FIBROBLAST GROWTH FACTOR-23 AND ITS ASSOCIATION WITH ARTERIAL STIFFNESS IN DIABETIC AND NON-DIABETIC CHRONIC KIDNEY DISEASE

Cardiovascular disease (CVD) represents the primary cause of death among patients with chronic kidney disease (CKD), and vascular stiffness is one of the key pathophysiological mechanisms linking renal dysfunction to adverse cardiovascular outcomes. Increased arterial stiffness results from progressive vascular calcification, endothelial dysfunction, and remodeling of the arterial wall, all of which are exacerbated by disturbances in mineral metabolism. Fibroblast Growth Factor-23 (FGF-23), a hormone primarily secreted by osteocytes, regulates phosphate excretion and vitamin D metabolism. Beyond its classical role in mineral balance, FGF-23 has emerged as a potential mediator of vascular injury and left ventricular hypertrophy in CKD. Elevated FGF-23 concentrations are frequently observed even in the early stages of CKD and have been proposed as a marker of subclinical cardiovascular dysfunction.Given that diabetic patients often exhibit both higher FGF-23 levels and more pronounced vascular alterations, the present study aimed to explore the relationship between circulating FGF-23 and indices of arterial stiffness in diabetic and non-diabetic CKD patients. 

An open-label, non-randomized, single-center clinical study was carried out from 2018 to 2022 at the Teaching Therapeutic Clinic of Azerbaijan Medical University. The study included 120 CKD patients (54 men, 66 women) who were divided into two groups according to disease etiology: diabetic CKD (n = 60) and non-diabetic CKD (n = 60). Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation, and patients with eGFR < 15 or > 60 mL/min/1.73 m² were excluded. CKD staging followed KDIGO-2012 guidelines. In addition to standard biochemical tests, arterial stiffness was assessed by applanation tonometry using the HDI PulseWave Profiling System after 15 minutes of supine rest. Measurements were obtained bilaterally from the radial arteries and repeated twice for reliability.

FGF-23 levels were markedly higher in diabetic CKD patients compared with non-diabetic counterparts (3728.9 ± 418 pg/mL vs 2614.5 ± 482 pg/mL; p = 0.018). Diabetic CKD patients also demonstrated significantly increased systemic vascular resistance (p = 0.017) and total vascular impedance (p = 0.010), along with decreased large- (p = 0.030) and small-artery elasticity indices (p = 0.011). A positive correlation was observed between FGF-23 levels and vascular stiffness (R = 0.45; p = 0.012), implying a link between FGF-23 dysregulation and arterial dysfunction. Additionally, the diabetic group showed higher prevalence of cardiovascular disease (p = 0.014), greater waist circumference (p = 0.019), and elevated serum glucose (p = 0.014) and total cholesterol (p = 0.045). These findings highlight the synergistic influence of metabolic abnormalities and FGF-23 elevation on vascular rigidity in CKD.

Elevated FGF-23 is closely associated with increased arterial stiffness in CKD, particularly among diabetic patients. These data suggest that FGF-23 may serve as an early biomarker of vascular injury and cardiovascular risk in CKD. Further interventional studies are warranted to determine whether modulation of FGF-23 can attenuate vascular calcification and improve cardiovascular outcomes.