keyword
https://read.qxmd.com/read/37981428/post-hoc-analysis-of-the-sonar-trial-potential-analgesic-effects-of-atrasentan
#1
COMMENT
Masao Iwagami
Chan et al. conducted a post hoc analysis of the Study of Diabetic Nephropathy with Atrasentan (SONAR) to demonstrate that atrasentan reduced chronic pain-related adverse events reported by investigators and the initiation of analgesics. This study creates an interesting hypothesis, but it is limited in that the pain information was collected as part of the adverse events and the presence/absence of pain at baseline was unknown. Thus, prospective clinical trials are required to confirm these findings.
December 2023: Kidney International
https://read.qxmd.com/read/37969640/endothelin-receptor-blocker-reverses%C3%A2-breast-cancer-induced-cardiac%C3%A2-remodeling
#2
JOURNAL ARTICLE
Zaid H Maayah, Mourad Ferdaoussi, Aristeidis E Boukouris, Shingo Takahara, Subhash K Das, Mostafa Khairy, John R Mackey, Edith Pituskin, Gopinath Sutendra, D Ian Paterson, Jason R B Dyck
BACKGROUND: Although some cancer therapies have overt and/or subclinical cardiotoxic effects that increase subsequent cardiovascular risk in breast cancer patients, we have recently shown that the breast tumor itself can also induce cardiac hypertrophy through the activation of the endothelin system to contribute to cardiovascular risk. However, the extent to which the suppression of the activation of the endothelin system could improve cardiac remodeling in breast cancer patients has yet to be investigated...
October 2023: JACC CardioOncology
https://read.qxmd.com/read/37872654/development-and-validation-of-a-new-hierarchical-composite-end-point-for-clinical-trials-of-kidney-disease-progression
#3
JOURNAL ARTICLE
Hiddo J L Heerspink, Niels Jongs, Patrick Schloemer, Dustin J Little, Meike Brinker, Christoph Tasto, Martin Karpefors, David C Wheeler, George Bakris, Vlado Perkovic, Richard Nkulikiyinka, Jerome Rossert, Samvel B Gasparyan
SIGNIFICANCE STATEMENT: The established composite kidney end point in clinical trials combines clinical events with sustained large changes in GFR but does not weigh the relative clinical importance of the end point components. By contrast, a hierarchical composite end point (HCE) accounts for the clinical importance of the end point components. The authors developed and validated a kidney HCE that combines clinical kidney outcomes with longitudinal GFR changes (GFR slope). They demonstrate that in seven major placebo-controlled kidney outcome trials with different medications, treatment effect estimates on the HCE were consistently in similar directions and of similar magnitudes compared with treatment effects on the established kidney end point...
December 1, 2023: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/37820676/efficacy-and-adverse-effects-of-atrasentan-in-patients-with-diabetic-nephropathy-a-meta-analysis
#4
JOURNAL ARTICLE
Shanshen Yu, Jia Sun, Xiafei Guo
BACKGROUND: About 30% of Type 1 diabetes (T1DM) patients and 40% of Type 2 diabetes (T2DM) patients were diagnosed with diabetic nephropathy, which has also greatly affected the global end-stage renal disease (ESRD) outcome. Atrasentan is a selective endothelin receptor type A (ETA) antagonist initially studied for the potential treatment of cancer. However, the role of Atrasentan was not sure in the DM. METHODS: The machine searches eight databases to find studies examining the impact of Atrasentan in people with diabetic nephropathy both domestically and overseas...
