Publications by authors named "Adeera Levin"

406 Publications

Canagliflozin Reduces Kidney-Related Adverse Events in Type 2 Diabetes and CKD: Findings From the Randomized CREDENCE Trial.

Am J Kidney Dis 2021 May 21. Epub 2021 May 21.

The George Institute for Global Health, UNSW Sydney, Sydney, Australia;; Concord Repatriation General Hospital, Sydney, Australia.

Rationale And Objective: Canagliflozin reduced the risk of kidney failure and related outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in the CREDENCE trial. This analysis of CREDENCE trial data examines the effect of canagliflozin on the incidence of kidney-related adverse events (AEs).

Study Design: A randomized, double-blind, placebo-controlled, multicenter, international trial.

Setting And Participants: 4,401 trial participants with T2DM, CKD, and urinary albumin:creatinine ratio >300-5000mg/g.

Interventions: Participants were randomly assigned to receive canagliflozin 100mg/day or placebo.

Outcomes: Rates of kidney-related AEs were analyzed using an on-treatment approach, overall and by screening estimated glomerular filtration rate (eGFR) strata (30-<45, 45-<60, and 60-<90 mL/min/1.73m).

Results: Canagliflozin was associated with a reduction in the overall incidence rate of kidney-related AEs (60.2 vs 84.0 per 1,000 patient-years; hazard ratio [HR]: 0.71 [95% confidence interval (CI): 0.61, 0.82]; P<0.001), with consistent results for serious kidney-related AEs (HR: 0.72 [95% CI: 0.51, 1.00]; P=0.05) and acute kidney injury (AKI; HR: 0.85 [95% CI: 0.64, 1.13]; P=0.3). The rates of kidney-related AEs were lower with canagliflozin relative to placebo across the 3 eGFR strata (HRs of 0.73, 0.60, and 0.81 for eGFR 30-<45, 45-<60, and 60-<90 mL/min/1.73m, respectively; P-interaction=0.3), with similar results for AKI (P-interaction=0.9). Full recovery of kidney function within 30 days after an AKI event occurred more frequently with canagliflozin versus placebo (53.1% vs 35.4%; odds ratio: 2.2 [95% CI: 1.0, 4.7]; P=0.04).

Limitations: Kidney-related AEs including AKI were investigator-reported and collected without central adjudication. Biomarkers of AKI and structural tubular damage were not measured and creatinine data after an AKI event were not available for all participants.

Conclusion: Canagliflozin compared to placebo was associated with a reduced incidence of serious and non-serious kidney-related AEs in patients with T2DM and CKD. These results highlight the safety of canagliflozin with regard to adverse kidney disease events.
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http://dx.doi.org/10.1053/j.ajkd.2021.05.005DOI Listing
May 2021

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in Western Europe.

Kidney Int Suppl (2011) 2021 May 12;11(2):e106-e118. Epub 2021 Apr 12.

Intensive Care Nephrology and Transplantation Department, Hopital Tenon, Assistance Publique-Hopitaux de Paris, Paris, France.

Populations in the high-income countries of Western Europe are aging due to increased life expectancy. As the prevalence of diabetes and obesity has increased, so has the burden of kidney failure. To determine the global capacity for kidney replacement therapy and conservative kidney management, the International Society of Nephrology conducted multinational, cross-sectional surveys and published the findings in the International Society of Nephrology Global Kidney Health Atlas. In the second iteration of the International Society of Nephrology Global Kidney Health Atlas, we aimed to describe the availability, accessibility, quality, and affordability of kidney failure care in Western Europe. Among the 29 countries in Western Europe, 21 (72.4%) responded, representing 99% of the region's population. The burden of kidney failure prevalence varied widely, ranging from 760 per million population (pmp) in Iceland to 1612 pmp in Portugal. Coverage of kidney replacement therapy from public funding was nearly universal, with the exceptions of Germany and Liechtenstein where part of the costs was covered by mandatory insurance. Fourteen (67%) of 21 countries charged no fees at the point of care delivery, but in 5 countries (24%), patients do pay some out-of-pocket costs. Long-term dialysis services (both hemodialysis and peritoneal dialysis) were available in all countries in the region, and kidney transplantation services were available in 19 (90%) countries. The incidence of kidney transplantation varied widely between countries from 12 pmp in Luxembourg to 70.45 pmp in Spain. Conservative kidney care was available in 18 (90%) of 21 countries. The median number of nephrologists was 22.9 pmp (range: 9.47-55.75 pmp). These data highlight the uniform capacity of Western Europe to provide kidney failure care, but also the scope for improvement in disease prevention and management, as exemplified by the variability in disease burden and transplantation rates.
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http://dx.doi.org/10.1016/j.kisu.2021.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084721PMC
May 2021

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in South Asia.

Kidney Int Suppl (2011) 2021 May 12;11(2):e97-e105. Epub 2021 Apr 12.

George Institute for Global Health, University of New South Wales (UNSW), New Delhi, India.

