Research Paper Volume 14, Issue 6 pp 2537—2547

Association between serum uric acid and α-klotho protein levels in the middle-aged population

Hyo-Jung Lee1, , Ju-Young Choi1, , Jaeho Lee1,4, , Donghoon Kim1,4, , Jin-Young Min2, , Kyoung-Bok Min1,3,4, ,

  • 1 Department of Preventive Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea
  • 2 Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul, Republic of Korea
  • 3 Institute of Health Policy and Management, Medical Research Center, Seoul National University, Seoul, Republic of Korea
  • 4 Institute Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, Republic of Korea

Received: December 2, 2021       Accepted: March 14, 2022       Published: March 29, 2022
How to Cite

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.


AKI: acute kidney injury; BMI: body mass index; CI: confidence interval; CKD: chronic kidney disease; eGFR: estimated glomerular filtration rate; ELISA: enzyme-linked immunosorbent assay; FGF23: fibroblast growth factor-23; NCHS: National Center for Health Statistics; NHANES: National Health and Nutrition Examination Survey; PTH: parathyroid hormone; SE: standard error.