4 research outputs found
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
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- Bakris George
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- Belo D
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- Bentley-Lewis R
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- Berenguer R
- Berli Ma
- Bermudez L
- Bernardo M
- Bhushan Rs
- Bijata-Bronisz R
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- Biscoveanu M
- Bompoint Severine
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- Botsyurko V
- Bowman-Stroud C
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- Bregman R
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- Brusco O
- Buganova I
- Bull Scott
- Burst V
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- Busegeanu Mm
- Calella P
- Camelo Sanches Fc
- Canaan Y
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- Capuano George
- Caringal C
- Cariou B
- Cartasegna Lr
- Castellino P
- Cercos E
- Cereto Castro F
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- Chacra Ar
- Chae Dw
- Chang Ct
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- Chapin L
- Charytan David M
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- Cheifetz A
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- Cherney D 3rd
- Chertow G
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- Chilito A
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- Commendatore V
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- Csiky B
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- Culak J
- Cuneo Ca
- Cunha Borges Jl
- Cunha V\ueancio Sa
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- Vyasam Rc
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- Wadud K
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- Wakasugi M
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- Watanabe T
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- Yao C
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- Ygpuara Mdl
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- Yu X
- Yumita W
- Yupanqui H
- Zaidman Cj
- Zalunardo N
- Zamarripa Escobedo R
- Zanata Petry Tb
- Zanella Mt
- Zaniewski-Singh M.
- Zanoli L
- Zaoui P
- Zateyshchikova A
- Zateyshshikov D
- Zaviriukha V
- Zemek S
- Zhang H
- Zhang Hong
- Zhao M
- Zheng H
- Zinman B
- Zinman Bernard
- Zlova T
- 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
Canagliflozin and renal outcomes in type 2 diabetes and nephropathy
- Author
- A Kaldun Nossuli
- Aamir Jamal
- Adalbert Schiller
- Adam Cheifetz
- Adarsh Daswani
- Adeera Levin
- Adline Ghazi
- Adrian Guinsburg
- Adriana Cif
- Adriana Gabriela Onaca
- Adriana Ilavska
- Adriana Villarino
- Agarwal R.
- Agnieszka Starzec
- Ahmed Arif
- Ahmed Awad
- Aiping Yin
- Akimichi Asano
- Alan Jackson
- Alan McMahon
- Alan Perlman
- Alberto Di Carlo
- Alberto Esquenazi
- Alejandra Oviedo
- Alejandro Valdes Depeda
- Aleksandra Kendereski
- Alex Valenzuela
- Alexander Dreval
- Alexander Gonzalez
- Alexander Shinkov
- Alexander Turchin
- Alexandre Klein
- Alfonso Soto Gonzalez
- Alfred Penfornis
- Alfredo Chew Wong
- Alfredo Wassermann
- Ali Torshizi
- Alicia Chilito
- Alina Agafyina
- Alison Dawson
- Alva Hansraj
- Amer Al-Karadsheh
- Amorin Remus Popa
- Amrendra Kumar
- Amy Sprague
- Ana Limos
- Ana Maria Cusumano
- Ana Maria Elosegui
- Anabella Amigo
- Anatoliy Kazmirchuk
- Andrea Phillips
- Andrea Stella
- Andreas Maddux
- Andrej Dzupina
- Andres Alvarisqueta
- Andrew Johnson
- Andrew O'Shaughnessy
- Andrew Steele
- Andrian Yakov
- Andrzej Januszewicz
- Andrzej Madej
- Angelina Angelova
- Anibal Gastaldi
- Anil Gupta
- Anita Bhajan Manocha
- Anjanette Tan
- Anna Kaminska
- Anna Maria Veronelli
- Anna Strzelecka
- Anna Zateyshchikova
- Anselmo Bordonava
- Antanas Navickas
- Anthony Gunstone
- Anthony Roberts
- Antonio Ceriello
- Antonio Galan Serrano
- Antonio Scafuto Scotton
- Antonio Terrelonge
- Antônio Roberto Chacra
- Anupama Gowda
- Arjun D Sinha
- Armando Perez
- Ashot Mkrtumyan
- Atanas Koundurdjiev
- Augusto Vallejos
- Aurelian-Emil Ranetti
- Ayim Akyea-Djamson
- Aysha Badat
- Bakris G.
