74 research outputs found
P5509The use of three-dimensional echocardiography to measure left ventricular ejection fraction would increase the number of patients with indication to receive implantable cardioverter defibrillators
- Author
- Publication venue
- Publication date
- 01/08/2017
- Field of study
n/
Discovery of a Novel, Isothiazolonaphthoquinone-Based Small Molecule Activator of FOXO Nuclear-Cytoplasmic Shuttling
- Author
- A Brunet
- A Eijkelenboom
- AE Webb
- Bastien Cautain
- BI Ferreira
- Bibiana I. Ferreira
- BJ Willcox
- C-D Pham
- CB Reese
- CE Blunt
- DR Calnan
- F Shi
- F Zanella
- F Zanella
- F Zanella
- F Zanella
- F Zanella
- F Zanella
- Francisca Vicente
- Francisco Castillo
- H Huang
- H Huang
- I Hoffmann
- IT Hogan
- JH Paik
- John F Ross
- JS Lazo
- JS Lazo
- K Nakae
- K Nakae
- K Stratmann
- L. P. Van Der Heide
- Loana Musso
- Lorena Rodriguez Quesada
- M Brisson
- M Brisson
- M Mori
- M Tarrado-Castellarnau
- MJ Sanders
- MN Patel
- MV Blagosklonny
- Mária A. Deli
- Nuria de Pedro
- R Cortes
- R Hill
- R Martins
- R Martins
- RK Howe
- RM Paton
- Sabrina Dallavalle
- Susana Machado
- TB Dansen
- TG Granda
- TR Kau
- TR Kau
- VP Peyregne
- W Link
- W Link
- W Link
- Wolfgang Link
- X Feng
- Publication venue
- 'Public Library of Science (PLoS)'
- Publication date
- 01/01/2016
- Field of study
FOXO factors are tumour suppressor proteins commonly inactivated in human tumours by posttranslational modifications. Furthermore, genetic variation within the FOXO3a gene is consistently associated with human longevity. Therefore, the pharmacological activation of FOXO proteins is considered as an attractive therapeutic approach to treat cancer and age-related diseases. In order to identify agents capable of activating FOXOs, we tested a collection of small chemical compounds using image-based high content screening technology. Here, we report the discovery of LOM612 (compound 1a), a newly synthesized isothiazolonaphthoquinone as a potent FOXO relocator. Compound 1a induces nuclear translocation of a FOXO3a reporter protein as well as endogenous FOXO3a and FOXO1 in U2OS cells in a dose-dependent manner. This activity does not affect the subcellular localization of other cellular proteins including NFkB or inhibit CRM1-mediated nuclear export. Furthermore, compound 1a shows a potent antiproliferative effect in human cancer cell lines
Prevention of postoperative pulmonary complications starts intraoperatively
- Author
- A Doyle
- A Dullenkopf
- A Dullenkopf
- A Karabinis
- A Strandberg
- A Strandberg
- A Strandberg
- A Zanella
- AM Arozullah
- C Ludwig
- CJ Joyce
- CK Dragoumanis
- DJ Morrow
- DK Rose
- DO Warner
- E Bouza
- E Futier
- EM Tschernko
- G Hedenstierna
- G Hedenstierna
- GA Sutherland
- GS Murphy
- GW Smetana
- H Heinze
- H Odenstedt
- H Reinius
- H Wrigge
- HH Bendixen
- J Canet
- J Hortal
- J Karsten
- J Liang
- J Nielsen
- J Nielsen
- J Poelaert
- J Poelaert
- J Pugin
- J Rello
- J Shim
- J Valles
- JB Dimick
- JC Lacherade
- JD Ricard
- JF Nunn
- K Smulders
- K Stonecypher
- L Gattinoni
- L Lorente
- L Magnusson
- L Minkovich
- M Delgado-Rodriguez
- M Duggan
- M Valencia
- MB Drakulovic
- MH Dave
- MH Kollef
- MJ Oyarzun
- N Fabregas
- OA Varban
- P Mahul
- PJ Young
- PS Sanjay
- S Nseir
- SO Labeau
- TS Panchabhai
- U Lucangelo
- WG Johanson Jr
- Y Akutsu
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2013
- Field of study
Year in review in Intensive Care Medicine 2009: I. Pneumonia and infections, sepsis, outcome, acute renal failure and acid base, nutrition and glycaemic control
- Author