October 13, 2023: Alternative Therapies in Health and Medicine
https://read.qxmd.com/read/37716952/insulin-resistance-kidney-outcomes-and-effects-of-the-endothelin-receptor-antagonist-atrasentan-in-patients-with-type-2-diabetes-and-chronic-kidney-disease
#5
JOURNAL ARTICLE
J David Smeijer, Donald E Kohan, Peter Rossing, Ricardo Correa-Rotter, Adrian Liew, Sydney C W Tang, Dick de Zeeuw, Ron T Gansevoort, Wenjun Ju, Hiddo J Lambers Heerspink
BACKGROUND: Insulin resistance (IR) is a pathophysiologic hallmark of type 2 diabetes and associated with the presence of chronic kidney disease (CKD). Experimental studies suggest that endothelin-1 increases IR. We assessed the association between IR and cardio-renal outcomes and the effect of the selective endothelin receptor antagonist atrasentan on IR in patients with type 2 diabetes and CKD. METHODS: We used data from the RADAR and SONAR trials that recruited participants with type 2 diabetes and CKD [eGFR 25-75 mL/min/1...
September 16, 2023: Cardiovascular Diabetology
https://read.qxmd.com/read/37657768/post-hoc-analysis-of-the-sonar-trial-indicates-that-the-endothelin-receptor-antagonist-atrasentan-is-associated-with-less-pain-in-patients-with-type-2-diabetes-and-chronic-kidney-disease
#6
RANDOMIZED CONTROLLED TRIAL
Kam Wa Chan, J David Smeijer, Meir Schechter, Niels Jongs, Priya Vart, Donald E Kohan, Ron T Gansevoort, Adrian Liew, Sydney C W Tang, Christoph Wanner, Dick de Zeeuw, Hiddo J L Heerspink
Pain is prevalent among patients with diabetes and chronic kidney disease (CKD). The management of chronic pain in these patients is limited by nephrotoxicity of commonly used drugs including non-steroidal anti-inflammatory drugs (NSAIDs) and opioids. Since previous studies implicated endothelin-1 in pain nociception, our post hoc analysis of the SONAR trial assessed the association between the endothelin receptor antagonist atrasentan and pain and prescription of analgesics. SONAR was a randomized, double-blind, placebo-controlled clinical trial that recruited participants with type 2 diabetes and CKD (estimated glomerular filtration rate 25-75 ml/min/1...
December 2023: Kidney International
https://read.qxmd.com/read/37119876/effects-of-newer-kidney-protective-agents-on-kidney-endpoints-provide-implications-for-future-clinical-trials
#7
JOURNAL ARTICLE
Hiddo L Heerspink, Niels Jongs, Brendon Neuen, Patrick Schloemer, Muthiah Vaduganathan, Lesley Inker, Robert A Fletcher, David C Wheeler, George Bakris, Tom Greene, Glenn M Chertow, Vlado Perkovic
Doubling of serum creatinine (equivalent to a 57% decline in the estimated glomerular filtration rate (eGFR)) is an accepted component of a composite kidney endpoint in clinical trials. Smaller declines in eGFR (40%, 50%) have been applied in several recently conducted clinical trials. Here, we assessed the effects of newer kidney protective agents on endpoints including smaller proportional declines in eGFR to compare relative event rates and the magnitude of observed treatment effects. We performed a post hoc analysis of 4401 patients in the CREDENCE, 4304 in the DAPA-CKD, 5734 in the FIDELIO-DKD, and 3668 in the SONAR trials, which assessed the effects of canagliflozin, dapagliflozin, finerenone and atrasentan in patients with chronic kidney disease...
April 28, 2023: Kidney International
https://read.qxmd.com/read/36874334/lifestyle-modifications-and-nutritional-and-therapeutic-interventions-in-delaying-the-progression-of-chronic-kidney-disease-a-review
#8
REVIEW
Lean Alkhatib, Lorena A Velez Diaz, Samyukta Varma, Arsh Chowdhary, Prachi Bapat, Hai Pan, Geetika Kukreja, Prasannalaxmi Palabindela, Sri Abirami Selvam, Kartik Kalra
Chronic kidney disease (CKD) is a debilitating progressive illness that affects more than 10% of the world's population. In this literature review, we discussed the roles of nutritional interventions, lifestyle modifications, hypertension (HTN) and diabetes mellitus (DM) control, and medications in delaying the progression of CKD. Walking, weight loss, low-protein diet (LPD), adherence to the alternate Mediterranean (aMed) diet, and Alternative Healthy Eating Index (AHEI)-2010 slow the progression of CKD...
