Influence of exogenous growth hormone administration on circulating concentrations of [alpha]-klotho in healthy and chronic kidney disease subjects: a prospective, single-center open case-control pilot study

Background The CKD-associated decline in soluble [alpha]-Klotho ([alpha]-Klotho) levels is considered detrimental. Some studies suggest a direct induction of [alpha]-Klotho concentrations by growth hormone (GH). In the present study, the effect of exogenous GH administration on [alpha]-Klotho concentrations in a clinical cohort with mild chronic kidney disease (CKD) and healthy subjects was studied. Methods A prospective, single-center open case-control pilot study was performed involving 8 patients with mild CKD and 8 healthy controls matched for age and sex. All participants received subcutaneous GH injections (Genotropin[R], 20 mcg/kg/day) for 7 consecutive days. [alpha]-Klotho concentrations were measured at baseline, after 7 days of therapy and 1 week after the intervention was stopped. Results [alpha]-Klotho concentrations were not different between CKD-patients and healthy controls at baseline (554 (388-659) vs. 547 (421-711) pg/mL, P = 0.38). Overall, GH therapy increased [alpha]-Klotho concentrations from 554 (405-659) to 645 (516-754) pg/mL, P < 0.05). This was accompanied by an increase of IGF-1 concentrations from 26.8 [+ or -] 5.0 nmol/L to 61.7 [+ or -] 17.7 nmol/L (P < 0.05). GH therapy induced a trend toward increased [alpha]-Klotho concentrations both in the CKD group (554 (388-659) to 591 (358-742) pg/mL (P = 0.19)) and the healthy controls (547 (421-711) pg/mL to 654 (538-754) pg/mL (P = 0.13)). The change in [alpha]-Klotho concentration was not different for both groups (P for interaction = 0.71). [alpha]-Klotho concentrations returned to baseline levels within one week after the treatment (P < 0.05). Conclusions GH therapy increases [alpha]-Klotho concentrations in subjects with normal renal function or stage 3 CKD. A larger follow-up study is needed to determine whether the effect size is different between both groups or in patients with more severe CKD. Trial registration This trial is registered in EudraCT (2013-003354-24). Keywords: [alpha]-Klotho, Growth hormone, Chronic kidney disease