New target for treating diabetic kidney disease, the leading cause of kidney failure

Treatment improves kidney health and function in diabetic mice

2012-10-19

(Press-News.org) Highlights A drug that activates the liver x receptor blocks expression of an inflammatory molecule involved in diabetic nephropathy, the leading cause of kidney failure. The drug improves kidney health and function in diabetic mice. Such a drug might help protect the health of diabetic patients' kidneys.

About 20%-30% of patients with diabetes develop evidence of diabetic nephropathy.

Washington, DC (October 18, 2012) — Researchers have discovered a new therapeutic target for diabetic nephropathy, the leading cause of kidney failure. The findings, appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN), could help protect the kidney health of individuals with diabetes.

While it's unclear precisely how diabetic nephropathy—kidney disease or damage that occurs in people with diabetes—develops, inflammation is likely involved. One particular inflammatory molecule, osteopontin, seems to play a prominent role, making it a potential target for future therapies.

In an attempt to inhibit osteopontin expression, Daisuke Ogawa, MD, PhD (Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, in Japan) and his colleagues tried activating a receptor that blocks the expression of genes involved in inflammation. This receptor, liver x receptor (LXR), can be activated with a drug named T0901317.

When diabetic mice with kidney damage were given T0901317, the animals' kidneys became healthier and functioned better. Also, the T0901317 treatment markedly decreased the expression of osteoponin and other inflammatory molecules in the kidneys. Laboratory experiments with kidney cells revealed that high sugar concentrations—like those seen in the blood of diabetics—increased osteopontin expression, which could be inhibited with T0901317.

"These observations support an important role for LXR agonists in suppressing the inflammatory responses in diabetic kidneys and preventing the development of nephropathy," said Dr. Ogawa.

### Study co-authors include Hiromi Tachibana, Yuichi Matsushita, Dennis Bruemmer, Jun Wada, Sanae Teshigawara, Jun Eguchi, Chikage Sato-Horiguchi, Haruhito Adam Uchida, Kenichi Shikata, and Hirofumi Makino.

Disclosures: The authors reported no financial disclosures.

The article, entitled "Activation of Liver X Receptor Inhibits Osteopontin and Ameliorates Diabetic Nephropathy," will appear online at http://jasn.asnjournals.org/ on October 18, 2012, doi: 10.1681/ASN.2012010022.

The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies.

Founded in 1966, and with more than 13,500 members, the American Society of Nephrology (ASN) leads the fight against kidney disease by educating health professionals, sharing new knowledge, advancing research, and advocating the highest quality care for patients.

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New target for treating diabetic kidney disease, the leading cause of kidney failure

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