Combining Creatinine and Cystatin C Markers May Be Useful for Confirming Chronic Kidney Disease

A study published on July 4 in The New England Journal of Medicine found that a combined creatinine-cystatin C equation may be useful as a confirmatory test for chronic kidney disease.

As the estimates of glomerular filtration rate (GFR) based on serum creatinine remain relatively imprecise and can lead to the overdiagnosis of chronic kidney disease, the authors looked at "two new equations for estimating GFR – one using standardized cystatin C alone and the other using cystatin C combined with standardized creatinine – in diverse populations."

Using cross-sectional analyses, the authors "developed estimating equations based on cystatin C alone and in combination with creatinine in diverse populations totaling 5,352 participants from 13 studies. These equations were then validated in 1119 participants from five different studies in which GFR had been measured."

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Results showed that "mean measured GFRs were 68 and 70 ml per minute per 1.73 m² of body-surface area in the development and validation data sets, respectively. In the validation data set, the creatinine-cystatin C equation performed better than the equations that used creatinine or cystatin C alone." The authors note that "precision was improved with the combined equation (interquartile range of the difference, 13.4 vs. 15.4 and 16.4 ml per minute per 1.73 m², respectively [P=0.001 and P<0.001]), and the results were more accurate (percentage of estimates that were >30 percent of measured GFR, 8.5 vs. 12.8 and 14.1, respectively [P>0.001 for both comparisons]).

"Cystatin C should not replace creatinine in general practice," note the authors. "However the combination of creatinine and cystatin C provides more precise GFR estimates, which may be useful for specific purposes."

The authors conclude that "the combination of serum creatinine and serum cystatin C is more accurate than either marker alone for estimating GFR." They add that their data "suggest that estimated GFR based on serum cystatin C could be used as a confirmatory test for chronic kidney disease."

In an editorial comment, Matthew Weir, MD, notes "as important as this new improvement is for estimating GFR, until albuminuria screening is brought into the mainstream as part of our classification strategy, many patients who might benefit from earlier intervention will be missed. Moreover, future studies are needed to show that automated reporting of estimated glomerular filtration rate (eGFR) with this new technology, in the presence or absence of albuminuria, will result in improved clinical care and a reduction in health care costs."

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