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

Abstract

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.

Creatinine in urine – a method comparison

“…Knowledge of the reliability of such a portable device may help the investigator on‐site, for example during roadside testing, to decide if an additional blood test to detect drugs of abuse is advisable. We refrained from testing the urine samples with an enzymatic assay using the Trinder Reaction, as various substances such as N‐acetylcysteine (NAC), calcium dobesilate, acetaminophen and the metabolite N‐acetyl‐p‐benzoquinone, metamizole, and the metabolites 4‐aminoantipyridine (4‐AAP) and 4‐methylaminoantipyrine (4‐MAP) cause falsified results for Trinder‐based assays . Acetaminophen and metamizole are often present in the studied population.…”

“…We refrained from testing the urine samples with an enzymatic assay using the Trinder Reaction, as various substances such as N-acetylcysteine (NAC), calcium dobesilate, acetaminophen and the metabolite N-acetyl-pbenzoquinone, metamizole, and the metabolites 4aminoantipyridine (4-AAP) and 4-methylaminoantipyrine (4-MAP) cause falsified results for Trinder-based assays. [5][6][7] Acetaminophen and metamizole are often present in the studied population.…”

Diabetic Nephropathy Can Be Treated with Calcium Dobesilate by Alleviating the Chronic Inflammatory State and Improving Endothelial Cell Function

“…But research using big data suggests that CaD does not affect the Cys C assay; thus, the use of Cys C is proposed for the assessment of renal function levels in patients using CaD. Cys C is commonly used as an indicator for assessing renal function and may be more sensitive than the traditional method [43]. Given that CaD interferes with the enzymatic assay of creatinine, we used Cys C and the GFR calculated using the CKD-EPI Cys C equation to assess renal function.…”

Negative interferences by calcium dobesilate in the detection of five serum analytes involving Trinder reaction-based assays

“…However, due to the poor substrate specificity of catalytic peroxidase for the Trinder reaction, multiple substances, such as ascorbic acid [ 1 , 2 ], etamsylate [ 3 ], N-acetylcysteine [ 4 ], and bilirubin [ 5 ], can interfere with the assay’s results. Recently, we confirmed that the medication calcium dobesilate produces significant negative interferences with the determination of creatinine using sarcosine oxidase-based assays, and the extent of interference differs significantly among the different assay systems [ 6 ].…”

“…The influence of drugs on the results of clinical testing is a common but often overlooked problem. As described in detail previously [ 6 ], calcium dobesilate (calcium 2,5-dihydroxybenzenesulfonate) is a vasoprotectant [ 7 ] that is widely used to treat diabetic retinopathy [ 8 ], chronic venous insufficiency [ 9 ], and various microangiopathy [ 10 ]. Recent studies have revealed its protective effects on diabetic nephropathy [ 11 ] and gentamicin-induced acute kidney injury [ 12 ] and have suggested potential protective effects against intestinal ischaemia-reperfusion injury by increasing antioxidant capacity [ 13 ].…”