidney and cardiovascular events. An economic evaluation will accompany the main trial., Conclusions: The Contrast RISK study leverages information technology systems to identify patient risk combined with evidence-based protocols, audit, and feedback to reduce CI-AKI in cardiac catheterization laboratories across Alberta. If effective, this intervention can be broadly scaled and sustained to improve the safety of cardiac catheterization., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There is ongoing controversy around the surrogacy of proteinuria or albuminuria, particularly for cardiovascular (CV) outcomes, which remain the leading cause of morbidity and mortality among patients with chronic kidney disease. We performed a systematic review and meta-analysis of the literature to assess the surrogacy of changing proteinuria or albuminuria for CV events, end-stage renal disease (ESRD), and all-cause mortality., Methods: CENTRAL, EMBASE, and MEDLINE were searched (from inception to October 2017). All randomized controlled trials in adults that reported change in proteinuria or albuminuria and ≥ 10 CV, ESRD, or all-cause mortality events were included. We calculated treatment effect ratios (TERs), defined as the ratio of the treatment effect on a clinical outcome and the effect on the change in the surrogate outcome. TERs close to 1 indicate greater agreement between the clinical outcome and changing proteinuria or albuminuria., Results: Thirty-six trials were included in the meta-analysis. We observed inconsistent treatment effects for proteinuria and CV events (20 trials; TER 1.11 [95% confidence interval (CI), 1.01-1.22]) with moderate heterogeneity (I 2  = 51%, P = 0.005). Treatment effects on proteinuria or albuminuria were also inconsistent with the effects on all-cause mortality (21 trials; TER 1.17 [95% CI, 1.07-1.28]; I 2  = 35%, P for heterogeneity = 0.06), although they were similar with the effects on ESRD (23 trials; TER 0.99 [95% CI, 0.88-1.13]; I 2  = 9%, P for heterogeneity = 0.337)., Conclusions: Change in proteinuria or albuminuria might be a suitable surrogate outcome for ESRD. However, overall treatment effects on these potential surrogates are inconsistent and overestimate the treatment effects on CV events and all-cause mortality., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Delivering evidence-based, personalized care that engages patients requires profound changes in the structure, process, and organization of care, along with revised incentives to support such changes. Health care providers must absorb and apply a vast, usually overwhelming, amount of scientific information to provide high-quality patient care. Accordingly, care remains inconsistent, with unintentional adverse consequences. Decision support tools can provide patient-specific assessments that support clinical decisions, improve prescribing practices, reduce medication errors, improve the delivery of primary as well as secondary prevention, and improve adherence to standards of care. Decision support tools are created using an individual patient's genetic, sociodemographic, and clinical characteristics to improve the delivery of precise, personalized care. Implementation requires ease of use for busy clinicians; uptake improves with active education, and gradual adoption of a tool integrated into care processes without disrupting clinical work flow. As health care systems continue to evolve and computerized support increases, increased implementation of decision support tools that are provided automatically as part of usual work flow, with clinically actionable recommendations at the point of care, requiring accountability for deviations from recommended therapy, represent an important opportunity to enhance quality of care by tailoring treatment to risk, improving the consistency of health care delivery, increasing patient knowledge and engagement, and avoiding specific therapeutic interventions in patients who will receive no benefit. However, successful implementation also requires strategies to engage providers in accepting and using these tools to improve care., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Patients with severely decreased glomerular filtration rate (GFR) (i.e., chronic kidney disease [CKD] G4+) are at increased risk for kidney failure, cardiovascular disease (CVD) events (including heart failure), and death. However, little is known about the variability of outcomes and optimal therapeutic strategies, including initiation of kidney replacement therapy (KRT). Kidney Disease: Improving Global