Avosentan reduces proteinuria but causes serious side effects

Feb 18, 2010

The drug avosentan substantially reduces urinary protein loss in people with type 2 diabetes and kidney disease, but the drug causes serious side effects, according to a study appearing in an upcoming issue of the Journal of the American Society Nephrology (JASN). The results suggest that lower doses of avosentan may have a more favorable risk/benefit ratio for patients.

Despite aggressive treatments, individuals with often experience proteinuria, or excessive loss of protein in the urine, which increases kidney damage. A key factor in the development of proteinuria is endothelin, which by constricting blood vessels and raising blood pressure, causes the kidney's filtering function to deteriorate. Researchers suspect that blocking the endothelin peptide could be a promising new treatment strategy for patients who develop proteinuria. Endothelin antagonists such as oral avosentan are already available and are prescribed for patients with cardiovascular conditions.

Johannes Mann, MD (Schwabing General Hospital and KfH Kidney Centre, in Munchen, Germany) and his colleagues examined the effects of avosentan on proteinuria and in patients with and kidney disease through a multicenter, multinational, double-blind, controlled trial. The Avosentan ASCEND study enrolled 1392 patients already being treated for kidney disease and randomized them to receive avosentan 25 mg, avosentan 50 mg, or placebo.

While avosentan at either dose lowered patients' urinary protein excretion by 40%-50% (compared with less than 10% in patients taking placebo), individuals taking the drug experienced a high incidence of serious, sometimes life-threatening side effects. These included complications of fluid overload such as pulmonary edema, as well as congestive . In addition, there were more deaths in the groups taking avosentan (21 and 17) than in the group taking placebo (12).

Dr. Mann noted that the findings from the ASCEND trial highlight the risks and potential benefits of endothelin antagonists in kidney disease patients with proteinuria and will help investigators design future studies to test the drugs' potential. Specifically, lower doses of avosentan may generate more positive results.

Explore further: West African airline suspends flights amid Ebola (Update)

More information: The article, entitled "Avosentan for Overt Diabetic Nephropathy," will appear online at http://jasn.asnjournals.org/ on February 18, 2010, doi 10.1681/ASN.2009060593 .

add to favorites email to friend print save as pdf

Related Stories

Weight loss is good for the kidneys

Sep 17, 2009

Losing weight may preserve kidney function in obese people with kidney disease, according to a study appearing in an upcoming issue of the Clinical Journal of the American Society Nephrology (CJASN). The findings indicate that t ...

At risk for kidney disease? Check your genes

Apr 15, 2009

Genetic differences can influence one's risk of developing proteinuria, a condition that increases the risk of cardiovascular disease and chronic kidney disease (CKD), according to a study appearing in an upcoming issue of ...

Recommended for you

West African airline suspends flights amid Ebola (Update)

3 hours ago

(AP)—Police officers deployed to Liberia's international airport to ensure passengers are screened for Ebola symptoms as a major regional airline announced Tuesday it was suspending flights to the cities hardest hit by ...

$1,000 pill now hepatitis C treatment of choice

10 hours ago

(AP)—A $1,000-per-pill drug that insurers are reluctant to pay for has quickly become the treatment of choice for a liver-wasting viral disease that affects more than 3 million Americans.

User comments : 0