Journal Article Epublish
PubMed: 41140975 DOI: 10.1093/ckj/sfaf231
Growth hormone treatment associates with improved circulating anti-aging protein Klotho and reduced arterial stiffness in children with CKD.
Clin Kidney J 18(9):sfaf231
Authors: Stella Stabouli, Maren Leifheit-Nestler, Michael Föller, Martina Feger, Aysun K Bayazit, Anke Doyon, Lukasz Obrycki, Bruno Ranchin, Jun Oh, Dusan Paripovic, Germana Longo, Jerome Harambat, Otto Mehls, Anette Melk, Uwe Querfeld, Franz Schaefer, Dieter Haffner
Affiliations
- 1st Department of Pediatrics, Aristotle University Thessaloniki, Hippokratio Hospital, Thessaloniki, Greece.
- Department of Pediatric Kidney Liver, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany.
- Department of Physiology, University of Hohenheim, Stuttgart, Germany.
- Department of Pediatric Nephrology, Cukurova University, Adana, Turkey.
- Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany.
- Department of Nephrology, Kidney Transplantation and Hypertension, The Children's Memorial Health Institute, Warsaw, Poland.
- Pediatric Nephrology Unit, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Université de Lyon, Lyon, France.
- Department of Pediatric Nephrology, University Hamburg-Eppendorf, Hamburg, Germany.
- Nephrology Department, University Children's Hospital, Belgrade, Serbia.
- Pediatric Nephrology, Dialysis and Transplant Unit, Department of Woman and Child Health, Azienda Ospedaliera-University of Padova, Padova, Italy.
- Pediatric Nephrology Unit, Centre Hospitalier Universitaire de Bordeaux, Université de Bordeaux, Bordeaux, France.
- Department of Pediatrics, Division of Gastroenterology, Nephrology and Metabolic Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, and Humboldt-Universität zu Berlin, Berlin, Germany.
Abstract
BACKGROUND
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.
METHODS
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.
RESULTS
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).
CONCLUSIONS
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.
MeSH
Growth, Blood, Aging, Somatomedins, Blood Pressure, Hormones, Morbidity, Therapeutics, Growth Hormone, Child