Glomerular Filtration Rate Estimation in Patients with Advanced Chronic Renal Insufficiency Based on Serum Cystatin C Levels

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Abstract
Background: Cystatin C has an obvious advantage in the recognition of the initial stages of renal impairment. It is questionable whether cystatin C possesses the same benefit in follow-up of pre-dialysis patients. If cystatin C were also a sensitive marker of GFR in pre-dialysis patients, then it could be expected that, for the same degree of a decrease in GFR, the increase in Scyst would be higher than in Scr because of the significant increase in tubular secretion of creatinine in residual nephrons. The aim of this study was to evaluate whether Scyst in patients with GFR ≤40 ml/min/1.73 m2 provides a more accurate estimate of GFR than Scr does. Methods: The study was performed in 67 patients (mean age 41.5 ± 7.6 years) with chronic renal insufficiency (GFR = 19.8 ± 9.9 ml/min/1.73 m2) caused by various chronic renal diseases (predominantly by chronic glomerulonephritis and chronic interstitial nephritis). GFR was measured by inulin clearance under conditions of stabilized plasma concentrations and water loading. Creatinine clearance and serum cystatin C concentration (using immunonephelometry) were measured at the same time. For statistical evaluation, linear regression analysis, receiver-operating characteristic (ROC) curves analysis and the method of Bland and Altman were used. Results: A significant correlation (r = 0.813, p < 0.001) was demonstrated between 1/Scyst and Cin as well as between 1/Scr and Cin (r = 0.815, p < 0.001). There were no significant differences between the regression coefficients and the intercepts of regression straight lines characterizing these relationships. ROC curves analysis using the cut-off values for Cin = 20 ml/min/1.73 m2 and Cin = 10 ml/min/ 1.73 m2 did not show significant differences of corresponding AUC values for Scyst and Scr although there was a trend for superiority of Scyst in comparison with Scr. The multiples of upper reference values of Scyst and Scr in examined patients did not differ significantly. There was a highly significant linear correlation between Cin and Ccr in pre-dialysis patients (r = 0.921, p < 0.001). The regression coefficient of this relation (1.279) was significantly higher than 1.0 (p < 0.001) and the value of intercept (6.50 ml/min/1.73 m2) was significantly higher than zero (p < 0.001). The average of Ccr/Cin in patients with Cin 2 was 2.11 (± 0.29) and 1.72 (± 0.35) for those with Cin 10–20 ml/min/1.73 m2. Conclusions: The findings suggest that in patients with advanced chronic renal insufficiency (CRI) for the same decrease in GFR the increase of Scyst is not significantly higher than that of Scr, although the tubular secretion of creatinine is significantly increased. Further studies (especially those focused on nonrenal elimination of cystatin C) are needed to elucidate the lack of difference between changes in Scyst and Scr in patients with CRI.

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