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

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Composição da captura de elasmobrânquios pela frota de emalhe de Imbé/Tramandaí – Litoral Norte do Rio Grande do Sul, Brasil

Os elasmobrânquios constituem um importante recurso pesqueiro no Rio Grande do Sul. Com o objetivo de agregar os dados das capturas destes animais, foram monitorados 39 desembarques realizados pela frota pesqueira de Imbé/Tramandaí entre setembro de 2011 e maio de 2012, além de outros dois desembarques monitorados, um em novembro e outro em dezembro de 2012. A frota é constituída por duas embarcações de madeira de 10 a 14m de comprimento. Durante a amostragem foram utilizadas redes de emalhe de fundo direcionadas a captura da Pescada-olhuda (Cynoscion striatus) (entre 8 e 10 cm de entrenó), Papa-terra (Menticirrus sp.) (7 cm de entrenó) e Raia-viola (Rhinobatos horkelii) (22 cm de entrenó) e redes de emalhe de superfície direcionadas a pesca de Tubarões-martelo (entre 13, 14 e 16 cm de entrenó). Foi registrada a captura de 4083 kg de elasmobrânquios, pertencentes a 23 táxons, 11 de tubarões e 12 de raias, este valor representou 23% da produção total da pesca. A espécie de tubarão mais capturada foi Sphyrna lewini, com 98,5% do total amostrado, seguida de Rhizoprionodon lalandii (0,8%) e Sphyrna zygaena (0,27%). Dentre as raias o táxon mais capturado foi Rhinobatos horkelii, representando 36,9% das capturas deste grupo, seguida de Rioraja agassizii (15,4%) e Sympterygia acuta (12,3%). Dentre as 22 espécies de teleósteos identificadas, a de maior incidência foi a Abrótea (Urophycis brasiliensis) e a com maior biomassa capturada foi a Pescada-olhuda com um total de 10042 kg, seguida da Castanha (Umbrina canosai), com 3921 kg e da Corvina (Micropogonias furnieri), com 2478 kg. As duas primeiras com um pico de captura em setembro e a terceira com pico em outubro. Um alto índice de neonatos e juvenis de S. lewini foi registrado, com todos os animais apresentando comprimento total entre 32,6 e 95 cm. Conclui-se que este é uma área de berçário, tendo em vista que os neonatos e juvenis permanecem em seus berçários ao longo de um ano após seu nascimento, e foram capturados em todas as estações do ano.Elasmobranch fishes are considerate an important fishery resource in Rio Grande do Sul. Having the objective to aggregate biological data from these animals, the present study has made 41 surveys of fisheries landing done by the artisanal fisheries situated on Imbé beach, north shore of Rio Grande do Sul state, Brazil, 39 of these fishery landings surveys has been done between September 2011 – may 2012, another landings were surveyed, one in November 2012 and another in December 2012. The artisanal fishery is constituted by two wooden boats of medium scale. During the surveys bottom set gillnets has been used objecting to catch Striped weakfish (Cynoscion striatus) (8-10 cm mesh), Kingfish (Menticirrus sp.) (7 cm mesh) and Brazilian Guitarfish (Rhinobatos horkelii) (22 cm mesh), surface set gillnets were used too, objecting to catch Hammerhead sharks (13,14 and 16 cm mesh). During the study 4083 kg of elasmobranchs were landed, it belongs to 21 species, 11 sharks and 12 skates and rays, these values had represented 23% of the total catching of the fisheries. The most hatched shark specie were Sphyrna lewini, representing 98, 5% of the total elasmobranch catches, followed by Rhizoprionodon lalandii (0,8%) and Sphyrna zygaena (0,27). Between the skates and rays the most captured specie was Rhinobatos horkelii, representing 36,9% of the total skates and rays catches, followed by Rioraja agassizii (15,4%) and Sympterygia acuta (12,3%). From the 22 species of bony fishes identified on the surveys, the most incident was Brazilian codling (Urophycis brasiliensis) and the specie with the greatest biomass captured was Striped weakfish, with 10042 kg registered, followed by Argentine croaker (Umbrina canosai) with 3921 kg registered and Whitemouth croaker (Micropogonias furnieri), with 2478 kg registered, the first two with a peak of catching in September and the third one with a peak of catch on October. A great percentage of neonates and juveniles of S. lewini was registered, with all the animals measured presenting total length between 32, 6 – 95 cm. The conclusion is that the place of study is a nursery area, considering that the juveniles and neonates stay in their nurseries along a year after their birth, and got caught in all seasons of the year