Studies confirm that chronic kidney disease independently increases the risk of developing cardiovascular disease

Sep 29 2004

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.