A new method for anti-negative interference of calcium dobesilate in serum creatinine enzymatic analysis.

BACKGROUND: Serum creatinine is a widely used biomarker for evaluating renal function. Sarcosine oxidase enzymatic (SOE) analysis is currently the most widely used method for the detection of creatinine. This method was negatively interfered with by calcium dobesilate, causing pseudo-reduced results. The aim of this study was to explore a new method to alleviate the negative interference of this drug on creatinine detection. METHOD: We formulated eight drug concentrations and 12 creatinine concentrations from serum. The SOE method, the new method, and the Jaffe method were used for detection in five systems. Creatinine biases were analyzed under the conditions with or without the interference of calcium dobesilate, at consistent or inconsistent creatinine concentrations. Creatinine concentrations were also analyzed at three medical decision levels (MDLs). RESULTS: Calcium dobesilate had negative interference in creatinine SOE analysis. With the increase in calcium dobesilate concentrations, the negative bias increases. The new BG method showed an anti-negative interference effect. In the Roche system, the BG method reduced the negative bias from -71.11% to -16.7%. In the Abbott system, bias was reduced from -45.15% to -2.74%. In the Beckman system, the bias was reduced from -65.36% to -7.58%. In the Siemens system, the bias was reduced from -58.62% to -7.58%. In the Mindray system, the bias was reduced from -36.29% to -6.84%. CONCLUSION: The new method alleviated the negative interference of calcium dobesilate in creatinine SOE detection. The negative bias could be reduced from -60% or -70% to less than -20%.

Strong Negative Interference by Calcium Dobesilate in Sarcosine Oxidase Assays for Serum Creatinine Involving the Trinder Reaction.

The vasoprotective drug calcium dobesilate is known to interfere with creatinine (Cr) quantifications in sarcosine oxidase enzymatic (SOE) assays. The aim of this study was to investigate this interference in 8 different commercially available assays and to determine its clinical significance. In in vitro experiments, interference was evaluated at 3 Cr levels. For this, Cr was quantified by SOE assays in pooled serum supplemented with calcium dobesilate at final concentrations of 0, 2, 4, 8, 16, 32, and 64 µg/mL. Percent bias was calculated relative to the drug-free specimen. For in vivo analyses, changes in serum concentrations of Cr, cystatin C (CysC; a renal function marker), and calcium dobesilate were monitored in healthy participants of group I before and after oral calcium dobesilate administration. In addition, variations in interference were also examined among different SOE assays using serum obtained from healthy participants of group II. Lastly, Cr levels from the 10 patients treated with calcium dobesilate were measured using 4 SOE assays and liquid chromatography-isotope dilution tandem mass spectrometry (LC-IDMS/MS) for comparison. Our in vitro analyses indicated that the presence of 8 µg/mL calcium dobesilate resulted in a -4.4% to -36.3% reduction in Cr serum concentration compared to drug-free serum for 8 SOE assays examined. In vivo, Cr values decreased relative to the baseline level with increasing drug concentration, with the lowest Cr levels obtained at 2 or 3 hours after drug administration in participants of group I. The observed Cr concentrations for participants in group II were reduced by -28.5% to -3.1% and -60.5% to -11.6% at 0 and 2 hours after administration related to baseline levels. The Cr values of 10 patients measured by Roche, Beckman, Maker, and Merit Choice SOE assays showed an average deviation of -20.0%, -22.4%, -14.2%, and -29.6%, respectively, compared to values obtained by LC-IDMS/MS. These results revealed a clinically significant negative interference with calcium dobesilate in all sarcosine oxidase-based Cr assays, but the degree of interference varied greatly among the assays examined. Thus, extra care should be taken in evaluating Cr quantification obtained by SOE assays in patients undergoing calcium dobesilate therapy.