February 2023: Curēus
https://read.qxmd.com/read/36834836/endothelin-receptor-antagonists-in-kidney-disease
#9
REVIEW
Irene Martínez-Díaz, Nerea Martos, Carmen Llorens-Cebrià, Francisco J Álvarez, Patricia W Bedard, Ander Vergara, Conxita Jacobs-Cachá, Maria José Soler
Endothelin (ET) is found to be increased in kidney disease secondary to hyperglycaemia, hypertension, acidosis, and the presence of insulin or proinflammatory cytokines. In this context, ET, via the endothelin receptor type A (ETA ) activation, causes sustained vasoconstriction of the afferent arterioles that produces deleterious effects such as hyperfiltration, podocyte damage, proteinuria and, eventually, GFR decline. Therefore, endothelin receptor antagonists (ERAs) have been proposed as a therapeutic strategy to reduce proteinuria and slow the progression of kidney disease...
February 8, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/36476039/endothelin-receptor-antagonism-improves-glucose-tolerance-and-adipose-tissue-inflammation-in-an-experimental-model-of-systemic-lupus-erythematosus
#10
JOURNAL ARTICLE
Osvaldo Rivera-Gonzalez, Clinton T Case, Natalie A Wilson, Joshua S Speed, Erin B Taylor
Endothelin-1 (ET-1) is elevated in patients with systemic lupus erythematosus (SLE), an autoimmune disease characterized by high rates of hypertension, renal injury, and cardiovascular disease. SLE is also associated with increased prevalence of obesity and insulin resistance compared to the general population. In the present study, we tested the hypothesis that elevated ET-1 in SLE is contributes to obesity and insulin resistance. For these studies, we used the NZBWF1 mouse model of SLE, which develops obesity and insulin resistance on a normal chow diet...
December 7, 2022: American Journal of Physiology. Endocrinology and Metabolism
https://read.qxmd.com/read/36361612/enhanced-cardiorenal-protective-effects-of-combining-sglt2-inhibition-endothelin-receptor-antagonism-and-ras-blockade-in-type-2-diabetic-mice
#11
JOURNAL ARTICLE
Ander Vergara, Conxita Jacobs-Cacha, Carmen Llorens-Cebria, Alberto Ortiz, Irene Martinez-Diaz, Nerea Martos, Pamela Dominguez-Báez, Mireia Molina Van den Bosch, Sheila Bermejo, Michael Paul Pieper, Begoña Benito, Maria Jose Soler
Treatments with sodium-glucose 2 cotransporter inhibitors (SGLT2i) or endothelin receptor antagonists (ERA) have shown cardiorenal protective effects. The present study aimed to evaluate the cardiorenal beneficial effects of the combination of SGLT2i and ERA on top of renin-angiotensin system (RAS) blockade. Type 2 diabetic mice (db/db) were treated with different combinations of an SGLT2i (empagliflozin), an ERA (atrasentan), and an angiotensin-converting enzyme inhibitor (ramipril) for 8 weeks. Vehicle-treated diabetic mice and non-diabetic mice were included as controls...
October 24, 2022: International Journal of Molecular Sciences
https://read.qxmd.com/read/36204993/endothelin-type-a-receptor-blockade-attenuates-aorto-caval-fistula-induced-heart-failure-in-rats-with-angiotensin-ii-dependent-hypertension
#12
JOURNAL ARTICLE
Petr Kala, Olga Gawrys, Matúš Miklovič, Zdenka Vaňourková, Petra Škaroupková, Šárka Jíchová, Janusz Sadowski, Elzbieta Kompanowska-Jezierska, Agnieszka Walkowska, Josef Veselka, Miloš Táborský, Hana Maxová, Ivana Vaněčková, Luděk Červenka
OBJECTIVE: Evaluation of the effect of endothelin type A (ETA) receptor blockade on the course of volume-overload heart failure in rats with angiotensin II-dependent hypertension. METHODS: Ren-2 renin transgenic rats (TGR) were used as a model of hypertension. Heart failure was induced by creating an aorto-caval fistula (ACF). Selective ETA receptor blockade was achieved by atrasentan. For comparison, other rat groups received trandolapril, an angiotensin-converting enzyme inhibitor (ACEi)...
