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

Attention deficit hyperactivity disorder (ADHD) in adults: social-demographic profile from a university hospital ADHD outpatient unit in São Paulo, Brazil Transtorno de déficit de atenção e hiperatividade (TDAH) no adulto: perfil sócio-demográfico de pacientes com TDAH atendidos em ambulatório de um hospital universitário de São Paulo, Brasil

PURPOSE: To describe the social-demographic variables, including interpersonal, academic, and professional performance in adult individuals with the diagnoses of attention deficit hyperactivity disorder (ADHD). There are no reports of this kind in the Brazilian population with ADHD. The ADHD is a common disorder, which can reach up to 3% of the general population. METHOD: Descriptive study of adults with ADHD, according to the DSM-IV criteria (American Psychiatric Association). The sample was selected from a specialized outpatient service in São Paulo city. The social-demographic data was obtained by personal interviews. RESULTS: There was a predominance of males in the sample (61.2%) and a high education level (90.2% had at least a high school degree) and 52% of the 102 patients had repeated their class at a least once during their school lives. In addition, 22.5% of the population sample were unemployed at the time of the interview. CONCLUSION: The distribution of the socio-demographic variables in adult ADHD is similar to other ADHD samples reported in other countries, despite the high education level met in our sample. Similarities between child and adult ADHD could also be traced.<br>OBJETIVO: Descrever as variáveis sócio-demográficas incluindo desempenho acadêmico, profissional e interpessoal em uma população adulta com diagnóstico de transtorno de déficit de atenção e hiperatividade (TDAH). Até o momento não há relato na literatura do perfil desses pacientes na população brasileira. O TDAH é comum na população geral, podendo chegar a 3% das pessoas. MÉTODO: Foram avaliados adultos que tomaram conhecimento do serviço de atendimento especializado em TDAH através da mídia. O diagnóstico de TDAH foi realizado utilizando-se os critérios da Associação Psiquiátrica Americana (DSM-IV). Os dados sócio-demográficos foram obtidos através de entrevista pessoal com cada paciente. RESULTADOS: 102 indivíduos preencheram critérios para TDAH. Houve predomínio do sexo masculino (61,2%) com alto nível de escolaridade (90,2% tinham no mínimo 2º grau completo). Cinquenta e três pacientes (52%) foram reprovados pelo menos uma vez durante vida estudantil. No momento da entrevista, 22,5% encontravam-se desempregados. CONCLUSÃO: Observou-se uma semelhança da distribuição das variáveis sócio-demográficas com os indivíduos adultos com TDAH de outros países, apesar da escolaridade ser acima da média nacional. Além disso, pode-se também observar semelhanças entre as populações infantil e adulta com TDAH