The Experts below are selected from a list of 105 Experts worldwide ranked by ideXlab platform
Michel Burnier - One of the best experts on this subject based on the ideXlab platform.
-
Clinical Medicine Reviews in Vascular Health 2010:2 41 Endothelin Receptors Antagonists as Renal Protective Agents
2015Co-Authors: Jessica Smol, Bruno Vogt, Marc Maillard, Grégoire Wuerzner, Michel BurnierAbstract:Abstract: Endothelin (ET) is an important modulator of renal function through its binding to ETA and ETB receptors in renal tissue. Various renal cells have the ability to synthesize and release endothelin-1 and elevated plasma and urinary endothelin levels have been measured in patients with chronic kidney diseases. Within the last 5 year, several studies have demonstrated that ET plays a role in the pathogenesis and progression of chronic kidney diseases and associated cardiovascular diseases. With this increasing evidence, several ET receptor antagonists have been developed, some of them being specifically investigated for their ability to provide renal protection in diabetic nephropathy. For this indication, a selective blockade of ETA receptors appears to be the preferred approach. Thus, recent clinical phase II and phase III studies have shown that ETA receptor blockers such as Avosentan are able to lower proteinuria signifi-cantly in type 2 diabetic patients even on top of a full treatment with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers. However, today, the clinical benefits of ET receptor antagonists appear to be limited by the development of fluid retention and peripheral edema which have been reported to occur with all antagonists, but more so with non-selective ET antagonists. Fluid reten-tion, like headache, nausea and nasal congestion probably represent class side-effects. Nevertheless, provided a good equilibrium can be obtained between their clinical benefits and their tolerability profile, ET receptor blockers remain promising for the management of patients with chronic kidney diseases
-
Endothelin Receptors Antagonists as Renal Protective Agents
2010Co-Authors: Jessica Smolander, Bruno Vogt, Marc Maillard, Grégoire Wuerzner, Michel BurnierAbstract:Endothelin (ET) is an important modulator of renal function through its binding to ETA and ETB receptors in renal tissue. Various renal cells have the ability to synthesize and release endothelin-1 and elevated plasma and urinary endothelin levels have been measured in patients with chronic kidney diseases. Within the last 5 year, several studies have demonstrated that ET plays a role in the pathogenesis and progression of chronic kidney diseases and associated cardiovascular diseases. With this increasing evidence, several ET receptor antagonists have been developed, some of them being specifically investigated for their ability to provide renal protection in diabetic nephropathy. For this indication, a selective blockade of ETA receptors appears to be the preferred approach. Thus, recent clinical phase II and phase III studies have shown that ETA receptor blockers such as Avosentan are able to lower proteinuria significantly in type 2 diabetic patients even on top of a full treatment with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers. However, today, the clinical benefits of ET receptor antagonists appear to be limited by the development of fluid retention and peripheral edema which have been reported to occur with all antagonists, but more so with non-selective ET antagonists. Fluid retention, like headache, nausea and nasal congestion probably represent class side-effects. Nevertheless, provided a good equilibrium can be obtained between their clinical benefits and their tolerability profile, ET receptor blockers remain promising for the management of patients with chronic kidney diseases.
-
Dose-dependent acute and sustained renal effects of the endothelin receptor antagonist Avosentan in healthy subjects.
Clinical pharmacology and therapeutics, 2009Co-Authors: J Smolander, Bruno Vogt, Marc Maillard, C Zweiacker, T Littke, T Hengelage, Michel BurnierAbstract:The endothelin receptor antagonist Avosentan may cause fluid overload at doses of 25 and 50 mg, but the actual mechanisms of this effect are unclear. We conducted a placebo-controlled study in 23 healthy subjects to assess the renal effects of Avosentan and the dose dependency of these effects. Oral Avosentan was administered once daily for 8 days at doses of 0.5, 1.5, 5, and 50 mg. The drug induced a dose-dependent median increase in body weight, most pronounced at 50 mg (0.8 kg on day 8). Avosentan did not affect renal hemodynamics or plasma electrolytes. A dose-dependent median reduction in the fractional renal excretion of sodium was found (up to 8.7% at Avosentan 50 mg); this reduction was paralleled by a dose-related increase in proximal sodium reabsorption. It is suggested that Avosentan dose-dependently induces sodium retention by the kidney, mainly through proximal tubular effects. The potential clinical benefits of Avosentan should therefore be investigated at doses of ≤ 5 mg. Clinical Pharmacology & Therapeutics (2009); 85, 6, 628–634 doi:10.1038/clpt.2009.15