October 5, 2022: Journal of Hypertension
https://read.qxmd.com/read/35892316/organic-anion-transporter-gene-variants-associated-with-plasma-exposure-and-long-term-response-to-atrasentan-in-patients-with-diabetic-kidney-disease
#13
JOURNAL ARTICLE
J David Smeijer, Jeroen V Koomen, Donald E Kohan, John J V McMurray, George L Bakris, Ricardo Correa-Rotter, Fan-Fan Hou, Dalane W Kitzman, Hirofumi Makino, Gert Mayer, Michal Nowicki, Vlado Perkovic, Peter Rossing, Sheldon Tobe, Hans-Henrik Parving, Dick de Zeeuw, Hiddo J L Heerspink
Plasma exposure of the endothelin receptor antagonist atrasentan varies between individuals and is associated with nephroprotective effects and the risk of heart failure. We examined the influence of genetic polymorphisms on atrasentan plasma exposure and pharmacodynamic effects. We performed a sub-study of the SONAR trial which enrolled adults with type 2 diabetes and chronic kidney disease [estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2 , and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g]...
July 27, 2022: Clinical Pharmacology and Therapeutics
https://read.qxmd.com/read/35772861/increase-in-bnp-in-response-to-endothelin-receptor-antagonist-atrasentan-is-associated-with-incident-heart-failure
#14
JOURNAL ARTICLE
J David Smeijer, Jeroen Koomen, Donald E Kohan, John J V McMurray, George L Bakris, Ricardo Correa-Rotter, Fan-Fan Hou, James L Januzzi, Dalane W Kitzman, Daniel M Kolansky, Hirofumi Makino, Vlado Perkovic, Sheldon Tobe, Hans-Henrik Parving, Dick de Zeeuw, Hiddo J L Heerspink
BACKGROUND: The endothelin receptor antagonist atrasentan reduced the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease (CKD) in the SONAR (Study of Diabetic Nephropathy with Atrasentan) trial, although with a numerically higher incidence of heart failure (HF) hospitalization. OBJECTIVES: The purpose of this study was to assess if early changes in B-type natriuretic peptide (BNP) and body weight during atrasentan treatment predict HF risk...
July 2022: JACC. Heart Failure
https://read.qxmd.com/read/35547199/novel-therapies-for-alport-syndrome
#15
REVIEW
Efren Chavez, Juanly Rodriguez, Yelena Drexler, Alessia Fornoni
Alport syndrome (AS) is a hereditary kidney disease associated with proteinuria, hematuria and progressive kidney failure. It is characterized by a defective glomerular basement membrane caused by mutations in type IV collagen genes COL4A3/A4/A5 which result in defective type IV collagen α3, α4, or α5 chains, respectively. Alport syndrome has three different patterns of inheritance: X-linked, autosomal and digenic. In a study of CKD of unknown etiology type IV collagen gene mutations accounted for the majority of the cases of hereditary glomerulopathies which suggests that AS is often underrecognized...
2022: Frontiers in Medicine
https://read.qxmd.com/read/35531905/lack-of-renoprotective-effects-of-targeting-the-endothelin-a-receptor-and-or-sodium-glucose-transporter-2-in-a-mouse-model-of-type-2-diabetic-kidney-disease
#16
JOURNAL ARTICLE
Deborah Stuart, Caitlin S Peterson, Chunyan Hu, Monica P Revelo, Yufeng Huang, Donald E Kohan, Nirupama Ramkumar
Two recent clinical trials, using sodium glucose cotransporter (SGLT2) or endothelin-A receptor (ET-A) blocker, reported the first efficacious treatments in 18 years to slow progression of diabetic kidney disease (DKD). We hypothesized that combined inhibition of SGLT2 and ET-A receptor may confer greater protection against renal injury than either agent alone. Uninephrectomized male db/db mice were randomized to four groups: vehicle, SGLT2 inhibitor (dapagliflozin (dapa), 1 mg/kg/day), ET-A blocker (atrasentan (atra), 5 mg/kg/day), or dual treatment from 10 weeks until 22 weeks of age...