Information about disease burden and the available infrastructure and workforce to care for patients with kidney disease was collected for the second edition of the International Society of Nephrology Global Kidney Health Atlas. This paper presents findings for the 8 countries in the South Asia region. The World Bank categorizes Afghanistan and Nepal as low-income; Bangladesh, Bhutan, India, and Pakistan as lower-middle-income; and Sri Lanka and the Maldives as upper-middle-income countries. The prevalence of chronic kidney disease (CKD) in South Asia ranged from 5.01% to 13.24%. Long-term hemodialysis and long-term peritoneal dialysis are available in all countries, but Afghanistan lacks peritoneal dialysis services. Kidney transplantation was available in all countries except Bhutan and Maldives. Hemodialysis was the dominant modality of long-term dialysis, peritoneal dialysis was more expensive than hemodialysis, and kidney transplantation overwhelmingly depended on living donors. Bhutan provided public funding for kidney replacement therapy (dialysis and transplantation); Sri Lanka, India, Pakistan, and Bangladesh had variable funding mechanisms; and Afghanistan relied solely on out-of-pocket expenditure. There were shortages of health care personnel across the entire region. Reporting was variable: Afghanistan and Sri Lanka have dialysis registries but publish no reports, whereas Bangladesh has a transplant registry. South Asia has a large, but poorly documented burden of CKD. Diabetes and hypertension are the major causes of CKD throughout the region with a higher prevalence of infectious causes in Afghanistan and a high burden of CKD of an unknown cause in Sri Lanka and parts of India. The extent and quality of care delivery is suboptimal and variable. Sustainable strategies need to be developed to address the growing burden of CKD in the region.
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http://dx.doi.org/10.1016/j.kisu.2021.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084730PMC
May 2021

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in Oceania and South East Asia.

Kidney Int Suppl (2011) 2021 May 12;11(2):e86-e96. Epub 2021 Apr 12.

Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.

Oceania and South East Asia (OSEA) is a socioeconomically, culturally, and ethnically diverse region facing a rising epidemic of noncommunicable diseases, including chronic kidney disease (CKD). The second iteration of the International Society of Nephrology Global Kidney Health Atlas aimed to provide a comprehensive evaluation of kidney care in OSEA. Of the 30 countries/territories in OSEA, 15 participated in the survey, representing 98.5% of the region's population. The median prevalence of treated kidney failure in OSEA was 1352 per million population (interquartile range, 966-1673 per million population), higher than the global median of 787 per million population. Although the general availability, access, and quality of kidney replacement therapy (i.e., dialysis and transplantation) was high in OSEA, inequalities in accessibility and affordability of kidney replacement therapy across the region resulted in variability between countries. According to the survey results, in a third of the participating countries (mostly lower-income countries), less than half the patients with kidney failure were able to access dialysis, whereas it was readily available to all with minimal out-of-pocket costs in high-income countries; similar variability in access to transplantation was also recorded. Limitations in workforce and resources vary across the region and were disproportionately worse in lower-income countries. There was little advocacy for kidney disease, moderate use of registries, restricted CKD detection programs, and limited availability of routine CKD testing in some high-risk groups across the region. International collaborations, as seen in OSEA, are important initiatives to help close the gaps in CKD care provision across the region and should continue receiving support from the global nephrology community.
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http://dx.doi.org/10.1016/j.kisu.2021.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084715PMC
May 2021

International Society of Nephrology Global Kidney Health Atlas: structures, organization and services for the management of kidney failure in North and East Asia.

Kidney Int Suppl (2011) 2021 May 12;11(2):e77-e85. Epub 2021 Apr 12.

Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.

Kidney failure (KF) is a public health problem in all regions of the world. We aim to provide comprehensive information regarding the disease burden of KF and capacity for providing optimal care in the International Society of Nephrology North and East Asia region based on data from the International Society of Nephrology Global Kidney Health Atlas project. Seven of eight jurisdictions participated, and wide variation was found in terms of KF burden and care capacity. Prevalence of long-term dialysis ranged from 88.4 per million population in mainland China to 3251 per million population in Taiwan. Hemodialysis was the predominant modality of dialysis in all jurisdictions, except for Hong Kong, where peritoneal dialysis (PD) was much more prevalent than hemodialysis. All jurisdictions provided public funding for kidney replacement therapy (dialysis and transplantation). Although the frequency and duration of hemodialysis followed a standard pattern in all investigated jurisdictions, the density of nephrologists and kidney replacement therapy centers varied according to income level. Conservative care, whether medically advised or chosen by patients, was available in most jurisdictions. All jurisdictions had official registries for KF and recognized KF as a health priority. These comprehensive data provide information about the burden of KF and capacity to provide optimal care in North and East Asia, which varied greatly across jurisdictions in the region.
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http://dx.doi.org/10.1016/j.kisu.2021.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084719PMC
May 2021

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in North America and the Caribbean.

Kidney Int Suppl (2011) 2021 May 12;11(2):e66-e76. Epub 2021 Apr 12.

Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

The International Society of Nephrology established the Global Kidney Health Atlas project to define the global capacity for kidney replacement therapy and conservative kidney care, and this second iteration was to describe the availability, accessibility, quality, and affordability of kidney failure (KF) care worldwide. This report presents results for the International Society of Nephrology North America and the Caribbean region. Relative to other regions, the North America and Caribbean region had better infrastructure and funding for health care and more health care workers relative to the population. Various essential medicines were also more available and accessible. There was substantial variation in the prevalence of treated KF in the region, ranging from 137.4 per million population (pmp) in Jamaica to 2196 pmp in the United States. A mix of public and private funding systems cover costs for nondialysis chronic kidney disease care in 60% of countries and for dialysis in 70% of countries. Although the median number of nephrologists is 18.1 (interquartile range, 15.3-29.5) pmp, which is approximately twice the global median of 9.9 (interquartile range, 1.2-22.7) pmp, some countries reported shortages of other health care workers. Dialysis was available in all countries, but peritoneal dialysis was underutilized and unavailable in Barbados, Cayman Islands, and Turks and Caicos. Kidney transplantation was primarily available in Canada and the United States. Economic factors were the major barriers to optimal KF care in the Caribbean countries, and few countries in the region have chronic kidney disease-specific national health care policies. To address regional gaps in KF care delivery, efforts should be directed toward augmenting the workforce, improving the monitoring and reporting of kidney replacement therapy indicators, and implementing noncommunicable disease and chronic kidney disease-specific policies in all countries.
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http://dx.doi.org/10.1016/j.kisu.2021.01.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084729PMC
May 2021

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in Newly Independent States and Russia.

