Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Potential heterogeneity in crustacean zooplankton assemblages in southern chilean saline lakes

The Chilean saline lakes are distributed mainly in the Atacama desert in northern Chile and the southern Patagonian plains. The scarce studies are restricted mainly to northern Chilean saline lakes, and these revealed that the main component in these ecosystems are the halophylic copepod Boeckella poopoensis Marsh 1906, or the brine shrimp Artemia franciscana (Kellog, 1906), and both species do not coexist. The present study consisted of field observations in zooplankton assemblages in southern Chilean saline lakes (51-53 degrees S). These first observations revealed three different patterns, one saline lake only with A. persimilis (Piccinelli and Prosdocimi, 1968), a second lake only with B. poopensis, and a third lake with A. persimilis, B. poopoensis and unidentified harpacticoid copepod. These results are different in comparison with the observations in the literature that described the non-coexistence between B. poopoensis with brine shrimps. Ecological and biogeographical topics were discussed

Daily vertical distribution of zooplankton in two oligo-mesotrophic north Patagonian lakes (39 degrees S, Chile)

The zooplankton communities often exhibit daily vertical migrations to avoid natural ultraviolet radiation and/or fish predation. However there is no information on this topic in Chilean North Patagonian lakes up to date. Therefore, this study deals with a first characterization of plankton crustacean daily vertical migration in two temperate, oligotrophic lakes (Villarrica and Panguipulli lakes, 39 degrees S) in Southern Chile. Zooplankton were collected at different depths intervals (0-10in, 10-20 m, 20-30m, 30-40m) at early morning, middle day, evening and night in the studied site. The results revealed that zooplankton species (Daphnia pulex. Ceriodaphnia dubia, Neobosmina chilensis, Alesocyclops araucanus, and Thopocyclops prasinus) are abundant in surface zones at night, early morning and evening, whereas at middle day the zooplankton abundances are high at deep zones. The results agree with observations for Argentinean and North American lakes where these daily migration patterns in crustacean zooplankton species were reported due mainly natural ultraviolet radiation exposure, whereas for northern hemisphere lakes the vertical migration is due to combined effect of natural ultraviolet radiation and fish predation exposure

Microcrustacean assemblages composition and environmental variables in lakes and ponds of the Andean region - South of Chile (37-39 degrees S)

The zooplankton assemblages in Chilean Patagonian lakes are characterised mainly by their low biodiversity and high predominance of calanoids copepods, a pattern that has been studied for large and deep lakes between 38-51 degrees S, and shallow ponds at 51 degrees S. The aim of the present study was analyse the zooplankton assemblages in different water bodies located in coastal zones, middle valleys and mountain zones between 37-39 degrees S. For this purpose, the following variables were considered: maximum depth, latitude, altitude, chlorophyll-a and species number, and to these variables, a Principal Component Analysis (PCA) was applied. A co-occurrence null model analysis was also applied for determining the existence of a random process in crustacean species associations. The results denoted low species richness, and different species associations for studied sites, and the null model analysis revealed the absence of a random process as regulator of species associations. Furthermore, a low species/genera ratio was identified, which denotes low productivity of the studied sites. These results were supported by a PCA analysis which denoted that the main determinant factors are chlorophyll concentration and species number that are directly associated. The obtained results are in agreement with descriptions in the literature for species diversity for lakes of Chilean Patagonia that describes oligotrophy as the main regulator of zooplankton assemblages. Other ecological and limnological topics are discussed in the present study

Risk factors associated with intestinal pathogenic parasites in schoolchildren

Diseases caused by intestinal parasites impose a substantial burden on population of middle income countries including Pakistan. This research was aimed to assess the risk factors for intestinal parasites in school children of Malakand, Pakistan. Two hundred and eighty eight students were enrolled between February and June 2016. Out of the total enrolled 184 were agreed to collect stool specimens. A questionnaire was also used to collect the data on socio-demographic and socio-economic characteristics of the participants. All the students were guided to collect at least 10gof their own stool specimens. Each of the stool specimens was diagnosed for the presence of any stage of helminth or protozoal parasites. Formal ether concentration method and wet mount techniques were applied. One way ANOVA was used for calculation of P value when it was less than 0.05 which was considered significant. Eighty two percent of the participants were found infected with one species of parasite while 69.9% of the participants were infected with more than one species of intestinal parasites. The most prevalent parasite was hook worm 33.4% (n = 99/296) followed by Taenia saginata 28.7% (n = 85/296), Ascaris lumbricoides 27.7% (n = 82/296), Hymenolepis nana 6.08% (n = 18/296), Entamoeba histolytica 3.37% (n = 10/296) and least for each Enterobius vermicularis and Fasciola hepatica 0.37% (n = 1/296). Previously used drugs, level in school, ages, weight and upper arm circumference were the most significantly (P < 0.05) related factors for the occurrence of intestinal parasite infection. Present research endorsed that risk factors play a key role in the transmission of parasitic diseases. Lack of safe water supply, using raw vegetables, animal keeping, which should be considered for sustainable strategies in the control of these infections preferably in remote parts of the world. (c) 2021 Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)