Single Serum Urate Measurements Deemed Unreliable for Identifying Hyperuricemia

Hyperuricemia is associated with vascular, cardiac, and renal disease, as well as gout. However, the reliability of a single measurement in defining hyperuricemia is unclear.

Single data point serum urate (sUA) measurements were proven undependable in classifying hyperuricemia, defined as elevated uric acid levels in the blood, due to spontaneous variation, according to a study published in BCM Rheumatology.1 However, results showed that patients with an sUA of < 6.0 mg/dL were less likely to have future hyperuricemic measurements.

“In addition to its well-described role in the pathogenesis of gout, hyperuricemia (sUA > 6.8 mg/dL) is associated with vascular, cardiac and renal disease. This hyperuricemic threshold, or similar ones based on sUA distributions in populations of men and women, are commonly used in epidemiological and clinical research,” investigators stated. “However, the reliability of a single sUA measurement in defining hyperuricemia is unclear.”

Information was taken from the cross-over clinical trial Serum Urate Reduction to Prevent Hypertension (SURPHER) study to determine the efficacy of single data point sUA measurements in young adults without the presence of gout. Patients included in the study were between the ages of 18 and 40 years, had systolic blood pressure (SBP) ≥ 120 and < 160 mmHg or diastolic blood pressure (DBP) ≥ 80 and < 100 mmHg, and a sUA of ≥5.0 mg/dL for men or ≥ 4.0 mg/dL for women. The sUA levels were measured at baseline and then in 2-to-4-week intervals. After the first interval, patients either received allopurinol 300 mg daily or placebo. sUA was then measured again after a washout period, which ensured the dissipation of the effects of allopurinol. sUA measurements were ideally taken between 7 and 11 AM and patients were instructed to fast the day prior.

Investigators analyzed sUA levels at screening, pre-intervention, pre-placebo, and post-placebo. Mean coefficient of variation for sUA was compared across all cohorts and analyzed to detect any differences. Conversion rates from normouricemia (≤6.8 mg/dL) to hyperuricemia (> 6.8 mg/dL) and from hyperuricemia to normouricemia were calculated and compared across subgroups.

In total, 85 participants completed all 4 sUA measurements. The mean age was 27.8 years, 39% were female, and 41% were African American. Unfortunately, of the 76% of patients in which time of day data was available, 84% were measured outside of the 4-hour timeframe.

Variation in sUA was 8.5% ± 4.9% (1 to 23%) and there was no significant difference between men (8.5%) and women (8.6%) (p = 0.88) or between those normouricemic (8.6%) and hyperuricemic (8.0%) (p = 0.68) at baseline. For patients in the normouricemic group, 21% were hyperuricemic at 1 or more follow-up visits. Initial sUA levels of < 6.0 (n = 54) were significantly less likely to have hyperuricemia when compared with participants with sUA levels between 6.0-6.8 (n = 18) (7% vs 39%, respectively). In patients with hyperuricemia at baseline, 46% were normouricemic at 1 or more follow-up.

While the small sample size was limiting, it may inspire larger studies in the future. The initial screening of sUA was not standardized to a certain time of day and several measurements were taken outside of the 2-to-4-week intervals, which may have impacted results, as concentration levels are higher in the morning. As participants were younger, it could limit generalizability to older patients. Allopurinol and placebo dosing may have affected results as well, but investigators minimized that chance by confirming dissipation of allopurinol with a 2-sample t-test. Finally, the SURPHER criteria required initial sUA of ≥5.0 mg/dL for men and ≥ 4.0 mg/dL for women, thus excluding patients with lower sUA levels.

“Our data is consistent with previous studies which have found significant variation in sUA levels over time, even when controlling for commonly identified influencers of sUA levels,” investigators concluded. “Future studies could examine the reliability of sUA checks in those with gout, as well as those on urate-lowering therapy (ULT), to determine whether a treat-to-target approach for gout flare suppression may be subject to these same fluctuations in sUA levels.”

Reference:

Shaffer A, Rahn E, Saag K, Mudano A, Gaffo A. Variation in serum urate levels in the absence of gout and urate lowering therapy. BMC Rheumatol. 2021;5(1):32. Published 2021 Sep 8. doi:10.1186/s41927-021-00202-6