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

Spartina densiflora demonstrates high tolerance to phenanthrene in soil and reduces it concentration

The present study was conducted to investigate the tolerance of Spartina densiflora to phenanthrene, and to test its ability in phenanthrene dissipation. A glasshouse experiment was designed to investigate the effect of phenanthrene from 0 to 1000mgkg-1 on growth and photosynthetic apparatus of S. densiflora by measuring chlorophyll fluorescence parameters, gas exchange and photosynthetic pigments. We also performed chemical analysis of plant samples, and determined the concentration of phenanthrene remaining in soil. S. densiflora survived to concentrations as high as 1000mgkg-1 phenanthrene in soil; in fact, there was no significant difference in RGR among the treatments after 30days. Otherwise, phenanthrene affected photosynthetic apparatus at 100 and 1000mgkg-1; thus, the lower ΦPSII could be explained by the declined photosynthetic pigment concentrations. Soil extraction indicated a more marked rate of phenanthrene disappearance in the soil in the presence of S. densiflora.Peer Reviewe

Morphological, molecular and phylogenetic analyses of the spirurid nematode Stegophorus macronectes (Johnston & Mawson, 1942)

Stegophorus macronectes (Johnston & Mawson, 1942) is a gastrointestinal parasite found in Antarctic seabirds. The original description of the species, which was based only on females, is poor and fragmented with some unclear diagnostic characters. This study provides new morphometric and molecular data on this previously poorly described parasite. Nuclear rDNA sequences (18S, 5.8S, 28S and internal transcribed spacer (ITS) regions) were isolated from S. macronectes specimens collected from the chinstrap penguin Pygoscelis antarctica Forster on Deception Island, Antarctica. Using 18S rDNA sequences, phylogenetic analyses (maximum likelihood, maximum parsimony and Bayesian inference) of the order Spirurida were performed to determine the phylogenetic location of this species. Primer pairs of the ITS regions were designed for genus-level identification of specimens, regardless of their cycle, as an alternative to coprological methods. The utility of this molecular method for identification of morphologically altered specimens is also discussed.This study was funded by the Spanish Ministry of Economy and Competiveness and the European Regional Development Fund Projects CGL2004-01348, POL2006-05175, CGL2007-60369 and CTM2011-24427. V.V. was supported by a PhD grant from the Spanish Council of Scientific Research (CSIC) and the European Social Fund (JAEPre08-01053).M.J.P.was supported by a PhDgrant from the Spanish Ministry of Science and Innovation (BES2005-8465).Peer Reviewe

Mode of attachment and pathology caused by Parorchites zederi in three species of penguins: Pygoscelis papua, Pygoscelis adeliae, and Pygoscelis antarctica in Antarctica

We identified and compared gross and microscopic lesions associated with the cestode, Parorchites zederi, in the digestive tracts of three species of penguins (Spheniscidae): the Chinstrap (Pygoscelis antarctica), Gentoo (Pygoscelis papua), and Adélie penguins (Pygoscelis adeliae). The gastrointestinal tracts of 79 recently dead individuals (71 chicks and eight adults) were collected in locations throughout the Antarctic Peninsula during summer field trips in 2006–09. Parorchites zederi was found in the small intestine of 37 animals (47%), and 23 (62%) of these had parasite-associated lesions. The cestodes were either free in the intestinal lumen, clustered within mucosal ulcers, or deeply embedded in the intestinal wall. Histopathologic changes were most severe in adult Gentoo Penguins and included transmural fibrogranulomatous enteritis, hemorrhage, and edema. This report of pathology associated with P. zederi in the digestive tracts of penguins can serve as reference to monitor health in Antarctic birds associated with environmental changes.Peer Reviewe

Hypoglycemia in noncritically ill patients receiving total parenteral nutrition: a multicenter study. (Study group on the problem of hyperglycemia in parenteral nutrition; Nutrition area of the Spanish Society of Endocrinology and Nutrition

[eng] Objective Hypoglycemia is a common problem among hospitalized patients. Treatment of hyperglycemia with insulin is potentially associated with an increased risk for hypoglycemia. The aim of this study was to determine the prevalence and predictors of hypoglycemia (capillary blood glucose <70 mg/dL) in hospitalized patients receiving total parenteral nutrition (TPN). Methods This prospective multicenter study involved 19 Spanish hospitals. Noncritically ill adults who were prescribed TPN were included, thus enabling us to collect data on capillary blood glucose and insulin dosage. Results The study included 605 patients of whom 6.8% (n = 41) had at least one capillary blood glucose <70 mg/dL and 2.6% (n = 16) had symptomatic hypoglycemia. The total number of hypoglycemic episodes per 100 d of TPN was 0.82. In univariate analysis, hypoglycemia was significantly associated with the presence of diabetes, a lower body mass index (BMI), and treatment with intravenous (IV) insulin. Patients with hypoglycemia also had a significantly longer hospital length of stay, PN duration, higher blood glucose variability, and a higher insulin dose. Multiple logistic regression analysis showed that a lower BMI, high blood glucose variability, and TPN duration were risk factors for hypoglycemia. Use of IV insulin and blood glucose variability were predictors of symptomatic hypoglycemia. Conclusions The occurrence of hypoglycemia in noncritically ill patients receiving PN is low. A lower BMI and a greater blood glucose variability and TPN duration are factors associated with the risk for hypoglycemia. IV insulin and glucose variability were predictors of symptomatic hypoglycemia