A prospective study of the association between serum klotho and mortality among adults with rheumatoid arthritis in the USA

Abstract Background While it is known that klotho has negative regulatory effects in a variety of diseases such as metabolic disorders and kidney disease, the specific role of klotho in rheumatoid arthritis (RA) and its effect on mortality are unclear. This study investigated the association between serum klotho levels and mortality in patients with RA. Methods This study included 841 adults with RA from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016 to extract the concentrations of serum klotho. The association between klotho and RA was determined using Cox regression, Kaplan–Meier (KM) curves, and restricted cubic spline (RCS) models. Results A total of 841 patients with RA were included in this study, who were divided into four groups based on the quartiles of serum klotho levels (Q1, Q2, Q3, and Q4). Cox regression analysis with adjustment for covariates revealed that high levels of klotho lowered the risk of both all-cause and cardiovascular mortality compared to the Q1 group. The KM curve analysis suggested that this effect was more pronounced for all-cause mortality. The RCS-fitted Cox regression model indicated a U-shaped correlation between serum klotho levels and RA mortality. The risk of all-cause mortality increased with decreasing serum klotho levels below a threshold of 838.81 pg/mL. Subgroup analysis revealed that the protective effect of klotho was more pronounced in patients with the following characteristics: male, white ethnicity, age ≥ 60 years, body mass index < 25 kg/m 2 , estimated glomerular filtration rate ≥ 60 mL/ (min × 1.73 m 2 ), and 25-hydroxyvitamin D level ≥ 50 nmol/L. Conclusion Serum klotho levels had a U-shaped correlation with all-cause mortality in patients with RA, indicating that maintain a certain level of serum klotho could prevent premature death.