Kidney Int Suppl (2011) 2021 May 12;11(2):e57-e65. Epub 2021 Apr 12.

High Technology Medical Center University Clinic, Tbilisi State Medical University, Tbilisi, Georgia.

The International Society of Nephrology Global Kidney Health Atlas analyzed the current state of kidney care in Newly Independent States and Russia. Our results demonstrated that the Newly Independent States and Russia region was not an exception and showed the same effect of chronic kidney disease on health and its outcomes, facing many difficulties and challenges in terms of improving kidney care across the countries. This work summarized and presented demographics, health information systems, statistics, and national health policy of the region, as well as characteristics of the burden of chronic kidney disease and kidney failure (KF) of participating countries. Besides significant economic advancement in the region, the collected data revealed existing shortage in KF care providers, essential medications, and health product access for KF care. Moreover, there was low reporting of kidney replacement therapy (dialysis and kidney transplantation) quality indicators and low capacity for long-term hemodialysis, peritoneal dialysis, and kidney transplantation. The financial issues and funding structures for KF care across the region needs strategic support for fundamental changes and further advancement. This article emphasizes the urgent need for further effective regional and international collaborations and partnership for establishment of universal health care systems for KF management.
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http://dx.doi.org/10.1016/j.kisu.2021.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084727PMC
May 2021

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in the Middle East.

Kidney Int Suppl (2011) 2021 May 12;11(2):e47-e56. Epub 2021 Apr 12.

Division of Nephrology, Department of Medicine, Hasheminejad Kidney Center, Iran University of Medical Sciences, Tehran, Iran.

Kidney failure is the permanent impairment of kidney function associated with increased morbidity, hospitalization, and requirement for kidney replacement therapy. A total of 11 countries in the Middle East region (84.6%) responded to the survey. The prevalence of chronic kidney disease in the region ranged from 5.2% to 10.6%, whereas prevalence of treated kidney failure ranged from 152 to 826 per million population. Overall, the incidence of kidney transplantation was highest in Iran (30.9 per million population) and lowest in Oman and the United Arab Emirates (2.2 and 3.0 per million population, respectively). Long-term hemodialysis services were available in all countries, long-term peritoneal dialysis services were available in 9 (69.2%) countries, and transplantation services were available in most countries of the region. Public funding covered the costs of nondialysis chronic kidney disease care in two-thirds of countries, and kidney replacement therapy in nearly all countries. More than half of the countries had dialysis registries; however, national noncommunicable disease strategies were lacking in most countries. The Middle East is a region with high burden of kidney disease and needs cost-effective measures through effective health care funding to be available to improve kidney care in the region. Furthermore, well-designed and sustainable health information systems are needed in the region to address current gaps in kidney care in the region.
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http://dx.doi.org/10.1016/j.kisu.2021.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084726PMC
May 2021

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in Latin America.

Kidney Int Suppl (2011) 2021 May 12;11(2):e35-e46. Epub 2021 Apr 12.

Department of Nephrology, Metro South and Ipswich Nephrology and Transplant Services, Princess Alexandra Hospital, Brisbane, Queensland, Australia.

Latin America is a region with a widely variable socioeconomic landscape, facing a surge in noncommunicable diseases, including chronic kidney disease and kidney failure, exposing significant limitations in the delivery of care. Despite region-wide efforts to explore and address these limitations, much uncertainty remains as to the capacity, accessibility, and quality of kidney failure care in Latin America. Through this second iteration of the International Society of Nephrology Global Kidney Health Atlas, we aimed to report on these indicators to provide a comprehensive map of kidney failure care in the region. Survey responses were received from 18 (64.2%) countries, representing 93.8% of the total population in Latin America. The median prevalence and incidence of treated kidney failure in Latin America were 715 and 157 per million population, respectively, the latter being higher than the global median (142 per million population), with Puerto Rico, Mexico, and El Salvador experiencing much of this growing burden. In most countries, public and private systems collectively funded most aspects of kidney replacement therapy (dialysis and transplantation) care, with patients incurring at least 1% to 25% of out-of-pocket costs. In most countries, >90% of dialysis patients able to access kidney replacement therapy received hemodialysis (n = 11; 5 high income and 6 upper-middle income), and only a small minority began with peritoneal dialysis (1%-10% in 67% of countries; n = 12). Few countries had chronic kidney disease registries or targeted detection programs. There is a large variability in the availability, accessibility, and quality of kidney failure care in Latin America, which appears to be subject to individual countries' funding structures, underreliance on cheap kidney replacement therapy, such as peritoneal dialysis, and limited chronic kidney disease surveillance and management initiatives.
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http://dx.doi.org/10.1016/j.kisu.2021.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084731PMC
May 2021

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in Eastern and Central Europe.

