Background: Cystatin C (Cys C) is measured by particle-enhanced nephelometric immunoassay (PENIA), particle-enhanced turbidimetric immunoassay (PETIA) and ELISA. Aim: To determine differences among these methods. Method: 80 normal human sera and 20 from patients with renal and/or heart disease were simultaneously assayed. Statistical analyses including receiver operating characteristics (ROC) of the three methods were compared. Results: There was a highly significant correlation across the assay range between the ELISA and PENIA (r2 = 0.94) and PETIA methods (r2 = 0.95). Analysis of variance and bias were poor between the ELISA and the other two methods. Mean difference between ELISA and PETIA was 0.65 ± 0.63 μg/ml, while it was 0.58 ± 0.53 μg/ml between ELISA and PENIA. Accuracy (at 30% range) was 17 and 11% between ELISA and PETIA and ELISA and PENIA, respectively. Normalization of the ELISA by a factor of 0.66 improved this relationship. AUC of ROC curves of PENIA, ELISA and normalized ELISA to predict Cys C levels measured from PETIA were all above 0.87 (p = not significant between curves). Criterion values of ELISA*.66 method was close to PETIA measurements. Conclusion: There is a significant difference in measured human Cys C levels among the three methods, and normalization of ELISA narrows these differences.

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