Abstract

Background:Uric acid can be non-enzymatically oxidized into allantoin and other products by reactive oxygen species. Allantoin has emerged as a reliable biomarker for monitoring oxidative status bothin vitroandin vivo1. In gout patients, significantly increased plasma levels of allantoin have been found compared to healthy controls2.Objectives:The aim of this pilot study was to measure allantoin as a biomarker of oxidative stress in patients with gout using newly developed UHPLC-HILIC-MS/MS method3and to investigate whether the allantoin levels are higher in patients with more severe disease (tophaceous gout).Methods:We used clinical data and frozen serum (-80°C) from 10 patients with chronic tophaceous gout, 10 patients with chronic gout without tophi and 10 healthy controls. Allantoin was determined in serum with sensitive UHPLC-MS/MS method using an isotopically labeled internal standard as we described before3. In addition, the concentrations of serum CRP, creatinine and uric acid were measured. Data are summarized as medians with interquartile range [IQR]. Differences between two patient groups were evaluated using the Wilcoxon signed-rank test.Results:The median concentrations of allantoin in the serum from patients with tophaceous gout were significantly higher than in patients with gout without tophi (4.2 [2.6] vs. 3.2 µM [1.5], p = 0.0273). There was no significant difference in other biochemical or demographic parameters (CRP, uric acid, creatinine, BMI, weight) between these two groups. Allantoin levels in healthy controls were significantly lower (0.5 vs. 4.2 [2.6], p = 0.0020, 0.5 vs. 3.2 [1.5], p < 0.0001) (Fig. 1).Fig. 1.Box plots of allantoin concentration in patients with tophaceous gout with tophi, without tophi and in healthy controls.Conclusion:We have observed significantly higher levels of serum allantoin in the patients with more advanced gout with tophi compared with the patients with chronic gout without tophi. We have found elevated values of allantoin in both groups in comparison with healthy controls. In our small cohort the level of allantoin correspond with the severity of disease presented by tophi. However, further studies in large cohorts are needed. We can speculate, whether higher level of oxidative stress may contribute to increased cardiovascular risk and mortality in patients with gout (and more so in severe gout)4.

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