Fibroblast Growth Factor 23 and Sarcopenia in Maintenance Haemodialysis Population

Sarcopenia is defined as the loss of muscle mass, strength, and/or performance. It is strongly associated with all-cause mortality. Fibroblast growth factor 23 (FGF23) is markedly elevated in patients with chronic kidney disease, especially those receiving maintenance dialysis. FGF23 has previously been shown to have a direct role in cardiac dysfunction mediated through left ventricular hypertrophy. However, its role in the development of (or protection from) sarcopenia is uncertain. This study is aimed at determining the relationship between FGF23 and muscle-related parameters and to assess the effect of FGF23 on skeletal muscle myoblasts.

A single centre, cross-sectional study examining maintenance haemodialysis patients was conducted. Sarcopenia was defined in accordance with the revised European Working Group on Sarcopenia in Older People and the Asian Working Group for Sarcopenia criteria. Clinical assessment methods included bioelectrical impedance analysis, anthropometric measurement, handgrip strength and physical performance appraisal. Both intact FGF23, which is biologically active, and the inactive C-terminal FGF23 were measured using enzyme-linked immunosorbent assays. The direct effects of FGF23 on skeletal muscle myoblast proliferation and myogenic differentiation were assessed using an in vitro culture system. Linear and logistic regression analyses were performed to examine the associations between FGF23 and muscle-related parameters and sarcopenia, respectively.

Eighty-one patients were included with a median age of 75 years (interquartile range 67-80), and 63% were male. Log-transformed serum FGF23 correlated positively with handgrip strength (r = 0.27, p = 0.01, 95% confidence interval (CI) 0.06-0.46) and calf circumference (r = 0.27, p = 0.01, 95% CI 0.06-0.46), and in multiple regression analyses, it was found to be a significant independent predictor of both handgrip strength (beta = 5.39, 95% CI 2.07-8.72) and sarcopenia (odds ratio = 0.14, 95% CI 0.02-0.75). FGF23 was found to promote myoblast proliferation but attenuate myogenic differentiation. At 48 h of differentiation, the expressions of MyoG and MyoD were significantly lower in cells treated with FGF23 than the control. The fusion index and myotube diameters were reduced on Day 7 of differentiation in FGF23-treated cells compared to the control.

Higher serum FGF23 levels were associated with stronger handgrip strength and lower odds of having sarcopenia in maintenance haemodialysis patients. Our findings suggest that supraphysiological levels of FGF23 might play a role in muscle regeneration by promoting myoblast proliferation but repressing myogenic differentiation to support the expansion of the proliferative pool. FGF23 could potentially serve as a serum biomarker for muscle health in dialysis populations.