Publications by authors named "Amber O Molnar"

44 Publications

The WISHED Randomized Controlled Trial: Impact of an Interactive Health Communication Application on Home Dialysis Use in People With Chronic Kidney Disease.

Can J Kidney Health Dis 2021 4;8:20543581211019631. Epub 2021 Jun 4.

Division of Nephrology, Department of Medicine, McMaster University, Hamilton, ON, Canada.

Background: While home dialysis therapies are more cost effective and may offer improved health-related quality of life, uptake compared to in-center hemodialysis remains low.

Objective: To test whether a web-based interactive health communication application (IHCA) compared to usual care would increase home dialysis use.

Design: Randomized control trial.

Setting: Patients were recruited from 3 multidisciplinary kidney clinics across Ontario, Canada (Hamilton, Kingston, London).

Patients: We included adults with advanced chronic kidney disease (CKD) followed in multidisciplinary kidney clinics. Patients who had not completed dialysis modality education, who did not have access to a home computer or the internet, who had significant hearing or vision impairment, who could not read/write/speak English, who had a medical contraindication for home dialysis, or who had selected conservative kidney care were excluded.

Measurements: The primary outcome was any use of home dialysis (peritoneal dialysis or home hemodialysis) within 90 days of dialysis initiation. Secondary outcomes were social support, decision conflict and dialysis knowledge measured at baseline, 6 months and 1 year.

Methods: Eligible patients were randomized to either usual care or the IHCA in addition to usual care in a 1:1 ratio. As part of usual care, all patients received education about dialysis modalities and kidney transplantation delivered by clinic nurses according to local practices. Randomization was performed using a computer-generated sequence in randomly permuted block sizes, stratified by site, and allocation occurred using sequentially numbered sealed, opaque envelopes. Participants, care providers, and outcome assessors were not blinded to the intervention. All analyses were performed blinded using an intention to treat approach. We estimated the effect of the ICHA on the odds of the primary outcome using unadjusted logistic regression models. Linear mixed models for repeated measures over time were used to analyze the impact of the IHCA on the secondary outcomes of interest.

Results: We randomized 140 (usual care, n = 71; IHCA, n = 69) out of a planned 264 patients (mean [SD] age 61 [14.5] years, 65% men). Among patients randomized to the IHCA group that completed 6-month and 1-year follow-up visits, 56.8% and 71.4%, respectively, had not accessed the IHCA website within the past month. There were 23 (32.4%) and 26 (37.7%) patients in the usual care and IHCA groups who received a home dialysis therapy within 90 days of dialysis initiation (odds ratio, OR = 1.3, 95% CI = [0.6-2.5], = .5). Among the 78 patients who initiated dialysis (n = 38 usual care, n = 40 IHCA), 60.5% and 65% in the usual care and IHCA groups received a home therapy within 90 days of dialysis initiation (OR = 1.2, 95% CI = [0.5-3.0], = .7). Secondary outcomes did not differ by intervention group over time.

Limitations: The trial was underpowered due to poor recruitment and use of the IHCA was low.

Conclusions: We did not find evidence of a difference in home dialysis uptake with IHCA use, but our analyses were notably underpowered. The incorporation of greater patient engagement, qualitative research and design research, and pilot implementation may help future evaluations of strategies to improve home dialysis uptake.

Trial Registration: NCT01403454, registration date: Jul 21, 2011.
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http://dx.doi.org/10.1177/20543581211019631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182179PMC
June 2021

An Environmental Scan of Ambulatory Care Quality Indicators for Patients With Advanced Kidney Disease Currently Used in Canada.

Can J Kidney Health Dis 2021 5;8:2054358121991096. Epub 2021 Feb 5.

Division of Nephrology, Kingston Health Sciences Center, Queen's University, Kingston, ON, Canada.

Background: Quality indicators can be used to identify gaps in care and drive frontline improvement activities. These efforts are important to prevent adverse events in the increasing number of ambulatory patients with advanced kidney disease in Canada, but it is unclear what indicators exist and the components of health care quality they measure.

Objective: We sought to identify, categorize, and evaluate quality indicators currently in use across Canada for ambulatory patients with advanced kidney disease.

Design: Environmental scan of quality indicators currently being collected by various organizations.

Setting: We assembled a 16-member group from across Canada with expertise in nephrology and quality improvement.

Patients: Our scan included indicators relevant to patients with chronic kidney disease in ambulatory care clinics.

Measurements: We categorized the identified quality indicators using the Institute of Medicine and Donabedian frameworks.

Methods: A 4-member panel used a modified Delphi process to evaluate the indicators found during the environmental scan using the American College of Physicians/Agency for Healthcare Research and Quality criteria. The ratings were then shared with the full panel for further comments and approval.

Results: The environmental scan found 28 quality indicators across 7 provinces, with 8 (29%) rated as "necessary" to distinguish high-quality from poor-quality care. Of these 8 indicators, 3 were measured by more than 1 province (% of patients on a statin, number of patients receiving a preemptive transplant, and estimated glomerular filtration rate at dialysis start); no indicator was used by more than 2 provinces. None of the indicators rated as necessary measured timely or equitable care, nor did we identify any measures that assessed the setting in which care occurs (ie, structure measures).

Limitations: Our list cannot be considered as an exhaustive list of available quality indicators at hand in Canada. Our work focused on quality indicators for nephrology providers and programs, and not indicators that can be applied across primary and specialty providers. We also focused on indicator constructs and not the detailed definitions or their application. Last, our panel does not represent the views of other important stakeholders.

Conclusions: Our environmental scan provides a snapshot of the scope of quality indicators for ambulatory patients with advanced kidney disease in Canada. This catalog should inform indicator selection and the development of new indicators based on the identified gaps, as well as motivate increased pan-Canadian collaboration on quality measurement and improvement.

Trial Registration: Not applicable as this article is not a systematic review, nor does it report results of a health intervention on human participants.
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http://dx.doi.org/10.1177/2054358121991096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868503PMC
February 2021

Dialysis Modality and Mortality in Heart Failure: A Retrospective Study of Incident Dialysis Patients.

Cardiorenal Med 2020 25;10(6):452-461. Epub 2020 Nov 25.

ICES, Toronto, Ontario, Canada.

Introduction: Prior studies reported lower mortality with hemodialysis (HD) compared to peritoneal dialysis (PD) in patients with heart failure (HF). We examined mortality rate by initial dialysis modality in incident dialysis patients with a history of HF using contemporary data and methods that ensure comparable HD and PD groups.

Methods: Retrospective cohort study using administrative databases in Ontario, Canada. Adults (age 50-80) with a history of HF who initiated maintenance dialysis between April 1, 2007 and March 31, 2016 were included. We excluded patients typically ineligible for PD as an initial modality (dialysis start in hospital, dementia, long-term care facility residency). We determined the cause-specific hazard ratio (transplant as a competing event) between initial dialysis modality (HD vs. PD) and all-cause mortality using an intention-to-treat approach.

Results: We included 2,199 patients with HF who initiated maintenance dialysis (77% HD and 23% PD). There were 1,152 (67.8%) and 340 (68.1%) mortality events over a median follow-up of 2.4 and 2.5 years in the HD and PD groups, respectively. Patients initiating HD versus PD was not associated with the mortality rate (adjusted hazard ratio 1.0, 95% CI 0.9-1.1). Similar results were seen in analyses censoring at modality switches and treating modality as time-varying.

