Iron status and the Pi/FGF-23-axis in HFrEF in relation to renal function

Abstract Background Recent studies linked dysregulated phosphate metabolism, fibroblast growth factor-23 (FGF-23) and iron deficiency (ID) with worse clinical outcome and mortality in heart failure with reduced ejection fraction (HFrEF). These factors are intertwined as FGF-23 regulates inorganic phosphate (Pi) through increased renal phosphate secretion and is stimulated by elevated Pi levels and ID. This interplay has recently gained attention as intravenous iron supplementation has hypophosphataemia as a side effect. The relationship between ID and the Pi/FGF-23-axis, particularly concerning renal function, has not been investigated in detail. Purpose We aimed to evaluate the relationship between iron status, Pi and FGF-23 in relation to renal function in HFrEF. Methods Stable HFrEF patients were enrolled at our outpatient clinic between 2018 and 2023 in a prospective registry. Baseline characteristics, medications and laboratory values were documented. For this study patients with complete phosphate, intact FGF-23 and iron status were analyzed (n = 429). Patients were divided into three groups based on their renal function determined by estimated glomerular filtration rate (GFR): GFR > 60, GFR 60-30, GFR < 30. Results The median age was 65 (IQR 52-74), 310 (72%) patients were male, median NT-proBNP was 1657 pg/ml (IQR 512-4116) and median GFR was 57 ml/min/BSA (IQR 37-74). Of the 429 patients, 180 (42%) suffered from ID. Pi levels did not vary based on NYHA stage and showed only a weak correlation with NT-proBNP (r = 0.13, p = 0.008). In contrast, FGF-23 increased with NYHA stage (NYHA I vs NYHA II vs NYHA III/IV: 69.9 (IQR 50-90.2) vs 82.4 (IQR 58.9-115.8) vs 104.2 (IQR 77-199.5), p