Studies Strengthen Kidney and Heart Disease
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A pair of new epidemiology studies confirms that chronic kidney
disease independently increases the risk of developing cardiovascular
disease, even among people with early kidney disease and after considering
other risk factors such as diabetes, hypertension and high cholesterol.
The studies appear in the September 23 New England Journal of
Medicine.
One of the studies, “Chronic Kidney Disease [CKD] and the
Risk of Death, Cardiovascular Events, and Hospitalization,”
was supported by the National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK) at NIH, part of the Department of Health
and Human Services.
These studies “reinforce the importance of early detection
of CKD, not only to slow progression to [kidney failure] but also
in this case to identify risk factors for cardiovascular disease,”
said Thomas H. Hostetter, M.D., in an editorial accompanying the
papers. Hostetter is a kidney specialist and director of the National
Kidney Disease Education Program at NIDDK.
The NIDDK-funded study followed more than 1.1 million adults from
the Kaiser Permanente Renal Registry in San Francisco for nearly
3 years; average age was 52 years. Led by Alan S. Go, M.D., the
investigators found that when kidney function (GFR) dropped, the
risk of death, cardiovascular events such as heart disease and stroke,
and hospitalization increased. Compared to patients whose GFR was
at least 60 (ml per min. per 1.73 m2):
- The increased risk of death ranged from 17 percent in
those whose GFR was between 45 and 59 to about 600 percent in
those whose GFR was less than 15
- The increased risk of CVD events ranged from 43 percent
in those whose GFR was between 45 and 59 to 343 percent in those
whose GFR was less than 15, and
- The increased risk of hospitalization ranged from 14
percent in those whose GFR was between 45 and 59 to 315 percent
in those whose GFR was less than 15.
The industry-funded VALIANT study related CKD to deaths from CVD
in a 2-year drug-treatment trial of more than 14,500 heart-attack
patients. The researchers found death rates ranging from
14.1 percent in patients whose GFR was at least 75 to 45.5 percent
in those whose GFR was less than 45. The investigators attribute
the increased risk of death from CVD in part to complications of
kidney disease, including anemia, oxidative stress, changes in calcium
and phosphate regulation, inflammation, and conditions promoting
clotting. The researchers also suggest that other kidney-related
factors such as protein in the urine and elevated blood levels of
both homocysteine and uric acid may increase the risk of CVD and
death. Furthermore, they found that common CVD therapies such as
aspirin and beta-blockers were “curiously underused”
in CKD patients with lower kidney function, perhaps inspired by
a fatalist mind-set that may be a self-fulfilling prophecy.
An estimated 10 to 20 million people have CKD. While many will
never develop kidney failure, others will, joining more than 400,000
people annually treated with dialysis or a kidney transplant. CVD
accounts for half of all deaths among people with kidney failure.
An ongoing study supported by NIDDK will help further explain the
connection between CKD and CVD and should lead to improved management
of these diseases. Investigators in the Chronic
Renal Insufficiency Cohort study are looking at earlier kidney
disease than most trials have previously studied and are conducting
the most thorough review to-date of the relative impact of known
risk factors for kidney and heart diseases.
NKDEP and its partners recommend regular creatinine testing and
the MDRD equation to estimate GFR in adults at high risk for kidney
disease those with diabetes, high blood pressure, or a family
history of kidney problems, especially African Americans, Hispanic
Americans, and Native Americans.
Both the Kaiser and VALIANT studies used the MDRD equation to estimate
GFR. The formula considers age, sex, race and the blood level of
a substance called creatinine. Creatinine alone is commonly used
to test for kidney disease, but up to two-thirds of kidney function
may be lost before the test raises suspicions. The MDRD equation
was developed in an NIDDK-supported clinical trial completed in
the early 1990s and is widely considered the best-validated method
for assessing kidney function. However, most labs and doctors still
aren’t using it.
This is unfortunate, since a simple web-based
calculator based on the MDRD equation can compute GFR, and since
creatinine is often measured in standard lab tests, according to
Hostetter’s editorial. NKDEP is encouraging doctors and labs
to use creatinine and the MDRD equation so that patients can be
diagnosed and treated earlier. The calculator may also be used on
hand-held devices.
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