New kidney function test helps doctors predict patient futures.

Cystatin-C, a new blood test for kidney function, is a better predictor of death and cardiovascular risk among the elderly than the standard measure of kidney function, according to a National Heart, Lung, and Blood Institute (NHLBI)-funded study published in the May 19 issue of the New England Journal of Medicine. This more sensitive test distinguishes those at low, medium and high cardiovascular risk, which may enable earlier detection.

Investigators for NHLBI's Cardiovascular Health Study compared the two measures of kidney function, cystatin-C and the standard test creatinine, as predictors of death from all causes, death from cardiovascular causes, and incidence of heart attack and stroke among 4,637 elderly participants in the study.

The 20 percent of the participants with the highest levels of cystatin-C had twice the risk of death from all causes as well as death from cardiovascular disease, and a 50 percent higher risk of heart attack and stroke compared with those who had the lowest levels of cystatin-C. In contrast, testing the same participants with creatinine detected a smaller high-risk group--about 10 percent of the participants--and all others appeared to be at average risk.

With cystatin-C investigators found that 60 percent had abnormal kidney function putting them at medium or high risk for cardiovascular complications.

It is estimated that 20 million Americans have significantly reduced kidney function, and that even a small loss of kidney function can double a person's risk of developing cardiovascular disease.

"This study affirms the important link between kidney function and cardiovascular health and survival in the elderly. If these findings are confirmed in other studies, cystatin-C could be a useful prognostic tool for evaluating older people at risk for not only kidney disease. but cardiovascular disease as well," said Elizabeth G. Nabel, M.D., NHLBI director.

The standard evaluation of kidney function is an estimate of the kidney's rate of filtration--called the glomerular filtration rate (GFR)--based on measurement of creatinine in the blood and a further calculation based on a patient's age, gender and race. Measurement of cystatin-C in the blood also appears to reflect the GFR, but does not require an additional calculation. Both creatinine and cystatin-C are proteins found in the blood and filtered through the kidneys. When the kidneys are not working well, these proteins accumulate in the blood, which provides a signal to the doctor that a person may have kidney disease. Because creatinine is a by-product of muscle cells, its levels in the blood can be affected by factors other than kidney disease, like age, gender, race, and lean muscle mass. Cystatin-C is produced by blood cells, and its levels in the blood are not impacted by age, gender, race, or lean muscle mass.

Cystatin-C is FDA-approved for diagnostic use, but the test is not yet widely available or commonly used in clinical settings. This and other studies have shown that cystatin-C may detect moderate kidney disease at earlier stages, before creatinine levels would rise, enabling identification of a much larger group of people at risk for death and cardiovascular complications.

"Our results show that a normal creatinine is not nearly as reassuring as we used to believe. In persons at a high risk for kidney disease, such as an older person or one with diabetes, hypertension, or cardiovascular disease, a normal creatinine level may be misleading us into thinking that the patient is safe from the cardiovascular effects of kidney disease," said the study's lead author Michael Shlipak, M.D.M.P.H, of University of California at San Francisco.

Dr. Shlipak noted that additional research is needed to determine the exact clinical role for this test, but that it may be most useful in high-risk patients with normal creatinine. Evaluating the mechanisms that underlie this strong association between the kidney and cardiovascular disease would be critical for targeting prevention efforts, he said.

Participants in the Cardiovascular Health Study were aged 65 or older at baseline. Their creatinine and cystatin-C measures were taken in 1992 or 1993 and the average follow-up period was 7.4 years. The study sites were Forsyth County, North Carolina, Sacramento County, California, Washington County, Maryland and the city of Pittsburgh.

NHLBI is part of the National Institutes of Health (NIH), the Federal Government's primary agency for biomedical and behavioral research. NIH is a component of the U.S. Department of Health and Human Services. Additional information about cardiovascular disease and other NHLBI-supported research and educational programs are available online at the NHLBI website, www.nhlbi.nih.gov.