Measurement of Cystatin C in Dried Blood Spot Specimens

Abstract

Dried blood spot (DBS) technologies can be used in a variety of clinical and research settings. Among other advantages, the use of DBS specimens facilitate the incorporation of biomarkers into demographic research, especially for large global studies conducted in remote areas with little or no laboratory infrastructure. Here, we report the results of an evaluation of a new method for measuring cystatin C (cysC) in DBS. We adapted a commercial ELISA kit designed to measure cysC in human plasma and were able to measure cysC concentrations across the physiologic range in DBS. Determinations from DBS were linearly correlated and near directly equivalent to cysC concentrations in DBS-matched plasma--intercept=-0.07 (95% confidence interval=-0.17to -0.01) and slope=0.98 (95% confidence interval=0.92 to 1.12), R=0.94. Bland Altman analysis of cysC concentrations in DBS vs. plasma revealed no bias and acceptable levels of agreement (Bias -0.02, 95% confidence interval=-0.21 to 0.17). The DBS-ELISA demonstrates utility as a screening tool; sensitivity and specificity for cysC concentrations outside the upper limit of the reference interval (0.51 mg/L to 1.02 mg/L) were 68% and 95% respectively; however, the DBS-ELISA had difficultly correctly assigning CKD stage from DBS. We further describe an intra-donor difference in cysC concentration between venous blood collected from venipuncture and capillary blood collected by fingerstick. The DBS-ELISA assay provides an opportunity to explore kidney function in large community-based studies.