Low serum urate levels are not associated with increased mortality risk during urate-lowering treatment in patients with gout

Aim: To study whether very low serum urate (sUA) levels are associated with increased mortality rate during urate-lowering therapy (ULT). Methods: This study analyzed data from a bidirectional cohort of gout patients. General variables (age, gender), disease variables (time from onset, number of flares, number of joints involved, tophi, previous and prescribed ULT, sUA levels at baseline and during follow-up), and comorbid conditions such as hypertension, hyperlipidemia, diabetes, chronic renal disease, previous vascular event, along with a comorbidity index were available for analysis. Very low sUA (< 3 mg/dL) was specifically pursued during ULT for patients with the most severe gout, i.e., polyarticular and tophaceous gout. Results: sUA levels during therapy were available from 1,618 patients with a mean follow-up period of 43.6 months. Univariate survival analysis showed that female gender, age, baseline sUA, sUA during follow-up, polyarticular joint involvement, hypertension, diabetes, previous vascular event, CKD, comorbidity, and tophaceous disease were associated with increased risk of mortality. sUA strata were associated with mortality only in the higher range, outside the therapeutic target. Multivariate survival analysis showed that age, gender, comorbidity, presence of subcutaneous tophi, sUA levels at baseline, and sUA strata during ULT were independently associated with increased risk of mortality. There was no difference between patients with sUA under or over 3 mg/dL but within the therapeutic range (< 6 mg/dL), but there was increased mortality in patients out of the therapeutic range, especially for those over 9 mg/dL. Conclusions: Very low sUA levels during ULT, at least for a limited period of time during urate-lowering debulking therapy, are not associated with increased mortality in patients with gout, while high sUA (6–8.9 mg/dL) and especially the highest (≥ 9 mg/dL) are associated with increased mortality.