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

Clinicopathological profile of gastrointestinal tuberculosis: a multinational ID-IRI study

Data are relatively scarce on gastro-intestinal tuberculosis (GITB). Most studies are old and from single centers, or did not include immunosuppressed patients. Thus, we aimed to determine the clinical, radiological, and laboratory profiles of GITB. We included adults with proven GITB treated between 2000 and 2018. Patients were enrolled from 21 referral centers in 8 countries (Belgium, Egypt, France, Italy, Kazakhstan, Saudi Arabia, UK, and Turkey). One hundred four patients were included. Terminal ileum (n = 46, 44.2%), small intestines except terminal ileum (n = 36, 34.6%), colon (n = 29, 27.8%), stomach (n = 6, 5.7%), and perianal (one patient) were the sites of GITB. One-third of all patients were immunosuppressed. Sixteen patients had diabetes, 8 had chronic renal failure, 5 were HIV positive, 4 had liver cirrhosis, and 3 had malignancies. Intestinal biopsy samples were cultured in 75 cases (78.1%) and TB was isolated in 65 patients (86.6%). PCR were performed to 37 (35.6%) biopsy samples and of these, 35 (94.6%) were positive. Ascites samples were cultured in 19 patients and M. tuberculosis was isolated in 11 (57.9%). Upper gastrointestinal endoscopy was performed to 40 patients (38.5%) and colonoscopy in 74 (71.1%). Surgical interventions were frequently the source of diagnostic samples (25 laparoscopy/20 laparotomy, n = 45, 43.3%). Patients were treated with standard and second-line anti-TB medications. Ultimately, 4 (3.8%) patients died and 2 (1.9%) cases relapsed. There was a high incidence of underlying immunosuppression in GITB patients. A high degree of clinical suspicion is necessary to initiate appropriate and timely diagnostic procedures; many patients are first diagnosed at surgery

Networked Pantheon: A Relational Database of Globally Famous People

This article presents Networked Pantheon, a relational database of biographies of globally famous people spanning the last 5,500 years of human history. This source of information is intended to complement Pantheon 1.0 (Yu et. al. 2016), a biographical dataset that includes temporal, spatial, gender, and occupational information on 11,341 world-renowned people –defined as those who have their biographies in 25 or more Wikipedia language-versions–. Networked Pantheon adds information about the biographical links between these historical figures, which was compiled from the hyperlinks between the biographies in English Wikipedia. This digital method allows technics from network analysis to be used to study the relationships between globally famous people, and thus to calculate different measures of historical centrality for individuals, cities, countries, genders, and occupations. Networked Pantheon complements the historical popularity indicators of Pantheon 1.0 with measurements of the centrality of the figures in the network of biographical references, allowing for an approximation to the information flows between different territories, genders, and occupations of famous people over time