iFGF23:cFGF23 Ratio Is a Questionable Diagnostic Marker for Distinguishing Between Acute and Chronic Kidney Disease

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 (<i>p</i> = 0.021) and a lower iFGF23:cFGF23 ratio (<i>p</i> = 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 (<i>p</i> > 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.