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Related Concept Videos

Diabetic Nephropathy01:28

Diabetic Nephropathy

Definition Diabetic nephropathy is a chronic kidney complication that results from prolonged hyperglycemia.Prevalence It is the most common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide, affecting up to half of individuals with diabetes.Pathophysiology • Sustained hyperglycemia triggers multiple hemodynamic and metabolic changes in the kidney. • Early in the disease, increased renal blood flow and glomerular hyperfiltration occur due to afferent arteriolar...
Diabetic Retinopathy01:27

Diabetic Retinopathy

DefinitionDiabetic retinopathy is a microvascular complication of diabetes affecting the retinal blood vessels.Risk FactorsDiabetic retinopathy is present in almost all individuals with type 1 diabetes and more than 60% of those with type 2 diabetes after two decades of disease.The risk increases with poor glycemic control, hypertension, dyslipidemia, smoking, pregnancy, and puberty.Although cataracts and glaucoma are also more frequent in people with diabetes, retinopathy remains the leading...
Diabetic Neuropathy01:22

Diabetic Neuropathy

DefinitionDiabetic neuropathy is nerve damage caused by long-standing diabetes mellitus. It results directly from prolonged high blood sugar levels.PathophysiologyThe pathophysiology of diabetic neuropathy involves both metabolic and vascular disturbances triggered by chronic hyperglycemia.Metabolic injury: Elevated glucose levels activate the polyol pathway within nerve cells, leading to the accumulation of sorbitol and fructose. This increases oxidative stress, disrupts normal nerve...
Antihypertensive Drugs: Direct Renin Inhibitors01:25

Antihypertensive Drugs: Direct Renin Inhibitors

The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists01:18

Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists

Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme (ECE). Of...
Diabetic Foot Ulcer01:31

Diabetic Foot Ulcer

Definition A diabetic foot ulcer (DFU) is a chronic, non-healing wound that develops in individuals with diabetes. It typically occurs on pressure-bearing areas such as the heel, metatarsal heads, or hallux, and carries a high risk of infection and amputation.Pathophysiology • The development of DFUs can be explained by four interconnected mechanisms: neuropathy, ischemia, infection, and impaired wound healing. • Neuropathy is the most common factor. Sensory neuropathy reduces pain perception,...

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Related Experiment Video

Updated: Jun 16, 2026

Antagonistic Effect of Jiawei Shengjiang San on a Rat Model of Diabetic Nephropathy: Related to EGFR/MAPK3/1 Signaling Pathway
08:15

Antagonistic Effect of Jiawei Shengjiang San on a Rat Model of Diabetic Nephropathy: Related to EGFR/MAPK3/1 Signaling Pathway

Published on: May 10, 2024

Avosentan for overt diabetic nephropathy.

Johannes F E Mann1, Damian Green, Kenneth Jamerson

  • 1Schwabing General Hospital, and Department of Medicine IV, University of Erlangen and KfH Kidney Centre, Munich, Germany.

Journal of the American Society of Nephrology : JASN
|February 20, 2010
PubMed
Summary

Avosentan reduced albuminuria in type 2 diabetes patients with nephropathy but increased risks of fluid overload and heart failure. The trial was stopped early due to cardiovascular events, with no significant difference in primary kidney outcomes.

Related Experiment Videos

Last Updated: Jun 16, 2026

Antagonistic Effect of Jiawei Shengjiang San on a Rat Model of Diabetic Nephropathy: Related to EGFR/MAPK3/1 Signaling Pathway
08:15

Antagonistic Effect of Jiawei Shengjiang San on a Rat Model of Diabetic Nephropathy: Related to EGFR/MAPK3/1 Signaling Pathway

Published on: May 10, 2024

Area of Science:

  • Nephrology
  • Cardiology
  • Endocrinology

Background:

  • Diabetic nephropathy is a leading cause of chronic kidney disease.
  • Endothelin receptor antagonists show potential for reducing proteinuria.
  • Long-term renal protection by avosentan in overt diabetic nephropathy remains unproven.

Purpose of the Study:

  • To evaluate the effect of avosentan on the progression of overt diabetic nephropathy.
  • To assess avosentan's impact on renal function and cardiovascular outcomes.
  • To determine safety and tolerability of avosentan in this patient population.

Main Methods:

  • Multicenter, multinational, double-blind, placebo-controlled trial.
  • 1392 participants with type 2 diabetes and overt nephropathy.
  • Oral avosentan (25 or 50 mg) or placebo, plus standard care (ACEi/ARB).
  • Primary outcome: composite of doubling serum creatinine, ESRD, or death.
  • Secondary outcomes: changes in albumin-to-creatinine ratio (ACR) and cardiovascular events.

Main Results:

  • Trial terminated early due to excess cardiovascular events with avosentan.
  • No significant difference in the primary composite outcome between avosentan and placebo groups.
  • Avosentan significantly reduced median ACR (44.3% and 49.3% for 25/50 mg) vs. placebo (9.7%).
  • Higher incidence of adverse events (fluid overload, congestive heart failure) with avosentan leading to discontinuation.

Conclusions:

  • Avosentan effectively reduces albuminuria in type 2 diabetes with overt nephropathy.
  • Avosentan is associated with increased risks of fluid overload and congestive heart failure.
  • The study did not demonstrate a benefit in slowing renal function decline and was halted due to safety concerns.