Outcomes (KDIGO) organized a Controversies Conference with an international expert group in December 2016 to address this gap in knowledge. In collaboration with the CKD Prognosis Consortium (CKD-PC) a global meta-analysis of cohort studies (n = 264,515 individuals with CKD G4+) was conducted to better understand the timing of clinical outcomes in patients with CKD G4+ and risk factors for different outcomes. The results confirmed the prognostic value of traditional CVD risk factors in individuals with severely decreased GFR, although the risk estimates vary for kidney and CVD outcomes. A 2- and 4-year model of the probability and timing of kidney failure requiring KRT was also developed. The implications of these findings for patient management were discussed in the context of published evidence under 4 key themes: management of CKD G4+, diagnostic and therapeutic challenges of heart failure, shared decision-making, and optimization of clinical trials in CKD G4+ patients. Participants concluded that variable prognosis of patients with advanced CKD mandates individualized, risk-based management, factoring in competing risks and patient preferences., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

In older people with chronic kidney disease (CKD) and comorbidities, the risk of death or disability may overshadow the risk of kidney failure. To help refine this we did a retrospective population-based cohort study to evaluate the relative likelihood of adverse outcomes as functions of age and comorbidity burden among 47,228 adults with severe non-dialysis dependent CKD. We identified comorbidities using 29 validated algorithms applied to administrative data and assessed death, end-stage renal disease (ESRD), cardiovascular disease (CVD) events, and long-term care. Over five years of follow-up, 53.4% of participants died, 24.1% had a CVD event, 14.3% were placed into long-term care and 5.3% developed ESRD. Death was 145 times more likely and 11 times more likely than ESRD for participants aged 80 years or more and 60-79 years, respectively; long-term care was 30 times more likely and 1.7 times as likely as ESRD for participants aged 80 years or more and 60-79 years, respectively. Increasing comorbidity burden was similarly associated with increased risk of death and long-term care placement but reduced the likelihood of ESRD, and the risks of increasing age were similarly incremental. Thus, among patients with severe CKD, older age and/or higher comorbidity burden, death and long-term care placement are markedly more likely than ESRD. Hence, clinicians, patients and families should all consider the relative magnitude of these risks when making decisions about renal replacement., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Bleeding complications accompanying coronary revascularization are associated with increased mortality; however, few data are available on subsequent bleeding risk. We used administrative data to assess the incidence of late bleeding events in patients with acute coronary syndrome (ACS) according to treatment allocation., Methods: The cohort and bleeding events were identified through the Canadian Institute for Health Information discharge abstract database. Crude and adjusted odds ratios (ORs) were calculated for index and postindex admission bleeding up to 1 year after discharge., Results: Of 31,941 patients hospitalized with ACS, 7681 (32.4%) patients were treated with medication alone, 3728 (15.2%) underwent angiography without intervention, and 13,075 (53.4%) underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The overall incidence of readmission with bleeding based on administrative codes was low (3.8% for medically treated patients, 2.8% for patients who underwent angiography alone, 2.6% for patients who underwent CABG, and 1.8% for patients who underwent PCI; P < 0.0001). Bleeding codes were mainly gastrointestinal bleeding (52%), but 7.8% were intracranial episodes of bleeding. Patients who received PCI had significantly lower odds of late bleeding compared with medically treated patients (OR, 0.76; 95% CI, 0.62-0.94). Late bleeding during the first year after ACS was associated with mortality (OR, 4.96; 95% CI, 2.47-9.93)., Conclusions: Patients who underwent revascularization procedures had a relatively low risk for late bleeding events after a hospitalization for ACS. Late bleeding events were associated with an increased risk of death., (Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Canadian indigenous (First Nations) have rates of kidney failure that are 2- to 