Cystatin C: An emerging glomerular filtration rate marker

Abstract

In this issue of SJCLI (pp. 111-124), Per Sjostrom and co-workers present a study on the ''Determination of the production rate and non-renal clearance of cystatin C and estimation of the glomerular filtration rate from the serum concentration of cystatin C in humans''. They have studied the non-renal clearance of cystatin C, which is of particular importance when using cystatin C for monitoring patients with severely decreased glomerular filtration rate (GFR), as non-renal clearance will have a relatively greater impact on the total clearance as the glomerular filtration decreases. They show that cystatin C has a significant non-renal clearance and they calculated this clearance. They have used the non-renal clearance to develop a new cystatin C formula that takes into account the non- renal clearance. The study shows that the production rate of cystatin C is independent of gender, age, lean body mass and GFR, which allows the use of simpler formulas for calculation of GFR. Lean body mass, weight and length are parameters that are often difficult to obtain for the laboratory. The study also presents data on the biological variability of production rate and extrarenal clearance. These are important contributions to our understanding of cystatin C as a GFR marker. Iohexol is usually considered the gold standard for GFR monitoring in Sweden. How iohexol GFR is analysed varies between laboratories. With decreasing GFR, the slope of the iohexol elimination curve becomes less pronounced. To my knowledge, no laboratory has a defined value for the slope of the elimination curve for rejecting a test result. Most laboratories thus probably compromise in the low GFR range with the assay quality rather than reporting that the test has to be repeated with longer time intervals between the injection and sampling time. There are also a number of methods for calculating the clearance and no external quality assurance programme, which would add to the total CV within the country. One could thus question how shiny the ''gold standard'' really is. Cystatin C has a low total CV and increases three to four times when GFR decreases from 50 ml/min to close to 0 ml/min. To me, these are important factors for a good test. In my opinion the present analytical characteristics favour cystatin C in the low GFR range while the fact that cystatin C is an endogenous substance favours iohexol as the best test. At