Three biomarkers better predict kidney disease, complications

Adding cystatin C to a diagnostic panel revealed one person in six who had chronic kidney disease that was undetected using the conventional test.

Using three biomarkers, instead of the current recommendation of two, is more effective at detecting and staging chronic kidney disease and predicting end-stage renal disease and death, say University of Alabama at Birmingham researchers in a study published online and in the April 20, 2011, print edition of JAMA.

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David Warnock

Chronic kidney disease (CKD) affects 26 million American adults, according to the National Kidney Foundation (NKF). People with diabetes, hypertension and a family history of kidney disease, plus African-Americans, Hispanics, Pacific Islanders, Native Americans and seniors are at an increased risk for developing the disease. But early detection often can help prevent the progression of kidney disease to kidney failure.

Currently, the NKF recommends using two biomarkers found in the blood called serum creatinine and albuminuria, or proteins in the urine, to detect kidney disease. The UAB study examining the effectiveness of adding a third biomarker – cystatin C – to the protocol provides valuable information as the NKF begins to revise its guidelines.

The study’s senior author, UAB nephrologist David Warnock, M.D., and colleagues say cystatin C, which also reveals how well the kidney filters blood, is a more sensitive measure than creatinine.

“Cystatin C may be a slightly better biomarker of kidney function than serum creatinine. This may be because a person’s serum creatinine level is influenced by their muscle mass, which can affect the accuracy of the test,” Warnock says. “While the current approach using serum creatinine and protein in the urine works well, our study showed that including cystatin C may improve the ability of physicians to properly diagnose kidney disease.” 

Warnock and his colleagues assessed kidney function in 26,643 participants enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. The researchers evaluated whether including a patient’s levels of cystatin C to the creatinine-albuminuria test would better identify risks associated with chronic kidney disease.

The study participants were, on average, 65 years old. Overall, 40 percent were black, 54 percent were women, 21 percent had diabetes and 59 percent had hypertension. During a median follow-up period of 4.6 years, 1,940 participants died and 177 developed incident end-stage renal disease.

The research revealed mortality rates among participants with CKD — defined by all three biomarkers — were 7.8 times greater than the mortality rates of those with CKD defined by creatinine-albuminuria alone, making the triple-marker approach the best predictor of end-stage renal disease and death.

“In our sample, one in six persons had CKD undetected by the conventional test,” Warnock says.

“This is important, timely research; guidelines for the evaluation and staging of CKD now are being revised by a working group managed by the National Kidney Foundation, using information gathered from several large studies. The REGARDS study is a part of this effort to develop staging systems that accurately reflect prognosis for chronic kidney disease complications.”

Warnock says the next step is to determine the cost-effectiveness of screening with cystatin C and identifying any sub-groups of individuals who may benefit most from having it measured. 

“As health-care costs rise, it is important to balance the addition of a new biomarker with its prognostic significance,” he says. “We hope to help identify high-risk populations that might benefit from a triple screen without burdening the health-care system with one more test required for all people.”

Monika M. Safford, M.D., from the UAB Division of Preventive Medicine, and Suzanne Judd, Ph.D., and Paul Muntner, Ph.D., from the UAB School of Public Health, were co-authors on the paper. The research was funded by the National Institute of Neurological Disorders and Stroke and Amgen.

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