Cystatin C measurement and its practical use in patients with various renal diseases

To evaluate the clinical usefulness in terms of estimation for glomerular filtration rate (GFR), we determined the cystatin C levels in the serum and urine of 33 healthy volunteers as well as in the serum and urine of 35 patients with various renal diseases and compared them with those of creatinine. In addition, we evaluated this substance as an indicator of removal rate of low molecular weight protein with high flux membranes in 6 hemodialysis (HD) patients.

Serum and urinary cystatin C levels were measured by using an enzyme-linked immunosorbent assay (ELISA) method, 24-hour creatinine clearance was used as an indicator of GFR.

Reference intervals with 95% ranges are 0.47-1.03 mg/l in the serum from healthy volunteers. There was a significant positive correlation between serum cystatin C and creatinine levels (r = 0.936, p < 0.001) in the patients with various renal diseases. Serum cystatin C and creatinine inversely and logarithmically correlated to creatinine clearance as shown in the following equations: log cystatin C = -0.564 x log creatinine clearance + 1.216 (r = -0.850), log creatinine = -0.678 x log creatinine clearance + 1.449 (r = -0.904). In these equations l/day is the unit used for creatinine clearance, mg/l is the unit used for serum cystatin C. The range for cystatin C is 0.67-6.15 mg/l, 0.66-7.23 mg/dl for creatinine and 8.9-186.3 l/day (6.2-129.4 ml/min) for creatinine clearance. Serum cystatin C levels started to increase over normal range when creatinine clearance fell below 135.9 l/day (94.4 ml/min), while serum creatinine remained within normal ranges. The daily urinary excretion of cystatin C was increased significantly in the group in which creatinine clearance was below 30 l/day (20.8 ml/min) compared to that in which creatinine clearance was higher than in 70 l/day (48.6 ml/min). Fractional clearance of cystatin C increased proportionally and markedly to the decrease of creatinine clearance. In a regular HD condition with high flux membrane, the cystatin C removal rate was 38.7 +/- 1.7%.

These data suggest that combined measurement of cystatin C in the serum and urine is useful to estimate GFR, especially to detect the mild reduction of GFR. Cystatin C measurement can also be used as an indicator of removal rate of low molecular weight protein with different types of high flux membranes in hemodialysis.