Conclusions: We found no difference in mortality by initial dialysis modality. Our data support the current practice of selecting dialysis modality based on patient preference for patients with pre-existing HF.
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http://dx.doi.org/10.1159/000511168DOI Listing
November 2020

A Higher Concentration of Dialysate Magnesium to Reduce the Frequency of Muscle Cramps: A Narrative Review.

Can J Kidney Health Dis 2020 22;7:2054358120964078. Epub 2020 Oct 22.

Division of Nephrology, Department of Medicine, Health Sciences Centre, University of Calgary, Calgary, AB, Canada.

Purpose Of Review: Strategies to mitigate muscle cramps are a top research priority for patients receiving hemodialysis. As hypomagnesemia is a possible risk factor for cramping, we reviewed the literature to better understand the physiology of cramping as well as the epidemiology of hypomagnesemia and muscle cramps. We also sought to review the evidence from interventional studies on the effect of oral and dialysate magnesium-based therapies on muscle cramps.

Sources Of Information: Peer-reviewed articles.

Methods: We searched for relevant articles in major bibliographic databases including MEDLINE and EMBASE. The methodological quality of interventional studies was assessed using a modified version of the Downs and Blacks criteria checklist.

Key Findings: The etiology of muscle cramps in patients receiving hemodialysis is poorly understood and there are no clear evidence-based prevention or treatment strategies. Several factors may play a role including a low concentration of serum magnesium. The prevalence of hypomagnesemia (concentration of <0.7 mmol/L) in patients receiving hemodialysis ranges from 10% to 20%. Causes of hypomagnesemia include a low dietary intake of magnesium, use of medications that inhibit magnesium absorption (eg, proton pump inhibitors), increased magnesium excretion (eg, high-dose loop diuretics), and a low concentration of dialysate magnesium. Dialysate magnesium concentrations of ≤0.5 mmol/L may be associated with a decrease in serum magnesium concentration over time. Preliminary evidence from observational and interventional studies suggests a higher dialysate magnesium concentration will raise serum magnesium concentrations and may reduce the frequency and severity of muscle cramps. However, the quality of evidence supporting this benefit is limited, and larger, multicenter clinical trials are needed to further determine if magnesium-based therapy can reduce muscle cramps in patients receiving hemodialysis. In studies conducted to date, increasing the concentration of dialysate magnesium appears to be well-tolerated and is associated with a low risk of symptomatic hypermagnesemia.

Limitations: Few interventional studies have examined the effect of magnesium-based therapy on muscle cramps in patients receiving hemodialysis and most were nonrandomized, pre-post study designs.
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http://dx.doi.org/10.1177/2054358120964078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585892PMC
October 2020

Canadian Society of Nephrology Commentary on the Kidney Disease Improving Global Outcomes 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder.

Can J Kidney Health Dis 2020 4;7:2054358120944271. Epub 2020 Aug 4.

Division of Nephrology, Department of Medicine, Department of Health Research, Evidence and Impact, McMaster University, Hamilton, ON, Canada.

Purpose Of Review: (1) To provide commentary on the 2017 update to the Kidney Disease Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD); (2) to apply the evidence-based guideline update for implementation within the Canadian health care system; (3) to provide comment on the care of children with chronic kidney disease (CKD); and (4) to identify research priorities for Canadian patients.

Sources Of Information: The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD.

Methods: The commentary committee co-chairs selected potential members based on their knowledge of the Canadian kidney community, aiming for wide representation from relevant disciplines, academic and community centers, and different geographical regions.

Key Findings: We agreed with many of the recommendations in the clinical practice guideline on the diagnosis, evaluation, prevention, and treatment of CKD-MBD. However, based on the uncommon occurrence of abnormalities in calcium and phosphate and the low likelihood of severe abnormalities in parathyroid hormone (PTH), we recommend against screening and monitoring levels of calcium, phosphate, PTH, and alkaline phosphatase in adults with CKD G3. We suggest and recommend monitoring these parameters in adults with CKD G4 and G5, respectively. In children, we agree that monitoring for CKD-MBD should begin in CKD G2, but we suggest measuring ionized calcium, rather than total calcium or calcium adjusted for albumin. With regard to vitamin D, we suggest against routine screening for vitamin D deficiency in adults with CKD G3-G5 and G1T-G5T and suggest following population health recommendations for adequate vitamin D intake. We recommend that the measurement and management of bone mineral density (BMD) be according to general population guidelines in CKD G3 and G3T, but we suggest against routine BMD testing in CKD G4-G5, CKD G4T-5T, and in children with CKD. Based on insufficient data, we also recommend against routine bone biopsy in clinical practice for adults with CKD or CKD-T, or in children with CKD, although we consider it an important research tool.

Limitations: The committee relied on the evidence summaries produced by KDIGO. The CSN committee did not replicate or update the systematic reviews.
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http://dx.doi.org/10.1177/2054358120944271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412914PMC
August 2020

Potentially inappropriate prescribing in older adults with advanced chronic kidney disease.

PLoS One 2020 20;15(8):e0237868. Epub 2020 Aug 20.

Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237868PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444541PMC
October 2020

Incidence of Direct Oral Anticoagulant Prescriptions in Kidney Transplant Recipients in Ontario, Canada.

Transplant Proc 2020 Dec 11;52(10):3144-3152. Epub 2020 May 11.

Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada; ICES, Toronto, Ontario, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada. Electronic address:

Background: Kidney transplant recipients (KTRs) are routinely excluded from direct oral anticoagulant (DOAC) trials. Given the lack of safety and efficacy data in this population, we examined real-world prescribing practices of DOACs in KTRs.

Methods: We conducted a retrospective cohort study using linked administrative data sets in Ontario, Canada. All adult KTRs (n = 5580) from June 23, 2009, to March 31, 2017, were included. The primary outcomes were the first prescription for a DOAC or warfarin. Patients were censored on graft failure, death, or end of follow-up.

Results: The mean age was 55 (SD, 14) years; 63% were male, and 65% had received a deceased donor kidney. Over a median follow-up of 5.5 and 4.7 years, 224 KTRs (4.0%) and 824 KTRs (14.8%) were prescribed DOACs and warfarin, respectively. The rates of DOAC and warfarin prescriptions were 8.1 and 32.6 per 1000 person-years, respectively. Older age, receipt of a kidney transplant in more recent years, and higher baseline estimated glomerular filtration rate were associated with DOAC prescription compared with warfarin. Patients with multiple comorbidities and a history of deep venous thromboembolism had a lower risk of DOAC prescription compared with warfarin. When examined by era, the incidence rate of both DOAC and warfarin prescriptions increased significantly over time.

Conclusions: Despite limited safety and efficacy data, DOACs are prescribed to KTRs. However, warfarin still remains more commonly prescribed in this selected patient population. Anticoagulant prescriptions overall are on the rise in KTRs. Further study is needed to determine the safety and efficacy of DOACs in KTRs.
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http://dx.doi.org/10.1016/j.transproceed.2020.02.171DOI Listing
December 2020

Risk of Cardiovascular Events and Mortality Among Elderly Patients With Reduced GFR Receiving Direct Oral Anticoagulants.

Am J Kidney Dis 2020 09 22;76(3):311-320. Epub 2020 Apr 22.

Department of Medicine, University of Ottawa, Ottawa; Division of General Internal Medicine, Geneva University Hospitals, Geneva, Switzerland; Section of Nephrology, University of Ottawa, Ottawa, Canada. Electronic address:

Rationale & Objective: Evidence for the efficacy of direct oral anticoagulants (DOACs) to prevent cardiovascular (CV) events and mortality in older individuals with a low estimated glomerular filtration rate (eGFR) is lacking. We sought to characterize the association of oral anticoagulant use with CV morbidity in elderly patients with or without reductions in eGFRs, comparing DOACs with vitamin K antagonists (VKAs).

