Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Bone Loss or a Case of Mistaken Gender?

International audienc

Comparação da densidade mineral óssea em mulheres praticantes de hidroginástica e sedentárias na pós-menopausa

O objetivo deste estudo foi comparar a densidade mineral óssea (DMO) em mulheres praticantes de hidroginástica e mulheres sedentárias. Fizeram parte da amostra 48 mulheres, sendo 22 praticantes de hidroginástica (54,5 ± 3,3 anos), e 26 sedentárias (52,0 ± 3,3). Todas as participantes do estudo estavam na pós-menopausa e fazendo terapia de reposição hormonal há, no mínimo, um ano. A densitometria óssea foi feita por um aparelho da marca lunar, modelo DPX-IQ. Foi obtida a DMO da coluna lombar (L2-L4), do fêmur (colo do fêmur e quadril total) e antebraço. Para a análise dos dados utilizou-se, como tratamento estatístico, a análise de variância (one-way ANOVA) para amostras independentes. Nas praticantes de hidroginástica comparadas com as sedentárias, a DMO foi mais elevada (p <0,05) em L2-L4 e quadril total, enquanto nos outros sítios analisados não houve diferença significativa. Concluindo, esses resultados sugerem que a hidroginástica mostrou ser positiva para uma maior DMO em relação à população sedentária nos sítio do L2-L4 e quadril total

Obesity, Bariatric Surgery, and Vitamin D

The high prevalence of obesity is a worldwide problem associated with multiple comorbidities, including cardiovascular diseases. Vitamin D deficiency with secondary hyperparathyroidism is common in obese individuals and can be aggravated after bariatric surgery. Moreover, there is no consensus on the optimal supplementation dose of vitamin D in postbariatric surgical patients. We present new data on the variability of 25(OH)D response to supplementation in postmenopausal obese women. It is important to recognize and treat vitamin D deficiency before bariatric surgery to avoid postoperative complications, such as metabolic bone disease with associated high fracture risk. The objective of this article is to discuss the bone metabolism consequences of vitamin D deficiency after bariatric surgery.Univ Catolica Brasilia, Ctr Pesquisa Clin Brasil, Brasilia, DF, BrazilUniv Fed Minas Gerais, Belo Horizonte, MG, BrazilUniv Fed Parana, Disciplina Endocrinol, Curitiba, Parana, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Disciplina Endocrinol, Sao Paulo, BrazilUniv Wisconsin, Med Sch, Madison, WI 53706 USAUniv Fed Sao Paulo, Escola Paulista Med, Disciplina Endocrinol, Sao Paulo, BrazilWeb of Scienc