Correlation of plasma concentrations of cystatin C and creatinine to inulin clearance in a pediatric population

Abstract

Measurement of blood concentrations of cystatin C (cysC), a cysteine protease inhibitor present in human plasma, has been suggested for use as an indicator of glomerular filtration rate (GFR) in a manner analogous to the use of plasma creatinine (SCR). In this study, cysC and SCR were measured in plasma from pediatric patients (4–19 years) with renal disease for whom a “gold standard” measurement of GFR via inulin clearance (CIN) was available. The data analyses were divided into two age groups: group A (4–12 years, n = 26) and group B (12–19 years, n = 34). For both age groups, the linear correlation coefficient of [cysC]−1 vs CIN (mL/min/1.73 m2) (r = 0.765 for group A and r = 0.869 for group B) was less than that of the linear correlation coefficient of [SCR]−1 vs CIN (r = 0.841 for group A and r = 0.892 for group B). As a single measurement for detection of abnormal GFR, however, the optimum receiver-operator characteristic point for cysC measurement (for group A at cysC >1.2 mg/L, sensitivity = 80%, specificity = 91%; and for group B at cysC >1.4 mg/L, sensitivity = 87%, specificity = 100%) was numerically superior to that for SCR measurement (for group A at SCR >8.0 mg/L, sensitivity = 67%, specificity = 100%; and for group B at SCR >9.0 mg/L, sensitivity = 91%, specificity = 91%), using a reference value for normal GFR of CIN > 90 mL/min/1.73 m2. However, these differences were not statistically significant. CysC measurement appears to be broadly equivalent to SCR measurement for estimation of GFR in pediatric patients.

Glomerular filtration rate: measure creatinine and height rather than cystatin C!

“…Therefore, a substantial proportion of patients with a reduced GFR would still display normal PcysC levels. These results are in accordance with a study undertaken in 67 children using the constant infusion technique for Cin determination (7), where the optimum ROC points were almost equivalent for serum cystatin C and creatinine, showing no greater power of cystatin to estimate GFR. Likewise, Chantrel et al compared serum concentrations of cystatin C and creatinine at different GFRs with the theoretical curves which would be obtained assuming glomerular filtration as the exclusive route of elimination (13).…”

“…However, as attractive as PcysC may seem to be, its reliability for assessing GFR in children has not yet been clearly defined. The validity of the methods used as reference measures of GFR is questionable (5,6), particularly those without urine collection (7,8). In addition, the cost of PcysC measurement is significantly higher than that of plasma creatinine (Pcreat) (approximately 12 and 6 Euros, respectively in our institution).…”

“…Moreover, it is important to add that, in order to simplify the presentation, we only reported the results with the cut-off value of 100 ml/min per 1.73 m 2 , which is the limit we use daily for GFR (12). However, as some studies performed in children used a lower cut-off value (5)(6)(7)25), the statistical analysis was also performed for every Cin from 80 to 102 ml/min per 1.73 m 2 . The same results were obtained: in all cases, PcysC performed better than Pcreat but was worse than the Haycock-Schwartz formula and Ccreat.…”

How to monitor renal function in pediatric solid organ transplant recipients

“…With the exception of one study (82), the reciprocal of cystatin C correlates better with a gold standard GFR measurement than serum creatinine (83)(84)(85)(86). The diagnostic performance of cystatin C in comparison with serum creatinine was recently analyzed in a meta-analysis on 46 studies, both in adults and children (87).…”

Cystatin C - an accurate marker of glomerular filtration rate after renal transplantation?

“…Serum cystatin C has been proposed in patients without transplantations as a screening test of reduced GFR [4,5,6,8,14,23,24]. Cystatin C is a cysteine proteinase inhibitor, which is produced by all nucleated cells at a constant rate [l].…”