Association between anemia and serum Klotho in middle-aged and older adults

Abstract

Background The role of Klotho as a multifunctional protein in anemia is unclear. This study aimed to determine the association between anemia and serum Klotho concentrations in middle-aged and elderly populations. Methods In this cross-sectional study, we used data collected from the National Health and Nutrition Examination Survey (NHANES) 2007-2016. A total of 13,357 individuals who received serum Klotho measurements, biochemical tests, and demographic surveys were analyzed. Multivariate linear regression models adjusting for covariates were used to investigate the associations between anemia and serum Klotho. Results Multivariable regression showed that serum Klotho correlates positively with hemoglobin and red blood cells and inversely with red cell distribution width. After adjusting for all covariates, compared with Q4, there was a significantly increased risk of anemia in serum Klotho quartiles 1 to 2 (OR=1.54, 95% CI:1.21-1.95, P=0.002; OR=1.30, 95% CI:1.02-1.64, P=0.042,respectively). Segmented regression showed that for every 100 pg/mL increase in serum Klotho <9.746 pg/mL, the risk of anemia was reduced by 10.9%, and this reduction was significant (P<0.001). Furthermore, stratified analyses yielded a stronger association between reduced anemia and high levels of Klotho in men and those with diabetes (P< 0.05 for interaction). However, this association was not found to be significantly altered by chronic kidney disease. Conclusions In summary, we indicated that low serum Klotho is associated with an increased likelihood of anemia using a nationally representative sample of middle-aged and older adults.

Association between serum Klotho levels and hypothyroidism in older adults: NHANES 2007–2012

“…Klotho is known as an anti-aging gene, and the expression of the Klotho gene decreases with age 35,36 . Moreover, many studies on Klotho in elderly-related diseases indicate that a decrease in serum Klotho levels may contribute to the prevalence of certain chronic conditions in the elderly population [37][38][39] . Therefore, it is speculated that a decrease in Klotho levels is unfavorable for inhibiting aging, and serum Klotho levels are negatively correlated with the prevalence of hypothyroidism in elderly individuals.…”

Anemia and Its Connections to Inflammation in Older Adults: A Review

“…Therefore, further studies on larger samples of elderly patients are necessary to confirm these findings [73]. A study by Chencheng et al [68] suggested that low serum Klotho levels were associated with an increased likelihood of anemia in middle-aged and older adults regardless of kidney disease.…”

“…The Klotho enzyme, which is mainly expressed in humans in the kidney and brain by the KL gene, especially its alpha-Klotho variant activated by fibroblast growth factor 23 (FGF23), has been indicated as another potential cause of inflammatory anemia in old age [66,67]. Most of the early as well as current studies have focused on the role of alpha-Klotho in chronic kidney disease (CKD) in elderly populations, and reported an age-related Klotho reduction and association with increased likelihood of anemia [68]. Klotho is involved in hematopoiesis regulation through its impact on the hypoxia-inducible factor (HIF1α) pathway.…”