Study Design: Population-based retrospective cohort study.

Settings & Participants: All individuals 66 years or older with an initial prescription for oral anticoagulants dispensed in Ontario, Canada, from 2009 to 2016.

Exposure: DOACs (apixaban, dabigatran, and rivaroxaban) compared with VKAs by eGFR group (≥60, 30-59, and<30mL/min/1.73m).

Outcomes: The primary outcome was a composite of a CV event (myocardial infarction, revascularization, or ischemic stroke) or mortality. Secondary outcomes were CV events alone, mortality, and hemorrhage requiring hospitalization.

Analytical Approach: High-dimensional propensity score matching of DOAC to VKA users and Cox proportional hazards regression.

Results: 27,552 new DOAC users were matched to 27,552 new VKA users (median age, 78 years; 49% women). There was significantly lower risk for CV events or mortality among DOAC users compared with VKA users (event rates of 79.78 vs 99.77 per 1,000 person-years, respectively; HR, 0.82 [95% CI, 0.75-0.90]) and lower risk for hemorrhage (event rates of 10.35 vs 16.77 per 1,000 person-years, respectively; HR, 0.73 [95% CI, 0.58-0.91]). There was an interaction between eGFR and the association of anticoagulant class with the primary composite outcome (P<0.02): HRs of 1.01 [95% CI, 0.92-1.12], 0.83 [95% CI, 0.75-0.93], and 0.75 [95% CI, 0.51-1.10] for eGFRs of≥60, 30 to 59, and<30mL/min/1.73m. No interaction was detected for the outcome of hemorrhage.

Limitations: Retrospective observational study design limits causal inference; dosages of DOACs and international normalized ratio values were not available; low event rates in some subgroups limited statistical power.

Conclusions: DOACs compared with VKAs were associated with lower risk for the composite of CV events or mortality, an association for which the strength was most apparent among those with reduced eGFRs. The therapeutic implications of these findings await further study.
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http://dx.doi.org/10.1053/j.ajkd.2020.02.446DOI Listing
September 2020

Perceived and Objective Kidney Disease Knowledge in Patients With Advanced CKD Followed in a Multidisciplinary CKD Clinic.

Can J Kidney Health Dis 2020 11;7:2054358120903156. Epub 2020 Feb 11.

Division of Nephrology, Department of Medicine, McMaster University, Hamilton, ON, Canada.

Background: One of the key components of multidisciplinary CKD clinics is education; however, kidney disease knowledge among patients followed in these clinics is not routinely measured.

Objective: The aim of this study was to determine objective and perceived kidney disease knowledge and patient characteristics associated with knowledge among patients followed in a multi-care kidney clinic.

Design: This is a cross-sectional survey study.

Setting: This study was conducted in a multi-care kidney clinic in Ontario, Canada.

Patients: Patients who did not speak English, who were unable to read due to significant vision impairment, or who had a known history of dementia or significant cognitive impairment were excluded.

Measurements: Perceived kidney disease knowledge was evaluated using a previously validated 9-item survey (PiKS). Each question on the perceived knowledge survey had 4 possible responses, ranging from "I don't know anything" (1) to "I know a lot" (4). Objective kidney disease knowledge was evaluated using a previously validated survey (KiKS).

Methods: The association between patient characteristics and perceived and objective kidney disease knowledge was determined using linear regression.

Results: A total of 125 patients were included, 57% were male, the mean (SD) age and eGFR were 66 (13) years and 16 (5.9) mL/min/1.73 m, respectively. The median (IQR) objective and perceived knowledge survey scores were 19 out of 27 (16, 21) and 2.9 out of 4 (2.4, 3.2), respectively. Only 25% of patients answered correctly that CKD can be associated with no symptoms, and 64% of patients identified correctly that the kidneys make urine. More than 60% of patients perceived themselves to know nothing or only a little about medications that help or hurt the kidney. Older age was independently associated with lower perceived and objective knowledge, but sex, income, and educational attainment were not.

Limitations: This is a single-center study. Cognitive impairment was based on the treating team's informal assessment or prior documentation in the chart; formal cognitive testing was not performed as part of this study.

Conclusions: Despite resource-intensive care, CKD knowledge of patients followed in a multidisciplinary clinic was found to be modest. Whether enhanced educational strategies can improve knowledge and whether increasing knowledge improves patient outcomes warrants further study.
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http://dx.doi.org/10.1177/2054358120903156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016305PMC
February 2020

Cultivating Innovative Pragmatic Cluster-Randomized Registry Trials Embedded in Hemodialysis Care: Workshop Proceedings From 2018.

Can J Kidney Health Dis 2019 26;6:2054358119894394. Epub 2019 Dec 26.

ICES, ON, Canada.

Hemodialysis is a life-sustaining treatment for persons with kidney failure. However, those on hemodialysis still face a poor quality of life and a short life expectancy. High-quality research evidence from large randomized controlled trials is needed to identify interventions that improve the experiences, outcomes, and health care of persons receiving hemodialysis. With the support of the Canadian Institutes of Health Research and its Strategy for Patient-Oriented Research, the Innovative Clinical Trials in Hemodialysis Centers initiative brought together Canadian and international kidney researchers, patients, health care providers, and health administrators to participate in a workshop held in Toronto, Canada, on June 2 and 3, 2018. The workshop served to increase knowledge and awareness about the conduct of innovative, pragmatic, cluster-randomized registry trials embedded into routine hemodialysis care and provided an opportunity to discuss and build support for new trial ideas. The workshop content included structured presentations, facilitated group discussions, and expert panel feedback. Partnerships and promising trial ideas borne out of the workshop will continue to be developed to support the implementation of future large-scale trials.
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http://dx.doi.org/10.1177/2054358119894394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933546PMC
December 2019

The Risk of Stroke and Stroke Type in Patients With Atrial Fibrillation and Chronic Kidney Disease.

Can J Kidney Health Dis 2019 4;6:2054358119892372. Epub 2019 Dec 4.

Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.

Background: Atrial fibrillation (AF) and chronic kidney disease (CKD) are known to increase the risk of stroke.

Objectives: We set out to examine the risk of stroke by kidney function and albuminuria in patients with and without AF.

Design: Retrospective cohort study.

Settings: Ontario, Canada.

Participants: A total of 736 666 individuals (>40 years) from 2002 to 2015.

Measurements: New-onset AF, albumin-to-creatinine ratio (ACR), and an estimated glomerular filtration rate (eGFR).

Methods: A total of 39 120 matched patients were examined for the risk of ischemic, hemorrhagic, or any stroke event, accounting for the competing risk of all-cause mortality. Interaction terms for combinations of ACR/eGFR and the outcome of stroke with and without AF were examined.

Results: In a total of 4086 (5.2%) strokes (86% ischemic), the presence of AF was associated with a 2-fold higher risk for any stroke event and its subtypes of ischemic and hemorrhagic stroke. Across eGFR levels, the risk of stroke was 2-fold higher with the presence of AF except for low levels of eGFR (eGFR < 30 mL/min/1.73 m, hazard ratio [HR]: 1.38, 95% confidence interval [CI]: 0.99-1.92). Similarly across ACR levels, the risk of stroke was 2-fold higher except for high levels of albuminuria (ACR > 30 mg/g, HR: 1.61, 95% CI: 1.31-1.99). The adjusted risk of stroke with AF differed by combinations of ACR and eGFR categories (interaction value = .04) compared with those without AF. Both stroke types were more common in patients with AF, and ischemic stroke rates differed significantly by eGFR and ACR categories.

