Cystatin C: a Marker of Renal Function Or Something More?(Editorials‪)‬

Over the past decade, we have come to appreciate that individuals with even moderately reduced renal function are at increased risk for cardiovascular morbidity and mortality. There is no consensus, however, on how renal function should be measured. The most precise and accurate methods (such as inulin clearance) are impractical in the clinical setting and for larger research studies. Serum creatinine has been the mainstay by which renal function has been estimated for decades, but it is crude and can often be misleading. Age, weight, sex, and race influence creatinine production and thus need to be taken into account when evaluating a serum creatinine value. For example, an elderly woman with a serum creatinine in the "normal" range can have severely reduced renal function. Although measurements of serum creatinine are relatively inexpensive and widely available, they do have limitations. In an attempt to address some of these limitations, equations have been derived to estimate either creatinine clearance or the glomerular filtration rate (GFR). The most commonly used equation for estimating creatinine clearance is the Cockcroft-Gault formula (1). GFR calculated by this equation correlates well with measured GFR when renal function is within the reference interval, but as renal function declines, it overestimates GFR because creatinine is removed not only by glomerular filtration by also by renal tubular secretion. When GFR is low, tubular secretion becomes an important factor. Another formula, the MDRD (Modification of Diet in Renal Disease) equation, is the most widely used to estimate GFR (2). It too has several limitations, including lack of validation within the reference interval, the susceptibility of the alkaline-picrate creatinine method to interferences, and the lack of harmonization of creatinine assays. The variation between laboratories for plasma creatinine may be 30% or more. This has serious implications when using an estimating equation that was derived with a different creatinine method (3).