Multicentre Evaluation of a Newly Developed Anti-Calcium Dobesilate-Enzymatic Creatinine Assay Based on Real-World Data in China

Abstract

BackgroundPreviously, we reported that calcium dobesilate (CaD), a vasoprotective agent mainly used for diabetic retinopathy, negatively interferes with enzymatic creatinine assays. Anewly developed enzymatic creatinine assay, the “Cr-R assay”, is commercially available and claims to have no interference from CaD. This study aimed to verify the performance of the Cr-R assay on clinical samples and to investigate the degree of CaD interference in a multicentre, real-world study.MethodsThe precision and accuracy ofthe Cr-R assay was evaluated in 23 hospitals in different regions of China. Interference was then calculated both in vitro and in clinical samples. Samples with potential interference were screened based on the different creatinine results between Cr-R and the creatinine assays commonly used in each participating hospital (Cr-C). Interference was confirmed by determining serum CaD concentration by directly using ultra-performance liquid chromatography (UPLC) methodand by assessing the “true” creatinine levels using the standard isotope dilution mass spectrometry (ID-MS/MS) method. ResultsTheprecision and bias and anti-interference ability of Cr-R assay on most platforms fulfilled the specification criteria. In the clinical setting, 67,469 samples were tested in 23 centres, and CaD concentration was measured in 818 samples, of which 257 contained CaD, accounting for 0.38% of the total and 31% of screened patients. In these 257 cases, the median CaD concentration was 11.356 (range, 1.350–121.519; IQR, 7.162–21.175) μg/mL. Creatinine levels measured using Cr-C assay were up to 35.1% (95%CI, 37.9–32.4 %; P < 0.001) lower than the “real” creatinine levels using the ID-MS/MSmethod. For Cr-R reagent, the average bias from the reference method was -6.2% (95%CI, -7.9–4.6%; P < 0.001), ranging from -17.9% to 7.1%.ConclusionsMulticentre tests confirmed that the precision, bias, and anti-CaD ability of the Cr-R assay met clinical needs. The prevalence of CaD interference should be considered when performing clinical enzymatic creatinine measurements.Other manufacturers should improve the anti-interference performance of creatinine reagents.