Serum cystatin C as a new marker of glomerular filtration rate [GFR]

ABSTRACT

Cystatin C is a 13 KD basic protein that is a member of the cystatin super-family of cysteine protease inhibitors. The cystatin C gene seems to be a house keeping gene, which is compatible with a stable production rate of cystatin C by most cells. This protein is freely filtered through the glomerulus and almost completely reabsorbed and catabolized by proximal tubular cells. Because of these characteristics cystatin C is assumed to be a better marker of glomerular filtration rate than other markers. 115 new cases of renal disease aged between 14 and 88 years and 121 healthy subjects, aged between 11 and 78 years were studied. In all of the subjects serum cystatin C and creatinine were determined and creatinine clearance was determined only in patients. Cystatin C was determined by a particle-enhanced turbidimetric assay and creatinine was measured by Jaffe's method. In addition, to assess the diagnostic efficiency of serum cystatin C in comparison to that of serum creatinine and creatinine clearance in predicting changes in GFR, we performed Tc99m - DTPA clearance on 53 subjects including controls and patients. A linear relationship was found between Tc99m - DTPA clearance and Y serum cystatin C [r= 0.712, p-value <0.001], 1/serum creatinine [r= 0.709, p-value< 0.001] and creatinine clearance [r= 0.777, p- value <0.001]. Diagnostic accuracy in the identification of reduced GFR measured as area under the receiver-operating characteristic plot was 0.878 +/- 050 [Mean +/- SE] for Scystatin C, 0.866 +/- 0.051 for creatinine and 0.866 +/- 0.051 for creatinine clearance. The serum cystatin C reference values [mean +/- 1.96 SD] determined was 0.83 -0.88 mg/L. A cutoff cystatin C concentration of 0.82 mg/L had 92% sensitivity and 79% specificity for detecting abnormal GFR. There was no significant correlation between cystatin C and age [p- value <0.219] and weight [p- value <0.193]. This study demonstrates that serum cystatin C has an increased diagnostic accuracy for reduced GFR when compared with serum creatinine and creatinine clearance. Hence, cystatin C seems to be an alternative for the estimation of GFR