K. A. M. Jandeleit-dahm - One of the best experts on this subject based on the ideXlab platform.
-
The endothelin receptor antagonist Avosentan ameliorates nephropathy and atherosclerosis in diabetic apolipoprotein E knockout mice
Diabetologia, 2009Co-Authors: A. M. D. Watson, C. Schumacher, M. Gasparo, B. Feng, M. C. Thomas, T. J. Allen, M. E. Cooper, K. A. M. Jandeleit-dahmAbstract:Aims/hypothesis There is convincing evidence that the endothelin system contributes to diabetic nephropathy and cardiovascular disease. This study aimed to assess the effects of the non-peptidergic endothelin receptor A (ETA) antagonist Avosentan in a mouse model of accelerated diabetic nephropathy and atherosclerosis in comparison with the ACE inhibitor, quinapril. Methods Apolipoprotein E ( Apoe ) knockout (KO) mice ( n = 20 per group, five groups) were randomised to the following groups: non-diabetic controls and streptozotocin-induced diabetic animals gavaged daily for 20 weeks with placebo, Avosentan (high dose: 30 mg/kg, or low dose: 10 mg/kg) or quinapril (given in drinking water, 30 mg/kg). Results BP was unchanged by Avosentan treatment but decreased with quinapril treatment. Diabetes-associated albuminuria was significantly attenuated by high-dose Avosentan after 10 and 20 weeks of treatment. Diabetic animals showed a decreased creatinine clearance, which was normalised by Avosentan treatment. In diabetic mice, high-dose Avosentan treatment significantly attenuated the glomerulosclerosis index, mesangial matrix accumulation, glomerular accumulation of the matrix proteins collagen IV, and renal expression of genes encoding connective tissue growth factor, vascular endothelial growth factor, transforming growth factor β and nuclear factor κB (p65 subunit). Furthermore, high-dose Avosentan treatment was also associated with reduced expression of the genes for ETA, ETB and angiotensin receptor 1. The renoprotective effects of Avosentan were comparable or superior to those observed with quinapril. High-dose Avosentan also significantly attenuated diabetes-associated aortic atherosclerosis in Apoe KO mice and reduced macrophage infiltration and aortic nitrotyrosine expression. Conclusions/interpretation This study demonstrates that ETA blockade with Avosentan may provide an alternate therapeutic strategy for the treatment of diabetic micro- and macrovascular complications.
-
The endothelin receptor antagonist Avosentan ameliorates nephropathy and atherosclerosis in diabetic apolipoprotein E knockout mice.
Diabetologia, 2009Co-Authors: A. M. D. Watson, C. Schumacher, M. Gasparo, B. Feng, M. C. Thomas, T. J. Allen, M. E. Cooper, K. A. M. Jandeleit-dahmAbstract:Aims/hypothesis There is convincing evidence that the endothelin system contributes to diabetic nephropathy and cardiovascular disease. This study aimed to assess the effects of the non-peptidergic endothelin receptor A (ETA) antagonist Avosentan in a mouse model of accelerated diabetic nephropathy and atherosclerosis in comparison with the ACE inhibitor, quinapril.
Anastasios N. Lasaridis - One of the best experts on this subject based on the ideXlab platform.
-
Endothelin antagonism for diabetic nephropathy
Nature Reviews Nephrology, 2010Co-Authors: Pantelis A. Sarafidis, Anastasios N. LasaridisAbstract:The ASCEND study was a large, international trial that aimed to assess the effects of Avosentan on diabetic nephropathy. To the disappointment of the nephrology community who had anticipated that the trial would demonstrate beneficial effects of this treatment, ASCEND was terminated early owing to excessive rates of adverse events, such as congestive heart failure associated with Avosentan use.
-
Diabetic nephropathy: Endothelin antagonism for diabetic nephropathy
Nature reviews. Nephrology, 2010Co-Authors: Pantelis A. Sarafidis, Anastasios N. LasaridisAbstract:The ASCEND study was a large, international trial that aimed to assess the effects of Avosentan on diabetic nephropathy. To the disappointment of the nephrology community who had anticipated that the trial would demonstrate beneficial effects of this treatment, ASCEND was terminated early owing to excessive rates of adverse events, such as congestive heart failure associated with Avosentan use.
J Smolander - One of the best experts on this subject based on the ideXlab platform.
-
Dose-dependent acute and sustained renal effects of the endothelin receptor antagonist Avosentan in healthy subjects.
Clinical pharmacology and therapeutics, 2009Co-Authors: J Smolander, Bruno Vogt, Marc Maillard, C Zweiacker, T Littke, T Hengelage, Michel BurnierAbstract:The endothelin receptor antagonist Avosentan may cause fluid overload at doses of 25 and 50 mg, but the actual mechanisms of this effect are unclear. We conducted a placebo-controlled study in 23 healthy subjects to assess the renal effects of Avosentan and the dose dependency of these effects. Oral Avosentan was administered once daily for 8 days at doses of 0.5, 1.5, 5, and 50 mg. The drug induced a dose-dependent median increase in body weight, most pronounced at 50 mg (0.8 kg on day 8). Avosentan did not affect renal hemodynamics or plasma electrolytes. A dose-dependent median reduction in the fractional renal excretion of sodium was found (up to 8.7% at Avosentan 50 mg); this reduction was paralleled by a dose-related increase in proximal sodium reabsorption. It is suggested that Avosentan dose-dependently induces sodium retention by the kidney, mainly through proximal tubular effects. The potential clinical benefits of Avosentan should therefore be investigated at doses of ≤ 5 mg. Clinical Pharmacology & Therapeutics (2009); 85, 6, 628–634 doi:10.1038/clpt.2009.15
Bruno Vogt - One of the best experts on this subject based on the ideXlab platform.
