Serum alpha-klotho levels associate with bone mineral density in chronic kidney disease patients from NHANES 2011 to 2016

Abstract

This study investigated the relationship between serum Alpha-Klotho (α-Klotho) levels and bone mineral density (BMD) in patients with chronic kidney disease (CKD) using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2016. A population of 781 CKD patients aged ≥ 40 years was analyzed using multiple linear regression models to examine the association between serum α-Klotho levels and BMD at different skeletal sites, with adjustments for demographic, lifestyle, and clinical factors. Results showed that serum α-Klotho levels were significantly correlated with BMD at thoracic spine (β = 0.004 g/cm², p = 0.00264), total BMD (β = 0.003 g/cm², p = 0.02591), and trunk BMD (β = 0.002 g/cm², p = 0.03708), while no significant associations were observed at the left leg, lumbar spine, or pelvis. Stratified analyses showed that the association was more pronounced in men, non-Hispanic whites, those with a body mass index greater than 29.9 kg/m², and those without hypertension and diabetes. The inconsistent associations observed across different skeletal sites suggest that it remains unclear whether serum α-Klotho levels are consistently associated with BMD in CKD patients. Additionally, the cross-sectional design precludes any determination of causality in the observed site-specific associations.

Keywords: Alpha-Klotho; Bone mineral density; Chronic kidney disease; NHANES.

Fig. 1

Participant Selection Flowchart for the Study Cohort. This study began with 29,902 participants from the NAHANSE 2011–2016 survey and sequentially excluded participants who did not meet the participants who did not meet the inclusion criteria. CKD was defined using KDIGO guideline criteria and calculated by the CKD-EPI formula.

Fig. 2

Correlation of serum α-klotho/100 levels with site-specific BMD. Analyzing linear and nonlinear relationships between α-Klotho and BMD using generalized additive models. The solid red line represents the smooth curve fit between variables. Blue bands represent the 95% confidence interval of the fit. Race, gender, age, education, income poverty ratio, alcohol, smoking, ALP, AST, ALT, total calcium, creatinine, globulin, phosphorus, hypertension, BMI, HGB, PLT, Hba1c, physical activity, dietary vitamin D, dietary calcium and 25(OH)vitamin D were adjusted.