Biomarkers may Provide Risk Prediction, Early Diagnosis in Gouty Arthritis

Out of a total of 150 analyzed serum samples from patients with acute gouty arthritis (AGA), hyperuricemia (HUA), and healthy controls, investigators identified 23 serum metabolic markers related to AGA and HUA. The findings indicate that the progression of disease may have biomarker involvement, which may aid in risk prediction and early diagnosis, according to a study published in Journal of Orthopaedic Surgery and Research.¹

“Metabonomics is a biological technology used to identify the global metabolic spectrum of endogenous small molecular substances,” investigators explained. “In recent years, metabonomics has been widely used in disease diagnosis and detection, which is of great significance to understand the pathogenesis of disease.”

Patients who went to the outpatient and inpatient clinics of the General Hospital of Western Theater Command, China, between August 2019 and June 2020, were invited to participate in the study. HUA was defined as blood uric acid > 420 µmol/L (7.0 mg/dL) in both fasting men and postmenopausal women and > 360 µmol/L (6.0 mg/dL) in women under a normal purine diet.

Investigators used gas chromatography/liquid chromatography-mass spectrometry (GC/LC-MS) to evaluate changes of serum metabolites from healthy controls to HUA to AGA to determine the pathophysiological mechanism and biological markers.

Fifty samples were included from each group, with statistically significant differential metabolites collected by combining multidimensional analysis and 1-dimensional analysis. Selected metabolites were searched in the KEGG database to analyze metabolic pathways and create a metabolic pathway map.

The ages of all groups were matched and all participants were male. Among the HUA and AGA groups, uric acid levels were high and both had normal renal function.

After multivariate analysis, metabolites were noted as potential biomarkers of AGA and HUA. A total of 23 different serum metabolic markers related to AGA and HUA were identified using metabonomics technology. According to a database search and literature review, most markers were related to uric acid metabolism and inflammatory response caused by AGA and HUA.

Interestingly, 3 biomarkers, kynurenic acid, thymine, and phosphatidylinositol (PI), were different from previous gout research. Nine metabolites with different trends from standard inflammation were identified, which may become specific biomarkers of high uric acid and gout.

Analysis showed that most metabolites have significant differences between AGA and HUA and serum concentration levels were opposite to the healthy control cohort. These findings are consistent with previous research that reported a lower serum uric acid concentration in patients with AGA when compared with HUA, which may be related to an increase in urinary acid excretion.²

“With the continuous innovation of metabonomics technology and the improvement of people's requirements for quality of life, scholars pay more attention to the early diagnosis of various diseases,” investigators concluded. “As a new screening technique, metabonomics has been used in the diagnosis of diseases and clinical application. In general, these potential biomarkers found in our study have important biological significance for the diagnosis of HUA and AGA.”

References

1. ^{Wang W, Kou J, Zhang M, et al. A metabonomic study to explore potential markers of asymptomatic hyperuricemia and acute gouty arthritis. J Orthop Surg Res. 2023;18(1):96. Published 2023 Feb 13. doi:10.1186/s13018-023-03585-z}
2. ^{Urano W, Yamanaka H, Tsutani H, et al. The inflammatory process in the mechanism of decreased serum uric acid concentrations during acute gouty arthritis. J Rheumatol. 2002;29(9):1950–3.}