OBJECTIVES: Both dimethylarginines are widely bound to chronic kidney disease (CKD). This study was focused to validate published LC-MS/MS method and compared the measured data with an immunoassay. DESIGN AND METHODS: The analysis was performed on a Dionex UltiMate 3000 UHPLC-Standard (Thermo Fisher Scientific, Waltham, Massachusetts, USA) with an amaZon SL ion trap (Bruker, Billerica, Massachusetts, USA). Comparison was evaluated by using Passing Bablok regression and Bland Altman plot. Healthy volunteers (n = 40) were used for validation and as control group to patients group (n = 40) with different stages of CKD. RESULTS: The results in healthy controls determined by the LC-MS/MS (ELISA) method were 0.52 ± 0.0892 with 95 % CI: 0.49-0.55 (0.61 ± 0.1213 with 95 % CI: 0.57-0.64) μmol/L for AD MA and 0.56 ± 0.0810 with 95 % CI: 0.53-0.58 (0.62 ± 0.0752 with 95 % CI: 0.57-0.65) μmol/L for SDMA. In the same way, the patient group values determined by the LC-MS/MS (ELISA) method were 0.82 ± 0.1604 with 95 % CI: 0.75-0.88 (1.06 ± 0.3002 with 95 % CI: 0.94-1.19) μmol/L and 2.14 ± 0.8778 with 95 % CI: 1.47-2.58 (1.65 ± 0.5160 with 95 % CI: 1.40-1.98) μmol/L for ADMA and SDMA, respectively. The correlation between the methods, expressed as the Spearman correlation coefficient (R), was 0.858 (0.8059) for ADMA (p < 0.0001) and 0.895 (0.9607) for SDMA (p < 0.0001). CONCLUSIONS: ADMA levels determined by the immunoassay were almost 30 % overestimated, in contrast to SDMA levels, which were 3 % underestimated. According to our findings, a better correlation could be obtained by simple sample dilution.
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INTRODUCTION: Multisystem inflammatory syndrome in children (MIS-C) is a new clinical entity that has emerged in the context of the COVID-19 pandemic. Despite the less severe course of the disease, varying degrees of cardiovascular events may occur in MIS-C; however, data on vascular changes occurring in MIS-C are still lacking. Endothelial dysfunction (ED) is thought to be one of the key risk factors contributing to MIS-C. BACKGROUND: We conducted a prospective observational study. We investigated possible manifestations of cardiac and endothelial involvement in MIS-C after the treatment of the acute stage and potential predictive biomarkers in patients with MIS-C. METHODS: Twenty-seven consecutive pediatric subjects (≥9 years), at least three months post-treated MIS-C of varying severity, in a stable condition, and twenty-three age- and sex-matched healthy individuals (HI), were enrolled. A combined non-invasive diagnostic approach was used to assess endothelial function as well as markers of organ damage using cardiac examination and measurement of the reactive hyperemia index (RHI), by recording the post- to pre-occlusion pulsatile volume changes and biomarkers related to ED and cardiac disease. RESULTS: MIS-C patients exhibited a significantly lower RHI (indicative of more severe ED) than those in HI (1.32 vs. 1.80; p = 0.001). The cutoff of RHI ≤ 1.4 was independently associated with a higher cardiovascular risk. Age and biomarkers significantly correlated with RHI, while serum cystatin C (Cys C) levels were independently associated with a diminished RHI, suggesting Cys C as a surrogate marker of ED in MIS-C. CONCLUSIONS: Patients after MIS-C display evidence of ED, as shown by a diminished RHI and altered endothelial biomarkers. Cys C was identified as an independent indicator for the development of cardiovascular disease. The combination of these factors has the potential to better predict the cardiovascular consequences of MIS-C. Our study suggests that ED may be implicated in the pathophysiology of this disease.
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