- A Boyer
- A Caricato
- A Herbland
- A Kumar
- A Perez-Parra
- A Riutta
- A Rodriguez
- A Torres
- A Torres
- A Umgelter
- A Vieillard-Baron
- A Zanella
- AG Saayman
- Alexandre Mebazaa
- AM Smet de
- B Delannoy
- B Jung
- B Metnitz
- B Redfors
- B Souweine
- BH Cuthbertson
- BP Guery
- BP Guery
- C Alberda
- C Guignant
- CJ Karvellas
- CS Hawe
- CT Buschmann
- CW Hogue Jr
- D Ledoux
- D Poole
- Daniel De Backer
- DJ Knight
- Duncan Macrae
- E Azoulay
- E Azoulay
- E Meyer
- Elie Azoulay
- F Barbier
- François Lemaire
- G Prat
- GC Funk
- Giorgio Conti
- Giuseppe Citerio
- GJ Oudhuis
- Goran Hedenstierna
- H Hanberger
- Haibo Zhang
- Herwig Gerlach
- J Hortal
- J Jiyong
- J Kreutziger
- J Silvestre
- JA Martinez
- Jan Wernerman
- Jean Chastre
- Jean-Charles Preiser
- Jerôme Pugin
- JF Dhainaut
- JJ Cordingley
- Jordi Mancebo
- L Senn
- L Su
- M Crivellari
- M Darmon
- M Heijden van der
- M Joannidis
- M Joannidis
- M Levy
- M Michalia
- M Wolkewitz
- Marc Bonten
- Massimo Antonelli
- Michael Joannidis
- MM Boniatti
- MM Ward
- O Baldesi
- PS Kruger
- R Bellomo
- RL Mehta
- RM Berg
- RP Moreno
- S Barlage
- S Eslami
- S Iribarren-Diarasarri
- S Patman
- S Rauch
- Salvatore M. Maggiore
- SE Wright
- SJ Thomson
- SM Bagshaw
- U Holzinger
- U Holzinger
- V Fencl
- V Fuhrmann
- V Novack
- V Peigne
- W Manzanares
- W Meersseman
- Publication venue
- Springer-Verlag
- Publication date
- 01/01/2010
- Field of study
Journal ArticleReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
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- A. -G. Wu
- A. C. Ma
- A. K. Au
- Abdel-Aziz A. K.
- Abdelfatah S.
- Abdellatif M.
- Abdoli A.
- Abel S.
- Abeliovich H.
- Abildgaard M. H.
- Abudu Y. P.
- Acevedo-Arozena A.
- Adamopoulos I. E.
- Adeli K.
- Adolph T. E.
- Adornetto A.
- Aflaki E.
- Agam G.
- Agarwal A.
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- Agnello M.
- Agostinis P.
- Agrewala J. N.
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- Ahmad S. T.
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- Aits S.
- Aizawa S.
- Akkoc Y.
- Akoumianaki T.
- Akpinar H. A.
- Al-Abd A. M.
- Al-Akra L.
- Al-Gharaibeh A.
- Alaoui-Jamali M. A.
- Alberti S.
- Alcocer-Gomez E.
- Alessandri C.
- Ali M.
- Alim Al-Bari M. A.
- Aliwaini S.
- Alizadeh J.
- Almacellas E.
- Almasan A.
- Alonso A.
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- Zwerschke W.
- Publication venue
- 'Informa UK Limited'
- Publication date
- 01/01/2021
- Field of study
Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis
- Author
- Abdallah J.
- Abdullah R.
- Abejuela Z.
- Abouglila K.
- Abramowitz M.
- Abusnana S.
- Acosta I.
- Agafyina A.
- Aggarwal N.
- Agra J.
- Ahmad N. N. F. N.
- Ahmed F.
- Aiello J.
- Ainsworth P.
- Aizenberg D.
- Akiyama H.
- Akright L.
- Akyea-Djamson A.
- Al-Karadsheh A.
- Alamartine E.
- Alappan R.
- Albisu J. P.
- Ali N.
- Ali Z.
- Alicic R.
- Allison D. C.
- Alonso R. D. V.
- Alva H.
- Alvarisqueta A.
- Amodeo C.
- Andreeva V.
- Angelescu L. M.
- Angelova A.
- Anghel V.
- Antic S.
- Aoki H.
- Aquitania G.
- Arauz-Pacheco C.
- Arcos E.
- Arenales J. A. S.
- Arfeen S.
- Arif A.
- Aronson R.
- Arutchelvam V.
- Arvind M.
- Asano A.
- Atray N.
- Avendano J.
- Avram R. -I.
- Awad A.
- Babikova J.
- Badat A.
- Bajaj H.
- Baker J.
- Bakris G.
- Ballesteros C. G.
- Barbarash O.
- Barna O.
- Barnard M.
- Barnhill P.
- Baron P. F.
- Barranco E.
- Barrera C.
- Barrios C.
- Bartaskova D.
- Bartolacci I.
- Barton P.
- Barysheva O.
- Beacom M.
- Behara V.
- Bellary S.
- Belo D.
- Belobradkova J.
- Bentley-Lewis R.
- Benusova O.
