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

Prevalence of allergic diseases and/or allergic sensitisation in children and adolescents with type 1 diabetes mellitus

Background: the prevalence of atopic diseases in children with type 1 diabetes mellitus (DM1) has been reported as lower. the aim of this study was to evaluate the prevalence of allergic diseases and allergic sensitisation in Brazilian children and adolescents with DM1.Patients and methods: 96 patients with DM1 (aged 4-18 years, 45 boys) followed for at least one year were evaluated for allergic disease through a detailed allergological anamnesis and skin prick tests (SPT) to inhalant allergens (Dermatophagoides pteronyssinus, D. farinae, Blomia tropicalis, Blattella germanica, Periplaneta americana, dog epithelium, cat epithelium, mix fungi), foods (cow's milk, egg-white, yolk, soy, wheat, corn), and positive (histamine 1 mg/ml) and negative (saline) controls. Wheals with a mean diameter of induration equal to or greater than 3 mm identified a positive SPT.Results: the prevalence values of rhinitis, asthma and atopic eczema (isolated or associated) were 68.0%, 59.1% and 44.4%, respectively. 20.6% of the patients had no allergic disease. 46.8% of the patients had been diagnosed with DM1 for at least four years and there was no relationship between the period of DM1 and the presence of allergic disease, nor of the gender. 48.0% patients were sensitised with predominance of D. pteronyssinus, B. topicalis and D. farinae. the frequency of positive SPT was significantly higher among patients with history of allergic disease (OR = 6.98, 95%CI: 2.60-18.74, p < 0.001).Conclusion: the prevalence of allergic diseases and sensitisation in patients with DM1 was higher than usually expected and deserves further investigation to identify possible causes for these findings and to evaluate their importance and influence on the metabolic control. (C) 2013 SEICAP. Published by Elsevier Espana, S.L.U. All rights reserved.Universidade Federal de São Paulo, Escola Paulista Med UNIFESP, Dept Pediat, Div Allergy Clin Immunol & Rheumatol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP, Dept Pediat, Div Endocrinol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP, Dept Pediat, Div Allergy Clin Immunol & Rheumatol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP, Dept Pediat, Div Endocrinol, São Paulo, BrazilWeb of Scienc

Growth hormone and treatment outcomes: expert review of current clinical practice

Although there are guidelines for treatment of short stature, open questions regarding optimal management of growth hormone therapy still exist. Experts attending six international meetings agree that successful therapy results in the patient attaining mid-parental height, and relies on correct diagnosis and early intervention. Experts advocate patient followup every 3-6 months, and that growth and adherence should be monitored at each visit. Growth response is variable, and an accepted definition of good/poor response is lacking. Combined with patient education and regular patient follow-up, a definition of treatment response could lead to improved treatment outcomes. Few experts use prediction models in clinical practice, but all agree that pharmacogenetics might improve prediction, enable early therapy modulation, and promote growth. Poor growth is often due to low adherence. Guidance on optimal management of growth hormone therapy is required, with focus on early diagnosis, dosing, treatment monitoring, adherence, and motivation

Growth hormone and treatment outcomes: Expert review of current clinical practice

Although there are guidelines for treatment of short stature, open questions regarding optimal management of growth hormone therapy still exist. Experts attending six international meetings agree that successful therapy results in the patient attaining mid-parental height, and relies on correct diagnosis and early intervention. Experts advocate patient follow-up every 3-6 months, and that growth and adherence should be monitored at each visit. Growth response is variable, and an accepted definition of good/poor response is lacking. Combined with patient education and regular patient follow-up, a definition of treatment response could lead to improved treatment outcomes. Few experts use prediction models in clinical practice, but all agree that pharmacogenetics might improve prediction, enable early therapy modulation, and promote growth. Poor growth is often due to low adherence. Guidance on optimal management of growth hormone therapy is required, with focus on early diagnosis, dosin

Growth hormone and treatment outcomes: expert review of current clinical practice

Although there are guidelines for treatment of short stature, open questions regarding optimal management of growth hormone therapy still exist. Experts attending six international meetings agree that successful therapy results in the patient attaining mid-parental height, and relies on correct diagnosis and early intervention. Experts advocate patient followup every 3-6 months, and that growth and adherence should be monitored at each visit. Growth response is variable, and an accepted definition of good/poor response is lacking. Combined with patient education and regular patient follow-up, a definition of treatment response could lead to improved treatment outcomes. Few experts use prediction models in clinical practice, but all agree that pharmacogenetics might improve prediction, enable early therapy modulation, and promote growth. Poor growth is often due to low adherence. Guidance on optimal management of growth hormone therapy is required, with focus on early diagnosis, dosing, treatment monitoring, adherence, and motivation