Kidney Int Suppl (2011) 2021 May 12;11(2):e24-e34. Epub 2021 Apr 12.

Division of Nephrology, Bezmialem Vakif University, Istanbul, Turkey.

Provision of adequate kidney care for patients with chronic kidney disease or kidney failure (KF) is costly and requires extensive resources. There is an inequality in the global distribution of wealth and resources needed to provide this care. In this second iteration of the International Society of Nephrology Global Kidney Health Atlas, we present data for countries in Eastern and Central Europe. In the region, the median prevalence of chronic kidney disease was 13.15% and treated KF was 764 per million population, respectively, slightly higher than the global median of 759 per million population. In most countries in the region, over 90% of dialysis patients were on hemodialysis and patients with a functioning graft represented less than one-third of total patients with treated KF. The median annual costs for maintenance hemodialysis were close to the global median, and public funding provided nearly universal coverage of the costs of kidney replacement therapy. Nephrologists were primarily responsible for KF care. All countries had the capacity to provide long-term hemodialysis, and 95% had the capacity to provide peritoneal dialysis. Home hemodialysis was generally not available. Kidney transplantation and conservative care were available across most of the region. Almost all countries had official dialysis and transplantation registries. Eastern and Central Europe is a region with a high burden of chronic kidney disease and variable capacity to deal with it. Insufficient funding and workforce shortages coupled with increasing comorbidities among aging patients and underutilization of cost-effective dialysis therapies such as peritoneal dialysis and kidney transplantation may compromise the quality of care for patients with KF. Some workforce shortages could be addressed by improving the organization of nephrological care in some countries of the region.
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http://dx.doi.org/10.1016/j.kisu.2021.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084718PMC
May 2021

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in Africa.

Kidney Int Suppl (2011) 2021 May 12;11(2):e11-e23. Epub 2021 Apr 12.

Urinary Tract Diseases Department, Faculty of Medicine and Pharmacy of Casablanca, University Hassan II of Casablanca, Casablanca, Morocco.

Despite positive economic forecasts, stable democracies, and reduced regional conflicts since the turn of the century, Africa continues to be afflicted by poverty, poor infrastructure, and a massive burden of communicable diseases such as HIV, malaria, tuberculosis, and diarrheal illnesses. With the rising prevalence of chronic kidney disease and kidney failure worldwide, these factors continue to hinder the ability to provide kidney care for millions of people on the continent. The International Society of Nephrology Global Kidney Health Atlas project was established to assess the global burden of kidney disease and measure global capacity for kidney replacement therapy (dialysis and kidney transplantation). The aim of this second iteration of the International Society of Nephrology Global Kidney Health Atlas was to evaluate the availability, accessibility, affordability, and quality of kidney care worldwide. We identified several gaps regarding kidney care in Africa, chief of which are (i) severe workforce limitations, especially in terms of the number of nephrologists; (ii) low government funding for kidney care; (iii) limited availability, accessibility, reporting, and quality of provided kidney replacement therapy; and (iv) weak national strategies and advocacy for kidney disease. We also identified that within Africa, the availability and accessibility to kidney replacement therapy vary significantly, with North African countries faring far better than sub-Sahara African countries. The evidence suggests an urgent need to increase the workforce and government funding for kidney care, collect adequate information on the burden of kidney disease from African countries, and develop and implement strategies to enhance disease prevention and control across the continent.
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http://dx.doi.org/10.1016/j.kisu.2021.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084720PMC
May 2021

Global variation in kidney care: national and regional differences in the care and management of patients with kidney failure.

Kidney Int Suppl (2011) 2021 May 12;11(2):e1-e3. Epub 2021 Apr 12.

Department of Nephrology, Metro South and Ipswich Nephrology and Transplant Services (MINTS), Princess Alexandra Hospital, Brisbane, Queensland, Australia.

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http://dx.doi.org/10.1016/j.kisu.2020.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084722PMC
May 2021

Therapy for Anemia in Chronic Kidney Disease - New Interventions and New Questions.

Authors:
Adeera Levin

N Engl J Med 2021 04;384(17):1657-1658

From the Division of Nephrology, University of British Columbia, Vancouver, Canada.

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http://dx.doi.org/10.1056/NEJMe2103937DOI Listing
April 2021

Temporal Trends in Hemoglobin, Use of Erythropoiesis Stimulating Agents, and Major Clinical Outcomes in Incident Dialysis Patients in Canada.

Kidney Int Rep 2021 Apr 5;6(4):1130-1140. Epub 2021 Jan 5.

University of British Columbia, Division of Nephrology, Vancouver, British Columbia, Canada.

Introduction: Several jurisdictions have adopted a more conservative approach to anemia in patients receiving dialysis amid safety concerns from target hemoglobin studies. It is largely unknown if this has contributed to a change in clinical outcomes.

Methods: A national registry was used to identify 35,945 adult patients who initiated and were maintained on dialysis for ≥90 days in Canada from January 2007 to December 2015. Outcomes were ascertained until March 2017 via linkage with hospital discharge diagnoses. Cox proportional hazards models were used to investigate the association between the era of dialysis initiation and the primary composite outcome (acute myocardial infarction [AMI], stroke, or mortality).