- Baldev Singh
- Barbara Greco
- Barbara Kaczmarek
- Barbara Rewerska
- Barry M Brenner
- Belia Martin Del Camp Blanco
- Bernard Zinman
- Bertrand Cariou
- Bertrand Dussol
- Bhasker Mehta
- Bhimavarapu Sudhakar
- Björn Paschen
- Bompoint S.
- Borys Mankovskyy
- Botond Csiky
- Boyan Nonchev
- Brenner B. M.
- Brett Kissela
- Brian Nichol
- Bruce Neal
- Bruce Trippe
- Bruno Geloneze Neto
- Bull S.
- Byung-Wan Lee
- C B Keshavamurthy
- Cannon C. P.
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- Carlos Perez
- Carmel Hawley
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- Carol Pollock
- Carolyn Droste
- Caroucel Chuateco
- Caryl David
- Cecilia Garcia Ballesteros
- Cecilia Jimeno
- Celso Amodeo
- Cesar Javier Zaidman
- Cesar Yoiti Hayashida
- Chamberlain Obialo
- Chang-Hsun Hsieh
- Charles Cook
- Charles Kaupke
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- Chek Loong Loh
- Chen Leia
- Cheol-Young Park
- Chih-Ching Lin
- Christopher P Cannon
- Christy Yao
- Chu P. -L.
- Chwen-Tzuei Chang
- Chye Lee Gan
- Clara Barrios
- Claude Galphin
- Claudia Goycoa
- Claudia Moreira de Brito
- Clodoaido Caringal
- Cristian Serafinceanu
- Cristina Toarba
- Cristobal Morales Portillo
- Csaba Kovesdy
- Cynthia Bowman-Stroud
- Cynthia Christiano
- Cynthia Mustieles Rocha
- Cyrus Desouza
- Cássio Slompo Ramos
- Dagmar Bartaskova
- Dale Crawford Allison
- Dalia Kozloviene
- Dan Scharfstein
- Dana Cosma
- Daniel Coyne
- Daniel Hiser
- Daniel Kolansky
- Daniel Panarotto
- Daniel Pella
- Daniel Weiner
- Daniil Chizhov
- Dariusz Sowinski
- Darren K McGuire
- Davesh Sennik
- David C Wheeler
- David Cherney 3rd
- David Gorson
- David Johnson
- David M Charytan
- David Packham
- David Scott
- David Wheeler
- De Zeeuw D.
- Debbie Cohen-Stein
- Debbie Mascaro
- Deepak Koppolu
- Dennis Levinson
- Derek Lewis
- Detian Li
- Devasmita Dev
- Devesh Patel
- Dewan Deepak
- Dick de Zeeuw
- Diego Aizenberg
- Dinesh Jain
- Dinesh Khullar
- Diogo Belo
- Dmitry Zateyshshikov
- Domenico Santoro
- Domingos d'Avila
- Donald Brandon
- Donald Fraser
- Dong-Wan Chae
- Dora Inés Molina de Salazar
- Dorota Mlodawska-Choluj
- Doru Negru
- Edgar Arcos
- Edoardo Mannucci
- Eduardo Farias
- Edward Watson
- Edwards R.
