38 research outputs found
The Trypanosoma cruzi Virulence Factor Oligopeptidase B (OPBTc) Assembles into an Active and Stable Dimer
- Author
- A Tsuji
- AM Bilate
- BA Burleigh
- BA Burleigh
- Christine Ebel
- D Rea
- David Neves
- E Cunha-Neto
- E Faudry
- EP Camargo
- Eric Faudry
- EV Caler
- Fabio T. M. Costa
- Flávia Nader Motta
- H Ponstingl
- H Usuki
- HL de Matos Guedes
- I Braakman
- IM Bastos
- IM Bastos
- Izabela M. D. Bastos
- J Lebowitz
- JA Rumfeldt
- Jaime Martins Santana
- JC Munday
- JM Santana
- João Alexandre R. G. Barbosa
- JR Lakowicz
- K McLuskey
- L Lauria-Pires
- L Polgar
- LC Fernandes
- Meire M. Lima
- Michel Ragno
- N Yoshida
- ND Rawlings
- NI Mohd Ismail
- P Schuck
- RE Morty
- RE Morty
- RE Morty
- RK Swenerton
- SH Qureshi
- SM Kelly
- Sônia Maria de Freitas
- T Gerczei
- TH Coetzer
- V Fulop
- WH Westerhuis
- Publication venue
- Public Library of Science
- Publication date
- 01/01/2012
- Field of study
Oligopeptidase B, a processing enzyme of the prolyl oligopeptidase family, is considered as an important virulence factor in trypanosomiasis. Trypanosoma cruzi oligopeptidase B (OPBTc) is involved in host cell invasion by generating a Ca2+-agonist necessary for recruitment and fusion of host lysosomes at the site of parasite attachment. The underlying mechanism remains unknown and further structural and functional characterization of OPBTc may help clarify its physiological function and lead to the development of new therapeutic molecules to treat Chagas disease. In the present work, size exclusion chromatography and analytical ultracentrifugation experiments demonstrate that OPBTc is a dimer in solution, an association salt and pH-resistant and independent of intermolecular disulfide bonds. The enzyme retains its dimeric structure and is fully active up to 42°C. OPBTc is inactivated and its tertiary, but not secondary, structure is disrupted at higher temperatures, as monitored by circular dichroism and fluorescence spectroscopy. It has a highly stable secondary structure over a broad range of pH, undergoes subtle tertiary structure changes at low pH and is less stable under moderate ionic strength conditions. These results bring new insights into the structural properties of OPBTc, contributing to future studies on the rational design of OPBTc inhibitors as a promising strategy for Chagas disease chemotherapy
Trends and factors associated with dengue mortality and fatality in Brazil
- Author
- Alcione Cunha Brasileiro
- Bruin J
- Costa MCN
- Da Cunha SS
- Davide Rasella
- Diaz-Quijano FA
- Enny Santos Paixão
- Figueiredo MAA
- Flauzino RF
- G Vecina Neto
- Guzmán MG
- Guzmán MG
- Hilbe JM
- Koh BK
- Laura Cunha Rodrigues
- Leo YS
- Ler TS
- Luciana Lobato Cardim
- Maria da Conceição Nascimento Costa
- Maria Gloria Lima Cruz Teixeira
- Moraes GH
- Nguyen K-H
- Pavão AL
- Rasella D
- Siegel M
- Suaya JA
- Teixeira MG
- Teixeira MG
- Teixeira TRA
- Tusting LS
- Wu SH
- Publication venue
- 'FapUNIFESP (SciELO)'
- Publication date
- Field of study
Identification of novel epitopes from human papillomavirus type 18 E7 that can sensitize PBMCs of multiple HLA class I against human cervical cancer
- Author
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Clotting Factor XIII and desmopressin improve hemostasis in uncontrolled bleeding
- Author
- Bagoly Z
- Brohi K
- Brummel KE
- Cohen MJ
- Cohen MJ
- Cohen MJ
- Daniel Dias Ribeiro
- Elizabeth Ribeiro da Silva Camargos
- Frith D
- Geeraedts Jr LM
- Holcomb JB
- Hsieh L
- Ibbotson SH
- Jambor C
- Joao Baptista de Rezende-Neto
- Jose Renan da Cunha Melo
- Levy JH
- Li T
- Lorand K
- Lusher J
- MacLeod JB
- Mannucci PM
- Mannucci PM
- Marcus Vinicius de Melo Andrade
- Nielsen VG
- Nielsen VG
- Paulo Roberto Lima Carreiro
- Porta CR
- Rezende-Neto JB
- Rizoli SB
- Sakariassen KS
- Sandro Baletotti Rizoli
- Schlimp CJ
- Shakur H
- Sondeen JL
- Theusinger OM
- Thiago de Assis Lisboa
- Wisel JW
- Publication venue
- 'FapUNIFESP (SciELO)'
- Publication date
- Field of study
Approaches in biotechnological applications of natural polymers
