# Growth hormone treatment associates with improved circulating anti-aging protein Klotho and reduced arterial stiffness in children with CKD

## TL;DR

Growth hormone treatment in children with chronic kidney disease is linked to higher levels of the anti-aging protein Klotho and lower arterial stiffness.

## Contribution

This study shows long-term GH treatment improves sKlotho and reduces arterial stiffness in pediatric CKD patients.

## Key findings

- GH-treated patients had higher sKlotho and IGF1 levels and lower PWV compared to controls.
- Multivariable analysis linked sKlotho levels to GH treatment and IGF1.
- PWV was associated with GH treatment, blood pressure, and parathyroid hormone levels.

## Abstract

Chronic kidney disease (CKD) is characterized by low levels of the anti-aging protein α-Klotho and accelerated cardiovascular (CV) morbidity. Short-term treatment with growth hormone (GH) was shown to enhance soluble Klotho (sKlotho), the circulating form of α-Klotho, and endothelial function in patients with CKD. We hypothesized that long-term GH treatment in pediatric patients with CKD improves sKlotho levels and CV morbidity.

We performed a case-cohort study within the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study including 101 children with CKD stages 3–5 treated with and without GH. Patients were assessed for serum sKlotho, intact fibroblast growth factor 23 (iFGF23), somatomedin insulin-like growth factor 1 (IGF1), pulse wave velocity (PWV), carotid intima thickness (cIMT), and left ventricular mass index (LVMI) at two time points 12 months apart.

GH-treated patients showed higher sKlotho (Δ1.2 SD) and IGF1 (Δ1.5 SD) z-scores, and lower PWV z-scores (Δ −0.9 SD) compared to controls (each P < .01), both at baseline and after 12 months of follow up. iFGF23 and cIMT z-scores, LVMI, and progression of CKD did not differ between groups. In the multivariable analysis, sKlotho z-scores associated with GH treatment, IGF1 and iFGF23 z-scores (each P < .01). PWV z-scores associated with GH treatment, diastolic blood pressure, and parathyroid hormone levels, while cIMT z-score and LVMI associated with diastolic blood pressure and hemoglobin only (each P < .05).

Long-term GH treatment is associated with reduced PWV in children with CKD, which is at least partly related to GH/IGF1-induced upregulation of sKlotho.

Graphical Abstract