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

Volume and process of care in high-risk cancer surgery The views expressed herein do not necessarily represent the views of Center for Medicare and Medicaid Services or the US Government.

BACKGROUND Although relations between procedure volume and operative mortality are well established for high-risk cancer operations, differences in clinical practice between high-volume and low-volume centers are not well understood. The current study was conducted to examine relations between hospital volume, process of care, and operative mortality in cancer surgery. METHODS Using the Medicare claims database (2000-2002), we identified all patients undergoing major resections for lung, esophageal, gastric, liver, or pancreatic cancer ( n = 71,558). Preoperative, intraoperative, and postoperative processes of care potentially related to operative mortality were identified from inpatient, outpatient, and physician claims files using appropriate International Classification of Diseases – Clinical Modification (ICD-9) and Current Procedural Terminology (CPT) codes. We then assessed variation in the use of each process according to hospital volume, adjusting for patient characteristics and procedure type. Study Participants were US Medicare patients. The main outcome measure was specific processes of care. RESULTS Relative to those at low-volume centers (lowest 20th by volume), patients at high-volume hospitals (highest 20th) were significantly more likely to undergo stress tests (odds ratio [OR]: 1.51, 95% confidence interval [CI]: 1.21-1.87), but not other preoperative imaging tests. They were more likely to see medical or radiation oncologists (OR: 1.37, 95% CI: 1.16-1.62), but not other specialists, preoperatively. Although blood transfusions and use of epidural pain management did not vary significantly by volume, patients at high-volume hospitals had significantly longer operations and were more likely to receive perioperative invasive monitoring (OR: 2.56, 95% CI: 1.82-3.60). Differences in measurable processes of care did not explain volume-related differences in operative mortality to any significant degree. CONCLUSIONS Although high-volume and low-volume hospitals differ with regard to many aspects of perioperative care, mechanisms underlying volume–outcome relations in high-risk cancer surgery remain to be identified. Cancer 2006. © 2006 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55221/1/21888_ftp.pd

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