4-fold higher than the non-indigenous general Canadian population. As such, a strategy of targeted screening and treatment for CKD may be cost-effective in this population. Our objective was to assess the cost utility of screening and subsequent treatment for CKD in rural Canadian indigenous adults by both estimated glomerular filtration rate and the urine albumin-to-creatinine ratio. A decision analytic Markov model was constructed comparing the screening and treatment strategy to usual care. Primary outcomes were presented as incremental cost-effectiveness ratios (ICERs) presented as a cost per quality-adjusted life-year (QALY). Screening for CKD was associated with an ICER of $23,700/QALY in comparison to usual care. Restricting the model to screening in communities accessed only by air travel (CKD prevalence 34.4%), this ratio fell to $7,790/QALY. In road accessible communities (CKD prevalence 17.6%) the ICER was $52,480/QALY. The model was robust to changes in influential variables when tested in univariate sensitivity analyses. Probabilistic sensitivity analysis found 72% of simulations to be cost-effective at a $50,000/QALY threshold and 93% of simulations to be cost-effective at a $100,000/QALY threshold. Thus, targeted screening and treatment for CKD using point-of-care testing equipment in rural Canadian indigenous populations is cost-effective, particularly in remote air access-only communities with the highest risk of CKD and kidney failure. Evaluation of targeted screening initiatives with cluster randomized controlled trials and integration of screening into routine clinical visits in communities with the highest risk is recommended., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Identification of patients at risk of contrast-induced acute kidney injury (CI-AKI) is valuable for targeted prevention strategies accompanying cardiac catheterization., Methods: We searched MedLine and EMBASE for articles that developed or validated a clinical prediction model for CI-AKI or dialysis after angiography or percutaneous coronary intervention. Random effects meta-analysis was used to pool c-statistics of models. Heterogeneity was explored using stratified analyses and meta-regression., Results: We identified 75 articles describing 74 models predicting CI-AKI, 10 predicting CI-AKI and dialysis, and 1 predicting dialysis. Sixty-three developed a new risk model whereas 20 articles reported external validation of previously developed models. Thirty models included sufficient information to obtain individual patient risk estimates; 9 using only preprocedure variables whereas 21 included preprocedural and postprocedure variables. There was heterogeneity in the discrimination of CI-AKI prediction models (median [total range] in c-statistic 0.78 [0.57-0.95]; I 2  = 95.8%, Cochran Q-statistic P < 0.001). However, there was no difference in the discrimination of models using only preprocedure variables compared with models that included postprocedural variables (P = 0.868). Models predicting dialysis had good discrimination without heterogeneity (median [total range] c-statistic: 0.88 [0.87-0.89]; I 2  = 0.0%, Cochran Q-statistic P = 0.981). Seven prediction models were externally validated; however, 2 of these models showed heterogeneous discriminative performance and 2 others lacked information on calibration in external cohorts., Conclusions: Three published models were identified that produced generalizable risk estimates for predicting CI-AKI. Further research is needed to evaluate the effect of their implementation in clinical care., (Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Comparative effectiveness studies are common in patients with nonvalvular atrial fibrillation (NVAF) and chronic kidney disease (CKD), but the accuracy of current thromboembolic (n = 4) and bleeding (n = 3) prediction scores used for risk adjustment are uncertain in these patients because previous studies have included few CKD patients., Methods: This was a retrospective cohort study, using Cox models adjusted for time-varying coefficients, of nonanticoagulated adults with incident NVAF and kidney function (defined into Kidney Disease: Improving Global Outcomes [KDIGO] CKD categories) between 2002 and 2013., Results: Of 58,451 patients (mean age 66 years, 31.3% with CKD) followed for a median of 31 months, 21.3% died, 12.6% had a thromboembolic event (4.2 per 100 patient-years), and 7.8% had a major bleed (2.6 per 100 patient-years). There were graded associations between kidney function and all-cause mortality (adjusted hazard ratio [aHR], 1.88 [95% confidence interval (CI), 1.79-1.98] for very high vs low risk KDIGO category), major bleeding (aHR, 1.61 [95% CI, 1.47-1.76]), and thromboembolic events (aHR, 1.13 [95% CI, 1.04-1.23]). All 7 prediction scores had significantly poorer c statistics in patients with CKD: 0.50-0.59; all P < 0.0001 compared with those with normal kidney function (c statistics 0.69-0.70 for the 4 thromboembolic risk scores and 0.60-0.68 for the 3 bleeding risk scores). Inclusion of KDIGO category did not improve calibration or discrimination statistics for current prediction scores., Conclusions: Existing NVAF risk scores exhibit poor discrimination in patients with CKD, limiting their utility for clinical decision-making or for risk adjustment in comparative effectiveness studies. Although CKD is an independent risk factor for adverse events, adding KDIGO class to current risk scores did not improve their performance., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Using a community-based cohort we sought to investigate the association between change in estimated glomerular filtration rate (eGFR) and risk of incident cardiovascular disease including congestive heart failure (CHF), acute myocardial infarction (AMI), and stroke., Methods: We identified 479,126 adults without a history of cardiovascular disease who had at least 3 outpatient eGFR measurements over a 4 year period in Alberta, Canada. Change in eGFR was estimated as the absolute annual rate of change (categorized as ≤-5, -4, -3, -2, -1, 0, 1, 2, 3, 4, and ≥5 mL/min/1.73 m2/year). In a sensitivity analysis we also estimated change as the annual percentage change (categorized as ≤-7, -6 to -5, -4 to -3, -2 to -1, 0, 1 to 2, 3 to 4, 5 to 6, and ≥7%/year). The adjusted risk of incident CHF, AMI, and stroke associated with each category of change in eGFR was estimated, using no change in eGFR as the reference,, Results: There were 2622 (0.6%) CHF, 3463 (0.7%) AMI, and 2768 (0.6%) stroke events over a median follow-up of 2.5 years. Compared to participants with stable eGFR, those with the greatest decline (≤-5 mL/min/1.73 m2/year) had more than a two-fold increased risk of CHF (HR 2.57; 95% CI: 2.28 to 2.89). Risk for AMI and stroke was increased by 31% and 29%, respectively. After adjusting for the last eGFR at the end of the accrual period, the observed association remained significantly higher for CHF but diminished for AMI and stroke. A similar pattern was observed when change in eGFR was quantified as annual percentage change., Conclusion: In this large community-based cohort, we observed that a declining eGFR was associated with an increased risk of CHF, AMI, and stroke. However, when the risk of CVD events was adjusted for the last eGFR measurement, decline in eGFR per se was no longer associated with increased risk of AMI or stroke, and the association with CHF remained significant but was attenuated. These results demonstrate the importance of monitoring change in eGFR over time to improve cardiovascular risk prognostication., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Chronic kidney disease (CKD) is associated with poor outcomes, perhaps due to a high burden of comorbidity. Most studies of CKD populations focus on concordant comorbidities, which cause CKD (such as hypertension and diabetes) or often accompany CKD (such as heart failure or coronary disease). Less is known about the burden of mental health conditions and discordant conditions (those not concordant but still clinically relevant, like dementia or cancer). Here we did a retrospective population-based cohort study of 530,771 adults with CKD residing in Alberta, Canada between 2003 and 2011. Validated algorithms were applied to data from the provincial health ministry to assess the presence/absence of 29 chronic comorbidities. Linkage between comorbidity burden and adverse clinical outcomes (mortality, hospitalization or myocardial infarction) was examined over median follow-up of 48 months. Comorbidities were classified into three categories: concordant, mental health/chronic pain, and discordant. The median number of comorbidities was 1 (range 0-15) but a substantial proportion of participants had 3 and more, or 5 and more comorbidities (25 and 7%, respectively). Concordant comorbidities were associated with excess risk of hospitalization, but so were discordant comorbidities and mental health conditions. Thus, discordant comorbidities and mental health conditions as well as concordant comorbidities are important independent drivers of the adverse outcomes associated with CKD.

