|New Kidney Function Test Better than
Standard at Predicting Death and Cardiovascular Outcomes
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
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
"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
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.
Study co-authors are supported by grants from the National
Institute of Diabetes and Digestive and Kidney Diseases.
To interview an NHLBI expert, please contact the NHLBI
Communications Office at 301-496-4236. To interview
Dr. Shlipak, please contact the University of California,
San Francisco Department of Public Affairs at 415-476-2557.
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.