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- Publication venue
- 'American Institute of Mathematical Sciences (AIMS)'
- Publication date
- 01/01/2016
- Field of study
Natural polymers, such as gums and mucilage, are biocompatible, cheap, easily available and non-toxic materials of native origin. These polymers are increasingly preferred over synthetic materials for industrial applications due to their intrinsic properties, as well as they are considered alternative sources of raw materials since they present characteristics of sustainability, biodegradability and biosafety. As definition, gums and mucilages are polysaccharides or complex carbohydrates consisting of one or more monosaccharides or their derivatives linked in bewildering variety of linkages and structures. Natural gums are considered polysaccharides naturally occurring in varieties of plant seeds and exudates, tree or shrub exudates, seaweed extracts, fungi, bacteria, and animal sources. Water-soluble gums, also known as hydrocolloids, are considered exudates and are pathological products; therefore, they do not form a part of cell wall. On the other hand, mucilages are part of cell and physiological products. It is important to highlight that gums represent the largest amounts of polymer materials derived from plants. Gums have enormously large and broad applications in both food and non-food industries, being commonly used as thickening, binding, emulsifying, suspending, stabilizing agents and matrices for drug release in pharmaceutical and cosmetic industries. In the food industry, their gelling properties and the ability to mold edible films and coatings are extensively studied. The use of gums depends on the intrinsic properties that they provide, often at costs below those of synthetic polymers. For upgrading the value of gums, they are being processed into various forms, including the most recent nanomaterials, for various biotechnological applications. Thus, the main natural polymers including galactomannans, cellulose, chitin, agar, carrageenan, alginate, cashew gum, pectin and starch, in addition to the current researches about them are reviewed in this article.. }To the Conselho Nacional de Desenvolvimento Cientfíico e Tecnológico (CNPq) for fellowships (LCBBC and MGCC) and the Coordenação de Aperfeiçoamento de Pessoal de Nvíel Superior (CAPES) (PBSA). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and COMPETE 2020 (POCI-01-0145-FEDER-006684) (JAT)
A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)
- Author
- Abbott TE
- Abdallah RI
- Abdel-Aal IR
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- Aitken LM
- Akalaev R
- Akbarzadeh A
- Akcan-Arikan A
- Akhlagh SH
- Akhtar N
- AKI Research Group
- Akiduki N
- Akin S
- Akizuki N
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- CAPCRI Study
- Capellier G
- Carbonara M
- Cardellino S
- Cardenas CL
- Cariou A
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- Carlesso E
- Carmona AF
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- Carmona SA
- Carmona SA
- Carmona SA
- Carone M
- Carpio D
- Carratalá A
- Carreira MM
- Carrero-Gómez F
- Carreño ER
- Carreño R
- Carvalho JP
- Carvalho KV
- Casals XN
- Casals XN
- Cassina T
- Castañeda DP
- Castellana D
- Castellanos A
- Castellanos A
- Castillo-Lorente E
- Castillo-Lorente E
- Catalan M
- Catalán RM
- Catena E
- Catena E
- Cauwenberghs H
- Cavalcanti D
- Cavalheiro AM
- Cavalier E
- Cavicchi FZ
- Cavicchi FZ
- Cengiz M
- Ceriani R
- Cermelli S
- Cerović O
- Cha YS
- Chabanne R
- Chacon-Alves S
- Champigneulle B
- Champigneulle B
- Chan KC
- Chan KK
- Chan WS
- Chang CH
- Chang WY
- Chao A
- Chao A
- Chao AS
- Chao HC
- Chaouat M
- Charitidou E
- Charpentier C
- Charpentier J
- Charron C
- Chatelon J
- Chaudhari HK
- Chaussard M
- Chavanon O
- Chaves S
- Chelly J
- Chemam S
- Chen CM
- Chen CM
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- Chen GQ
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- Chen YS
- Chen YS
- Chen YS
- Cheng CC
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- Cheng KC
- Cheng YJ
- Chernyshuk S
- Chevret S
- Chhor V
- Chiang CC
