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Discovery May Prevent Life-Threatening Wasting Disease In Patients With Chronic Kidney Disease

   Portland, Ore.

Epidemic of chronic kidney disease in America makes finding particularly significant

Researchers at Oregon Health & Science University's Doernbecher Children's Hospital have uncovered a unique therapeutic strategy to combat cachexia - severe malnutrition and physical wasting away - in children and adults with chronic kidney disease (CKD). The study is published in the June issue of the Journal of Clinical Investigation.

Although the exact cause of cachexia - a common life-threatening complication of CKD, cancer, AIDS and heart failure patients - is unknown, Doernbecher researchers found elevated levels of leptin, a hormone that is produced by fat cells and plays a role in weight regulation, may be the cause. Leptin signals through the hypothalamic melanocortin 4 receptor (MC4-R) pathway in the brain, and blocking this pathway may be an important avenue for treatment, they report. The study was conducted in mice.

"Understanding why patients develop cachexia is important because it is associated with very high mortality in patients with chronic kidney disease," said study investigator Robert Mak, M.D., professor of pediatrics in the OHSU School of Medicine and head of pediatric nephrology, Doernbecher Children's Hospital. "Through this research, we have found a novel therapeutic strategy to combat this life-threatening complication of chronic renal disease, which affects more than 10 percent of the population and costs $40 billion each year to treat."

In an accompanying editorial commentary, William Mitch, M.D., past president of the American Society of Nephrology and Edward Randall Distinguished Chairman in Medicine, University of Texas Medical Branch, wrote that this study "provides a quantum increase in our understanding of CKD-associated anorexia."

Other OHSU investigators involved in the research include: Wai Cheung, postdoctoral fellow in pediatrics, School of Medicine; Pin Xuan Yu, research assistant, Vollum Institute; Brian Little, senior research assistant in pediatrics, School of Medicine; Roger Cone, Ph.D., senior scientist in the Vollum Institute; and Daniel Marks, M.D., assistant professor of medicine (pediatric nephrology), School of Medicine.


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