-
Clinical Medicine Reviews in Vascular Health 2010:2 41 Endothelin Receptors Antagonists as Renal Protective Agents
2015Co-Authors: Jessica Smol, Bruno Vogt, Marc Maillard, Grégoire Wuerzner, Michel BurnierAbstract:Abstract: Endothelin (ET) is an important modulator of renal function through its binding to ETA and ETB receptors in renal tissue. Various renal cells have the ability to synthesize and release endothelin-1 and elevated plasma and urinary endothelin levels have been measured in patients with chronic kidney diseases. Within the last 5 year, several studies have demonstrated that ET plays a role in the pathogenesis and progression of chronic kidney diseases and associated cardiovascular diseases. With this increasing evidence, several ET receptor antagonists have been developed, some of them being specifically investigated for their ability to provide renal protection in diabetic nephropathy. For this indication, a selective blockade of ETA receptors appears to be the preferred approach. Thus, recent clinical phase II and phase III studies have shown that ETA receptor blockers such as Avosentan are able to lower proteinuria signifi-cantly in type 2 diabetic patients even on top of a full treatment with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers. However, today, the clinical benefits of ET receptor antagonists appear to be limited by the development of fluid retention and peripheral edema which have been reported to occur with all antagonists, but more so with non-selective ET antagonists. Fluid reten-tion, like headache, nausea and nasal congestion probably represent class side-effects. Nevertheless, provided a good equilibrium can be obtained between their clinical benefits and their tolerability profile, ET receptor blockers remain promising for the management of patients with chronic kidney diseases
-
Endothelin Receptors Antagonists as Renal Protective Agents
2010Co-Authors: Jessica Smolander, Bruno Vogt, Marc Maillard, Grégoire Wuerzner, Michel BurnierAbstract:Endothelin (ET) is an important modulator of renal function through its binding to ETA and ETB receptors in renal tissue. Various renal cells have the ability to synthesize and release endothelin-1 and elevated plasma and urinary endothelin levels have been measured in patients with chronic kidney diseases. Within the last 5 year, several studies have demonstrated that ET plays a role in the pathogenesis and progression of chronic kidney diseases and associated cardiovascular diseases. With this increasing evidence, several ET receptor antagonists have been developed, some of them being specifically investigated for their ability to provide renal protection in diabetic nephropathy. For this indication, a selective blockade of ETA receptors appears to be the preferred approach. Thus, recent clinical phase II and phase III studies have shown that ETA receptor blockers such as Avosentan are able to lower proteinuria significantly in type 2 diabetic patients even on top of a full treatment with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers. However, today, the clinical benefits of ET receptor antagonists appear to be limited by the development of fluid retention and peripheral edema which have been reported to occur with all antagonists, but more so with non-selective ET antagonists. Fluid retention, like headache, nausea and nasal congestion probably represent class side-effects. Nevertheless, provided a good equilibrium can be obtained between their clinical benefits and their tolerability profile, ET receptor blockers remain promising for the management of patients with chronic kidney diseases.
-
Dose-dependent acute and sustained renal effects of the endothelin receptor antagonist Avosentan in healthy subjects.
Clinical pharmacology and therapeutics, 2009Co-Authors: J Smolander, Bruno Vogt, Marc Maillard, C Zweiacker, T Littke, T Hengelage, Michel BurnierAbstract:The endothelin receptor antagonist Avosentan may cause fluid overload at doses of 25 and 50 mg, but the actual mechanisms of this effect are unclear. We conducted a placebo-controlled study in 23 healthy subjects to assess the renal effects of Avosentan and the dose dependency of these effects. Oral Avosentan was administered once daily for 8 days at doses of 0.5, 1.5, 5, and 50 mg. The drug induced a dose-dependent median increase in body weight, most pronounced at 50 mg (0.8 kg on day 8). Avosentan did not affect renal hemodynamics or plasma electrolytes. A dose-dependent median reduction in the fractional renal excretion of sodium was found (up to 8.7% at Avosentan 50 mg); this reduction was paralleled by a dose-related increase in proximal sodium reabsorption. It is suggested that Avosentan dose-dependently induces sodium retention by the kidney, mainly through proximal tubular effects. The potential clinical benefits of Avosentan should therefore be investigated at doses of ≤ 5 mg. Clinical Pharmacology & Therapeutics (2009); 85, 6, 628–634 doi:10.1038/clpt.2009.15
