Beyond Uric Acid: Allantoin Reflects Oxidative Stress, Disease Burden, and Cardiovascular Comorbidities in Hyperuricemia and Gout.

Objectives

Uric acid (UA) can be non-enzymatically oxidized to allantoin and other products by reactive oxygen species under conditions of increased oxidative stress. This study assessed serum allantoin levels and the allantoin/UA ratio in patients with gout and asymptomatic hyperuricemia, with respect to disease severity and cardiovascular comorbidities.

Methods

Clinical and biochemical data were collected from 154 patients with gout, 55 individuals with asymptomatic hyperuricemia, and 47 healthy controls. Allantoin was quantified using a fully validated UHPLC-MS/MS method. Associations with clinical outcomes were evaluated using logistic regression adjusted for eGFR, age, and sex.

Results

Serum allantoin levels and the allantoin/UA ratio were significantly higher in patients compared to controls (p < 0.001), with no difference between the gout and hyperuricemia groups. Allantoin correlated with renal function (eGFR: r = -0.25, p < 0.001) and CRP (r = 0.22, p = 0.001), both of which remained independent predictors in multivariable analysis, whereas UA did not (p = 0.14). In adjusted logistic regression, allantoin was independently associated with tophi (OR 2.34, p = 0.050) and arterial hypertension (OR 2.26, p = 0.046), with a borderline association with gout flares (OR 2.52, p = 0.053). These estimates remained unchanged after additional adjustment for UA, indicating that allantoin reflects oxidative processes beyond substrate availability.

Conclusion

Serum allantoin and the allantoin/UA ratio are elevated in hyperuricemia and gout, particularly in patients with tophaceous disease or concomitant arterial hypertension. After adjustment for renal function, age, and sex, allantoin remains independently associated with disease severity and cardiovascular comorbidity, supporting its role as a marker of oxidative stress burden.