- Chiang CH
- Chiang CH
- Chiang CH
- Chiappa C
- Chiou KR
- Chiou KR
- Chiou KR
- Chiu LC
- Chiumello D
- Chiurazzi C
- Chiurazzi C
- Cho Y
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- Choi JY
- Choi JY
- Choi KS
- Choi S
- Choi YJ
- Choi YY
- Chok L
- Cholkraisuwat J
- Cholley B
- Chondropoulos S
- Chou W
- Chouris I
- Chouvarda I
- Christopher KB
- Chrétien JM
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- Chumaev A
- Chung CR
- Churchill K
- Chytas A
- Cinel I
- Cinnella G
- Citerio G
- Citerio G
- Clavel M
- Clemente EA
- Clermont G
- Cleyet M
- Cohen Y
- Colaprico A
- Colino L
- Collange O
- Colombo A
- Colombo A
- Colson P
- Combes A
- Concha P
- Connolly B
- Constan A
- Constan A
- Constan A
- Conte V
- Conti G
- Conti G
- Contreras KM
- Contreras MR
- Cook DJ
- Coombs M
- Cordeiro CP
- Cordero M
- Cordolcini V
- Cordovilla-Guardia S
- Cordón J
- Corona A
- Corona A
- Corradi F
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- Corradi F
- Correa-Chamorro E
- Corte FD
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- Corzo L
- Coss-Bu JA
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- Cotoia A
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- Cottle D
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- Creagh-Brown B
- Cressoni M
- Creteur J
- Creteur J
- Creteur J
- Creteur J
- Creteur J
- Creteur J
- Creteur J
- Creteur J
- Crimella F
- Cron N
- Cuellar AI
- Cui N
- Cunha MM
- Curiel-Balsera E
- Curiel-Balsera E
- Curinga M
- Curtis A
- Cuthbertson BH
- Cutuli SL
- Câmara M
- D'Arsigny C
- da Silva SL
- da Silva VZ
- Daga-Ruiz D
- Dalhuisen A
- Dalorzo M
- Damas P
- Dambrosio M
- Damås JK
- Das Neves A
- David H
- Davis C
- Davis P
- Day A
- de Abreu MG
- De Backer A
- De Brito-Ashurst I
- De Cassai A
- De Freitas FF
- De Gasperi A
- de Hoyos EA
- De la Calle-Pedrosa N
- de la Fuente MV
- De La Fuente-Martos C
- De La Fuente-Martos C
- De La Rica AS
- De la Torre MA
- De Maglie M
- De Maglie M
- de Molina FJ
- De Morton N
- de Oca Sandoval MA
- De Pascale G
- De Rosa S
- De Sanctis F
- De Silva AP
- De Sousa I
- de Vera AP
- de Wilde W
- De Zani D
- Deblier I
- DeBrunnar R
- Del Arco A
- Del Moral OL
- Del Olmo R
- Del Rosario CG
- Del Sorbo L
- Delgado CP
- Delgado MJ
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- Demirkiran O
- Demoule A
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- Der Kinderen EP
- Descotte E
- Deshpande K
- Desmard M
- Desmard M
- Deveugele M
- Deye N
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- Di Gravio V
- Di Gregorio A
- Di Mussi R
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- Diaz DD
- Diaz P
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- Dimitrov BD
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- Dimopoulou IK
- Dinh A
- Divatia JV
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- Dougall PC
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- Drover J
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- Dubrawski A
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- Durand M
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- Durrant J
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- Díaz E
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- Díaz M
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- Dünser MW
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- E YY
- Ebeling G
- Echeverri JE
- Echeverría JG
- Ediboglu O
- Ediboglu O
- Egea-Guerero JJ
- Egginton JS
- Egi M
- El Adawy AS
- El Hamid MA
- El Hossainy R
- El Sayed E
- El Sayed F
- El Sayed I
- El-Hamamsy M
- El-Keraie A
- Eladawy S
- Elbers PW
- Elgendy M
- Eliet J
- Emmanuel J
- Emmerich M
- Encina B
- Endacott R
- Endacott R
- Engelberts D
- ENVIN-HELICS Study Group
- Erb J
- Erdogan M
- Eroles AA
- Escalada SH
- Escalada SH
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- Escórcio S
- Eslami S
- Espinasse F
- Espinel E
- Estagnasie P
- Esteban A
- Estella A
- Estenssoro E
- Evelein-Brugman S
- Facchin F
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- Fang M
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- Farias P