- Egle Gaupsiene
- Egle Urbanaviciene
- Ekaterina Velichkova
- Elena Christofides
- Elena Grineva
- Elena Kolmakova
- Elena Shutemova
- Eleonora Harcsa
- Elizabeth Barranco
- Elizabeth Gelersztein
- Elizabeth Kern
- Elizete Keitel
- Eloisa Tellez Chavez
- Emanuela Orsi
- Emil Martinka
- Emyr Davies
- Enrique Gonzalez
- Eric Alamartine
- Eric Hernandez Triana
- Eric Thervet
- Erick Turcios Juarez
- Esteban Cercos
- Eugenia Galindo-Ramos
- Eva Peterfai
- Evaly Chen
- Evandro de Souza Portes
- Evgueniy Vazelov
- Fabian Otreras
- Fabiana Loss de Carvalho Contieri
- Fabio Malberti
- Fadi Saba
- Fadlo Fraige Filho
- Favio Edmundo Enriquez Sosa
- Fayzal Ahmed
- Ferdinando Carlo Sasso
- Fernanco Augusto Alves da Costa
- Fernanda Cristina Camelo Sanches
- Fernando Cereto Castro
- Fernando Flores Lozano
- Fernando Jimenez Florez
- Fernando Krynski
- Fernando M Edwin
- Fernando Thomé
- Fernando Trespalacios
- Florence Santos
- Florencia Kraft
- Fracisco Javier Gonzalez Martinez
- Fran Morren
- Franciso Jose Tinahones Madueno
- Frank Eder
- Franklin Joseph
- Franklin Paul Haase
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- François Dubé
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- Freemu Varghese
- Gabriela Cecilia Coloma
- Gabriela Genova-Hristova
- Gabriele von Ingersleben
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- Gary Meininger
- Gema Fernandez Fresnedo
- Georg Plassmann
- George Bakris
- George Hon
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- Gerald DaRoza
- Gerald Keightley
- Gerry Tan
- Giacomo Garibotto
- Giorgio Fuiano
- Giovanni Frascà
- Giovanni Gambaro
- Giuseppe Derosa
- Gizella Petro
- Glenn Chertow
- Gnyandev Patel
- Godwin Simon
- Goga Vukotic
- Gopal Krishna
- Grace Aquitania
- Grace Lin
- Graham Hillis
- Graziano Di Cianni
- Grazyna Orlowska-Kowalik
- Grazyna Popenda
- Greene T.
- Greg Fulcher
- Gregorio Obrador
- Gregorio Obrador Vera
- Grit Faulmann
- Guadalupe Morales Franco
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- Gulam Latiff
- Gustavo Cristian Greloni
- Guy Chouinard
- Gyongyi Csecsei
- Gyorgy Paragh
- Halyna Tomashkevych
- Hans Prozesky
- Harpreet Bajaj
- Hasnain Khandwala
- Hector Rodriguez
- Heerspink H. J. L.
- Helena Oosthuizen
- Hendrik Nortje
- Henry Watson
- Hermann Haller
- Hernan Finkelstein
- Hernan Yupanqui
- Hiddo J L Heerspink
- Hiralal Maheshwari
- Hiroko Oishi
- Hiromi Aoki
- Hiromi Rodriguez Pattzi
- Hiroshi Kono
- Hitoshi Akiyama
- Holly Wang
- Hong Mao
- Hong Zhang
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- James Conway
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- James Welker
- Jan Culak
- Jana Babikova
- Jana Belobradkova
- Jana Dzuponova
- Janos Mucsi
- Jardine M. J.
- Jason Gaglia
- Javier Narvarte
- Javier Nieto Iglesias
- Jayameena Peringat
- Jayant Kumar
- Jean Carlo Tibes Hachmann
- Jean Welsh
- Jean-Pierre Fauvel
- Jeevren Reddy
- Jeffrey Kropp
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- Jiao Sun
- Jinkui Yang
- Jiri Lastuvka
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- Jose Hector Sanchez Mijangos
- Jose L Górriz
- Jose Luis Accini Mendoza
- Jose Ma Portoles Perez
- Jose Osvaldo Fretes
- Jose Ricardo Correa Rotter
- Joseph Abdallah
- Joseph Aiello
- Joseph Feuerstein
- Joseph O'Hare
- Joseph Proietto
- Josier Nisnisan
- José Vicente Sanchez Polo
- João Lindolfo Cunha Borges
- João Soares Felício
- Juan Alfredo Tamayo Y Orozco
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- Juan Carlos Santos
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- Juan Frias
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- Juan Villagordoa Mesa
- JungEun Lee
- Kamal Abouglila
- Karel Peterka
- Karina Hufert
- Karlton Pettis
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- Kathy Nicholls
- Kati De Brouwer
- Kazuhiro Yanagida
- Kazunori Koyama
- Kazuyuki Mizuyama
- Kee Sing Ng
- Kenneth Cohen
- Kenneth Deck
- Kenneth Hershon
- Kenneth Liss
- Kenneth W Mahaffey
- Khalid Abdul Kadir
- Khurram Wadud
- Kim Travis
- Kiril Hristozov
- Kook-Hwan Oh
- Krisztian Kiss
- Kun Ho Yoon
- Lachezar Lozanov
- Lajos Major
- Lalaine Delos Santos
- Landman Lombard
- Larisha Pillay-Ramaya
- Larry Distiller
- Larysa Pererva
- Laszlo Deak
- Laszlo Konyves
- Laura Akright
- Laura Coffee
- Lawrence Distiller
- Lawrence Lehrner
- Lawrence Leiter
- Lech Lazuka
- Lee-Ming Chuang
- Lenka Dohnalova
- Leslie Spry
- Levin A.
