Abstract

Objective. This study aimed to analyze biochemical determinants of calcification by assessing calcium–phosphate product, magnesium, iPTH, vitamin D3 , NF-κB, and SGLT2 expression as potential markers of vascular injury in chronic kidney disease (CKD). Materials and methods. This cross-sectional study was conducted at Dr. Soetomo General Academic Hospital, involving 30 adult ESRD patients undergoing chronic hemodialysis via radiocephalic arteriovenous fistula. SGLT2 expression was evaluated using immunohistochemistry with a monoclonal antibody against SGLT2 (1:100 dilution, Biocare Medical). Statistical analysis was conducted using the Statistical Package for the Social Sciences (SPSS version 21; IBM Corp., Armonk, NY, USA) and R version 4.5.1. Results. Among 30 CKD patients, vascular calcification was detected in 30% of cases. Patients with calcification showed slightly lower median calcium levels [7.83 (6.3–8.8) vs. 8.6 (7.2–9.1)] mg/dL and phosphate levels [4.50 (2.40–8.73) vs. 4.61 (1.70–13.10)] mg/dL, with no significant differences in magnesium, iPTH, or vitamin D3 (p > 0.05). Logistic regression revealed that neither calcium–phosphate product (OR = 0.989, 95% CI: 0.915–1.069, p = 0.781) nor SGLT2 expression independently predicted calcification. Conclusion. In this exploratory cross-sectional study, none of the investigated biochemical or molecular markers showed a statistically significant association with vascular calcification. The small sample size and limited number of calcification events restrict statistical power and causal inference. Larger multicenter studies are required to clarify the role of mineral metabolism and vascular molecular signaling in CKD-related calcification.

Keyword: biomarkers, chronic kidney disease, sodium-glucose transporter 2, vascular calcification

INTRODUCTION

Vascular calcification (VC) is a common and serious complication in chronic kidney disease (CKD), contributing significantly to cardiovascular morbidity and mortality. It is no longer considered a passive mineral deposition but an active, cell-mediated process in which vascular smooth muscle cells (VSMCs) transform into osteoblast-like phenotypes under the influence of hyperphosphatemia, oxidative stress, and chronic inflammation [1,2]. Phosphate and calcium overload, as well as an elevated calcium–phosphate product, contribute to VSMC osteogenic transformation, while magnesium and hormonal regulators such as PTH and vitamin D modulate mineral balance. Local molecular networks further influence the calcific response, although systemic disturbances alone do not fully explain interindividual variability [3–6]. The NF-κB signaling pathway serves as a pivotal regulator of inflammatory and survival mechanisms in vascular tissue. Activation of the IKK2/NF-κB axis in VSMCs under CKD conditions has been shown to attenuate vascular stiffness by preventing apoptosis and reducing the release of calcifying extracellular vesicles [7]. Conversely, under pro-inflammatory or high-phosphate conditions, NF-κB activation can enhance vascular calcification by downregulating mineralization inhibitors such as ANKH, highlighting its context-dependent dual role in modulating vascular pathology [8]. In addition, metabolic modifiers such as SGLT2 inhibitors have recently been reported to alleviate vascular calcification in animal and in vitro models by reducing oxidative stress, inhibiting Runx2-mediated osteogenic reprogramming, and suppressing endoplasmic reticulum stress [9]. Given these insights, this study aimed to investigate the biochemical factors contributing to vascular calcification by evaluating calcium–phosphate product, magnesium, iPTH, vitamin D3 , NF-κB, and SGLT2 expression as potential indicators of vascular injury in CKD.