Background and aims Fibroblast growth factor 23 (FGF23) has been implicated in the excess cardiovascular risk of chronic kidney disease (CKD), but its prognostic value remains uncertain. We conducted a systematic review and meta-analysis to assess the association of FGF23 with all-cause mortality, heart failure (HF), and atherosclerotic cardiovascular (aCV) events across the CKD spectrum. Methods PubMed/MEDLINE and Embase were searched from inception to February 9, 2026. Observational studies enrolling adults with CKD G1-G5, end-stage kidney disease (ESKD), or kidney transplant were eligible if they reported adjusted hazard ratios for baseline intact FGF23 (iFGF23) or C-terminal FGF23 (cFGF23). Random-effects models were used for quantitative synthesis. Results Forty-one studies were included in the systematic review and 31 studies (25,104 patients) in the meta-analysis. Higher continuous FGF23 was associated with increased all-cause mortality (HR 1.52, 95% CI 1.26–1.83), HF (HR 1.34, 95% CI 1.22–1.58), and aCV events (HR 1.23, 95% CI 1.08–1.41). Assay type contributed importantly to heterogeneity. For mortality, cFGF23 showed a robust association, whereas iFGF23 did not (P interaction <0.001). A similar pattern was observed for HF, with stronger associations for cFGF23. For aCV events, no significant assay-related subgroup difference emerged. Sensitivity analyses using categorical FGF23 were consistent, and in ESKD the highest FGF23 category was associated with higher mortality. Conclusions Higher FGF23 levels are associated with adverse cardiovascular outcomes and mortality across the CKD spectrum, but the strength and consistency of these associations vary by assay type. cFGF23 showed more consistent associations, particularly for mortality and HF, although the clinical utility of this finding remains to be established.
Vetrano et al. (Mon,) studied this question.