The benchmark dose estimation of reference levels of serum urate for gout.

Hyperuricemia is the main risk factor for gout. Although the threshold of hyperuricemia has been recommended, the reference levels of serum urate for gout have not been clarified. In the present study, we estimated the reference levels of serum urate for gout. A study has shown the association between serum urate and incidence of gout during 5-15 years of follow-up. We calculated the reference levels of serum urate for gout based on the previous published data by using the benchmark dose (BMD) method. The subjects were divided into six groups according to serum urate levels (6.0, 6.5, 7.5, 8.5, 9.5, and 10 mg/dL). Gamma, LogLogistic, and LogProbit models were used in BMD calculation. If the benchmark response (BMR) was set at 5%, the 95% lower confidence bounds of BMD (BMDL) of serum urate for the total population were 8.09-8.14 mg/dL during 5 years of follow-up, 7.27-7.30 mg/dL during 10 years of follow-up, and 6.73-6.99 mg/dL during 15 years of follow-up. If the BMR was set at 1%, the BMDL further decreased by 1.4 mg/dL. They were 6.68-6.85 mg/dL, 5.97-6.03 mg/dL, and 5.25-5.36 mg/dL, respectively. Similar results were observed in men and women. A threshold of 7.0 mg/dL of serum urate may be not a sufficient goal for protection against gout. A stricter threshold of serum urate (< 6.0 mg/dL) should be made.