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- Fave G
- Feehan A
- Feijoo AM
- Feliot E
- Ferez MA
- Fernandes MJ
- Fernandes N
- Fernandez NG
- Fernandez R
- Fernandez-Zamora MD
- Fernández IF
- Fernández L
- Fernández MV
- Fernández PA
- Fernández-Barat L
- Fernández-Mondéjar E
- Fernández-Ortega JF
- Ferraz AB
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- Ferri F
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- Ferré A
- Ferrón FR
- Ferrón FR
- Fiks T
- Fiks T
- Fileković S
- Filho CA
- Filho CA
- Filho CA
- Filipe E
- FINNRESUSCI Study Group
- Fischer G
- Fleischmann E
- Fless K
- Floccard B
- Flowers E
- Follin A
- Follin A
- Fong KY
- Fontaiña LP
- Fontana V
- Fontenot T
- Forel JM
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- Fox B
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- Frantzeskaki F
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- Frat JP
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- Frithiof R
- Fritz C
- FROG ICU Investigators
- Fromentin M
- Frontera PR
- Fuentes M
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- Gadgil S
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- Garcia-Alvarez JM
- Garcia-Alvarez JM
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- García-Martínez MV
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- Gavrychenko D
- Gayat E
- Geantot MA
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- Genc D
- Genève C
- Georgopoulos D
- Geri G
- GETGAG Working Group
- GETGAG/SEMICYUC
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- Ghazal S
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- Giannopoulos A
- Giesinger RE
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- Godoy K
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- Golovnya E
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- Gommers D
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- González AS
- González BS
- González JC
- González-Jiménez AI
- Gonçalves B
- Goodwin S
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- Gordillo-Brenes A
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- Gordon M
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- Gottlieb J
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- Gracia RM
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- Granada RM
- Granados PR
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- Grangé S
- Granillo JF
- Grassi L
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- Grossestreuer A
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- Guarracino F
- Gubianas CM
- Guerrero AP
- Guerrero JE
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- Guerrero-López F
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- Guidet B
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- Gupta A
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- Gutierrez LA
- Gutiérrez-Pizarraya A
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- Gálvez V
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- Gómez-Jiménez C
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- Hernandis V
- Hernández A
- Hernández AA
- Hernández AA
- Hernández AA
- Hernández AA
- Hernández AA
- Hernández AA
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- Hernández-Tejedor A
- Herpain A
- Herrera AN
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- Herrera AN
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- Hikasa Y
- Hillier SD
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- Houzé S
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- Hualde JB
- Hualde JB
- Hualde JB
- Hualde JB
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- Huang WC
- Huang WC
- Huang WC
- Huang WC
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- Huber W
- Huddart S
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- Hung CY
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- Hutchings S
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- Hwang GS
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- Ibsen M
- Idei M
- Idei M
- Idone FA
- Iesu E
