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SGLT2 inhibition diabetic kidney disease

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https://www.readbyqxmd.com/read/29735306/renoprotective-effects-of-sodium-glucose-cotransporter-2-inhibitors
#1
REVIEW
Hiddo J L Heerspink, Mikhail Kosiborod, Silvio E Inzucchi, David Z I Cherney
Over the past two years, our understanding of anti-hyperglycemic medications used to treat patients with type 2 diabetes (T2D) has fundamentally changed. Before the EMPA-REG OUTCOME trial, agents used to lower blood glucose were felt to prevent or delay the development of microvascular complications, but were not known to definitively reduce cardiovascular risk or mortality. Previous studies with then novel sodium-glucose cotransport-2 (SGLT2) inhibitors demonstrated improvements in several cardiovascular and renal risk factors, including HbA1c, blood pressure, weight, renal hyperfiltration, and albuminuria...
May 5, 2018: Kidney International
https://www.readbyqxmd.com/read/29663292/the-potential-role-of-sglt2-inhibitors-in-the-treatment-of-type-1-diabetes-mellitus
#2
Hadi Fattah, Volker Vallon
Type 1 diabetes mellitus is a difficult disease to treat due to the relative paucity of therapeutic options other than injectable insulin. The latter, however, can induce hypoglycemia, which has been linked to enhanced cardiovascular risk. Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-hyperglycemic medications that do not increase the hypoglycemia risk and are US Food and Drug Administration (FDA) approved in type 2 diabetes mellitus. SGLT2 inhibitors may also be of benefit in type 1 diabetic patients, in addition to insulin, although they have not yet been approved for this indication...
April 16, 2018: Drugs
https://www.readbyqxmd.com/read/29604389/effects-of-sodium-glucose-cotransporter-2-inhibitors-on-cardiovascular-disease-death-and-safety-outcomes-in-type-2-diabetes-a-systematic-review
#3
REVIEW
Karin Rådholm, Jason Hy Wu, Muh Geot Wong, Celine Foote, Gregory Fulcher, Kenneth W Mahaffey, Vlado Perkovic, Bruce Neal
AIM: Sodium glucose co-transporter 2 (SGLT2) inhibitors appear to protect against increased risks of cardiovascular and kidney disease in patients with type 2 diabetes but also cause some harms. Whether effects are comparable across drug class or specific to individual compounds is unclear. This meta-analysis assessed the class and individual compound effects of SGLT2 inhibition versus control on cardiovascular events, death, kidney disease and safety outcomes in patients with type 2 diabetes...
March 28, 2018: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29507299/comprehensive-renoprotective-effects-of-ipragliflozin-on-early-diabetic-nephropathy-in-mice
#4
Michitsugu Kamezaki, Tetsuro Kusaba, Kazumi Komaki, Yohei Fushimura, Noriko Watanabe, Kisho Ikeda, Takashi Kitani, Noriyuki Yamashita, Masahiro Uehara, Yuhei Kirita, Yayoi Shiotsu, Ryosuke Sakai, Takuya Fukuda, Masahiro Yamazaki, Michiaki Fukui, Satoaki Matoba, Keiichi Tamagaki
Clinical and experimental studies have shown that sodium glucose co-transporter 2 inhibitors (SGLT2i) contribute to the prevention of diabetic kidney disease progression. In order to clarify its pharmacological effects on the molecular mechanisms underlying the development of diabetic kidney disease, we administered different doses of the SGLT2i, ipragliflozin, to type 2 diabetic mice. A high-dose ipragliflozin treatment for 8 weeks lowered blood glucose levels and reduced urinary albumin excretion. High- and low-dose ipragliflozin both inhibited renal and glomerular hypertrophy, and reduced NADPH oxidase 4 expression and subsequent oxidative stress...