Background: Diabetes is regarded as a coronary heart disease risk equivalent-ie, people with the disorder have a risk of coronary events similar to those with previous myocardial infarction. We assessed whether chronic kidney disease should be regarded as a coronary heart disease risk equivalent., Methods: We studied a population-based cohort with measures of estimated glomerular filtration rate (eGFR) and proteinuria from Alberta, Canada. We used validated algorithms based on hospital admission and medical-claim data to classify participants with baseline history of myocardial infarction or diabetes and to ascertain which patients were admitted to hospital for myocardial infarction during follow-up (the primary outcome). For our primary analysis, we defined baseline chronic kidney disease as eGFR 15-59·9 mL/min per 1·73 m(2) (stage 3 or 4 disease). We used Poisson regression to calculate unadjusted rates and relative rates of myocardial infarction during follow-up for five risk groups: people with previous myocardial infarction (with or without diabetes or chronic kidney disease), and (of those without previous myocardial infarction), four mutually exclusive groups defined by the presence or absence of diabetes and chronic kidney disease., Findings: During a median follow-up of 48 months (IQR 25-65), 11,340 of 1,268,029 participants (1%) were admitted to hospital with myocardial infarction. The unadjusted rate of myocardial infarction was highest in people with previous myocardial infarction (18·5 per 1000 person-years, 95% CI 17·4-19·8). In people without previous myocardial infarction, the rate of myocardial infarction was lower in those with diabetes (without chronic kidney disease) than in those with chronic kidney disease (without diabetes; 5·4 per 1000 person-years, 5·2-5·7, vs 6·9 per 1000 person-years, 6·6-7·2; p<0·0001). The rate of incident myocardial infarction in people with diabetes was substantially lower than for those with chronic kidney disease when defined by eGFR of less than 45 mL/min per 1·73 m(2) and severely increased proteinuria (6·6 per 1000 person-years, 6·4-6·9 vs 12·4 per 1000 person-years, 9·7-15·9)., Interpretation: Our findings suggest that chronic kidney disease could be added to the list of criteria defining people at highest risk of future coronary events., Funding: Alberta Heritage Foundation for Medical Research., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The estimated glomerular filtration rate (eGFR) is a powerful predictor of adverse outcomes, but most attention has focused on studies in the setting of reduced eGFR. Here we tested whether patients with an eGFR higher than 60-89.9 ml/min per 1.73 m(2) could also be at elevated risk of adverse outcomes. Further, we tested whether concomitant proteinuria further increases the risk of outcomes among individuals with an eGFR equal to or above 90 ml/min per 1.73 m(2), as it does for those with reduced eGFR. Using data from a population-based outpatient laboratory data set of 1,526,437 patients, we measured adjusted associations between eGFR calculated by the modification of diet in renal disease equation, urine dipstick proteinuria, and adverse clinical outcomes. The adjusted risk of all-cause mortality was lowest at an eGFR of 60-74.9 ml/min per 1.73 m(2) (referent) and increased at both lower and higher levels of eGFR. Specifically, the hazard ratio of death was 3.7 and 1.8 among patients with an eGFR equal to or above 105 and 90-104.9 ml/min per 1.73 m(2), respectively, compared to the referent group. Similar results were seen when the CKD-EPI equation (sensitivity analyses) was used to assess eGFR. Higher levels of eGFR were not associated with the risk of kidney failure or myocardial infarction. Thus, the presence and severity of proteinuria was significantly associated with graded increases in the risk of clinical outcomes for both lower and higher eGFR. We do not know, however, whether the finding at higher eGFR could be due to inadequacies of the eGFR formula at low serum creatinine levels.

Many patients with non-dialysis dependent chronic kidney disease (CKD) live far from the closest nephrologist; although reversible, this might constitute a barrier to optimal care. In order to evaluate outcomes, we selected 31,452 outpatients older than 18 years with an estimated glomerular filtration rate (eGFR) less than 45 ml/min per 1.73 m² who had serum creatinine measured at least once during 2005 in Alberta, Canada. We then used logistic regression to examine the association between outcomes of 6545 patients who lived more than 50 km from the nearest nephrologist. Over a median follow-up of 27 months, 7684 participants died and 15,075 were hospitalized at least once. Compared with those living within 50 km, those further away were significantly less likely to visit a nephrologist or a multidisciplinary CKD clinic within 18 months of the index measurement of the eGFR. Similarly, remote dwellers with diabetes were significantly less likely to have hemoglobin A1c evaluated within 1 year of the index eGFR measurement, to have urinary albumin assessed biannually, or to receive an angiotensin converting enzyme inhibitor or receptor blocker in the setting of diabetes or proteinuria. Remote-dwelling participants were also significantly more likely to die or be hospitalized during follow-up than those living closer. Thus, among people with CKD, remote dwellers were less likely to receive specialist care, recommended laboratory testing, and appropriate medications, and were more likely to die or be hospitalized compared with those living closer to a nephrologist.

