Interferences of homogentisic acid (HGA) on routine clinical chemistry assays in serum and urine and the implications for biochemical monitoring of patients with alkaptonuria

Curtis, S.L.; Roberts, Norman B.; Ranganath, L.R.

doi:10.1016/j.clinbiochem.2013.12.016

Cited by 21 publications

(12 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been shown previously that the presence of HGA in the urine and serum interfere with standard urine creatinine enzymatic assays for kidney dysfunction [16], our present results might indicate that CysC assays is not suitable in case of AKU too, due to the high CatD. Although these results need further verification, they indicate how the proposed ApreciseKUre database can be used as an useful tool in the future for becoming aware of the failure of biomarkers clinically used and for improving the detection of more exploitable prognostic biomarkers.…”

Section: Utility and Discussionmentioning

confidence: 99%

ApreciseKUre: an approach of Precision Medicine in a Rare Disease

Spiga

Cicaloni

Bernini

et al. 2017

BMC Med Inform Decis Mak

View full text Add to dashboard Cite

BackgroundAlkaptonuria (AKU; OMIM:203500) is a classic Mendelian genetic disorder described by Garrod already in 1902. It causes urine to turn black upon exposure to air and also leads to ochronosis as well as early osteoarthritis.Main body of the abstractOur objective is the implementation of a Precision Medicine (PM) approach to AKU. We present here a novel ApreciseKUre database facilitating the collection, integration and analysis of patient data in order to create an AKU-dedicated “PM Ecosystem” in which genetic, biochemical and clinical resources can be shared among registered researchers. In order to exploit the ApreciseKUre database, we developed an analytic method based on Pearson’s correlation coefficient and P value that generates as refreshable correlation matrix. A complete statistical analysis is obtained by associating every pair of parameters to examine the dependence between multiple variables at the same time.Short conclusionsEmploying this analytic approach, we showed that some clinically used biomarkers are not suitable as prognostic biomarkers in AKU for a more reliable patients’ clinical monitoring. We believe this database could be a good starting point for the creation of a new clinical management tool in AKU, which will lead to the development of a deeper knowledge network on the disease and will advance its treatment. Moreover, our approach can serve as a personalization model paradigm for other inborn errors of metabolism or rare diseases in general.Electronic supplementary materialThe online version of this article (doi:10.1186/s12911-017-0438-0) contains supplementary material, which is available to authorized users.

show abstract

Section: Utility and Discussionmentioning

confidence: 99%

ApreciseKUre: an approach of Precision Medicine in a Rare Disease

Spiga

Cicaloni

Bernini

et al. 2017

BMC Med Inform Decis Mak

View full text Add to dashboard Cite

show abstract

“…As part of the robustness analysis, we also investigated, following indications from previous literature (Curtis et al 2014), whether the presence of high concentration of HGA in the urine of AKU patients could interfere with the enzymatic reaction of the creatininase used in the creatinine a Biomarkers measured in ng/ml except CTX-I/Cre and CTX-II/Cre, mg/mmol creatinine assay and of the peroxidase used in the ELISAs. The correlation analysis of the creatinine levels measured with a creatininase-based assay and a Jaffé-based assay, which is not influenced by HGA, demonstrated that high urinary HGA levels interfere with the creatininase, leading to a lower signal and an underestimation of creatinine concentration.…”

Section: Discussionmentioning

confidence: 99%

Investigating the Robustness and Diagnostic Potential of Extracellular Matrix Remodelling Biomarkers in Alkaptonuria

et al. 2015

View full text Add to dashboard Cite

show abstract

“…For the remaining samples, the observed differences may be partially attributable to systemic differences between different reagents or other unknown interference factors in the serum samples. A number of substances may interfere with creatinine quanti cation using enzymatic assays [24][25][26][27][28][29]. For some patients with large deviating Cr-R and Cr-C assay results who did not have detectable serum CaD, we evaluated the patient's medical records and compared the creatinine levels with those determined by the reference method and identi ed ten cases where this discrepancy may have been caused by the presence of etamsylate.…”

Section: Discussionmentioning

confidence: 99%

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

Guo¹,

Hou²,

Lu³

et al. 2020

Preprint

View full text Add to dashboard Cite

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.

show abstract

Interferences of homogentisic acid (HGA) on routine clinical chemistry assays in serum and urine and the implications for biochemical monitoring of patients with alkaptonuria

Cited by 21 publications

References 17 publications

ApreciseKUre: an approach of Precision Medicine in a Rare Disease

ApreciseKUre: an approach of Precision Medicine in a Rare Disease

Investigating the Robustness and Diagnostic Potential of Extracellular Matrix Remodelling Biomarkers in Alkaptonuria

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

Contact Info

Product

Resources

About