Results: The mean hemoglobin at dialysis initiation decreased from 102.9 g/l in 2007 to 95.5 g/l in 2015, corresponding with a higher prevalence of hemoglobin <80 g/l (8% to 17%) and a reduction in erythropoiesis stimulating agent (ESA) use (49% to 44%). After multivariable adjustment, Era 3 (2013-2015) was associated with an 8% relative risk reduction in the primary outcome compared with Era 1 (2007-2009) (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.88-0.96), a 10% relative reduction in mortality (HR 0.90, 95% CI 0.85-0.94) but no significant change in AMI or stroke. In a model without era, neither hemoglobin nor ESA use was an independent predictor of outcome.

Conclusion: There have been modest declines in average hemoglobin values and ESA use among incident dialysis patients in Canada with no change in major cardiovascular outcomes. Patient survival has improved over time, likely for reasons other than anemia management.
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http://dx.doi.org/10.1016/j.ekir.2020.12.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071619PMC
April 2021

Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis.

Stroke 2021 May 20;52(5):1545-1556. Epub 2021 Apr 20.

Westmead Applied Research Centre, University of Sydney, Sydney, Australia (R.I.L.).

Background And Purpose: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus.

Methods: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis.

Results: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HR, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HR, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HR, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HR, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HR, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (=0.01), with protection in the lowest estimated glomerular filtration rate (<45 mL/min/1.73 m]) subgroup (HR, 0.50 [95% CI, 0.31-0.79]).

Conclusions: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791.
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http://dx.doi.org/10.1161/STROKEAHA.120.031623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078131PMC
May 2021

Evidence-Based Decision Making 4: Clinical Practice Guidelines.

Methods Mol Biol 2021 ;2249:455-466

Division of Nephrology, University of British Colombia, Vancouver, BC, Canada.

Clinical practice guidelines (CPGs) are systematically developed statements to assist practitioners and patient to reach appropriate health-care decisions. The synthesis and translation of a large amount of evidence into practice recommendations should ultimately reduce the use of unnecessary or harmful interventions, help patients to achieve maximum benefit, and minimize risk, all at an acceptable cost.In the past, CPGs were developed based on expert opinion, and using consensus methodology either formally or informally. Over the last 30 years, the evolution of increasingly transparent and robust methodology has led to more "evidence-based" recommendations. Clinical practice guidelines should be developed within the principles of bias minimization, systematic evidence retrieval and review, and a focus on patient relevant outcomes. Multiple nationally based and international groups now have published specific guidance for the development, dissemination, and evaluation of CPG.This chapter describes the key principles of CPG development, including the importance of updating, disseminating, and evaluating the impact of CPG , and attempts to differentiate CPG intended for populations of patients from "evidence-based decision making" for individual patients, recognizing that the fundamental principles are the same.
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http://dx.doi.org/10.1007/978-1-0716-1138-8_24DOI Listing
January 2021

Controversies in optimal anemia management: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference.

Kidney Int 2021 Jun 8;99(6):1280-1295. Epub 2021 Apr 8.

Inserm Unit 1018, Team 5, CESP, Hôpital Paul Brousse, Paris-Sud University (UPS), Villejuif, France; Versailles Saint-Quentin-en-Yvelines University (Paris-Ile-de-France-Ouest University, UVSQ), Villejuif, France. Electronic address:

In chronic kidney disease, anemia and disordered iron homeostasis are prevalent and associated with significant adverse consequences. In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) issued an anemia guideline for managing the diagnosis, evaluation, and treatment of anemia in chronic kidney disease. Since then, new data have accrued from basic research, epidemiological studies, and randomized trials that warrant a re-examination of previous recommendations. Therefore, in 2019, KDIGO decided to convene 2 Controversies Conferences to review the latest evidence, explore new and ongoing controversies, assess change implications for the current KDIGO anemia guideline, and propose a research agenda. The first conference, described here, focused mainly on iron-related issues, including the contribution of disordered iron homeostasis to the anemia of chronic kidney disease, diagnostic challenges, available and emerging iron therapies, treatment targets, and patient outcomes. The second conference will discuss issues more specifically related to erythropoiesis-stimulating agents, including epoetins, and hypoxia-inducible factor-prolyl hydroxylase inhibitors. Here we provide a concise overview of the consensus points and controversies resulting from the first conference and prioritize key questions that need to be answered by future research.
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http://dx.doi.org/10.1016/j.kint.2021.03.020DOI Listing
June 2021

The Global Kidney Health Atlas: Burden and Opportunities to Improve Kidney Health Worldwide.

Ann Nutr Metab 2020 26;76 Suppl 1:25-30. Epub 2021 Mar 26.

Division of Nephrology, Providence Health Care, University of British Columbia, Vancouver, British Columbia, Canada.

CKD is a growing public health problem. The Global Kidney Health Atlas (GKHA) is an important initiative of the International Society of Nephrology. The GKHA aims to improve the understanding of inter- and intranational variability across the globe, focusing on capacity for kidney care delivery. The GKHA survey was launched in 2017 and then again in 2019, using the same core data, supplemented by information about dialysis access and conservative care. Based on a WHO framework of the 6 building blocks essential for health care, the GKHA assesses capacity in 6 domains: information systems, services delivery, workforce, financing, access to essential medicines, and leadership/governance. In addition, the GKHA assesses the capacity for research in all regions of the world, across all domains (basic, translational, clinical, and health system research). The results of the GKHA have informed policy and been used to enhance advocacy strategies in different regions. In addition, through documentation of the disparities within and between countries and regions, initiatives have been launched to foster change. Since the first survey, there has been an increase in the number of countries which have registries to document the burden of CKD or dialysis. For many, information about the burden of disease is the first step toward addressing care delivery issues, including prevention, delay of progression, and access to services. Worldwide collaboration in the documentation of kidney health and disease is an important step toward the goal of ensuring equitable access to kidney health worldwide.
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http://dx.doi.org/10.1159/000515329DOI Listing
March 2021

Validity of different dose reduction criteria for apixaban.