May 7, 2022: Canadian Journal of Physiology and Pharmacology
https://read.qxmd.com/read/34918049/the-acute-pressure-natriuresis-response-is-suppressed-by-selective-eta-receptor-blockade
#17
JOURNAL ARTICLE
Geoffrey Culshaw, David Binnie, Neeraj Dhaun, Patrick Hadoke, Matthew Bailey, David J Webb
Hypertension is a major risk factor for cardiovascular disease.  In a significant minority of people, it develops when salt intake is increased (salt-sensitivity).  It is not clear whether this represents impaired vascular function or disruption to the relationship between blood pressure (BP) and renal salt-handling (pressure natriuresis, PN).  Endothelin-1 (ET-1) regulates BP via ETA and ETB receptor subtypes.  Blockade of ETA receptors reduces BP, but promotes sodium retention by an unknown mechanism...
December 17, 2021: Clinical Science (1979-)
https://read.qxmd.com/read/34909290/endothelin-receptor-antagonists-as-a-potential-treatment-of-diabetic-nephropathy-a-systematic-review
#18
REVIEW
Noorain Ahmad, Harish Veerapalli, Chetan Reddy Lankala, Everardo E Castaneda, Afia Aziz, Amy G Rockferry, Pousette Hamid
Diabetic nephropathy is becoming a more predominant cause of end-stage renal disease, as the prevalence of diabetes mellitus worldwide is on the rise. In this systematic review, we aimed to define the role of endothelin receptor antagonists, in the prevention and treatment of diabetic nephropathy, in addition to determining their safety. For this review, PubMed, Google Scholar, and Cochrane Library databases, in addition to ClinicalTrials.gov, were searched for publications in the last 20 years. We included 14 studies, seven randomized control trials, and seven post hoc analyses in this paper...
November 2021: Curēus
https://read.qxmd.com/read/34853063/atrasentan-the-difficult-task-of-integrating-endothelin-a-receptor-antagonists-into-current-treatment-paradigm-for-diabetic-kidney-disease
#19
EDITORIAL
Alberto Ortiz, Beatriz Fernandez-Fernandez
No abstract text is available yet for this article.
December 1, 2021: Clinical Journal of the American Society of Nephrology: CJASN
https://read.qxmd.com/read/34853062/the-effect-of-atrasentan-on-kidney-and-heart-failure-outcomes-by-baseline-albuminuria-and-kidney-function-a-post-hoc-analysis-of-the-sonar-randomized-trial
#20
JOURNAL ARTICLE
Simke W Waijer, Ron T Gansevoort, George L Bakris, Ricardo Correa-Rotter, Fan-Fan Hou, Donald E Kohan, Dalane W Kitzman, Hirofumi Makino, John J V McMurray, Vlado Perkovic, Sheldon Tobe, Hans-Henrik Parving, Dick de Zeeuw, Hiddo J L Heerspink
BACKGROUND AND OBJECTIVES: Atrasentan reduces the risk of kidney failure but increases the risk of edema and, possibly, heart failure. Patients with severe CKD may obtain greater absolute kidney benefits from atrasentan but may also be at higher risk of heart failure. We assessed relative and absolute effects of atrasentan on kidney and heart failure events according to baseline eGFR and urinary albumin-creatinine ratio (UACR) in a post hoc analysis of the Study of Diabetic Nephropathy with Atrasentan (SONAR) trial...
December 1, 2021: Clinical Journal of the American Society of Nephrology: CJASN
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