Copyright: © 2022 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
This study investigated the association between hyperuricemia and serum klotho protein levels in a representative sample of adults in the United States. We included 11,734 adults aged 40–80 years with available data of serum klotho, uric acid, covariates related to demographics, health behavior-related variables, and medical histories. Hyperuricemia was defined as a serum uric acid level of ≥7.0 mg/dL in men and ≥6.0 mg/dL in women. The geometric mean of serum klotho was 806.5 pg/mL (95% confidence interval: 801.7–811.4). The log-klotho level was negatively correlated with the uric acid level (r = −0.154; p < 0.0001). After adjustment for potential covariates, each one-unit increase in uric acid was significantly associated with a decrease in the log-klotho level (adjusted beta = −0.028; p < 0.0001). Compared with subjects without hyperuricemia, those with hyperuricemia had significantly lower serum klotho levels (adjusted beta = −0.062; p < 0.0001). We found a significant inverse association between serum uric acid and serum klotho levels in the general population, that is, an increase in serum uric acid levels was associated with a decrease in klotho levels. This finding suggests that loss of klotho may be due to the progression of hyperuricemia or, subsequently, gout.