Am Heart J 2021 Mar 21;238:12-15. Epub 2021 Mar 21.

Centre for Cardiovascular Innovation, University of British Columbia, Vancouver, British Columbia, Canada.

Reduced-dose apixaban is recommended in patients fulfilling 2 of 3 criteria: age ≥80 years, body weight ≤60 kg, and serum creatinine ≥1.5 mg/dL. However, patient weight is often not available in electronic health data. We examined the validity of alternative definitions based on age and renal function alone using an observational dataset of patients with atrial fibrillation and chronic kidney disease which included weight measurements.
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http://dx.doi.org/10.1016/j.ahj.2021.03.004DOI Listing
March 2021

The CSN COVID-19 Rapid Response Program.

Can J Kidney Health Dis 2020 21;7:2054358120949110. Epub 2020 Oct 21.

Faculty of Medicine, The Ottawa Hospital, Ontario, Canada.

The coronavirus disease (COVID-19) pandemic has created unprecedented challenges in caring for individuals living with kidney disease. In response to a growing call for up-to-date information and evidence-informed advice, the Canadian Society of Nephrology has established a COVID-19 Rapid Response Team that will leverage existing evidence and national expertise to inform kidney care practices in the COVID-19 era. Given limited published evidence and compressed timelines, formal clinical practice guidelines are not feasible, and we have adopted rapid review methods to instead provide interim guidance across identified priority areas. In this article, we describe the methodological approach that was applied in developing a first iteration of guidance documents addressing clinical and operational aspects of care for patients treated with in-center hemodialysis, home dialysis, those with advanced chronic kidney disease, those with glomerulonephritis, and those with acute kidney injury. We further describe strategies for maintaining ongoing engagement with the renal community to elicit emerging needs and perspectives as the situation unfolds.
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http://dx.doi.org/10.1177/2054358120949110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907929PMC
October 2020

Slowing Progression in CKD: DAPA CKD and Beyond.

Clin J Am Soc Nephrol 2021 Mar 10. Epub 2021 Mar 10.

Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada

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http://dx.doi.org/10.2215/CJN.20211220DOI Listing
March 2021

QALYs, DALYs and Now PALYs: Strengthening the Argument for Prevention of CKD.

J Am Soc Nephrol 2021 Mar 9. Epub 2021 Mar 9.

Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada

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http://dx.doi.org/10.1681/ASN.2021020208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017541PMC
March 2021

Maintaining the Uptake of Peritoneal Dialysis During the COVID-19 Pandemic: A Research Letter.

Can J Kidney Health Dis 2021 15;8:2054358120986265. Epub 2021 Feb 15.

Division of Nephrology, University of British Columbia, Vancouver, Canada.

Background: Due to inherent challenges in maintaining physical distancing in hemodialysis units, the Canadian Society of Nephrology has recommended peritoneal dialysis as the preferred modality for patients requiring maintenance dialysis during the coronavirus disease 19 (COVID-19) pandemic. However, pursuing peritoneal dialysis is not without risk due to the requirement for in-person contact during catheter insertion and training, and there is a paucity of data regarding the experience of peritoneal dialysis during the early phases of the pandemic.

Objective: To examine the incidence and outcomes of peritoneal dialysis between March 17 and June 01, 2020 compared to the same time period in preceding years.

Design: Retrospective observational study.

Setting: British Columbia, Canada. After the pandemic was declared on March 17, 2020, patients continued to be trained in peritoneal dialysis. In an effort to limit time spent in hospital, patients were preferentially trained in continuous ambulatory peritoneal dialysis, training times were truncated for some patients, and peritoneal dialysis catheters were inserted by a physician at the bedside whenever feasible.

Patients: All patients aged >18 years who started chronic maintenance dialysis during the period March 17 to June 01 in the years 2018 to 2020 inclusive. The time period was extended to include the years 2010 to 2020 inclusive to evaluate longer term trends in dialysis incidence.

Measurements: A provincial clinical information system was used to capture the date of commencing dialysis, dialysis modality, and complications including peritonitis. Overall uptake of peritoneal dialysis included new starts and transitions to peritoneal dialysis from in-center hemodialysis during the observation period.

Methods: The incidence of dialysis during the specified time period, overall and by modality, was calculated per million population using census figures for the population at risk. Patients were followed for a minimum of 30 days from the start of peritoneal dialysis to capture episodes of peritonitis and COVID-19.

Results: A total of 211 patients started maintenance dialysis between March 17 and June 01, 2020. The incidence dialysis rate (41.3 per million population) was lower than that expected based on the 10-year trend from 2010 to 2019 inclusive (expected rate 45.7 per million population, 95% confidence interval 41.7 to 50.1). A total of 93 patients started peritoneal dialysis, including 32 patients who transitioned from in-center hemodialysis, contributing to a higher overall uptake of peritoneal dialysis compared to preceding years. The incidence rate for peritoneal dialysis of 18.2 per million population was higher than that expected (16.3 per million population, 95% confidence interval 14.0 to 19.0). Half of patients (48%) underwent a bedside peritoneal dialysis catheter insertion by a physician. During 30 days of follow-up, 2 (2.2%) patients experienced peritonitis and no patients were diagnosed with COVID-19.

