Avosentan Reduces Proteinuria

but Causes Serious Side

Effects (Feb 19, 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 kidney disease 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 kidney function in patients with type 2 diabetes 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 heart failure. 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.
 Speedel Pharma Ltd, Switzerland, sponsored the study and appointed the
contract research organization Quintiles Ltd for study set-up, initiation,
management, and analysis. Study co-authors include Damian Green (Quintiles
Ltd, Strasbourg, France); Kenneth Jamerson, MD (University of Michigan); Luis
Ruilope, MD (Hospital 12 de Octubre, Madrid, Spain); Susan Kuranoff, Thomas
Littke, MD (Speedel Pharma Ltd, Basel, Switzerland); and Giancarlo Viberti, MD,
FRCP (King’s College London School of Medicine, Guy’s Hospital, London, UK)
for the ASCEND Study Group.

Disclosures: Susan Kuranoff and Thomas Littke were employees of the

sponsor, and all other authors have consulting funds from Speedel Pharma Ltd.

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.

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adverse effects. This content should not be used during a medical emergency or
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Founded in 1966, the American Society of Nephrology (ASN) is the

world’s largest professional society devoted to the study of kidney disease.
Comprised of 11,000 physicians and scientists, ASN continues to promote expert
patient care, to advance medical research, and to educate the renal community.
ASN also informs policymakers about issues of importance to kidney doctors and
their patients. ASN funds research, and through its world-renowned meetings
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Source:

American Society of Nephrology (2010, February 18). Avosentan reduces

proteinuria but causes serious side effects. Retrieved February 20, 2010, from
http://www.health.am/ab/more/avosentan-reduces-proteinuria-but-causes-
serious-side-effects/
Reaction and Recommendations:

A drug or a medication is formulated to relieve signs and symptoms of an

illness or cure a disease condition. But aside from pros it also have its cons.
Though they have their proven efficacy most of them also have their side effects.

In the article that I’ve researched the drug avosentan is said to be proven
substantially reducing urinary protein loss in people with type 2 diabetes and
kidney disease, but the drug causes serious side effects including complications
of fluid overload such as pulmonary edema, as well as congestive heart failure.
Avosentan is a potent, selective endothelin A receptor blocker and there is
convincing evidence that the endothelin system contributes to diabetic
nephropathy and cardiovascular disease. Many groups are working with this
drug. Now researchers from Schwabing General Hospital and KfH Kidney
Centre, in Munchen, Germany have come out with interesting results, as per
claim by the lead researcher, Dr.Johannes Mann, the drug avosentan
substantially reduces urinary protein loss in people with type 2 diabetes and
kidney disease, but the drug causes serious side effects.

Avosentan at either dose (25 & 50 mg) 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 heart failure. In addition, there were
more deaths in the groups taking avosentan (21 and 17) than in the group taking
placebo.

Experts have reviewed the usage and according to them a decrease in the
dosage of the drug could yield to more positive effects. With that they should
highlight the risks and potential benefits of endothelin antagonists in kidney
disease patients with proteinuria and these will help investigators design future
studies to test the drugs' potential. Specifically, lower doses of avosentan may
generate more positive results....

It is good that continuous innovations in medicine are being made. Every

now and then there would be new drugs to give remedy to some certain
conditions. The safer they are to use the more that they are being a lot beneficial
to the people.

Suggestions and recommendations are addressed to groups of people would be

somehow involved or at least concerned about the issue.

To the pharmaceutical companies:

 They should make sure that the good effects of the drug outweigh the bad
ones and they should not make any false claims or deceive the trust of the
consumers. They should treat the health of the clients as the primary
consideration in releasing a newly discovered drug.

To the government:

This is addressed specially to the health agencies. They should review

the safety of use and efficacy of drugs before allowing them to be sold to the
public.

To the consumers:

Read the label and consult the physician about the medicines. Have an
idea on drugs which they are using and choose wisely. Read well the side effects
and instructions for use as well as the contraindication before even thinking
about using it or taking it.

To the Health care providers:

This is addressed especially to us nurses. The vital role that we perform is

not only the simple administration of meds but also the giving of health teachings
and dissemination of knowledge to the people.