Limitations: Medication information was not included.

Conclusions: Patients with CKD and AF are at a high risk of total, ischemic, and hemorrhagic strokes; the risk is highest with lower eGFR and higher ACR and differs based on eGFR and the degree of ACR.
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http://dx.doi.org/10.1177/2054358119892372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893926PMC
December 2019

The association of beta-blocker use with mortality in elderly patients with congestive heart failure and advanced chronic kidney disease.

Nephrol Dial Transplant 2020 05;35(5):782-789

Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.

Background: Whether the survival benefit of β-blockers in congestive heart failure (CHF) from randomized trials extends to patients with advanced chronic kidney disease (CKD) [estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 but not receiving dialysis] is uncertain.

Methods: This was a retrospective cohort study using administrative datasets. Older adults from Ontario, Canada, with incident CHF (median age 79 years) from April 2002 to March 2014 were included. We matched new users of β-blockers to nonusers on age, sex, eGFR categories (>60, 30-60, <30), CHF diagnosis date and a high-dimensional propensity score. Using Cox proportional hazards models, we examined the association of β-blocker use versus nonuse with all-cause mortality.

Results: We matched 5862 incident β-blocker users (eGFR >60, n = 3136; eGFR 30-60, n = 2368; eGFR <30, n = 358). There were 2361 mortality events during follow-up. β-Blocker use was associated with reduced all-cause mortality [adjusted hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.54-0.64]. This result was consistent across all eGFR categories (>60: adjusted HR 0.55, 95% CI 0.49-0.62; 30-60: adjusted HR 0.63, 95% CI 0.55-0.71; <30: adjusted HR 0.55, 95% CI 0.41-0.73; interaction term, P = 0.30). The results were consistent in an intention-to-treat analysis and with β-blocker use treated as a time-varying exposure.

Conclusions: β-Blocker use is associated with reduced all-cause mortality in elderly patients with CHF and CKD, including those with an eGFR <30. Randomized trials that examine β-blockers in patients with CHF and advanced CKD are needed.
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http://dx.doi.org/10.1093/ndt/gfz167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203558PMC
May 2020

Risk Factors for Unplanned Dialysis Initiation: A Systematic Review of the Literature.

Can J Kidney Health Dis 2019 13;6:2054358119831684. Epub 2019 Mar 13.

McMaster University, Hamilton, ON, Canada.

Background: Unplanned dialysis initiation is common in patients with chronic kidney disease (CKD).

Objective: To determine common definitions and patient risk factors for unplanned dialysis.

Design: Systematic review.

Setting: MEDLINE, EMBASE, and the Cochrane Library were searched from inception to February 2018.

Patients: Studies that included incident chronic dialysis patients or patients with CKD that cited a definition or examined risk factors for unplanned dialysis were included.

Measurements: Definitions and criteria for unplanned dialysis reported across studies. Patient characteristics associated with unplanned dialysis.

Methods: Two reviewers independently extracted data using a standardized data abstraction form and assessed study quality using a modified New Castle Ottawa Scale.

Results: From 2797 citations, 48 met eligibility criteria. Reported definitions for unplanned dialysis were variable. Most publications cited dialysis initiation under emergency conditions and/or with a central venous catheter. The association of patient characteristics with unplanned dialysis was reported in 26 studies, 18 were retrospective and 21 included incident dialysis patients. The most common risk factors in univariate analyses were (number of studies) increased age (n = 7), cause of kidney disease (n = 6), presence of cardiovascular disease (n = 7), lower serum hemoglobin (n = 9), lower serum albumin (n = 10), higher serum phosphate (n = 6), higher serum creatinine or lower estimated glomerular filtration rate (eGFR) at dialysis initiation (n = 7), late referral (n = 5), lack of dialysis education (n = 6), and lack of follow-up in a predialysis clinic prior to dialysis initiation (n = 5). A minority of studies performed multivariable analyses (n = 10); the most common risk factors were increased age (n = 4), increased comorbidity score (n = 3), late referral (n = 5), and lower eGFR at dialysis initiation (n = 3).

Limitations: Comparison of results across studies was limited by inconsistent definitions for unplanned dialysis. High-quality data on patient risk factors for unplanned dialysis are lacking.

Conclusions: Well-designed prospective studies to determine modifiable risk factors are needed. The lack of a consensus definition for unplanned dialysis makes research and quality improvement initiatives in this area more challenging.
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http://dx.doi.org/10.1177/2054358119831684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419254PMC
March 2019

The Association of Kidney Function and Albuminuria With the Risk and Outcomes of Syncope: A Population-Based Cohort Study.

Can J Cardiol 2018 12 28;34(12):1631-1640. Epub 2018 Aug 28.

Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; Division of Nephrology, Western University, London, Ontario, Canada; Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. Electronic address:

Background: The risks and subsequent outcomes of syncope among seniors with chronic kidney disease (CKD) are unclear.

Methods: We conducted a population-based retrospective cohort study of 272,146 patients ≥ 66 years old, in Ontario, Canada, from April 1, 2006, to March 31, 2016. Using administrative health care databases, we examined the association of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR) with incident syncope and the association of incident syncope with the composite outcome of myocardial infarction, stroke, and death by levels of eGFR/ACR, using adjusted Cox proportional hazards models.

Results: A total of 15,074 incident syncopal events occurred during the study period. The adjusted risk for syncope was higher with a lower eGFR and higher ACR in a stepwise manner (eGFR 60 to < 90: HR 1.17 [1.09-1.26] vs eGFR < 30: HR 1.67 (1.50-1.87) with eGFR ≥ 90 referent; ACR > 30: HR 1.15 [1.07-1.24] with ACR < 3 referent). Among the 12,710 patients with a first syncope event and 1 year of follow-up, the adjusted risk for the composite outcome was higher with a lower eGFR and higher ACR in a stepwise manner (eGFR 60 to < 90: HR 1.05 [0.90-1.22] vs eGFR < 30: HR 1.62 [1.34-1.96] with eGFR ≥ 90 referent; ACR > 30: HR 1.77 [1.60-1.96], ACR < 3 referent).

Conclusions: A lower eGFR and higher ACR are associated with a higher risk of a hospital encounter for syncope and of related complications among persons of advanced age.
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http://dx.doi.org/10.1016/j.cjca.2018.08.033DOI Listing
December 2018

Albuminuria, Reduced Kidney Function, and the Risk of ST - and non-ST-segment-elevation myocardial infarction.