Limitations: Results are short term and generalizable only to regions with similarly low community rates of transmission of severe acute respiratory syndrome coronavirus 2.

Conclusions: These preliminary findings indicate that peritoneal dialysis can be safely started and perhaps expanded as a means of mitigating the anticipated surge in in-center hemodialysis during the COVID-19 pandemic. Important contributors to the uptake of peritoneal dialysis in British Columbia were bedside catheter insertions and expediting transitions from in-center hemodialysis to peritoneal dialysis.
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http://dx.doi.org/10.1177/2054358120986265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894581PMC
February 2021

Kidney, Cardiovascular, and Safety Outcomes of Canagliflozin according to Baseline Albuminuria: A CREDENCE Secondary Analysis.

Clin J Am Soc Nephrol 2021 Mar 22;16(3):384-395. Epub 2021 Feb 22.

The George Institute for Global Health, University of New South Wales Sydney, Sydney, Australia.

Background And Objectives: The kidney protective effects of renin-angiotensin system inhibitors are greater in people with higher levels of albuminuria at treatment initiation. Whether this applies to sodium-glucose cotransporter 2 (SGLT2) inhibitors is uncertain, particularly in patients with a very high urine albumin-to-creatinine ratio (UACR; ≥3000 mg/g). We examined the association between baseline UACR and the effects of the SGLT2 inhibitor, canagliflozin, on efficacy and safety outcomes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) randomized controlled trial.

Design, Setting, Participants, & Measurements: The study enrolled 4401 participants with type 2 diabetes, an eGFR of 30 to <90 ml/min per 1.73 m, and UACR of >300 to 5000 mg/g. Using Cox proportional hazards regression, we examined the relative and absolute effects of canagliflozin on kidney, cardiovascular, and safety outcomes according to a baseline UACR of ≤1000 mg/g (=2348), >1000 to <3000 mg/g (=1547), and ≥3000 mg/g (=506). In addition, we examined the effects of canagliflozin on UACR itself, eGFR slope, and the intermediate outcomes of glycated hemoglobin, body weight, and systolic BP.

Results: Overall, higher UACR was associated with higher rates of kidney and cardiovascular events. Canagliflozin reduced efficacy outcomes for all UACR levels, with no evidence that relative benefits varied between levels. For example, canagliflozin reduced the primary composite outcome by 24% (hazard ratio [HR], 0.76; 95% confidence interval [95% CI], 0.56 to 1.04) in the lowest UACR subgroup, 28% (HR, 0.72; 95% CI, 0.56 to 0.93) in the UACR subgroup >1000 to <3000 mg/g, and 37% (HR, 0.63; 95% CI, 0.47 to 0.84) in the highest subgroup (=0.55). Absolute risk reductions for kidney outcomes were greater in participants with higher baseline albuminuria; the number of primary composite events prevented across ascending UACR categories were 17 (95% CI, 3 to 38), 45 (95% CI, 9 to 81), and 119 (95% CI, 35 to 202) per 1000 treated participants over 2.6 years (=0.02). Rates of kidney-related adverse events were lower with canagliflozin, with a greater relative reduction in higher UACR categories.

Conclusions: Canagliflozin safely reduces kidney and cardiovascular events in people with type 2 diabetes and severely increased albuminuria. In this population, the relative kidney benefits were consistent over a range of albuminuria levels, with greatest absolute kidney benefit in those with an UACR ≥3000 mg/g.

Clinical Trial Registry Name And Registration Number: ClinicalTrials.gov: CREDENCE, NCT02065791.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_02_22_CJN15260920_final.mp3.
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http://dx.doi.org/10.2215/CJN.15260920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011002PMC
March 2021

Adapting Nephrology Training Curriculum in the Era of COVID-19.

Can J Kidney Health Dis 2021 5;8:2054358120988446. Epub 2021 Feb 5.

Division of Nephrology, The University of British Columbia, Vancouver, Canada.

Purpose Of Review: The COVID-19 pandemic has widespread implications not only for clinical practice but also for academic medicine and postgraduate training. The need to promote physical distancing and flexibility within our department has generated important revisions to the core curriculum for the Adult Nephrology Training Program in Vancouver, Canada.

Sources Of Information: We reviewed available educational resources and objectives to develop curricular adaptations informed by staff and trainee feedback.

Methods: Many facets of the program including clinical rotations, scholarly activities, evaluation, and wellness have been impacted, and thus revised for online delivery where possible. Trainees have personalized a learning plan based on individual goals and supplemented by a list of internet-based resources for independent review. Changes in learning objectives and methods for specific rotations have occurred and are described. Ongoing evaluation will be undertaken.

Key Findings: Curriculum adaptation in the era of COVID-19 is necessary to ensure ongoing high-quality education for future nephrologists. We describe existing changes to formal training in British Columbia (BC), which will be tailored as the pandemic evolves, and anticipate them to have lasting impact on the way we structure training programs in the future. Standardization and harmonization of modified curriculum may be possible across Canada with sharing of these learnings.