March 5, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29482993/sglt2-inhibitors-and-renal-outcomes-in-type-2-diabetes-with-or-without-renal-impairment-a-systematic-review-and-meta-analysis
#5
Samuel Seidu, Setor K Kunutsor, Xavier Cos, Syed Gillani, Kamlesh Khunti
BACKGROUND: Sodium-glucose co-transporter 2 (SGLT2) inhibitors may have renal protective effects in people with impaired kidney function. We assessed the use of SGLT2 inhibitors in people with type 2 diabetes with or without renal impairment [defined as estimated glomerular filtration rate (eGFR) of ≥30 and <60ml/min/1.73m2 and/or UACR>300 and ≤5000mg/g] by conducting a systematic review and meta-analysis of available studies. METHODS: Randomised controlled trials (RCTs) were identified from MEDLINE, EMABASE, Web of Science, the Cochrane Library, and search of bibliographies to March 2017...
June 2018: Primary Care Diabetes
https://www.readbyqxmd.com/read/29424089/cardiovascular-benefits-of-sglt2-inhibition-in-diabetes-and-chronic-kidney-diseases
#6
EDITORIAL
A T Layton, V Vallon
No abstract text is available yet for this article.
April 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29409087/-chronic-kidney-disease-update-2018
#7
Markus Ketteler, Christoph Wanner
SGLT2-INHIBITION IN DIABETIC AND NON-DIABETIC KIDNEY DISEASE:  The CANVAS Program Collaborative Group study confirmed nephroprotective actions by canagliflocin comparable to empagliflozin as published in the EMPA-REG Outcome study. Treatment with Liraglutide (LEADER study) also suggests nephroprotection via albuminuria reduction a decreased eGFR decline in subgroups and depending on stages of diabetic nephropathy. KDIGO CKD-MBD GUIDELINE UPDATE 2017:  In July 2017, an update of the KDIGO (Kidney Disease: Improving Global Outcomes) 2009 guideline on diagnostic and treatment chronic kidney disease - mineral and bone disorders (CKD-MBD) was published...
February 2018: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29361669/sglt2-inhibition-in-a-kidney-with-reduced-nephron-number-modeling-and-analysis-of-solute-transport-and-metabolism
#8
Anita T Layton, Volker Vallon
Sodium-glucose cotransporter 2 (SGLT2) inhibitors enhance urinary glucose, Na+ and fluid excretion, and lower hyperglycemia in diabetes by targeting Na+ and glucose reabsorption along the proximal convoluted tubule. A goal of this study was to predict the effects of SGLT2 inhibitors in diabetic and nondiabetic patients with chronic kidney disease. To that end, we employed computational rat kidney models to explore how SGLT2 inhibition affects renal solute transport and metabolism when nephron populations are normal or reduced...
May 1, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29349558/sglt2-inhibitors-and-mechanisms-of-hypertension
#9
REVIEW
Alexandros Briasoulis, Omar Al Dhaybi, George L Bakris
PURPOSE OF REVIEW: We sought to review currently available data on the safety and efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors in type 2 diabetes mellitus patients with hypertension. RECENT FINDINGS: Inhibition of SGLT2 in the renal proximal tubule results in increased urinary glucose excretion and modest improvements of hemoglobin A1C. Treatment with any of the three currently FDA-approved SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) results in sustained systolic and diastolic blood pressure reduction, in part via minimal natriuresis and possible reductions in sympathetic tone...
January 19, 2018: Current Cardiology Reports
https://www.readbyqxmd.com/read/29177922/sglt1-and-sglt1-inhibitors-a-role-to-be-assessed-in-the-current-clinical-practice
#10
Leonardo Spatola, Silvia Finazzi, Claudio Angelini, Marco Dauriz, Salvatore Badalamenti
Diabetes is a complex disease of increasingly common occurrence worldwide. Attaining optimal glycemic control is the main challenge to prevent the development of diabetes-related complications and/or to stop their progression. In recent years, the pharmacologic toolkit for the treatment of diabetes has considerably expanded, thus paving the way to more pathophysiology-oriented therapies. For instance, the sodium-glucose cotransporters SGLT2 and SGLT1 have been in the spotlight because of better knowledge of their physiology and therapeutic potential...
