Cystatin C—Incremental Improvement in Measurement and Understanding of Results

Abstract

Ever since the use of cystatin C as a marker for renal function was described (1), laboratory scientists and the in vitro diagnostics industry have worked along two paths; one leading to analytical performance improvement and standardization of the assays and another leading to better understanding of the clinical use of cystatin C as a marker of renal dysfunction and cardiovascular disease. Endogenous substances in plasma such as creatinine and cystatin C, and the exogenous substances iohexol and Cr-EDTA, are believed to be freely filtered by the glomeruli and thus suitable as markers for glomerular filtration rate (GFR). However, the size of these molecules varies by a factor of 10 (the Stokes–Einstein radius for creatinine is 0.3 nm compared to 3–4 nm for cystatin C). It would not be too surprising if this size difference between the molecules resulted in different properties for their filtration in the glomeruli. If a renal disease results in a reduced number of glomeruli, but with intact function of all the remaining units, a parallel change of creatinine and cystatin C concentration in plasma is to be expected as a consequence of reduced GFR. On the other hand, if a renal disease results in small changes in the glomeruli, selectively reducing the passage of only larger molecules like cystatin C, then the accompanying …