- Li Yuan Lee
- Lidia Bermudez
- Ligia Petrica
- Lilia Beatriz Schiavi
- Liliana Monica Angelescu
- Liliia Zub
- Liliya Martynyuk
- Lin Sun
- Lincoln Chapin
- Linong Ji
- Lisa Rich
- Liudmila Kvitkova
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- László Rosivall
- Ma Dovie Lallaine Ygpuara
- Mahaffey K. W.
- Manel Terns Riera
- Manish Saxena
- Manthi Hettiarachchi
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- Manuela Schmidt
- Marc Rendell
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- Marcus Gomes
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- Maria Florencia Fernandez
- Maria Isabel Klyver
- Maria Jaime
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- Maria Valdez
- Marializa Bernardo
- Marianna Zsom
- Mario Alberto Berli
- Mario Burgos Soto
- Mark Davies
- Mark Vannorsdall
- Mark Warren
- Markus Faghih
- Marsha Tolentino
- Marta Dominquez Lopez
- Marta Molnar
- Martin Lukac
- Martin Valis
- Martine Destree
- Mary Anne Lim-Abrahan
- Mary Lawrence
- Mary Seeber
- Maryna Vlasenko
- María Alicia Fernández Montenegro
- María Angustias Quesada Simón
- Masahiko Takai
- Masahiro Koizumi
- Masakiyo Wakasugi
- Masayo Yamada
- Mastura Ismail
- Matthew Abramowitz
- Matthew Beacom
- Meg J Jardine
- Meg Jardine
- Meininger G.
- Melchor Alpizar Salazar
- Melemadathil Sreelatha
- Merce Perez Vera
- Mercedes Velo Plaza
- Michael Oliver
- Michael Robinson
- Michael Shanik
- Michael Thompson
- Michael Williams
- Michal Nowicki
- Michał Nowicki
- Michelle Zaniewski-Singh
- Mick Kumwenda
- Miguel Nazzer Hissa
- Migues Angel Reyes Rosano
- Mihaela Biscoveanu
- Mihaela-Magdalena Busegeanu
- Mihaly Dudas
- Milan Gupta
- Min Jeong Kwon
- Minara Shamkhalova
- Minghui Zhao
- Miodrag Djordjevic
- Mircea Munteanu
- Mitsuru Tsujimoto
- Mohamed El-Shahawy
- Mohamed Mookadam
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- Mona Wahba
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- Monika Dhillon
- Moogali Arvind
- Moon-Kyu Lee
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- Moustafa Moustafa
- Muhammad Shakeel
- Mukesh Joshi
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- Nadia Zalunardo
- Nadiya Tryshchuk
- Nan Chen
- Narayan Prasad
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- Navdeep Tangri
- Naveen Atray
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- Nina Patel
- Nizar Daboul
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- Norman Muirhead
- Norsiah Ali
- Oleg Legun
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- Oleksandr Golovchenko
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- Oleksii Korzh
- Olga Barbarash
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- Peggy Barnhill
- Peggy Lin
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- Peter Danos
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- Philip Nicol
- Philippe Zaoui
- Phyllis August
- Piermarco Piatti
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- Pierre-Jean Saulnier
- Pietro Castellino
- Pilar Trueba
- Ping Tu
- Pollock C.