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- Ignacio ML
- Iida A
- Iijima H
- Ilan R
- Ilyina V
- Imanaka H
- Inaloo S
- Ince C
- Iotti GA
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- Iotti GA
- IPREA Study Group
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- Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study group
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- Jayasinghe S
- Jean-Baptiste S
- Jean-Baptiste S
- Jensen AE
- Jensen JU
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- Jiao LR
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- Jiménez GJ
- Jo YH
- Joachim J
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- Jones C
- Joshi R
- Joshi V
- Jovaisa T
- JSEPTIC (Japanese Society of Education for Physicians and Trainees in Intensive Care) Clinical Trial Group
- Juan WC
- Juanas CA
- Judickas S
- Juez A
- Juliarena A
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- Junior JM
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- Kaminsky GE
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- Kim HJ
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- Kim JM
- Kim JW
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- Koco E
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- Kolnikova I
- Komuro T
- Kondili E
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- Krishna B
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- Kulkarni AP
- Kumari BK
- Kumbamu A
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- Kurmukov IA
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- Kwon HM
- Kwon WY
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- Kyle UG
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- Labra C
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- Lafuente E
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- Latini R
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- Lichtenstein D
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- Lin KC
- Lin KC
- Lin KC
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- Lin KL
- Lin PH
- Lin SC
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- Lischinsky A
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- Liu CP
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- Lobo-Civico A
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- Lombardo MD
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- Loudet CI
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- Maghsoudi B
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- Martínez F
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- Martínez M
- Martínez MP
- Martínez MV
- Martínez NA
- Martínez-Carmona JF
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- Mejías CR
- Mellis C
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- Melo N
- Mendes A
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- Mendonca AV
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- Menendez R
- Mengelle C
- Mercat A
- Mercat A
- Mercat A
- Mergulhão PJ
- Merino-Vega D
- Messenger D
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- Michel L
- Midwinter MJ
- Mignot T
- Miguelena PR
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- Publication date
- 01/01/2016
- Field of study
Meeting abstrac
O mosaico patogênico da pancreatite aguda grave
- Author
- Andersen DK
- Balthazar EJ
- Becker V
- Beger HG
- Beger HG
- Beger HG
- Bhatia M
- Bradley EL
- Büchler M
- Carneiro MC
- Chavez Rossell M
- Chebli JM
- Chebli JMF
- Chen X
- Cunha Neto SH
- Dernevis CG
- Farhoud S
- Gomez-Cambronero LG
- Greenberger NJ
- Hotchkiss RS
- Karne S
- Klöppel G
- Kylanpaa-Back ML
- Liu HS
- Maggioni LCR
- Meirelles Jr RF
- Meirelles Jr RF
- Márcio Cavalcante Carneiro
- Ranson JH
- Rodrigo Siqueira-Batista
- Saluja A
- Siqueira-Batista R
- Siqueira-Batista R
- Steer MC
- Steer ML
- Steer ML
- Steer ML
- Steer ML
- Tavares W
- Teague BD
- Vital ML
- Weber CK
- Windsor JA
- Yeo CJ
- Young LS
- Zhang Q
- Publication venue
- 'FapUNIFESP (SciELO)'
- Publication date
- Field of study
Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.
