Biological variation of cystatin C: implications for the assessment of glomerular filtration rate.

To assess the inherent potential for detecting mild to moderate reductions in glomerular filtration rate, this study determined the biological variability of serum cystatin C and creatinine in 12 healthy subjects. After accounting for analytical variation, interindividual variance accounted for 93% and intraindividual variance accounted for 7% of serum creatinine biological variation. As such, to lie outside the assay reference interval, some subjects must exceed 13 SD from their usual mean value, whereas in others, a change of only 2 SD would be sufficient. For cystatin C, interindividual variation explained 25% and intraindividual variance explained 75% of biological variability. Therefore, the upper limit of the population reference interval for cystatin C is seldom more than 3-4 SD from the mean value of any healthy individual. The critical difference for sequential values significant at P < or = 0.05 was calculated as 37% for serum cystatin C and 14% for serum creatinine. We conclude that cystatin C is potentially a better marker for detecting impaired renal function than serum creatinine, but serum creatinine is probably still the better marker for detecting temporal changes of renal function in individuals with established renal disease.