Baseline fibroblast growth factor 23 predicts incident heart failure and cardiovascular mortality in patients with chronic kidney disease: A 3-year follow-up study

Abstract

Background

Heart failure (HF) is a significant cause of death among patients with chronic kidney disease (CKD). Emerging data suggest a crucial role of fibroblast growth factor 23 (FGF23) in the pathogenesis of HF in CKD patients. The present study aimed to investigate whether the serum intact FGF23 (iFGF23) level is elevated when ejection fraction (EF) is preserved and to evaluate its predictive value for incident HF and cardiac mortality in CKD patients with preserved EF.

Methods and results

We prospectively recruited 209 patients (mean age 52.7 ± 11.9 years, 37.3 % male) with CKD stages 3–5 and preserved EF, including those on peritoneal dialysis (PD) from a nephropathy center from November 2020 until July 2024.

Results

Over a median follow-up of 29 (IQR 24–35) months, 60 (28.7 %) patients met the primary composite endpoints, including 53 (25.4 %) incident HF events and 7 (3.3 %) cardiac deaths. The cumulative incidence of composite endpoints was approximately 2-fold higher in patients with the highest quartile (Q4) level of lgiFGF23, compared with the lower quartiles (Q1-3). Baseline iFGF23 concentration was significantly associated with an increased risk of composite endpoint in the multivariable-adjusted Cox model, independent of kidney function, traditional cardiovascular risk factors, echocardiographic parameters, and α-Klotho. In a competing risk analysis, the Q4 level of lgiFGF23 (HR 2.43, 95 %CI 1.44–4.11; P = 0.001) was independently associated with HF and cardiac death.

Conclusion

In CKD patients with preserved EF, serum iFGF23 was elevated before LVEF declined. A higher baseline serum iFGF23 level is significantly associated with the incidence of HF and cardiovascular mortality over a 3-year follow-up, demonstrating independent and incremental predictive value beyond traditional risk factors.