J Am Heart Assoc 2018 10;7(20):e009995

1 Department of Medicine University of Ottawa Ontario Canada.

Background Chronic kidney disease is a recognized independent risk factor for cardiovascular disease, but whether the risks of ST-segment-elevation myocardial infarction ( STEMI ) and non-ST-segment-elevation myocardial infarction ( NSTEMI ) differ in the chronic kidney disease population is unknown. Methods and Results Using administrative data from Ontario, Canada, we examined patients ≥66 years of age with an outpatient estimated glomerular filtration rate ( eGFR ) and albuminuria measure for incident myocardial infarction from 2002 to 2015. Adjusted Fine and Gray subdistribution hazard models accounting for the competing risk of death were used. In 248 438 patients with 1.2 million person-years of follow-up, STEMI , NSTEMI , and death occurred in 1436 (0.58%), 4431 (1.78%), and 30 015 (12.08%) patients, respectively. The highest level of albumin-to-creatinine ratio (>30 mg/mmol) was associated with a 2-fold higher adjusted risk of both STEMI and NSTEMI among patients with eGFR ≥60 mL/(min·1.73 m) compared to albumin-to-creatinine ratio <3 mg/mmol. The lowest level of eGFR (<30 mL/[min·1.73 m]) was not associated with higher STEMI risk but with a 4-fold higher risk of NSTEMI compared to those with eGFR ≥60 mL/(min·1.73 m). The lowest eGFR (<30 mL/[min·1.73 m]) and highest albumin-to-creatinine ratio (>30 mg/mmol) were associated with a greater than 4-fold higher risk of both STEMI and NSTEMI (subdistribution hazard models [95% confidence interval] 4.53 [3.30-6.21] and 4.42 [3.67-5.32], respectively) compared to albumin-to-creatinine ratio <3 mg/mmol and eGFR ≥60 mL/(min·1.73 m). Conclusions Elevations in albuminuria are associated with a higher risk of both NSTEMI and STEMI , regardless of kidney function, whereas reduced kidney function alone is associated with a higher NSTEMI risk.
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http://dx.doi.org/10.1161/JAHA.118.009995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474966PMC
October 2018

Hospitalizations in Dialysis Patients in Canada: A National Cohort Study.

Can J Kidney Health Dis 2018 1;5:2054358118780372. Epub 2018 Jun 1.

Division of Nephrology, Department of Medicine, University of Ottawa, Ontario, Canada.

Background: Hospitalizations of chronic dialysis patients have not been previously studied at a national level in Canada. Understanding the scope and variables associated with hospitalizations will inform measures for improvement.

Objective: To describe the risk of all-cause and infection-related hospitalizations in patients on dialysis.

Design: Retrospective cohort study using health care administrative databases.

Setting: Provinces and territories across Canada (excluding Manitoba and Quebec).

Patients: Incident chronic dialysis patients with a dialysis start date between January 1, 2005, and March 31, 2014. Patients with a prior history of kidney transplantation were excluded.

Measurements: Patient characteristics were recorded at baseline. Dialysis modality was treated as a time-varying covariate. The primary outcomes of interest were all-cause and dialysis-specific infection-related hospitalizations.

Methods: Crude rates for all-cause hospitalization and infection-related hospitalization were determined per patient year (PPY) at 7 and 30 days, and at 3, 6, and 12 months postdialysis initiation. A stratified, gamma-distributed frailty model was used to assess repeat hospital admissions and to determine the inter-recurrence dependence of hospitalizations within individuals, as well as the hazard ratio (HR) attributed to each covariate of interest.

Results: A total of 38 369 incident chronic dialysis patients were included: 38 088 adults and 281 pediatric patients (age less than 18 years). There were 112 374 hospitalizations, of which 11.5% were infection-related hospitalizations. The all-cause hospitalization rate was similar for all adult age groups (age 65 years and older: 1.40, 1.35, and 1.18 admissions PPY at 7 days, 30 days, and 6 months, respectively). The all-cause hospitalization rate was higher for pediatric patients (1.67, 2.48, and 2.47 admissions PPY at 7 days, 30 days, and 6 months, respectively; adjusted HR: 2.73, 95% confidence interval [CI]: 2.37-3.15, referent age group: 45-64 years). Within the first 7 days after dialysis initiation, patients on peritoneal dialysis had a higher risk of all-cause hospitalization (HR: 1.27, 95% CI: 1.07-1.50) and infection-related hospitalization (HR: 2.05, 95% CI: 1.19-3.55) compared with patients on hemodialysis. Beyond 7 days, the risk did not differ significantly by dialysis modality. Female sex and Indigenous race were significant risk factors for all-cause hospitalization.

Limitations: The cohort had too few home hemodialysis patients to examine this subgroup. The outcome of infection-related hospitalization was determined using diagnostic codes. Dialysis patients from Manitoba and Quebec were not included.

Conclusions: In Canada, the rates of hospitalization were not influenced by dialysis modality beyond the initial 7-day period following dialysis initiation; however, the rate of hospitalization in pediatric patients was higher than in adults at every time frame examined.
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http://dx.doi.org/10.1177/2054358118780372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985541PMC
June 2018

Patient Engagement in Kidney Research: Opportunities and Challenges Ahead.

Can J Kidney Health Dis 2017 29;4:2054358117740583. Epub 2017 Nov 29.

Faculty of Nursing, University of Alberta, Edmonton, Canada.

Purpose Of Review: Patient engagement in research is increasingly recognized as an important component of the research process and may facilitate translation of research findings. To heighten awareness on this important topic, this review presents opportunities and challenges of patient engagement in research, drawing on specific examples from 4 areas of Canadian kidney research conducted by New Investigators in the Kidney Research Scientist Core Education and National Training (KRESCENT) Program.

Sources Of Information: Research expertise, published reports, peer-reviewed articles, and research funding body websites.

Methods: In this review, the definition, purpose, and potential benefits of patient engagement in research are discussed. Approaches toward patient engagement that may help with translation and uptake of research findings into clinical practice are highlighted. Opportunities and challenges of patient engagement are presented in both basic science and clinical research with the following examples of kidney research: (1) precision care in focal and segmental glomerulosclerosis, (2) systems biology approaches to improve management of chronic kidney disease and enhance kidney graft survival, (3) reducing the incidence of suboptimal dialysis initiation, and (4) use of patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) in kidney practice.

Key Findings: Clinical research affords more obvious opportunities for patient engagement. The most obvious step at which to engage patients is in the setting of research priorities. Engagement at all stages of the research cycle may prove to be more challenging, and requires a detailed plan, along with funds and infrastructure to ensure that it is not merely tokenistic. Basic science research is several steps removed from the clinical application and involves complex scientific concepts, which makes patient engagement inherently more difficult.

Limitations: This is a narrative review of the literature that has been partly influenced by the perspectives and experiences of the authors and focuses on research conducted by the authors. The evidence base to support the suggested benefits of patient engagement in research is currently limited.

Implications: The formal incorporation of patients' priorities, perspectives, and experiences is now recognized as a key component of the research process. If patients and researchers are able to effectively work together, this could enhance research quality and efficiency. To effectively engage patients, proper infrastructure and dedicated funding are needed. Going forward, a rigorous evaluation of patient engagement strategies and their effectiveness will be needed.
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http://dx.doi.org/10.1177/2054358117740583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714072PMC
November 2017

Incident Atrial Fibrillation and the Risk of Congestive Heart Failure, Myocardial Infarction, End-Stage Kidney Disease, and Mortality Among Patients With a Decreased Estimated GFR.

Am J Kidney Dis 2018 02 16;71(2):191-199. Epub 2017 Nov 16.

Institute for Clinical Evaluative Sciences, Ontario, Canada; Division of Nephrology, University of Ottawa, Ottawa, Canada; Ottawa Hospital Research Institute, Ottawa, Canada. Electronic address:

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 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. Because the risk is exceedingly high within the first 6 months after AF diagnosis, therapeutic interventions and monitoring may improve outcomes.
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http://dx.doi.org/10.1053/j.ajkd.2017.08.016DOI Listing
February 2018

Risk and complications of venous thromboembolism in dialysis patients.

Nephrol Dial Transplant 2018 05;33(5):874-880

Institute for Clinical Evaluative Sciences (ICES), Ontario, Canada.

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.
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http://dx.doi.org/10.1093/ndt/gfx212DOI Listing
May 2018

Risk of Venous Thromboembolism in Patients by Albuminuria and Estimated GFR.