February 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29141939/dapagliflozin-in-focal-segmental-glomerulosclerosis-a-combined-human-rodent-pilot-study
#11
Harindra Rajasekeran, Heather N Reich, Michelle A Hladunewich, Daniel Cattran, Julie A Lovshin, Yuliya Lytvyn, Petter Bjornstad, Vesta Lai, Josephine Tse, Leslie Cham, Syamantak Majumder, Bridgit B Bowskill, M Golam Kabir, Suzanne L Advani, Ian W Gibson, Manish M Sood, Andrew Advani, David Z I Cherney
Focal segmental glomerulosclerosis (FSGS) is an important cause of nondiabetic chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibition (SGLT2i) therapy attenuates the progression of diabetic nephropathy, but it remains unclear whether SGLT2i provides renoprotection in nondiabetic CKD such as FSGS. The primary aim of this pilot study was to determine the effect of 8 wk of dapagliflozin on glomerular filtration rate (GFR) in humans and in experimental FSGS. Secondary end points were related to changes in renal hemodynamic function, proteinuria, and blood pressure (BP)...
March 1, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29127757/-gliflozins-slow-down-the-progression-of-diabetic-kidney-disease
#12
REVIEW
Vladimír Tesař, Jan Vachek
Until recently progression of diabetic kidney disease could have been slowed down only by the inhibition of the renin-angiotensin system. Inhibitors of SGLT2 (sodium-glucose transporter 2) in the proximal tubulus of the kidney induce natriuresis and by the activation of the tubuloglomerular feedback increase the tone of the afferent arteriole and decrease the glomerular pressure. Empagliflozin in the study EMPA-REG Outcome significantly decreased the risk of progression of diabetic kidney disease and further analyses also demonstrated its potent antiproteinuric effect...
December 0: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29084249/the-effect-of-sodium-glucose-cotransporter-2-sglt2-inhibition-on-the-urinary-proteome
#13
David Cherney, Bruce A Perkins, Yuliya Lytvyn, Hiddo Heerspink, María E Rodríguez-Ortiz, Harald Mischak
Treatment with empagliflozin, an inhibitor of the sodium/glucose cotransporter 2 (SGLT2), is associated with slower progression of diabetic kidney disease. In this analysis, we explored the hypothesis that empagliflozin may have an impact on urinary peptides associated with chronic kidney disease (CKD). In this post-hoc, exploratory analysis, we investigated urine samples obtained from 40 patients with uncomplicated type 1 diabetes (T1D) before and after treatment with empagliflozin for 8 weeks to for significant post-therapy changes in urinary peptides...
2017: PloS One
https://www.readbyqxmd.com/read/28840540/a-more-tubulocentric-view-of-diabetic-kidney-disease
#14
REVIEW
Letizia Zeni, Anthony G W Norden, Giovanni Cancarini, Robert J Unwin
Diabetic nephropathy (DN) is a common complication of Diabetes Mellitus (DM) Types 1 and 2, and prevention of end stage renal disease (ESRD) remains a major challenge. Despite its high prevalence, the pathogenesis of DN is still controversial. Initial glomerular disease manifested by hyperfiltration and loss of glomerular size and charge permselectivity may initiate a cascade of injuries, including tubulo-interstitial disease. Clinically, 'microalbuminuria' is still accepted as an early biomarker of glomerular damage, despite mounting evidence that its predictive value for DN is questionable, and findings that suggest the proximal tubule is an important link in the development of DN...
December 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28760224/hemodynamic-and-renal-implications-of-sodium-glucose-cotransporter-2-inhibitors-in-type-2-diabetes-mellitus
#15
Alberto Tejedor Jorge
In DM2, there is increased expression of the proximal glucose transporter SGLT2. The increased glucose reabsorption from the urine to the proximal tubule and subsequently to the bloodstream, has three direct effects on the prognosis of patients with DM2: a) it increases the daily glucose load by raising the renal threshold for glucose, thus augmenting requirements for oral antidiabetics and insulin. This progressive increase occurs throughout the course of the disease and in parallel with the increase in renal mass (renal hypertrophy); b) because of the greater glucose reabsorption, glycosuria is lower than the level corresponding to glycaemia, decreasing the stimulus on the tubuloglomerular feedback system of the distal nephron...
