Novel drug acts in unique way to protect against kidney injury

July 11, 2013

New research reveals the mechanism by which an experimental drug can protect the kidneys from sudden damage, called acute kidney injury (AKI). The findings, which appear in an upcoming issue of the Journal of the American Society of Nephrology (JASN), show how the drug may be able to save many lives and cut medical costs related to the condition.

AKI, which affects millions of people worldwide and increases the risk of developing and dying early, is most often caused by reduced or blocked blood flow to the kidney (called ischemia). This can occur in many clinical situations, including shock, trauma, sepsis, heart attack, and during heart surgery. Taking high potency statins to is also linked with an increased risk for AKI. Unfortunately, there are no approved drugs that reduce the incidence or severity of AKI.

Ischemia damages cells' mitochondria, which make a form of energy called ATP that keeps cells alive and functioning. When mitochondria are damaged by ischemia, cells have a limited ability to regenerate ATP when blood flow is later restored. This causes cell death and inflammation.

In studies designed to investigate potential for AKI, Alexander Birk, PhD, Shaoyi Liu, MD, and Hazel Szeto, MD, PhD (Weill Cornell Medical College) and their colleagues recently reported that a novel agent called SS-31 (also known as Bendavia™) can accelerate ATP recovery after ischemia and reduce AKI, but its mechanism of action remained unclear. Their latest research—which uses chemical, biochemical, and approaches—shows that Bendavia helps protect a unique fatty compound, or phospholipid (called cardiolipin), on the inner mitochondrial membrane that is critical in the pathway that leads to ATP production. Cardiolipin helps form the foldings of the inner mitochondrial membrane that are studded with protein complexes involved in ATP production. The loss of cardiolipin during ischemia causes mitochondria to lose their membrane folding and reduce their ability to produce ATP. Using a method called transmission electron microscopy, the researchers were able to confirm that treatment with Bendavia prior to kidney ischemia dramatically preserved mitochondrial membrane foldings and accelerated ATP recovery to protect cell structure and function.

"Recent studies have shown that AKI has more than doubled since 2000, causing nearly 39,000 deaths in 2009 alone. The discovery of a therapeutic agent that can minimize AKI will have enormous medical and economic impact," said Dr. Szeto. "Bendavia is a first-in-class protective agent that holds promise in preventing not only AKI, but also ischemia-related injury in multiple organs," she added. Bendavia is currently being evaluated in several phase 2 clinical trials in the United States and Europe for heart and kidney disease.

In an accompanying editorial, Andrew Hall, PhD (University of Zurich, in Switzerland) wrote, "It seems clear that SS-31 can ameliorate adverse changes in mitochondrial structure and function in ischemic AKI, with the result that tubular cell structure and overall kidney function are better preserved."

Explore further: Obese patients face increased risk of kidney damage after heart surgery

More information: The article, entitled "Cardiolipin as a Novel Target to Re-Energize Ischemic Mitochondria," will appear online on July 11, 2013, doi: 10.1681/ASN.2012121216.
The editorial, entitled "Maintaining Mitochondrial Morphology in AKI: Looks Matter," will appear online on July 11, 2013, doi: 10.1681/ASN.2013050519.

Related Stories

Obese patients face increased risk of kidney damage after heart surgery

May 24, 2012
Oxidative stress may put obese patients at increased risk of developing kidney damage after heart surgery, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). Effective ...

Markers warn of progressive kidney problems after heart surgery

March 1, 2012
Blood and urine markers can indicate which patients with an abrupt kidney injury following heart surgery will experience progressive kidney problems, according to a study appearing in an upcoming issue of the Journal of the ...

Kidney injury: A serious risk to the health and survival of today's soldiers

December 8, 2011
Acute kidney injury (AKI), an abrupt or rapid decline in kidney function, is a serious and increasingly prevalent condition. Little information has been available about how common or how severe AKI is in military personnel ...

Serious acute kidney injury: More common than ever

December 6, 2012
Acute kidney injury (AKI), an abrupt or rapid decline in kidney function, is a serious and increasingly prevalent condition that can occur after major infections, major surgery, or exposure to certain medications. The incidence ...

Patients with persistent kidney injuries rarely see specialists

December 8, 2011
Most patients with an abrupt kidney injury that does not get better do not see a kidney specialist within a year, according to a study appearing in an upcoming issue of the Journal of the American Society Nephrology (JASN). ...

Prophylactic sodium bicarbonate infusion and acute kidney injury after open heart surgery

April 16, 2013
Contrary to the positive findings of a previous pilot study, administration of a sodium bicarbonate-based infusion to induce urinary alkalinization during and after surgery does not reduce the incidence of acute kidney injury ...

Recommended for you

Google searches can be used to track dengue in underdeveloped countries

July 20, 2017
An analytical tool that combines Google search data with government-provided clinical data can quickly and accurately track dengue fever in less-developed countries, according to new research published in PLOS Computational ...

MRSA emerged years before methicillin was even discovered

July 19, 2017
Methicillin resistant Staphylococcus aureus (MRSA) emerged long before the introduction of the antibiotic methicillin into clinical practice, according to a study published in the open access journal Genome Biology. It was ...

New test distinguishes Zika from similar viral infections

July 18, 2017
A new test is the best-to-date in differentiating Zika virus infections from infections caused by similar viruses. The antibody-based assay, developed by researchers at UC Berkeley and Humabs BioMed, a private biotechnology ...

'Superbugs' study reveals complex picture of E. coli bloodstream infections

July 18, 2017
The first large-scale genetic study of Escherichia coli (E. coli) cultured from patients with bloodstream infections in England showed that drug resistant 'superbugs' are not always out-competing other strains. Research by ...

Ebola virus can persist in monkeys that survived disease, even after symptoms disappear

July 17, 2017
Ebola virus infection can be detected in rhesus monkeys that survive the disease and no longer show symptoms, according to research published by Army scientists in today's online edition of the journal Nature Microbiology. ...

Mountain gorillas have herpes virus similar to that found in humans

July 13, 2017
Scientists from the University of California, Davis, have detected a herpes virus in wild mountain gorillas that is very similar to the Epstein-Barr virus in humans, according to a study published today in the journal Scientific ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.