Am J Kidney Dis 2017 12 18;70(6):826-833. Epub 2017 Aug 18.

Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Epidemiology, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada. Electronic address:

Background: The risk for venous thromboembolism (VTE) is elevated with albuminuria or a low estimated glomerular filtration rate (eGFR). However, the VTE risk due to the combined effects of eGFR and albuminuria are unknown.

Study Design: Population-based cohort study.

Settings & Participants: 694,956 adults in Ontario, Canada, from 2002 to 2012.

Factors: eGFR and albumin-creatinine ratio (ACR).

Outcome: VTE.

Results: 15,180 (2.2%) VTE events occurred during the study period. Both albuminuria and eGFR were independently associated with VTE. The association of albuminuria and VTE differed by level of eGFR (P for ACR × eGFR interaction < 0.001). After considering the competing risk for death, there was a 61% higher rate of VTE in patients with normal eGFRs (eGFRs>90mL/min/1.73m) and heavy albuminuria (ACR>300mg/g) compared with those with normal eGFRs and no albuminuria (subdistribution HR, 1.61; 95% CI, 1.38-1.89). Among those with reduced kidney function (eGFR, 15-29mL/min/1.73m), the risk for VTE was only minimally increased, irrespective of albuminuria (subdistribution HRs of 1.23 [95% CI, 1-1.5] and 1.09 [95% CI, 0.82-1.45] for ACR<30 and >300mg/g, respectively).

Limitations: Only single determinations of ACR and eGFR were used. Diagnostic/International Classification of Diseases codes were used to define VTE.

Conclusions: Albuminuria increases the risk for VTE markedly in patients with normal eGFRs compared with those with lower eGFRs.
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http://dx.doi.org/10.1053/j.ajkd.2017.07.003DOI Listing
December 2017

Predicting in a predicament: Stroke and hemorrhage risk prediction in dialysis patients with atrial fibrillation.

Semin Dial 2018 01 11;31(1):37-47. Epub 2017 Jul 11.

Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Canada.

Whether to anticoagulate dialysis patients with atrial fibrillation is a common clinical dilemma with limited high-quality data to inform decision-making. While the efficacy and safety of anticoagulation for stroke prevention in dialysis patients with atrial fibrillation has long been debated and remains unclear, the more upstream issue of stroke risk assessment from atrial fibrillation has received relatively little attention. In the general population, a handful of risk scores to help predict stroke and hemorrhage risk in the setting of atrial fibrillation are widely validated and applied in clinical practice. But are they applicable to the dialysis population? The most commonly used stroke risk scores, CHADS2 and CHA2DS2-VASC, have limited validation in the dialysis population, and when validated, have shown poor performance (c-statistics <0.70). Stroke risk scores derived in the general atrial fibrillation population may perform poorly in dialysis patients for a number of reasons. Dialysis patients have unique stroke risk factors, such as chronic inflammation and vascular calcification, and a much higher competing risk of death, none of which are accounted for in current risk scores. Further complicating the dilemma of anticoagulation is hemorrhage risk, which is known to be exceedingly high in dialysis patients. Currently available hemorrhage risk scores, such as HAS-BLED, have not been validated in dialysis patients and will likely underestimate hemorrhage risk. Moving forward, risk tools specific to the dialysis population are needed to accurately assess and balance stroke and hemorrhage risks in dialysis patients with atrial fibrillation.
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http://dx.doi.org/10.1111/sdi.12637DOI Listing
January 2018

Association of Proteinuria and Incident Atrial Fibrillation in Patients With Intact and Reduced Kidney Function.

J Am Heart Assoc 2017 Jul 6;6(7). Epub 2017 Jul 6.

Institute for Clinical Evaluative Sciences, London, Ontario, Canada

Background: Early evidence suggests proteinuria is independently associated with incident atrial fibrillation (AF). We sought to investigate whether the association of proteinuria with incident AF is altered by kidney function.

Methods And Results: Retrospective cohort study using administrative healthcare databases in Ontario, Canada (2002-2015). A total of 736 666 patients aged ≥40 years not receiving dialysis and with no previous history of AF were included. Proteinuria was defined using the urine albumin-to-creatinine ratio (ACR) and kidney function by the estimated glomerular filtration rate (eGFR). The primary outcome was time to AF. Cox proportional models were used to determine the hazard ratio for AF censored for death, dialysis, kidney transplant, or end of follow-up. Fine and Grey models were used to determine the subdistribution hazard ratio for AF, with death as a competing event. Median follow-up was 6 years and 44 809 patients developed AF. In adjusted models, ACR and eGFR were associated with AF (<0.0001). The association of proteinuria with AF differed based on kidney function (ACR × eGFR interaction, <0.0001). Overt proteinuria (ACR, 120 mg/mmol) was associated with greater AF risk in patients with intact (eGFR, 120) versus reduced (eGFR, 30) kidney function (adjusted hazard ratios, 4.5 [95% CI, 4.0-5.1] and 2.6 [95% CI, 2.4-2.8], respectively; referent ACR 0 and eGFR 120). Results were similar in competing risk analyses.

Conclusions: Proteinuria increases the risk of incident AF markedly in patients with intact kidney function compared with those with decreased kidney function. Screening and preventative strategies should consider proteinuria as an independent risk factor for AF.
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http://dx.doi.org/10.1161/JAHA.117.005685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5586292PMC
July 2017

Warfarin and the Risk of Stroke and Bleeding in Patients With Atrial Fibrillation Receiving Dialysis: A Systematic Review and Meta-analysis.

Can J Cardiol 2017 06 20;33(6):737-746. Epub 2017 Feb 20.

Division of Nephrology, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; Li Ka Shing Knowledge Institute of St Michael's Hospital, Toronto, Ontario, Canada.

Background: Patients with atrial fibrillation who receive dialysis are at a high risk of ischemic stroke. The role of warfarin in mitigating this risk in patients with atrial fibrillation who receive dialysis is uncertain. Our objective was to examine the safety and efficacy of warfarin in patients who have atrial fibrillation and receive dialysis.

Methods: We used MedLine, Embase, and the Cochrane Library to conduct a systematic review and meta-analysis of published and unpublished observational and interventional studies related to the use of warfarin in patients with atrial fibrillation who receive dialysis, and provided data on the risk of stroke and/or bleeding outcomes relative to placebo or no anticoagulation therapy. A random effects model was used to calculate pooled adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for these outcomes.

Results: No randomized controlled trials met the criteria for inclusion. Fourteen observational studies (20,398 participants) were included in the analysis. The use of warfarin was not associated with ischemic stroke (14 studies; 20,398 participants; aHR, 0.77; 95% CI, 0.55-1.07), intracranial hemorrhage (hemorrhagic stroke; 4 studies; 15,726 participants; aHR, 1.93; 95% CI, 0.93-4.00), gastrointestinal bleeding (3 studies; 14,693 participants; aHR, 1.19; 95% CI, 0.8-1.76), or all-cause mortality (7 studies; 16,172 participants; aHR, 0.89; 95% CI, 0.72-1.11).

Conclusions: Observational studies suggest that warfarin was not associated with a clear benefit or harm among patients who have atrial fibrillation and receive dialysis. These estimates were limited by study heterogeneity including the inability to account for a number of important confounders such as the time in the therapeutic range. Because of the high prevalence of atrial fibrillation, stroke, and bleeding complications in this population, well designed clinical trials of warfarin and other anticoagulants are urgently needed.
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http://dx.doi.org/10.1016/j.cjca.2017.02.004DOI Listing
June 2017

Lower serum magnesium is associated with vascular calcification in peritoneal dialysis patients: a cross sectional study.

