Diagnostic sensitivity of serum cystatin for impaired glomerular filtration rate

Recently, the reciprocal of cystatin C (Cys-C), a non-glycosylated 13-kilodalton protein that is produced by all investigated nucleated cells, was found to correlate closely with glomerular filtration rate (GFR). In order to determine the diagnostic validity in children for the detection of impaired GFR, venous blood samples from 381 children (aged 1.7-18 years) with various renal pathology referred for Cr-51-EDTA clearance investigations were obtained for measurement of Cys-C as well as beta(2)-microglobulin (beta(2)-MG) and serum creatinine. Two hundred and sixteen children with clearance values >90 ml/min per 1.73 m(2) constituted a control group, with a normal GFR. In the control group, Cys-C values were normally distributed with a mean of 0.94+/-0.27 mg/l and an upper reference limit (97.5th percentile) of 1.47 mg/l. In all children, there was a positive correlation between 51Cr-EDTA clearance and the reciprocal of Cys;C (r = 0.64, P < 0.0001), beta(2)-MG (r = 0.59, P < 0.0001), creatinine (r = 0.55, P < 0.0001), and the height/creatinine ratio (r = 0.73, P < 0.0001). Receiver-operating characteristics analysis showed that there were no significant differences between these three parameters for discriminating between patients with normal and reduced C;FR, although there was a tendency towards the best diagnostic sensitivity of the GFR estimate according to the Schwartz formula. We conclude that for the detection of mildly impaired GFR, a full clearance study cannot be replaced by measurement of serum Cys-C or beta(2)-MG concentrations.