Background: Low values of estimated glomerular filtration rate (eGFR) predispose to acute kidney injury, and proteinuria is a marker of kidney disease. We aimed to investigate how eGFR and proteinuria jointly modified the risks of acute kidney injury and subsequent adverse clinical outcomes., Methods: We did a cohort study of 920,985 adults residing in Alberta, Canada, between 2002 and 2007. Participants not needing chronic dialysis at baseline and with at least one outpatient measurement of both serum creatinine concentration and proteinuria (urine dipstick or albumin-creatinine ratio) were included. We assessed hospital admission with acute kidney injury with validated administrative codes; other outcomes were all-cause mortality and a composite renal outcome of end-stage renal disease or doubling of serum creatinine concentration., Findings: During median follow-up of 35 months (range 0-59 months), 6520 (0·7%) participants were admitted with acute kidney injury. In those with eGFR 60 mL/min per 1·73 m(2) or greater, the adjusted risk of admission with this disorder was about 4 times higher in those with heavy proteinuria measured by dipstick (rate ratio 4·4 vs no proteinuria, 95% CI 3·7-5·2). The adjusted rates of admission with acute kidney injury and kidney injury needing dialysis remained high in participants with heavy dipstick proteinuria for all values of eGFR. The adjusted rates of death and the composite renal outcome were also high in participants admitted with acute kidney injury, although the rise associated with this injury was attenuated in those with low baseline eGFR and heavy proteinuria., Interpretation: These findings suggest that information on proteinuria and eGFR should be used together when identifying people at risk of acute kidney injury, and that an episode of acute kidney injury provides further long-term prognostic information in addition to eGFR and proteinuria., Funding: The study was funded by an interdisciplinary team grant from Alberta Heritage Foundation for Medical Research., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

To determine whether acute kidney injury results in later long-term decline in kidney function we measured changes in kidney function over a 3-year period in adults undergoing coronary angiography who had serum creatinine measurements as part of their clinical care. Acute kidney injury was categorized by the magnitude of increase in serum creatinine (mild (50-99% or >or=0.3 mg/dl) and moderate or severe (>or=100%)) within 7 days of coronary angiography. Compared to patients without acute kidney injury, the adjusted odds of a sustained decline in kidney function at 3 months following angiography increased more than 4-fold for patients with mild to more than 17-fold for those with moderate or severe acute kidney injury. Among those with an estimated glomerular filtration rate after angiography less than 90 ml/min per 1.73 m(2), the subsequent adjusted mean rate of decline in estimated glomerular filtration rate during long-term follow-up (all normalized to 1.73 m(2) per year) was 0.2 ml/min in patients without acute kidney injury, 0.8 ml/min following mild injury, and 2.8 ml/min following moderate to severe acute kidney injury. Thus, acute kidney injury following coronary angiography is associated with a sustained loss and a larger rate of future decline in kidney function.

Chronic kidney disease is a common disorder and its prevalence is increasing worldwide. Early diagnosis on the basis of presence of proteinuria or reduced estimated glomerular filtration rate could permit early intervention to reduce the risks of cardiovascular events, kidney failure, and death that are associated with chronic kidney disease. In developed countries, screening for the disorder is most efficient when targeted at high-risk groups including elderly people and those with concomitant illness (such as diabetes, hypertension, or cardiovascular disease) or a family history of chronic kidney disease, although the role of screening in developing countries is not yet clear. Effective strategies are available to slow the progression of chronic kidney disease and reduce cardiovascular risk. Treatment of high blood pressure is recommended for all individuals with, or at risk of, chronic kidney disease. Use of angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers is preferred for patients with diabetic chronic kidney disease or those with the proteinuric non-diabetic disorder. Glycaemic control can help prevent the onset of early stages of chronic kidney disease in individuals with diabetes. Use of statins and aspirin is beneficial for most patients with chronic kidney disease who are at high cardiovascular risk, although research is needed to ascertain how to best prevent cardiovascular disease in this cohort. Models of care that facilitate delivery of the many complex aspects of treatment simultaneously could enhance management, although effects on clinical outcomes need further assessment. Novel clinical methods to better identify patients at risk of progression to later stages of chronic kidney disease, including kidney failure, are needed to target management to high-risk subgroups., (Copyright 2010 Elsevier Ltd. All rights reserved.)