Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Architecture and domestic culture in eighteenth-century China

This thesis examines architectural discourse and spatial practices as manifestations and experiences of order in eighteenth-century Qing dynasty China. It reviews the development of the historiography of Chinese architectural history as an academic discipline, and proposes that in the Qing there was an unprecedented rupture between domestic architectural style from that of the court. An alternative design strategy in spatial planning and detailing was adopted. It is argued that the Qing architectural discourse, its intertextuality, was implicitly linked to the historical formation of the Qing self, and that it was pivotal to the rise of domestic culture. The study approaches architecture as historical statements and arguments, and focuses on the production of space, human agency, gender, and subject positioning in early modern China. The study analyzes the Yugong mansion, Beijing, the Rong mansion in the Qing novel The Dream of the Red Chamber, and the Manchu imperial city, as examples

Sites of learning: the architecture of educational reform in Toronto, 1847-1917

Compulsory education represents one facet of a larger social transformation of working-class children and families in the late nineteenth century. Competing ideas of schooling children and their well-being informed the cultural ferment of these years, as educationists, reformers, specialists, and politicians debated the idea of childhood. By 1917, the Toronto Public School Board’s multiple locations of reform consisted of ninety-nine sites in the city, ranging from the ubiquitous school buildings to more specialized spaces such as industrial and open-air schools. From its formation in 1847 until 1917 when the Department of Health took over children’s public health, the Toronto Public School Board aside from providing free education also acted as an agency of social, juvenile penal, and health reform of children. This dissertation analyzes these years of reform by exploring various architectural sites designed purposefully to implement modern reforms from 1847 to 1917. In examining the Ontario Educational Exhibit of 1876; the Toronto Normal School and Model Schools; the Toronto public school buildings; the Victoria Industrial School for Boys in Mimico; the open-air schools; playgrounds and other material culture of education, I show the complex links education had to industrial capitalism, popular education, school design, juvenile penal reform, architectural practice, and medicine. Organized in a loose chronological order, the six chapters illuminate the ways in which architecture and spatial dimensions informed the process of schooling children, legislating children and childhoods, defining professionalism, and other forces in the educational landscapes that shaped both the experience of the makers and users in these formative years.L'éducation obligatoire représente une facette de la transformation sociale des enfants dela classe ouvrière qui a eu lieu à la fin du 19e siècle. Différentes idées à l'époque, concernant l'éducation et le bienêtre des enfants, ont contribuée à une sorte d'agitation culturelle alors que les éducateurs, les réformateurs, les spécialistes, et les politiciens se débattaient sur la question l'idée d'enfance. En 1917, la commission scolaire de Toronto comptait quatre-vingt-dix neuf emplacements en ville ou la reforme se déroulait. Tout comme dans des écoles typiques de l' époque que dans des espaces spécialisés tel que des écoles industrielles. De sa naissance en 1847 jusqu'à 1917 au moment ou le départementde la santé a pris la relève du dossier de la santé publique des enfants, la commission scolaire de Toronto au de la de fournir l'éducation gratuitement. Elle a agit comme intermédiaire représente en ce qui a trait a la reforme sociale, la reforme de la santé et la reforme du système pénal juvénile. En examinant l'exposition de 1876 sur l'éducation Ontarienne, l'école Toronto Normal et les écoles modèles, les édifices hébergeant les écoles publiques, l'école The Victoria Industrial School for Boys au Mimico, les écoles a plein-aire et les cours de recreation, je démontre la complexité du rapport qu' existait entre l'éducation et le capitalisme industriel, et l'éducation populaire, et leur design, et la reforme du système pénal juvénile, les pratiques architecturales, et la médicine. Organise de façon plutôt chronologique, les six chapitres révèlent l'interrelation entre l'architecture et les dimensions spatiales, et le rôle qu'a joue celle-ci dans le processus d'éducation des enfants, les actes législatives régularisant les enfants et l'enfance, du professionnalisme, et d'autres forces qui ont affecte l'expérience de ceux vivants durant ces temps de reforme

Development Through Design

The new Trudeau government has made a tonal shift in Canada’s international development policies. However, not unlike many governments in the overdeveloped world, Canadian policies are still used to export and embed neoliberal rationales perpetuating global inequalities that development policies are supposed to right. Mah and Rivers suggest how design and social science, together, can advance a more progressive international development agenda. They do this by highlighting their ongoing Democratic Crèche project. This sustainable development project entails the prototyping of two early childhood development (ECD) centres, or daycare centres, in South African townships. Beyond the realization of physical structures that enhance children’s wellbeing, the project ultimately demonstrates the difference made when social design is used “to do” and “to study” development in alternative and critically engaged ways. “Alternative” and “critical,” here, necessitate development policies and projects emanating as much from townships as Global North capitals. About the Lecturers: Kai Wood Mah is a registered architect, design historian, and professor. Patrick Lynn Rivers is a political scientist and professor at a leading school of art and design. Together, they co-direct Afield, a design research practice bringing comparative interdisciplinary perspective to contemporary social issues

Empagliflozin in Patients with Chronic Kidney Disease

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to < 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of & GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P < 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo