Szczykowska-Miller Joanna, Hryszko Tomasz, Koc-Żórawska Ewa, Naumnik Beata
1st Department of Nephrology, Transplantation and Internal Medicine with Dialysis Unit, Medical University of Bialystok, ul. Zurawia 14, 15-540 Bialystok, Poland.
2nd Department of Nephrology, Hypertension and Internal Medicine with Dialysis Unit, Medical University of Bialystok, ul. Sklodowskiej-Curie 24a, 15-276 Bialystok, Poland.
Int J Mol Sci. 2025 Aug 18;26(16):7952. doi: 10.3390/ijms26167952.
Elevated concentrations of FGF23 are commonly observed in patients with impaired kidney function. It has been hypothesized that acute kidney injury (AKI), in contrast to chronic kidney disease (CKD), may be associated with increased FGF23 cleavage, resulting in a decreased ratio of intact to C-terminal FGF23 (iFGF23:cFGF23). However, data on the diagnostic utility of this ratio in differentiating AKI from CKD remain limited. A single-center cohort study involving 173 patients admitted to the Nephrology Department with abnormal serum creatinine levels between March 2018 and July 2021 was conducted. Blood samples were collected within 24 h of admission to measure FGF23 concentrations using both intact and C-terminal ELISAs. The iFGF23:cFGF23 ratio was calculated and analyzed across diagnostic groups. Generalized estimating equations with doubly robust adjustment were used to account for the relevant clinical and biochemical covariates. In unadjusted analyses, patients with AKI had significantly higher cFGF23 concentrations ( = 0.021) and a lower iFGF23:cFGF23 ratio ( = 0.017) compared to patients with stable CKD. No significant difference in iFGF23 levels was observed. However, after multivariable adjustment for age, serum creatinine, markers of mineral metabolism (calcium, phosphate, and parathormone) and inflammation (CRP), the observed differences were no longer statistically significant ( > 0.5 for all), and the interaction terms revealed no consistent modifiers of the exposure effect. The ROC analysis demonstrated modest discriminatory ability of the iFGF23:cFGF23 ratio, with an AUC of 0.60. After robust adjustment for key confounders, the iFGF23:cFGF23 ratio does not serve as a reliable independent marker for differentiating AKI from CKD. These results were supported by the ROC analysis, reflecting limited clinical utility for this ratio as a standalone biomarker. Our findings suggest that the observed differences in FGF23 metabolism are primarily driven by underlying disturbances in mineral metabolism and inflammation rather than the acute or chronic nature of the kidney injury itself.
肾功能受损患者中常见FGF23浓度升高。据推测，与慢性肾脏病（CKD）相比，急性肾损伤（AKI）可能与FGF23裂解增加有关，导致完整FGF23与C端FGF23的比例（iFGF23:cFGF23）降低。然而，关于该比例在区分AKI与CKD方面的诊断效用的数据仍然有限。开展了一项单中心队列研究，纳入了2018年3月至2021年7月间因血清肌酐水平异常而入住肾病科的173例患者。在入院后24小时内采集血样，使用完整和C端ELISA法测量FGF23浓度。计算并分析各诊断组的iFGF23:cFGF23比例。采用具有双重稳健调整的广义估计方程来考虑相关的临床和生化协变量。在未调整分析中，与稳定CKD患者相比，AKI患者的cFGF23浓度显著更高（P = 0.021），iFGF23:cFGF23比例更低（P = 0.017）。未观察到iFGF23水平有显著差异。然而，在对年龄、血清肌酐、矿物质代谢标志物（钙、磷和甲状旁腺激素）以及炎症（CRP）进行多变量调整后，观察到的差异不再具有统计学意义（所有P均>0.5），且交互项未显示出一致的暴露效应修饰因素。ROC分析显示iFGF23:cFGF23比例的鉴别能力一般，AUC为0.60。在对关键混杂因素进行稳健调整后，iFGF23:cFGF23比例不能作为区分AKI与CKD的可靠独立标志物。这些结果得到了ROC分析的支持，反映出该比例作为单一生物标志物的临床效用有限。我们的研究结果表明，观察到的FGF23代谢差异主要由矿物质代谢和炎症的潜在紊乱驱动，而非肾损伤本身的急性或慢性性质。
