Soluble alpha klotho-impact of biological variables and reference intervals for adults

Concentrations of soluble alpha klotho (sαKL) are higher in active acromegaly compared with healthy controls. However, reference intervals based on large population-based samples are lacking, and the impact of many biological variables is unclear.

Cross-sectional study.

We measured sαKL concentrations in samples from an adult population (20-89 years, 435 males, 455 females). Associations with sex, age, body mass index, waist-hip-ratio, estimated glomerular filtration rate (eGFR), IGF-I and IGFBP 3, glucose-, lipid-, calcium- and liver-metabolism, fasting, and estrogen status were analyzed. Reference intervals were calculated using LMS quantile regression with a Box-Cox transformation to normality. We also analyzed sαKL in patients with non-functioning pituitary adenoma (NFPA, n = 18) and prolactinoma (n = 65).

Across all ages, sαKL concentrations (pg/mL, median [interquartile ranges]) were slightly, but significantly higher in females compared with males (678 (537-859) vs. 651 (537-812), P = .01), suggesting an impact of estrogens. SαKL exhibited a weak negative correlation with age, and positive correlations with eGFR and IGF-I (P < .001 for both). Correlations to other biological factors including glucose, liver and calcium metabolism and duration of fasting were negligible (P > .05 for all). Compared with sαKL, IGF-I more often was correlated significantly to other biological variables. SαKL was not different in patients with NFPA, but slightly higher in patients with prolactinoma (P < .05).

Our findings suggest sαKL is a stable GH-sensitive biomarker that may be less impacted by biological variables compared with IGF-I and IGFBP 3. Our reference intervals will facilitate the potential use of sαKL in GH-related diseases.