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

Objective: 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.

Design: Cross-sectional study.

Methods: 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).

Results: 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).

Conclusion: 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.