BMC Nephrol 2017 04 6;18(1):129. Epub 2017 Apr 6.

Division of Nephrology, Department of Medicine, McMaster University, Hamilton, ON, Canada.

Background: Coronary artery calcification (CAC) is highly prevalent among dialysis patients and is associated with increased cardiovascular and all cause mortality. Magnesium (Mg) inhibits vascular calcification in animal and in-vitro studies but whether the same effect occurs in humans is uncertain.

Methods: A single centre cross-sectional study of 80 prevalent peritoneal dialysis (PD) patients; on PD only for a minimum of 3 months. A radiologist blinded to patient status calculated their abdominal aortic calcification (AAC) scores on lateral lumbar spine radiographs, a validated surrogate for CAC.

Results: Eighty patients provided informed consent and underwent lumbar spine radiography. The mean serum Mg was 0.8 mmol/L (standard deviation 0.2) and mean AAC score 8.9 (minimum 0, maximum 24). A higher serum Mg level was associated with a lower AAC score (R  = 0.06, unstandardized coefficient [B] = -7.81, p = 0.03), and remained after adjustment for age, serum phosphate, serum parathyroid hormone, low-density lipoprotein cholesterol, smoking history, and diabetes (model adjusted R  = 0.36, serum Mg and AAC score B = -11.44, p = 0.00). This translates to a 0.1 mmol/L increase in serum Mg being independently associated with a 1.1-point decrease in AAC score.

Conclusions: Our findings suggest that Mg may inhibit vascular calcification. If this association is replicated across larger studies with serial Mg and vascular calcification measurements, interventions that increase serum Mg and their effect on vascular calcification warrant further investigation in the PD population.
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http://dx.doi.org/10.1186/s12882-017-0549-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382660PMC
April 2017

Derivation of a Predictive Model for Graft Loss Following Acute Kidney Injury in Kidney Transplant Recipients.

Can J Kidney Health Dis 2017 30;4:2054358116688228. Epub 2017 Jan 30.

Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ontario, Canada; Division of Nephrology, Department of Medicine, University of Ottawa, Ontario, Canada.

Background: Acute kidney injury (AKI) is common in the kidney transplant population.

Objective: To derive a multivariable survival model that predicts time to graft loss following AKI.

Design: Retrospective cohort study using health care administrative and laboratory databases.

Setting: Southwestern Ontario (1999-2013) and Ottawa, Ontario, Canada (1996-2013).

Patients: We included first-time kidney only transplant recipients who had a hospitalization with AKI 6 months or greater following transplant.

Measurements: AKI was defined using the Acute Kidney Injury Network criteria (stage 1 or greater). The first episode of AKI was included in the analysis. Graft loss was defined by return to dialysis or repeat kidney transplant.

Methods: We performed a competing risk survival regression analysis using the Fine and Gray method and modified the model into a simple point system. Graft loss with death as a competing event was the primary outcome of interest.

Results: A total of 315 kidney transplant recipients who had a hospitalization with AKI 6 months or greater following transplant were included. The median (interquartile range) follow-up time was 6.7 (3.3-10.3) years. Graft loss occurred in 27.6% of the cohort. The final model included 6 variables associated with an increased risk of graft loss: younger age, increased severity of AKI, failure to recover from AKI, lower baseline estimated glomerular filtration rate, increased time from kidney transplant to AKI admission, and receipt of a kidney from a deceased donor. The risk score had a concordance probability of 0.75 (95% confidence interval [CI], 0.69-0.82). The predicted 5-year risk of graft loss fell within the 95% CI of the observed risk more than 95% of the time.

Limitations: The CIs of the estimates were wide, and model overfitting is possible due to the limited sample size; the risk score requires validation to determine its clinical utility.

Conclusions: Our prognostic risk score uses commonly available information to predict the risk of graft loss in kidney transplant patients hospitalized with AKI. If validated, this predictive model will allow clinicians to identify high-risk patients who may benefit from closer follow-up or targeted enrollment in future intervention trials designed to improve outcomes.
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http://dx.doi.org/10.1177/2054358116688228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308519PMC
January 2017

The association of anticoagulation, ischemic stroke, and hemorrhage in elderly adults with chronic kidney disease and atrial fibrillation.

Kidney Int 2017 04 22;91(4):928-936. Epub 2016 Dec 22.

Division of Nephrology, University of Ottawa, Ottawa, Ontario, Canada; Institute for Clinical Evaluative Sciences, Ontario, Canada; Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. Electronic address:

The utility of anticoagulants for ischemic stroke prophylaxis in elderly patients with chronic kidney disease (CKD) and atrial fibrillation remains uncertain. In this population-based retrospective cohort study, we determined the association of anticoagulant use with ischemic stroke or hemorrhage in elderly patients (66 years and older) with advanced chronic kidney disease (eGFR under 45 ml/min/1.73m) and atrial fibrillation. We followed 6,544 patients with CKD and new onset atrial fibrillation, of whom 1,475 filled a prescription for an anticoagulant. We used propensity-score matched Cox proportional hazards and competing risk models to determine the time to first event of ischemic stroke, hemorrhage or mortality. After matching to examine exposure to anticoagulants, 1,417 matched pairs were identified. The crude rate of ischemic stroke and hemorrhage were 41.3 and 61.3 with anticoagulants and 34.4 and 34.3 without anticoagulants per 100 person-years, respectively. The hazard ratios of ischemic stroke, hemorrhage, and mortality for receipt of an anticoagulation prescription were 1.10 (95% confidence interval, 0.78-1.56), 1.42 (1.04-1.93), and 0.74 (0.62-0.88) as compared to non-receipt of anticoagulation. After accounting for the competing risk of death, the hazard ratios for ischemic stroke and hemorrhage were 1.12 (0.90-1.39) and 1.60 (1.31-1.97), respectively. The findings were consistent in a sensitivity analysis accounting for time varying anticoagulant exposure. Thus, in older patients with CKD and atrial fibrillation, receipt of an anticoagulant was not associated with a lower risk of ischemic stroke, but a higher risk of hemorrhage and a lower risk of mortality.
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http://dx.doi.org/10.1016/j.kint.2016.10.017DOI Listing
April 2017

Corticosteroid Use and Growth After Pediatric Solid Organ Transplantation: A Systematic Review and Meta-Analysis.

Transplantation 2017 Apr;101(4):694-703

1 Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada. 2 Division of Nephrology, Children's Hospital of Eastern Ontario, Ottawa, Canada. 3 Division of Nephrology, Kidney Research Centre, Department of Medicine, University of Ottawa, Ottawa, Canada. 4 Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Canada.

Background: A number of corticosteroid minimization and avoidance protocols for post-solid organ transplant have been developed. The study objective was to examine the effect of corticosteroid withdrawal/avoidance on growth and safety parameters in pediatric solid organ transplant recipients.

Methods: A systematic review using Medline and Embase was performed. All randomized controlled trials (RCT) and observational studies comparing corticosteroid withdrawal/avoidance to controls receiving corticosteroids in pediatric transplant recipients which reported growth as change in height or final height were included. Two reviewers independently abstracted study data and assessed quality.