- Prasanth Surampudi
- Pusadee Suchinda
- Qinkai Chen
- Rachel Bregman
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- Ramon Berenguer
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- Roberto Pecoits-Filho
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- Rohana Abdul Ghani
- Rohit Pankhaniya
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- Ronald Goldenberg
- Ronald Harris
- Ronald Watts
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- Ronnie Aronson
- Rosa Isela Luna Ceballos
- Rosângela Milagres
- Ruben Dario Vargas Alonso
- Rury Holman
- Russell Scott
- Sacha De Serres
- Sahay Manisha
- Saiful Shahrizal Bin Shudim
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- Salah Abusnana
- Salvatore De Cosmo
- Sam Henein
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- Samy Hadjadj
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- Sanjeev Rastogi
- Sara Jaffer
- Sarah Olelewe
- Satoshi Ota
- Satu Pesickova
- Scott Kasner
- Secundino Cigarran Guldris
- Senan Sultan
- Serge Cournoyer
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- Sergio Saul Irizar Santana
- Shahabul Arfeen
- Shahnaz Shahinfar
- Shang-Jyh Hwang
- Shelley Williams
- Shenaz Ramtoola
- Shenglian Gan
- Sherry Sussman
- Shizuo Kajiyama
- Shozo Miyauchi
- Silvia Ines Orio
- Silvia Nicolai
- Simon Davies
- Simon Roger
- Simon Young
- Sin Gon Kim
- Singhan Krishnan
- Sini George
- Slobodan Antic
- Sohan Dua
- Sonia Hermida
- Soo Kun Lim
- Sophie Borot
- Souhila Ounadjela
- Sreedhar Mandayam
- Srikanth Bellary
- Stanislav Zemek
- Stanislaw Mazur
- Stefan Dimitrov
- Stephan Maxeiner
- Stephen Grubb
- Stephen Smith
- Steven Fishbane
- Stuart Handelsman
- Suely Keiko Kohara
- Sun Kim
- Sun-Hee Park
- Sunil Sheth
- Susumu Kashine
- Svetlana Goykhman
- Svitlana D Bilyk
- Swee Win Lam
- Sylvia Rosas
- Sylvia Shaw
- Szilard Vasas
- Sérgio Alberto Cunha Vêncio
- Sérgio Yamada
- Tadashi Iitsuka
- Takamoto Kodera
- Takashi Wada
- Takayuki Watanabe
- Tamara Malek Marin
- Tamas Oroszlan
- Tara Chang
- Tareq Nassar
- Tarissa Beatrice Zanata Petry
- Tatiana Koroleva
- Tatiana Morugova
- Tatiana Raskina
- Tatyana Zykova
- Te-Lin Hsia
- Terue Sakakibara
- Tetiana Zlova
- Tetsuji Niiya
- Tetyana Pertseva
- Tiago Schuch
- Timothy Hall
- Tom Christensen
- Tom Greene
- Tomas Drasnar
- Tomas Smith Casabella
- Tonatiu Diaz Escalante
- Toshihiko Yanase
- Toshio Kawada
- Vadym Vizir
- Vanassa Ratnasingam
- Venessa Tsang
- Venkata Behara
- Vera Klokocnikova
- Vera Krane
- Veronica Anghel
- Veselka Genadieva
- Vesna Popovic-Radinovic
- Viacheslav Marasaev
- Victor Commendatore
- Victor Saavedra Gajardo
- Vijayaraman Arutchelvam
- Viktor Margaritov
- Viktor Zaviriukha
- Viktoria Andreeva
- Vimladhevi Govender
- Vincent Pichette
- Vincent Woo
- Vira Tseluyko
- Virginia Esther Visco
- Vivek Sood
- Vivekan Jha
- Vladimir Dobronravov
- Vladimir Khirmanov
- Vladimir Tesar
- Vlado Perkovic
- Volker Burst
- Volodymyr Botsyurko
- Walter Guillermo Douthat
- Walter Pharr
- Wasim Hanif
- Wataru Yumita
- Wayne H-H Sheu
- Wayne Turner
- Wei Yen Kong
- Weihong Song
- Weiping Lu
- Wendy Lane
- Wenge Li
- Wheeler D. C.
- Wladmir Saporito
- Xuemei Li
- Xueqing Yu
- Yamil Canaan
- Yan Ren
- Yannick Le Meur
- Yaozhong Kong
- Yasuro Kumeda
- Yasushi Wakida
- Yavin Y.
- Yeong Hoon Kim
- Yevgeniya Svyshchenko
- Young Min Cho
- Yulia Samoylova
- Yung-Chuan Lu
- Yuriy Mostovoy
- Yuriy Shwartz
- Yvette Ethel Yap
- Zaynab Abejuela
- Zdravko Kamenov
- Zeid Khitan
- Zhang H.
- Zinman B.
