Reference intervals for the glomerular filtration rate and cell-proliferation markers: serum cystatin C and serum beta(2)microglobulin/cystatin C-ratio

Recent studies have indicated that serum and plasma cystatin C are better markers for glomerular filtration rate (GFR) than serum creatinine, ubiquitously used for this purpose. To fully exploit the value of serum and plasma cystatin C as GFR markers, reliable age and sex-correlated reference intervals are required. The present study comprised cystatin C determinations in plasma and sera from 259 individuals from a well-defined area in the southernmost part of Sweden. From demographic lists two men and two women were randomly selected from each one-year birth cohort above 20 years of age. No sex differences were found for plasma and serum cystatin C, whereas an increase in the cystatin C levels with age was noted, corresponding to the known age-related decrease in GFR. The following reference intervals are recommended for practical clinical use: S-Cystatin C (both sexes): 20-50 years, 0.70-1.21 mg l(-1) and 50+ years, 0.84-1.55 mg l(-1). The same samples were also used for determination of beta(2)-microglobulin levels in order to calculate reference intervals for the beta(2)-microglobulin/cystatin C-ratio, which is a more distinct marker for cell proliferation, particularly lymphoproliferation, than is the serum level of beta(2)-microglobulin alone, since the ratio should be virtually uninfluenced by GFR. The beta(2)-microglobulin/cystatin C-ratios were uninfluenced by sex and age and 1.45-2.43 is recommended as the serum reference interval for practical clinical use. Serum creatinine was determined in the same samples and the creatinine level was found to be strongly influenced by sex and weakly by age.