ALLANTOIN - A BIOMARKER OF OXIDATIVE STRESS - IS HIGHER IN PATIENTS WITH GOUT THAN IN HEALTHY VOLUNTEERS, AND CORRESPONDS WITH SEVERITY OF DISEASE

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 both in vitro and in vivo . In gout patients, significantly increased plasma levels of allantoin have been found compared to healthy controls . 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 method and 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 before . 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) . REFERENCES: [1]Marrocco I, Altieri F, Peluso I Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans. Oxidative med and cell. longev. 2017:6501046. [2]Stamp LK, Turner R, Khalilova IS, Zhang M, Drake J, Forbes LV, Kettle AJ. Myeloperoxidase and oxidation of uric acid in gout: implications for the clinical consequences of hyperuricaemia. Rheumatology (Oxford, England) 53 (11):1958-1965 [3]Kozlik P, Hasikova L, Stiburkova B, Zavada J, Kalikova K. Rapid and reliable HILIC-MS/MS method for monitoring allantoin as a biomarker of oxidative stress. Anal. Biochem. 2020 Jan 15; 589:113509 [4]Perez-Ruiz F, Martinez-Indart L, Carmona L, Herrero-Beites AM, Pijoan JI, Krishnan E. Tophaceous gout and high level of hyperuricaemia are both associated with increased risk of mortality in patients with gout. Ann Rheum Dis. 2014 Jan; 73(1):177-182. Acknowledgments: This work was supported by the project (Ministry of Health, Czech Republic) for consensual development of research organization 00023728 (Institute of Rheumatology). Disclosure of Interests: Lenka Hasikova: None declared, Petr Kozlik: None declared, Kveta Kalikova: None declared, Blanka Stiburkova: None declared, Jakub Zavada Speakers bureau: Abbvie, UCB, Sanofi, Elli-Lilly, Novartis, Zentiva, Accord Citation: Ann Rheum Dis, volume 79, supplement 1, year 2020, page 128Session: Inflammation and crystal diseases – what’s hot? (Oral Presentations)