Determination of Serum Cystatin C: Biological Variation and Reference Values

Abstract

Human cystatin C is a low molecular weight protein which has been proposed as a better marker of glomerular filtration rate than creatinine. To be able to interpret results obtained in different patient populations it is necessary to define cystatin C reference values. We measured serum concentration of cystatin C in 1223 subjects using a particle-enhanced nephelometric assay. Subjects were aged 4 to 79 years and were selected among apparently healthy individuals who came to the Centre for Preventive Medicine in Vandoeuvre-Lès-Nancy, France. We observed a Gaussian distribution of cystatin C concentration in serum. We did not find any effect of age or gender in children, hormonal status in women (puberty, menopause, oral contraceptives or hormone replacement therapy) or alcohol intake. Cystatin C concentration was slightly lower in female than in male adults below the age of 60 years. Cystatin C levels significantly increased above the age of 60 in both males and females, probably due to physiological aging of renal function. No other significant differences were observed between males and females. Using multiple regression analysis, moderate correlations were observed between body mass index and cystatin C, and between smoking and cystatin C, but these were not biologically significant. According to the literature, only methylprednisolone and cyclosporin A increased and decreased cystatin C levels, respectively. The reference values for cystatin C obtained in a carefully selected population were 0.75+/-0.089 mg/l for children aged 4-19 years, 0.74+/-0.100 mg/l for males and 0.65+/-0.085 mg/l for females (aged 20-59 years), and 0.83+/-0.103 mg/l for older individuals (> or =60 years).

Cystatin C: current position and future prospects

“…Amongst the extra renal factors which may influence CysC values in healthy people, the most recent work has shown that in adults under 60 years old, CysC concentrations are lower in women than in men, the difference disappearing over the age of 60 years old (30)(31)(32). These results contradict the older studies which did not recommend establishing sex-related reference values (24,(33)(34)(35)(36)(37), except for results found by Pergande and Jung (38).…”

“…Higher values are found in neonates regardless of sex, weight or the child's height (39)(40)(41), including premature infants (35): falling after birth to return to identical values to those in adults by the age of 4 years old (30). Caution is however required in very young children and premature infants in whom high CysC values may reflect low GFR as part of the renal maturation process (35,42).…”

“…Caution is however required in very young children and premature infants in whom high CysC values may reflect low GFR as part of the renal maturation process (35,42). Most studies in adults show that age has a significant impact on CysC concentrations, implying different reference values for people over 50-60 years old (30,33,34,37). It is important to note that reference values in both adults and children are systematically lower when measured by the Dade-Behring Siemens PENIA method (vs. the various PETIA applications of the DakoCytomation kit) ( Table 2).…”

Age, Gender, and Race Effects on Cystatin C Levels in US Adolescents

“…The estimates from this investigation are representative of the civilian, noninstitutionalized population of the United States aged 12 to 19 yr in 1988 through 1994. Previous studies of cystatin levels in adolescents have been conducted in relatively small, selected study populations or study populations limited to one institution or ethnicity (7,8,(11)(12)(13). Thus, one of the largest advantages to this study is the generalizability of the results, presenting the distribution of cystatin C levels in a diverse population of race and ethnicity from across the United States.…”

Increased urinary cystatin C indicated higher risk of cardiovascular death in a community cohort

“…It has important protective extracellular functions by inhibiting cysteine proteinases, such as papain, ficin, and cathepsins [2], which otherwise cause uncontrolled proteolysis and tissue damage. Serum concentrations of CysC are seemingly independent of sex and muscular mass and constant up to 60 years of age [3,4]. The low molecular weight and positive charge at physiological pH allows CysC to filter freely in the kidney glomerulus with no retrieval back to the circulation, thus serum CysC is a clinically established biomarker for estimating glomerular filtration rate (GFR) [5][6][7].…”