Limitations: Formal evaluation of these changes in terms of knowledge acquisition and examination performance has not yet been undertaken. Next steps will include assessing and documenting the impact of this curricular transformation to further optimize scheduling, educational yield, and trainee wellness.
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http://dx.doi.org/10.1177/2054358120988446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868498PMC
February 2021

Balancing the Needs of Acute and Maintenance Dialysis Patients during the COVID-19 Pandemic: A Proposed Ethical Framework for Dialysis Allocation.

Clin J Am Soc Nephrol 2021 Feb 8. Epub 2021 Feb 8.

Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

The COVID-19 pandemic continues to strain health care systems and drive shortages in medical supplies and equipment around the world. Resource allocation in times of scarcity requires transparent, ethical frameworks to optimize decision making and reduce health care worker and patient distress. The complexity of allocating dialysis resources for both patients receiving acute and maintenance dialysis has not previously been addressed. Using a rapid, collaborative, and iterative process, BC Renal, a provincial network in Canada, engaged patients, doctors, ethicists, administrators, and nurses to develop a framework for addressing system capacity, communication challenges, and allocation decisions. The guiding ethical principles that underpin this framework are () maximizing benefits, () treating people fairly, () prioritizing the worst-off individuals, and () procedural justice. Algorithms to support resource allocation and triage of patients were tested using simulations, and the final framework was reviewed and endorsed by members of the provincial nephrology community. The unique aspects of this allocation framework are the consideration of two diverse patient groups who require dialysis (acute and maintenance), and the application of two allocation criteria (urgency and prognosis) to each group in a sequential matrix. We acknowledge the context of the Canadian health care system, and a universal payer in which this framework was developed. The intention is to promote fair decision making and to maintain an equitable reallocation of limited resources for a complex problem during a pandemic.
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http://dx.doi.org/10.2215/CJN.07460520DOI Listing
February 2021

Blood Pressure Effects of Canagliflozin and Clinical Outcomes in Type 2 Diabetes and Chronic Kidney Disease: Insights From the CREDENCE Trial.

Circulation 2021 May 8;143(18):1735-1749. Epub 2021 Feb 8.

The George Institute for Global Health (N.Y., M.J.J., M.O., C.H., A.E.S., C.A., B.N., D.C.W., G.L.D.T., V.P., B.L.N.), University of New South Wales, Sydney, Australia.

Background: People with type 2 diabetes and chronic kidney disease experience a high burden of hypertension, but the magnitude and consistency of blood pressure (BP) lowering with canagliflozin in this population are uncertain. Whether the effects of canagliflozin on kidney and cardiovascular outcomes vary by baseline BP or BP-lowering therapy is also unknown.

Methods: The CREDENCE trial (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) randomized people with type 2 diabetes and chronic kidney disease to canagliflozin or placebo. In a post hoc analysis, we investigated the effect of canagliflozin on systolic BP across subgroups defined by baseline systolic BP, number of BP-lowering drug classes, and history of apparent treatment-resistant hypertension (BP ≥130/80 mm Hg while receiving ≥3 classes of BP-lowering drugs, including a diuretic). We also assessed whether effects on clinical outcomes differed across these subgroups.

Results: The trial included 4401 participants, of whom 3361 (76.4%) had baseline systolic BP ≥130 mm Hg, and 1371 (31.2%) had resistant hypertension. By week 3, canagliflozin reduced systolic BP by 3.50 mm Hg (95% CI, -4.27 to -2.72), an effect maintained over the duration of the trial, with similar reductions across BP and BP-lowering therapy subgroups (all interaction ≥0.05). Canagliflozin also reduced the need for initiation of additional BP-lowering agents during the trial (hazard ratio, 0.68 [95% CI, 0.61-0.75]). The effect of canagliflozin on kidney failure, doubling of serum creatinine, or death caused by kidney or cardiovascular disease (hazard ratio, 0.70 [95% CI, 0.59-0.82]) was consistent across BP and BP-lowering therapy subgroups (all interaction ≥0.35), as were effects on other key kidney, cardiovascular, and safety outcomes.

Conclusions: In people with type 2 diabetes and chronic kidney disease, canagliflozin lowers systolic BP across all BP-defined subgroups and reduces the need for additional BP-lowering agents. These findings support use of canagliflozin for end-organ protection and as an adjunct BP-lowering therapy in people with chronic kidney disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.048740DOI Listing
May 2021

Effects of canagliflozin on cardiovascular, renal, and safety outcomes in participants with type 2 diabetes and chronic kidney disease according to history of heart failure: Results from the CREDENCE trial.

Am Heart J 2021 03 22;233:141-148. Epub 2020 Dec 22.

Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA. Electronic address:

We aimed to assess the efficacy and safety of canagliflozin in patients with type 2 diabetes and nephropathy according to prior history of heart failure in the Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation (CREDENCE) trial. We found that participants with a prior history of heart failure at baseline (15%) were more likely to be older, female, white, have a history of atherosclerotic cardiovascular disease, and use diuretics and beta blockers (all P < .001), and that, compared with placebo, canagliflozin safely reduced renal and cardiovascular events with consistent effects in patients with and without a prior history of heart failure (all efficacy P interaction >.150). These results support the efficacy and safety of canagliflozin in patients with type 2 diabetes and nephropathy regardless of prior history of heart failure.
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http://dx.doi.org/10.1016/j.ahj.2020.12.008DOI Listing
March 2021