- Zishan Ali
- Zuzana Ochodnicka
- Ângela Regina Nazario Sabbag
- 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 <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >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 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<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
Deficiency of the E3 ubiquitin ligase TRIM32 in mice leads to a myopathy with a neurogenic component
- Author
- Albor
- Attaix
- Balastik
- Banker
- Blacque
- Borg
- Brown
- Burke
- Burke
- Canete-Soler
- Canete-Soler
- Chiang
- Cullheim
- Cullheim
- Cullheim
- Dum
- Edds
- El-Husseini
- Elder
- Elena Kudryashova
- Fabrizi
- Fiori
- Fridell
- Frosk
- Georgiou
- Gordon
- Havton
- Jerusalem
- Jiang
- Jordanova
- Jun Wu
- Kano
- Kohn
- Kramerova
- Kudryashova
- Lariviere
- Leif A. Havton
- Limos
- Liu
- Malandrini
- Melissa J. Spencer
- Mersiyanova
- Muller-Felber
- Ohkawa
- Parnaik
- Pickart
- Reymond
- Runeberg-Roos
- Saccone
- Schoser
- Schwartz
- Shokeir
- Shokeir
- Swash
- Swash
- Talmadge
- Tobin
- Trout
- Wigston
- Yokota
- Zhu
- Publication venue
- Oxford University Press
- Publication date
- Field of study
Limb-girdle muscular dystrophy type 2H (LGMD2H) and sarcotubular myopathy are hereditary skeletal muscle disorders caused by mutations in TRIM32. We previously identified TRIM32 as an E3 ubiquitin ligase that binds to myosin and ubiquitinates actin. To date four TRIM32 mutations have been linked to LGMD2H, all of which occur in the C-terminal NHL domains. Unexpectedly, a fifth mutation in the B-box of TRIM32 causes a completely different, multisystemic disorder, Bardet–Biedl syndrome type 11. It is not understood how allelic mutations in TRIM32 can create such diverse phenotypic outcomes. To generate a tool for elucidating the complex in vivo functions of TRIM32, we created the first murine Trim32 knock-out model (T32KO). Histological analysis of T32KO skeletal muscles revealed mild myopathic changes. Electron microscopy showed areas with Z-line streaming and a dilated sarcotubular system with vacuoles—the latter being a prominent feature of sarcotubular myopathy. Therefore, our model replicates phenotypes of LGMD2H and sarcotubular myopathy. The level of Trim32 expression in normal mouse brain exceeds that observed in skeletal muscle by more than 100 times, as we demonstrated by real-time PCR. Intriguingly, analysis of T32KO neural tissue revealed a decreased concentration of neurofilaments and a reduction in myelinated motoraxon diameters. The axonal changes suggest a shift toward a slower motor unit type. Not surprisingly, T32KO soleus muscle expressed an elevated type I slow myosin isotype with a concomitant reduction in the type II fast myosin. These data suggest that muscular dystrophy due to TRIM32 mutations involves both neurogenic and myogenic characteristics
Intoxikationen
- Author
- A Abderhalden
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- D Adlersberg
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- E Appel
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- T Kang
- T Leary
- T Lehoczky de
- T Lewis
- T Lids
- T Linz
- T Mclardy
- T Ohkuma
- T Röder-Kutsch
- T Schreuss
- T Schroeder
- T Schöndorf
- T Seldon
- T Simon
- T Sollmann
- T Spiegel
- T Sutton
- T Suzucki
- T Tanaka
- T Upners
- T Upners
- TA Gonzales
- Takasu
- Takeya-Sikô
- Takeya-Sikô
- TAL Davies
- Tarpeiner
- Tauber
- TC Butler
- TC Godwin
- TCM Young
- TD Rivers
- TD Spies
- TE Bachhuber
- TE Machella de
- TF Dixon
- TG Stewart
- TIC Storch
- TJ Fatherree
- TJ Kennedy Jr.
