Fibroblast growth-factor 23-Klotho axis is associated with systemic inflammation and myokine profile in children with chronic kidney disease.

Background: Chronic kidney disease is linked to a disturbed fibroblast growth factor-23 (FGF23)-Klotho axis and an imbalance between myostatin and insulin-like growth factor-1 (IGF-1) expression. This cross-sectional study investigates the association of the FGF23-Klotho axis and myokine profile with serum interleukin-6 (IL-6) and their interactions in pediatric patients.

Methods: Serum calcium, phosphorus, 25-hydroxyvitamin D, parathormone, c-terminal FGF23, a-Klotho, myostatin, follistatin, IGF-1, and IL-6 were measured in 53 patients with GFR < 60 ml/min/1,73m. Myostatin to lean mass (LM) and to IGF-1 ratios were calculated. IL-6 level > 3rd quartile was considered as high.

Results: Myostatin, IGF-1, and follistatin were correlated to LM (rs = 0.513, p < 0.001, rs = 0.652, p < 0.001, rs=-0.483, p < 0.001). Myostatin and follistatin were correlated to IGF-1 (rs = 0.340, p = 0.014, rs=-0.385, p = 0.005). Myostatin/LM but not myostatin or myostatin/IGF-1 ratio was significantly higher in CKD 5D patients (p = 0.001,p = 0.844, p = 0.111). Among mineral bone parameters, lnFGF23 was correlated to lnIL-6 (rs = 0.397, p = 0.004) and associated with high IL-6 (OR 1.905, 95% CI 1.023-3.548). Among myokines, myostatin/IGF-1 ratio was correlated to lnIL-6 (rs = 0.395, p = 0.004) and associated with high IL-6 (OR 1.113, 95% CI 1.028-1.205). All associations were adjusted to CKD stage. Myostatin was correlated to lnFGF23 (rs = 0.331, p = 0.025) and myostatin/IGF-1 ratio to lnKlotho (rs=-0.363, p = 0.013), after adjustment for CKD stage, lnIL-6 and other mineral bone parameters.

Conclusions: In pediatric CKD, FGF23 and myostatin/IGF-1 ratio are associated with IL-6, indicating a link between systemic inflammation, mineral bone, and myokine disorders. The correlations between myostatin and FGF23 and between myostatin/IGF-1 and Klotho suggest an interaction between mineral bone and muscle metabolism.