August 29, 2007

(DAVIS, Calif.) — A two-year pilot research grant awarded to physicians and scientists in the entomology, food science and technology, and internal medicine departments at UC Davis  may determine if omega 3-fatty acids, commonly found in fish oils, can help reverse a chronic inflammatory disease of the kidneys.

"Immunoglobulin A nephropathy" or IgAN, the most chronic inflammatory disease of the glomerulus, a filtering structure in the kidneys, can strike people of all ages, said Angela Zivkovic, a post-doctoral researcher in the Department of Entomology  lab. Characterized by blood and protein in the urine and swelling of the hands and feet, the disease occurs when deposits of the protein IgA disrupt the filtering process.

"In more than 30 percent of IgAN patients, the disease progresses to end-stage kidney disease, resulting in the need for ongoing hemodialysis treatments or a kidney transplant,” she said. “The disease is not well understood, and there are no proven treatments."

The $84,000 multidisciplinary grant, “Development of a Metabolic Assessment Tool for Chronic Kidney Disease,” is funded by the UC Davis Center for Health and Nutrition Research. Bruce Hammock, professor of entomology, is the principal investigator of the study.

"This study is extremely important due to both the prevalence of this disease and its resistance to treatment," said Robert Weiss, chief of the UC Davis Division of Nephrology  and another member of the study team. "Our study will help to select IgAN patients who are more likely to respond to fish oil and help us better understand the mechanism of this disease. My laboratory will help determine the metabolites in the urine and blood of IgAN patients and identify which signaling pathways are affected. If we are able to select patients who respond to fish oil, and identify the metabolic pathways that are not working properly in them, we may ultimately come up with new therapeutic targets."

The research team's work involves substances that make up omega-3 acids.

"Signaling lipids, or eicosanoids, are derived from essential fatty acids, which include omega-3 and omega-6 fatty acids," Zivkovic said. "These fatty acids are essential because they cannot be synthesized in the body, and therefore need to be obtained from the diet. Whereas omega-6 fatty acids are abundant in the western diet in the form of grains and cooking oils, long-chain omega-3 fatty acids can be obtained only from marine sources. Fish oil is an excellent source of omega-3 fatty acids, and it has been shown to improve kidney function in animal studies but in human trials shows inconsistency."

Preliminary evidence shows that IgAN patients have deficiencies in omega-3 fatty acids. Whereas in some IgAN patients, omega-3 fatty acids help reverse kidney disease and improve kidney function, in other patients, there is no benefit, and the reason for this inconsistency is unclear.

"Our study will answer the question: do certain IgAN patients have metabolic disturbances in omega-3 fatty acid metabolism that play causative roles in disease development by way of eicosanoids in the kidney?" said Zivkovic. "We will also determine how these metabolic disturbances in omega-3 fatty acid and eicosanoid metabolism are involved in mediating the effectiveness of treatment with fish oil."

The scientists will measure the comprehensive blood lipid and eicosanoid profiles of IgAN patients and compare them with healthy individuals. Both groups will be measured before and after supplementation with fish oil. "We aim to find new biomarkers that will be used to assess metabolic status in patients with IgAN," she said. "With these new biomarkers it will be possible to detect responsiveness to fish oil and monitor treatment progress. By comparing the changes in omega-3 fatty acids and eicosanoids that are associated with IgAN and fish oil treatment, we will also begin to unravel the causes of this disease and how omega-3 fatty acids play a role in its reversal."

Said Hammock: "This is a unique opportunity for collaboration, using state-of-the-art new mass spectrometry equipment in our lab to probe the mechanism of action of common food supplements."

Hammock maintains an active research program in insect developmental biology and innovative methods of insect pest control. Due to his interest in the effects of pesticides on the environment and on human health, he developed broad interests in the human cardiovascular and inflammatory systems and how nutritional status and exposure to environmental chemicals may influence health.

"At a fundamental level, the basic biology of insects is not so different from that of man," he said.

Hammock has long collaborated with Bruce German, a biochemist noted for his work in using an analytical technique known as metabolomics to move toward individualizing medicine. Clinician and cell biologist Weiss pursues a variety of interests, including hardening of the arteries, restenosis and renal disease.

Zivkovic, who received her doctorate in nutritional biology from UC Davis, researches the development of tools for metabolic health assessment. Her ultimate research goal is to pave the way to personalized nutrition approaches that can improve health and prevent disease in individuals.

"Recently available mass spectrometry equipment at UC Davis opens the door to personalized medicine," she said.

In addition to her research work with Hammock, Zivkovic consults for Lipomics Technologies, Inc., a biotech company based in West Sacramento, and owns and operates her own personalized nutrition consultation practice.