The Effect of Growth Hormone Treatment on Klotho Blood Levels in Children with Growth Hormone Deficiency 

Presentation Number: OR40-6
Date of Presentation: April 4th, 2016

Ido Wolf1, Tami Rubinek1, Shiri Shahmoon1, Yael Levy-Shraga2, Michal Ben Ami2, Yonatan Yeshayahu2, Ram Doolman3, Rina Hemi4, Hannah Kanety5 and Dalit Modan-Moses*2
1Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, 2The Edmond and Lily Safra Children's Hospital, Ramat Gan, Israel, 3Sheba Medical Center, Ramat Gan, Israel, 4Chaim Sheba Medical Center, Ramat-Gan, 5Chaim Sheba Medical Center, Ramat Gan, Israel

Abstract

Objective: Klotho is an aging-mudulating protein expressed mainly in the kidneys, which can be cleaved and shed from the membrane to act as a hormone. Several lines of evidence suggest a tight interaction between klotho and the GH-IGF-I axis. In a previous study we demonstrated decreased klotho levels in pediatric patients with organic growth hormone deficiency (GHD). We aimed to investigate the effect of GH therapy on klotho levels in children and adolescents treated for GHD.

Patients and Methods: Twenty-nine children and adolescents (Males=15, aged 12.2±3.3 years), treated with GH for GHD (mean duration 2.5±2.8 years) were included in this study. Nineteen patients had samples obtained both before and during GH treatment; ten patients had samples obtained only under GH treatment. Data from 59 growth hormone sufficient (GHS) pediatric patients was used as a reference. Klotho serum levels were measured using an α-klotho ELISA kit. Klotho secretion from tissue culture cells was evaluated by Western blot of proteins precipitate.

Results: As expected, patients' height-SDS, weight-SDS and IGF-I-SDS increased significantly with GH treatment (p=0.009, p=0.02, and p<0.001, respectively). Klotho levels increased significantly (p<0.001) under GH treatment (from 1321.5±691.5pg/ml to 3380±2120.1pg/ml), and were significantly (<0.001) higher compared to GHS participants (1645±778pg/ml). Fold–increase in klotho was significantly correlated (r=0.63, p=0.004) with fold-increase in IGF-I. No correlation was found between klotho levels under treatment and age, height-SDS, weight-SDS, BMI-SDS, GH dose, duration of treatment with GH, growth velocity or IGF-I-SDS. There was no difference in klotho levels between males and females and between pre-pubertal and pubertal participants. Finally, treatment of klotho-transfected HEK293 kidney cells with IGF-1 induced secretion of klotho to media.

Conclusions: We have shown, for the first time, an increase in klotho levels under GH treatment of pediatric patients with GHD. This increase was associated with an increase in IGF-I levels. We suggest a mechanistic explanation as IGF-1 induced secretion of klotho from cells. Our findings add further support for the close association between klotho and the GH/IGF-I axis, and may help to discern the nature of this interaction. Under GH treatment, klotho levels reached supra-physiological levels. The clinical significance of this finding is still to be elucidated.

 

Nothing to Disclose: IW, TR, SS, YL, MB, YY, RD, RH, HK, DM