Results: The search yielded 930 records, 14 separate studies involving 1146 patients. Renal RCTs (n = 5) showed that corticosteroid withdrawal/avoidance was associated with a significant increase in growth (mean difference in height standard deviation score [SDS], 0.18; 95% confidence interval [95% CI], 0.07-0.29; P = 0.001) compared with those remaining on steroids. In liver RCTs (n = 2), mean difference in height SDS was -0.20 (95% CI, -1.08 to 0.68; P = 0.66). Results for renal observational studies (n = 5) was 0.34 (95% CI, 0.03-0.65; P = 0.03). The most pronounced effect was seen in prepubertal children with SDS of 0.28 (95% CI, 0.14-0.41; P < 0.0001). In pubertal participants this was not observed (SDS, 0.06; 95% CI, -0.04 to 0.15; P = 0.24). Corticosteroid withdrawal/avoidance was not associated with acute rejection (odds ratio [OR], 0.87; P = 0.63), graft failure (OR, 0.45; P = 0.08), or death (OR, 0.34; P = 0.16) in renal trials.

Conclusions: Corticosteroid withdrawal/avoidance in pediatric renal transplantation is associated with a significant improvement in height. Prepubertal patients appeared to have the greatest benefit. Importantly, the improvement in growth was not accompanied by increased rejection or worsening patient/allograft survival in the short term.
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http://dx.doi.org/10.1097/TP.0000000000001320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228591PMC
April 2017

The association of urinary sodium excretion and the need for renal replacement therapy in advanced chronic kidney disease: a cohort study.

BMC Nephrol 2016 09 5;17(1):123. Epub 2016 Sep 5.

Division of Nephrology, Department of Medicine, The Ottawa Hospital, Ottawa, Canada.

Background: Restriction of dietary sodium is routinely recommended for patients with chronic kidney disease (CKD). Whether or not sodium intake is associated with the progression of CKD and mortality remains controversial. We evaluated the association of urinary sodium excretion (as a surrogate for sodium intake) on the need for renal replacement therapy and mortality in patients with advanced CKD.

Methods: We conducted a retrospective study of patients followed at a CKD clinic of a tertiary care hospital from January 2010 to December 2012. Adult patients with advanced CKD (estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m(2)) were included. Using a time-to-event analysis, we examined the association of urinary sodium excretion as a continuous and also as a categorical variable (categorized as low sodium diet - LSD (<100 mEq/day), medium sodium diet - MSD (100-150 mEq/day), and high sodium diet - HSD (>150 mEq/day) and the outcomes of interest. The primary outcome was defined as composite of progression to end-stage renal disease requiring any type of renal replacement therapy and mortality. The secondary outcome was change in eGFR/year.

Results: 341 patients (82 LSD, 116 MSD and 143 HSD) were included in the study (mean follow up of 1.5 years) with a mean eGFR decline of 2.7 ml/min/1.73 m(2)/year. 105 patients (31 %) required renal replacement therapy and 10 (3 %) died. There was no association between urinary sodium excretion and change in the eGFR or need for renal replacement therapy and mortality in crude or adjusted models (unadjusted HR 1.002; 95%CI 1.000-1.004, adjusted HR 1.001; 95%CI 0.998-1.004).

Conclusion: In patients with advanced CKD (eGFR < 30 ml/min/1.73 m(2)), sodium intake does not appear to impact the progression of CKD to end-stage renal disease; however, more definitive studies are needed.
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http://dx.doi.org/10.1186/s12882-016-0338-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011929PMC
September 2016

Risk factors for unplanned and crash dialysis starts: a protocol for a systematic review and meta-analysis.

Syst Rev 2016 07 19;5(1):117. Epub 2016 Jul 19.

Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

Background: Many patients with kidney failure "crash" onto dialysis or initiate dialysis in an unplanned fashion. There are varying definitions, but essentially, a patient is labeled as having a crash dialysis start if he or she has little to no care by a nephrologist prior to starting dialysis. A patient is labeled as having an unplanned dialysis start when he or she starts dialysis with a catheter or during a hospitalization. Given the high prevalence and poor outcomes associated with crash and unplanned dialysis starts, it is important to establish a better understanding of patient risk factors.

Methods: We will conduct a systematic review and meta-analysis with a focus on both crash and unplanned dialysis starts. The first objective will be to determine patient risk factors for crash and unplanned dialysis starts. Secondary objectives will be to determine the most common criteria used to define both crash and unplanned dialysis starts and to determine outcomes associated with crash and unplanned dialysis starts. We will search MEDLINE, EMBASE and Cochrane Library from inception to the present date for all studies that report the characteristics and outcomes of patients who have crash vs. non-crash dialysis starts or unplanned vs. planned dialysis starts. We will also extract from included studies the criteria used to define crash and unplanned dialysis starts. If there are any eligible randomized controlled trials, quality assessment will be performed using the Cochrane Risk of Bias Assessment Tool. Observational studies will be evaluated using the Newcastle-Ottawa Scale. Data will be pooled in meta-analysis if deemed appropriate.

Discussion: The results of this review will inform the design of strategies to help reduce the incidence of crash and unplanned dialysis starts.

Systematic Review Registration: Prospero CRD42016032916.
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http://dx.doi.org/10.1186/s13643-016-0297-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950106PMC
July 2016

Validation of administrative database codes for acute kidney injury in kidney transplant recipients.

Can J Kidney Health Dis 2016 7;3:18. Epub 2016 Apr 7.

Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario Canada ; Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario Canada.

Background: Validation studies of acute kidney injury (AKI) diagnostic codes performed in the general population have shown poor sensitivity, but the accuracy of such codes in the kidney transplant population remains unknown.

Objective: The objective of this study is to determine the accuracy of AKI diagnostic codes in kidney transplant recipients. We hypothesized that the sensitivity of diagnostic codes would be significantly greater in the kidney transplant population since these patients are closely followed by nephrologists and are more likely to have serum creatinine measured.

Design: The design is a population-based retrospective cohort study using healthcare administrative and laboratory databases.

Setting: The setting is in Southwestern Ontario and Ottawa, Ontario, Canada, from 2003 to 2012.

Patients: We included first-time kidney transplant recipients admitted to hospital for whom serum creatinine was measured in hospital and within 6 months prior (n = 524).

Methods: Patients meeting the Acute Kidney Injury Network (AKIN) classification serum creatinine change criteria were classified as having AKI. We determined the sensitivity, specificity, and negative and positive predictive values for the ICD-10-CA code for AKI when present as an admission diagnosis, most responsible diagnosis, or any diagnosis compared to a reference standard of AKI defined by the AKIN criteria (stage 1 or greater, stage 2 or greater, or stage 3).

Results: Forty-five percent of included kidney transplant patients had a diagnosis of AKI. The most sensitive coding algorithm (reference standard AKIN stage 2 or greater, ICD-10 code present as any diagnosis) had a sensitivity of 42.1 % (95 % CI 31.7, 53.3), a specificity of 90.6 % (95 % CI 87.6, 93.0), and a positive likelihood ratio of 4.5. The median (IQR) rise in serum creatinine from baseline in patients with and without AKI codes was 104 (57 to 158) μmol/L and 16 (-3 to 41) μmol/L, respectively (Mann-Whitney test, p < 0.0001).

Limitations: The low sensitivity of the AKI code may be due to an alternative diagnosis of acute rejection being assigned in certain cases. The cause of AKI could not be determined.

Conclusions: Similar to the general population, the ICD-10 N17x code misses many kidney transplant patients with AKI during their hospitalization. This makes the code unusable for studying the incidence and consequences of AKI in hospitalized kidney transplant patients.
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http://dx.doi.org/10.1186/s40697-016-0108-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823855PMC
April 2016
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