November 2016: Medicina Clínica
https://www.readbyqxmd.com/read/28759755/the-roles-of-sodium-glucose-cotransporter-2-inhibitors-in-preventing-kidney-injury-in-diabetes
#16
REVIEW
Krit Jaikumkao, Anchalee Pongchaidecha, Varanuj Chatsudthipong, Siriporn C Chattipakorn, Nipon Chattipakorn, Anusorn Lungkaphin
Diabetic nephropathy (DN) is the leading cause of end stage renal disease (ESRD) worldwide. The early effective treatment of high plasma glucose could delay or prevent the onset of DN. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are new target treatments for ameliorating high plasma glucose and help to maintain glucose homeostasis in diabetic patients. Reduced renal glucose reabsorption by SGLT2 inhibition seems to have high potential to improve glycemic control in diabetes mellitus (DM) not only through glucose lowering but also through glucose-independent effects such as blood pressure-lowering and direct renal effects in diabetes...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28749169/effects-of-sodium-glucose-cotransporter-2-inhibitors-on-serum-uric-acid-in-type-2-diabetes-mellitus
#17
Hala Ahmadieh, Sami Azar
Hyperuricemia has been linked to metabolic syndrome, cardiovascular disease, and chronic kidney disease. Hyperuricemia and type 2 diabetes mellitus were inter-related, type 2 diabetes mellitus was more at risk of having a higher serum uric acid level, and also individuals with higher serum uric acid had higher risk of developing type 2 diabetes in the future. Insulin resistance seems to play an important role in the causal relationship between metabolic syndrome, type 2 diabetes, and hyperuricemia. Oral diabetic drugs that would have additional beneficial effects on reducing serum uric acid levels are of importance...
September 2017: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/28663934/effects-of-sodium-glucose-co-transporter-2-sglt2-inhibition-on-renal-function-and-albuminuria-in-patients-with-type-2-diabetes-a-systematic-review-and-meta-analysis
#18
Lubin Xu, Yang Li, Jiaxin Lang, Peng Xia, Xinyu Zhao, Li Wang, Yang Yu, Limeng Chen
AIM: To evaluate the effects of sodium-glucose co-transporter 2 (SGLT2) inhibition on renal function and albuminuria in patients with type 2 diabetes. METHODS: We conducted systematic searches of PubMed, Embase and Cochrane Central Register of Controlled Trials up to June 2016 and included randomized controlled trials of SGLT2 inhibitors in adult type 2 diabetic patients reporting estimated glomerular filtration rate (eGFR) and/or urine albumin/creatinine ratio (ACR) changes...
2017: PeerJ
https://www.readbyqxmd.com/read/28506519/sodium-glucose-co-transporters-and-their-inhibition-clinical-physiology
#19
REVIEW
Ele Ferrannini
Sodium-glucose cotransporter-2 (SGLT2) is selectively expressed in the human kidney, where it executes reabsorption of filtered glucose with a high capacity; it may be overactive in patients with diabetes, especially in the early, hyperfiltering stage of the disease. As a therapeutic target, SGLT2 has been successfully engaged by orally active, selective agents. Initially developed as antihyperglycemic drugs, SGLT2 inhibitors have deployed a range of in vivo actions. Consequences of their primary effect, i...
July 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28431667/the-potential-and-pitfalls-of-glp-1-receptor-agonists-for-renal-protection-in-type-2-diabetes
#20
Merlin C Thomas
Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RA) offer substantial benefits for the management of glucose levels in type 2 diabetes. In addition, recent data from clinical trials have demonstrated that treatment with Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RA) are also able to reduce new onset macroalbuminuria. These benefits may be consistent with the known effects of GLP-1 RA on traditional risk factors for progressive kidney disease including glucose lowering, blood pressure lowering, reduced insulin levels and weight reduction...
April 2017: Diabetes & Metabolism
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