- TJ Putnam
- TL Althausen
- TL Duffy
- Traina
- Trimborn
- Trossarelli
- Tröger
- TS Evans
- U Bassi
- U Bassi
- U Cerletti
- U Friedeman
- U Friedeman
- U Luft
- U Mrrsutasii
- U Testa
- U Vollrate
- V Adinolfi
- V Albertini
- V Ascoli
- V Becker
- V Benoit
- V Calvo
- V Dhers
- V Fellenius
- V Gaupp
- V Kesztele
- V Koszler
- V Lachnpt
- V Leigheb
- V Meduna
- V Menon
- V Moellendorff
- V Monakow
- V Plavec
- V Tschisch
- V Zahle
- Vas
- Velden van der
- VH Vogel
- Villaverde
- Villaverde
- Villaverde
- Villaverde
- Villaverde
- VR Mason
- VR Mason
- W Altmann
- W Anschitz
- W Arcisz
- W Arnold
- W Beiglböck
- W Berger
- W Block
- W Blume
- W Blume
- W Blume
- W Boor de
- W Brainrussel
- W Bredemann
- W Brown
- W Cone
- W Cordes
- W Dameshek
- W Dontenwill
- W Ehrhardt
- W Filehne
- W Friemann
- W Gennerich
- W Goldfarb
- W Guiljarowski
- W Hay
- W Haymaker
- W Heine
- W Heineke
- W Heineke
- W Heinichen
- W Herkel
- W Hesse
- W Heubner
- W Heubner
- W Hoerburger
- W Hortsch
- W Huecx
- W Höfer
- W Höirer
- W Kat
- W Kirschbaum
- W Klein
- W Kürbitz
- W Laubender
- W Laubmann
- W Ludwig
- W Mahoney
- W Noell
- W Noell
- W Noell
- W Noell
- W Noell
- W Palmer
- W Paulus
- W Reiml
- W Reisert
- W Riese
- W Riese
- W Roehl
- W Rotter
- W Rotter
- W Rotter
- W Rotter
- W Schclz
- W Scholz
- W Scholz
- W Scholz
- W Scholz
- W Scholz
- W Scholz
- W Scholz
- W Scholz
- W Scholz
- W Schopper
- W Schorz
- W Schulemann
- W Schwarzacher
- W Schütze
- W Souullenberg
- W Spalteholz
- W Spielmeyer
- W Spielmeyer
- W Spielmeyer
- W Spielmeyer
- W Spielmeyer
- W Spielmeyer
- W Stecher
- W Steinbrinck
- W Stepp
- W Stich
- W Stocker
- W Straub
- W Uhthoff
- W Uhthoff
- W Uhthoff
- W Uhthoff
- W Wechselmann
- W Wechselmann
- W Weigeldt
- W Weigeldt
- W Weimann
- W Weimann
- W Weimann
- W Weimann
- W Weimann
- W Weimann
- W Weimann
- W Weimann
- W Weise
- W Wild
- WA Bastedo
- WA Horwitz
- WA Jacobs
- WA Jacobs
- WA Jacobs
- Wachholz
- Wagner-Jauregg
- Wassmuth
- WB Cadwalader
- WB Chew
- WC Black
- WD Mcnally
- WD Mcnally
- WD Vögtlin
- WE Clark
- WE Dixon
- WE Loomis
- WE Machle
- Weese
- Westphal
- WF Oettingen
- WG Haynes
- WG Lennox
- WG Lennox
- WG Lennox
- WG Lennox
- WG Spuiller
- WH Büel
- WH Eddy
- WH Hill
- WH Sebrell
- WH Sebrell
- Wieil
- Wiese
- Wirth
- WJ Buchanan
- WJ Dilling
- WJ Eicke
- WJ Eicre
- WJ Horsey
- WJ Horsey
- WJ Mccardie
- WJ Turner
- WJ Waters
- WJ Waters
- WJC Verhaart
- WJC Verhaart
- WJC Verhaart
- WK Hare
- WL Craddock
- WL Lillie
- WL Ritter
- WL Vögtlin
- WL Vögtlin
- WM Stephens
- WM Yater
- WN Aldrige
- WN Bispham
- WN Kemp
- WO Umiker
- Wohlwill
- Wolkow
- WP Lawson
- WR Bowen
- WR Hess
- WR Hess
- WR Hess
- WR Murray
- WT Haverfield
- WT Oettingen
- WU Mcclenahan
- WW Jetter
- WW Jetter
- WW Woons
- Y Jacksch
- Y Okamoto
- Y Tsiminakis
- YC Chang
- Z Swetnik
- Z Wechsler
- Z Wechsler
- Zangger
- Ziegler
- Zutt
- Ä Swansson
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/1958
- Field of study