- Author
- Ab Majid MA
- Ab Rahman AS
- Ab Rahman R
- Abayasinghe C
- Abbott T
- Abdullah NH
- Abdur-Rahman L
- Abeloos J
- Abernethy C
- Abidin UN
- Abrunhosa A
- Absar M
- Adam S
- Adams D
- Adams G
- Adamson M
- Adekola O
- Adelaja Y
- Ademola A
- Adenekan A
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- Zaimi D
- Zakynthinos S
- Zamudio D
- Zangrillo A
- Zapata DDM
- Zbitnew G
- Zeidan L
- Zeng Q
- Zerman L
- Zettergren J
- Zhang B
- Zhang E
- Zhang H
- Zhang H
- Zhang H
- Zhang J
- Zhang K
- Zhang L
- Zhang M
- Zhang M
- Zhang Q
- Zhang R
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- Zhang W
- Zhang X
- Zhang X
- Zhang X
- Zhang X
- Zhang Y
- Zhang Y
- Zhang Y
- Zhang Y
- Zhao B
- Zhao B
- Zhao C
- Zhao J
- Zhao J
- Zhao L
- Zhao L
- Zhao S
- Zhao T
- Zhao W
- Zhao W
- Zhao X
- Zhen J
- Zheng K
- Zheng L
- Zheng T
- Zhong Y
- Zhou C
- Zhou D
- Zhou H
- Zhou H
- Zhou J
- Zhou J
- Zhou J
- Zhou X-J
- Zhu X
- Zhu X
- Zhu Y
- Zhu Z
- Zhuang X
- Zilis G
- Zin NHM
- Zingerle N
- Zingg U
- Zoerner F
- Zonneveldt H
- Zou X
- Zoulamoglou M
- Zsisku L
- Publication venue
- 'Oxford University Press (OUP)'
- Publication date
- 01/01/2016
- Field of study
BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700
Multi-messenger observations of a binary neutron star merger
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- Aartsen MG
- Abbott BP
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- Yu P-C
- Yuan T
- Yuan X
- Yurkov VV
- Yushkov A
- Yvert M
- Zaborov D
- Zacharias M
- Zadrozny A
- Zadrozny A
- Zaharijas G
- Zaltzman M
- Zanin R
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- Zhang Y
- Zhang Y
- Zhang Y-H
- Zhang YF
- Zhang YJ
- Zhang Z
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- Zhu SJ
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- Ziegler A
- Zimmerman AB
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- Zorn J
- Zornoza JD
- Zou CL
- Zuccarello F
- Zucker ME
- Zuniga J
- Zweizig J
- Zywucka N
- Publication venue
- 'American Astronomical Society'
- Publication date
- 01/01/2017
- Field of study
On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta
Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy
- Author
- Abdallah J
- Abdul Ghani R
- Abdul Kadir K
- Abdullah R
- Abejuela Z
- Abouglila K
- Abraham O
- Abrahamsen I
- Abraira Munoz Ld
- Abramowitz M
- Abusnana S
- Accini Mendoza Jl
- Acosta I
- Agafyina A
- Agarwal R
- Agarwal Rajiv
- Aggarwal N
- Agra J
- Ahmed F
- Ahuad Guerrero Ra
- Aiello J
- Ainsworth P
- Aizenberg D
- Akiyama H
- Akright L
- Akyea-Djamson A
- Al-Karadsheh A
- Alamartine E
- Alappan R
- Albisu Jp
- Ali N
- Ali Z
- Alicic R
- Allison Dc
- Alvarez Garcia P
- Alvarisqueta A
- Alves da Costa Fa
- Amerena J
- Amigo A
- Amodeo C
- Andreeva V
- Andreotti Turatti La
- Angelescu Lm
- Angelova A
- Anghel V
- Antic S
- Aoki H
- Aquitania G
- Arauz-Pacheco C
- Arcos E
- Arfeen S
- Arif A
- Aronson R
- Arutchelvam V
- Arvind M
- Asano A
- Asmarats Mercadal L
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- August P
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- Bijata-Bronisz R
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- Cheifetz A
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- Chertow G
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- Chilito A
- Chiovato L
- Chizhov D
- Cho Ym
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- Goldenberg R
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- Irizar Santana Ss
- Ismail M
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- Januszewicz A
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- Keshavamurthy Cb
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- Marasaev V
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- Zemek S
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- Zhang Hong
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- Zinman B
- Zinman Bernard
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- Zsom M
- Zub L
- Zykova T
- Publication venue
- 'Massachusetts Medical Society'
- Publication date
- 01/01/2019
- Field of study
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