- Berenguer R.
- Berli M. A.
- Bermudez L.
- Bernardo M.
- Bijata-Bronisz R.
- Bilyk S. D.
- Biscoveanu M.
- Bonadonna R.
- Bordonava A.
- Borges J. L. C.
- Borot S.
- Botsyurko V.
- Bowman-Stroud C.
- Brandon D.
- Breedt J.
- Bregman R.
- Brusco O.
- Buganova I.
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- Varghese F.
- Vasas S.
- Vejar M.
- Velasquez-Mieyer P.
- Velichkova E.
- Vencio S. A. C.
- Vengadasalam P.
- Ventrapragada S.
- Vera G. O.
- Vera M. P.
- Veronelli A. M.
- Vila M. A. M.
- Villarino A.
- Villegas I.
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- Vizir V.
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- Vorobyev S.
- Vukotic G.
- Vyasam R. C.
- Wada T.
- Wadud K.
- Wahba M.
- Wakasugi M.
- Wakeling J.
- Wakida Y.
- Walker R.
- Wang G.
- Warren M.
- Wassermann A.
- Watanabe T.
- Watson E.
- Watson H.
- Watts R.
- Weiner D.
- Weiner P.
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- Williams M.
- Williams S.
- Winocour P.
- Wong A. C.
- Woo V.
- Yakov A.
- Yamada M.
- Yamada S.
- Yanagida K.
- Yanase T.
- Yang J.
- Yao C.
- Yap Y. E.
- Ygpuara M. D. L.
- Yin A.
- Yoon K. H.
- Young S.
- Yu X.
- Yumita W.
- Yupanqui H.
- Yusof M. D. C.
- Zaidman C. J.
- Zalunardo N.
- Zanella M. T.
- Zaniewski-Singh M.
- Zanoli L.
- Zaoui P.
- Zateyshchikova A.
- Zateyshshikov D.
- Zemek S.
- Zhao M.
- Zheng H.
- Zhou Z.
- Zlova T.
- Zsom M.
- Zub L.
- Zykova T.
- Publication venue
- 'Ovid Technologies (Wolters Kluwer Health)'
- Publication date
- 01/01/2021
- Field of study
BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.
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- Abdel-Aziz AK
- Abdelfatah S
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- Zimmermann CM
- Ziviani E
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- Zong W-X
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- Zorzano A
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- Zwerschke W
- Álvarez ÉMC
- Ávalos Y
- Önal G
- Üstün S
- Čolić M
- Đokić J
- Žerovnik E
- Publication venue
- 'Informa UK Limited'
- Publication date
- 01/01/2021
- Field of study
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field
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
- Avendano J
- Avram Ri
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- Babikova J
- Badat A
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- Baker J
- Bakris G
- Bakris George
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- Bellary S
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- Bentley-Lewis R
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- Berenguer R
- Berli Ma
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- Bernardo M
- Bhushan Rs
- Bijata-Bronisz R
- Bilyk Sd
- Bin Shudim Ss
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- Buganova I
- Bull Scott
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- Camelo Sanches Fc
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- Capuano George
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- Cartasegna Lr
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- Chilito A
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- Christensen T
- Christiano 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
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
- Author
- A Abbott
- A Abou-Raya
- A Aljandali
- A Ambesi-Impiombato
- A Aydin
- A Balcerczyk
- A Besarab
- A Brzezinski
- A Campbell
- A Carrillo-Vico
- A Cavalli
- A Chattopadhyay
- A Chattopadhyay
- A Cherubini
- A Dey
- A Doms
- A Donovan
- A Donovan
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- A Gaeta
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- A Gopalakrishnan
- A Hald
- A Henney
- A Hirayama
- A Hoffmann
- A Huber
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- Publication venue
- Publication date
- 09/08/2008
- Field of study
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
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.
- Capuano G.
- Carlo Giorda
- Carlos Alberto Cuneo
- Carlos Arauz-Pacheco
- Carlos Barrera
- Carlos Perez
- Carmel Hawley
- Carmen Crisan
- 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
- Charytan D. M.
- 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
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- Cyrus Desouza
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- Dagmar Bartaskova
- Dale Crawford Allison
- Dalia Kozloviene
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- Dana Cosma
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- Daniel Hiser
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- Daniel Panarotto
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- Dariusz Sowinski
- Darren K McGuire
- Davesh Sennik
- David C Wheeler
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- David Gorson
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- David M Charytan
- David Packham
- David Scott
- David Wheeler
- De Zeeuw D.
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- Tareq Nassar
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- Tatiana Koroleva
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- Tatyana Zykova
- Te-Lin Hsia
- Terue Sakakibara
- Tetiana Zlova
- Tetsuji Niiya
- Tetyana Pertseva
- Tiago Schuch
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- 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
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