Association of combined fractional excretion of phosphate and FGF23 with heart failure and cardiovascular events in moderate and advanced renal disease

Background High levels of FGF23 associate with adverse events in CKD. The urinary fractional excretion of phosphate (FePi) might modify this association, although data are limited in moderate and advanced CKD. We investigated the association of combined FePi and serum FGF23 with incident heart failure, cardiovascular events and mortality in patients with CKD stages 2–4. Methods Patients from the Chronic Renal Insufficiency Cohort were divided into four groups according to the median of FePi and FGF23: low-FePi/low-FGF23, reference group; high-FePi/low-FGF23; low-FePi/high-FGF23; high-FePi/high-FGF23. Primary outcomes were: the composite of cardiovascular death or hospitalization for heart failure; cardiovascular death; hospitalization for heart failure; and death from any cause. Survival analysis and adjusted regression analyses were performed. Results We analyzed 3684 patients with a mean age of 58 ± 11 years of whom 45% were male. Mean eGFR was 44 ± 15 ml/min/1.73 m 2 . The median time of follow-up was 12 (IQR 7–13) years. The risk of the composite of cardiovascular death or hospitalization for heart failure was increased in the low-FePi/high-FGF23 group (HR 1.35; 95%CI 1.09–1.67) and in the high-FePi/high-FGF23 group (HR 1.50; 95%CI 1.20–1.86), compared to the low-FePi/low-FGF23 group. Cardiovascular death and hospitalization for heart failure were also increased in both groups with high FGF23. Death from any cause was increased in the low-FePi/high-FGF23 group (HR 1.56 (95%CI 1.30–1.89) and in the high-FePi/high-FGF23 (HR 1.57 (95%CI 1.29–1.90)). Conclusions High FGF23 was associated with heart failure and cardiovascular death in patients with low FePi and high FePi with moderate to advanced CKD. This contrasts with reports in mild CKD. Graphical abstract