Atrasentan Back on the SONAR for Diabetes and Kidney Disease Atrasentan Back on the SONAR for Diabetes and Kidney Disease

A trial of the experimental drug suggests major benefits for patients with diabetes and chronic kidney disease, an analysis of data conducted after the SONAR study was halted shows.Medscape Medical News
Source: Medscape Medical News Headlines - Category: Consumer Health News Tags: Nephrology News Source Type: news

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Background: Glomerular hyperfiltration (GH) is a hallmark of renal dysfunction in diabetes and obesity. Recent clinical trials demonstrated that SGLT2 inhibitors are renoprotective, possibly by abating hyperfiltration. The present review considers the current evidence for a cause-to-effect relationship between hyperfiltration-related physical forces and the development of chronic kidney disease (CKD).Summary: Glomerular hyperfiltration is associated with glomerular and tubular hypertrophy. Hyperfiltration is mainly due to an increase in glomerular capillary pressure, which increases tensile stress applied to the capillary ...
Source: Nephron - Category: Urology & Nephrology Source Type: research
Conclusion As a critical regulator of inflammation and cell survival, the NFκB pathway is a promising target for diagnosing and treating kidney diseases. For modulation of the NFκB pathway in the clinic, a number of molecules can effectively inhibit NFκB signaling by targeting the receptors, associated adaptors, IKKs, IκBs and transcriptional regulators (144). There is further clinical evidence on small-molecule inhibitors of IKKα and NIK from recent trials on anti-cancer therapies (145). These clinical trials showed that the cancer-selective pharmacodynamic response of DTP3, the co-inhibitor...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In conclusion, the present study identified canagliflozin as a potent inhibitor of human EC proliferation. The anti-proliferative action of canagliflozin is observed in ECs isolated from both the venous and arterial circulation, and is partly due to the blockade of cyclin A expression. In addition, this study found that canagliflozin inhibits tube formation in cultured ECs and mouse aortic rings. Notably, these actions are specific for canagliflozin and not seen with other SGLT2 inhibitors. The ability of canagliflozin to exert these pleiotropic effects on EC function may contribute to both the adverse and salutary actions...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 14 April 2019Source: The LancetAuthor(s): Katherine R Tuttle
Source: The Lancet - Category: General Medicine Source Type: research
We report the long-term effects of treatment with atrasentan on major renal outcomes.MethodsWe did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR) 25–75 mL/min per 1·73 m2 of body surface area, and a urine albumin-to-creatinine ratio (UACR) of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period befor...
Source: The Lancet - Category: General Medicine Source Type: research
Source: Johnson and Johnson - Category: Pharmaceuticals Source Type: news
A drug that’s used to help control blood sugar in people with diabetes has now been shown to help prevent or slow kidney disease, which causes millions of deaths each year and requires hundreds of thousands of people to use dialysis to stay alive. Doctors say it’s hard to overstate the importance of this study, and what it means for curbing this problem, which is growing because of the obesity epidemic. The study tested Janssen Pharmaceuticals’ drug Invokana. Results were discussed Sunday at a medical meeting in Australia and published by the New England Journal of Medicine. About 30 million Americans and...
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized medicine onetime overnight Source Type: news
New England Journal of Medicine, Ahead of Print.
Source: New England Journal of Medicine - Category: Internal Medicine Authors: Source Type: research
Publication date: Available online 13 April 2019Source: The Lancet Diabetes &EndocrinologyAuthor(s): Katherine R Tuttle
Source: The Lancet Diabetes and Endocrinology - Category: Endocrinology Source Type: research
This study is registered with ClinicalTrials.gov, number NCT02547935 and is completed.FindingsThe study took place between July 14, 2015, and May 18, 2018. 1187 patients were screened, of whom 461 were randomly assigned: 145 to the dapagliflozin group, 155 to the dapagliflozin–saxagliptin group, and 148 to the placebo group (13 patients were excluded because of data integrity issues). Dapagliflozin and dapagliflozin–saxagliptin reduced UACR versus placebo throughout the study period. At week 24, the difference (vs placebo; n=134 patients with available data) in mean UACR change from baseline was −21&middo...
Source: The Lancet Diabetes and Endocrinology - Category: Endocrinology Source Type: research
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