Sources of variation and reference intervals for serum cystatin C in a healthy Japanese adult population

Background: To derive reference intervals (Ris) for cystatin C (CysC), we examined sources of variation in its serum concentration by multiple regression analysis. Methods: A total of 596 healthy subjects (30-75 years of age) who underwent an annual health check were chosen as candidate reference individuals who did not have any chronic illness requiring medication. Serum CysC was measured together with routine screening tests (basic clinical chemistry and complete blood count). Results: Multivariate analysis revealed that CysC concentrations were higher in males by an average of 0.082 mg/L. Levels were positively associated with age (+0.047 mg/L for every 10 years), body fat (BF%) and cigarette smoking, and negatively associated with alcohol consumption. A subgroup analysis revealed that the gender difference was not significant for those over 50 years of age. Rls were determined using a "latent abnormal values exclusion method" involving deletion of individuals with two or more abnormal results in the screening tests. Rls were partitioned into three categories by age and gender: 0.60-0.95 mg/L for males aged 30-50 years; 0.55-0.84 mg/L for females aged 30-50 years; and 0.64-1.05 mg/L for all subjects aged 51-75 years. Creatinine levels showed little age-related change, but a conspicuous gender difference; they increased with body weight, but not with BF%. Conclusions: In interpreting serum CysC levels, BF%, cigarette smoking, and alcohol consumption may need to be considered, in addition to age and gender, as sources of variation.