Fibroblast growth factor 23 levels and the risk of diabetic kidney disease: a systematic review and meta-analysis.

Objective: Diabetic kidney disease (DKD) represents one of the most serious microvascular complications associated with diabetes mellitus (DM), and its early diagnosis is crucial for improving prognosis. While fibroblast growth factor 23 (FGF23) has been linked to DKD risk in numerous studies, the existing evidence remains controversial. This study sought to synthesize existing observational data through a systematic review and meta-analysis to clarify the overall association between FGF23 levels and DKD and explore its significance as a potential biomarker. Methods: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of Cochrane Library, PubMed, Embase, and Web of Science was conducted to identify eligible studies published up to October 23, 2025. We included observational studies that compared FGF23 levels between patients with DKD and non-DKD controls, or evaluated DKD risk. Two researchers independently screened the literature, extracted data, and evaluated methodological quality using the Newcastle-Ottawa Scale (NOS). Statistical analyses were performed with Stata version 15.1. Effect sizes were expressed as standardized mean differences (SMDs) and odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Between-study heterogeneity was quantified using the I² statistic, and subgroup, sensitivity, and publication bias analyses were carried out. Results: Nine eligible studies involving 3,799 participants were included. Meta-analysis indicated that serum FGF23 levels were markedly elevated in patients with DKD compared with those without DKD (SMD = 1.144, 95% CI: 0.361 to 1.928, p = 0.004). Although the pooled OR for DKD with high FGF23 levels was 1.136 (95% CI: 0.656 to 1.968), this association was not statistically significant in dichotomous variable analysis (p = 0.649), with substantial heterogeneity across studies (I² > 80%). Subgroup analyses indicated that region, control type, publication year, DM type, and DKD stage did not fully explain the observed heterogeneity. Sensitivity analyses confirmed the robustness of the mean difference results. Conclusion: FGF23 levels are associated with the progression of DKD, suggesting that it may reflect metabolic disturbances associated with DKD. Given that the OR analysis did not show statistical significance and heterogeneity was substantial, this association should be considered exploratory. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD420251180089.