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New test can predict complications from kidney disease

Cystatin C, a blood marker of kidney function, proved significantly more accurate than the standard blood marker, creatinine, in predicting serious complications of kidney disease, in a study by researchers at the San Francisco VA Medical Center and the University of California, San Francisco. Among adults who were identified as having chronic kidney disease by high creatinine levels, the researchers found that only patients who also had abnormally high levels of cystatin C were at high risk for death, cardiovascular disease, heart failure, or kidney failure. People with high creatinine but normal cystatin C levels had risks similar to those with normal creatinine levels.

The researchers also found that a small but important segment of the study population was missed by creatinine but identified by cystatin C as being at significant risk of serious complications, according to lead author Carmen A. Peralta, MD, MAS, an SFVAMC researcher and an assistant professor of medicine in residence in the division of nephrology at UCSF.

The study of 11,909 participants appears online on December 16, 2010, in the JASN Express section of the Journal of the American Society of Nephrology. The authors analyzed patient data from two prospective studies: the Multi-Ethnic Study of Atherosclerosis and the Cardiovascular Health Study, both sponsored by the National Heart, Lung, and Blood Institute.

Principal investigator Michael G. Shlipak, MD, MPH, chief of general internal medicine at SFVAMC, said that the current study highlights a potential clinical use for cystatin C as a method for confirming a diagnosis of chronic kidney disease. Shlipak has been a leader among physicians in identifying cystatin C as an alternative, accurate, and reliable marker of kidney function.

Both cystatin C and creatinine are substances made in the body and filtered by the kidneys. High levels of the substances in the blood indicate that the kidneys are losing the ability to filter them, and thus are losing function. However, explained Peralta, creatinine is a byproduct made in muscles, so it is affected by what you eat and especially by how much muscle you have. Thus, a bodybuilder with healthy kidneys might have an elevated creatinine level because of high muscle mass, whereas a frail elderly person might have normal or even low levels of creatinine, but in fact this persons kidneys are not working well – its just that theres not much creatinine because theres not much muscle.

In contrast, cystatin C is a protein made in cells throughout the body. In studies so far, it does not seem to be that affected by age or muscle mass or diet, said Shlipak, who is also a professor in residence of medicine and epidemiology and biostatistics at UCSF.

Shlipak proposes that cystatin C, which can cost as little as $17 per test, be added as a method for confirming or staging chronic kidney disease in guidelines that are currently being formulated by nephrologists. Its vital that we have an accurate diagnostic test, because kidney disease does not show symptoms until its too late, when your kidneys have almost failed completely, he said. Being missed by creatinine is an important limitation in our current method of diagnosing kidney disease, said Peralta. Yet, she adds, being falsely identified with kidney disease through inaccurate test results can be disastrous as well. There is fear and psychological stress, particularly in communities of color, where people have a lot of friends and family members who are on dialysis, she noted. You can also be subjected to unnecessary and expensive tests and medications.

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Brown Rice and Cardiovascular Protection

Brown Rice and Angiotensin II

The subaleurone layer of Japanese rice, which is located between the white center of the grain and the brown fibrous outer layer, is rich in oligosaccharides and dietary fibers, making it particularly nutritious. However, when brown rice is polished to make white rice, the subaleurone layer is stripped away and the rice loses some of its nutrients. The subaleurone layer can be preserved in half-milled (Haigamai) rice or incompletely-milled (Kinmemai) rice. These types of rice are popular in Japan because many people there believe they are healthier than white rice.

The Temple team and their colleagues at the Wakayama Medical University Department of Pathology and the Nagaoka National College of Technology Department of Materials Engineering in Japan sought to delve into the mysteries of the subaleurone layer and perhaps make a case for leaving it intact when rice is processed. Because angiotensin II is a perpetrator in such lethal cardiovascular diseases, the team chose to focus on learning whether the subaleurone layer could somehow inhibit the wayward protein before it wreaks havoc.

First, the team removed the subaleurone tissue from Kinmemai rice. Then they separated the tissue's components by exposing the tissue to extractions of various chemicals such as ethanol, methanol and ethyl acetate. The team then observed how the tissue affected cultures of vascular smooth muscle cells. Vascular smooth muscle cells are an integral part of blood vessel walls and are direct victims of high blood pressure and atherosclerosis.

During their analysis, the team found that subaleurone components that were selected by an ethyl acetate extraction inhibited angiotensin II activity in the cultured vascular smooth muscle cells. This suggests that the subaleurone layer of rice offers protection against high blood pressure and atherosclerosis. It could also help explain why fewer people die of cardiovascular disease in Japan, where most people eat at least one rice-based dish per day, than in the U.S., where rice is not a primary component of daily nutrition.

“Our research suggests that there is a potential ingredient in rice that may be a good starting point for looking into preventive medicine for cardiovascular diseases,” said Dr. Eguchi. “We hope to present an additional health benefit of consuming half-milled or brown rice [as opposed to white rice] as part of a regular diet.”

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