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.
Growth hormone treatment associates with improved circulating anti-aging protein Klotho and reduced arterial stiffness in children with CKD / S. Stabouli, M. Leifheit-Nestler, M. Föller, M. Feger, A.K. Bayazit, A. Doyon, L. Obrycki, B. Ranchin, J. Oh, D. Paripovic, G. Longo, J. Harambat, O. Mehls, A. Melk, U. Querfeld, F. Schaefer, D. Haffner, N. Null, G. Cortina, K. Arbeiter, J. Dusek, J. Harambat, B. Ranchin, M. Fischbach, A. Zaloszyc, U. Querfeld, J. Gellermann, S. Habbig, M. Liebau, M. Galiano, R. Büscher, C. Gimpel, M. Kemper, J. Oh, A. Melk, D. Thurn-Valassina, A. Doyon, E. Wühl, F. Schaefer, U. John, S. Wygoda, N. Jeck, B. Kranz, M. Wigger, F. Mencarelli, F. Lugani, S. Testa, G. Montini, W. Morello, E. Vidal, E. Benetti, L. Murer, C. Matteucci, S. Picca, A. Jankauskiene, K. Azukaitis, A. Zurowska, I. Zagozozon, D. Drodz, T. Urasinski, M. Litwin, A. Niemirska, L. Obrycki, M. Szczepanska, A. Texeira, A. Peco-Antic, D. Paripovic, G. Simonetti, G. Laube, A. Anarat, A.K. Bayazit, F. Yalcinkaya, E. Baskin, N. Cakar, O. Soylemezoglu, A. Duzova, Y. Bilginer, H. Erdogan, O. Donmez, A. Balat, A. Kiyak, S. Caliskan, N. Canpolat, M. Civilibal, C. Candan, S. Emre, A. Yilmaz, H. Alpay, G. Ozcelik, S. Mir, B. Sözeri, I.K. Bulut, N. Aksu, O. Yavascan, Y. Tabel, P. Ertan, E. Yilmaz, R. Shroff. - In: CLINICAL KIDNEY JOURNAL. - ISSN 2048-8505. - 18:9(2025 Sep), pp. sfaf231.1-sfaf231.12. [10.1093/ckj/sfaf231]
Growth hormone treatment associates with improved circulating anti-aging protein Klotho and reduced arterial stiffness in children with CKD
G. Montini;
2025
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.
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