Fibroblast Growth Factor 23, Endogenous Erythropoietin, Erythropoiesis-Stimulating Agents, and Erythropoietin Resistance in Hemodialysis Patients

Introduction:Recent experimental studies have reportedthatfibroblast growth factor 23 (FGF23) inhibits erythropoi-esis by suppressing erythropoietin (EPO) production anddownregulating the EPO receptor. Conversely, either en-dogenous or exogenous EPO has been shown to stimulateFGF23 production. However, little is known about the rela-tionships between FGF23, erythropoiesis-stimulating agent(ESA) treatment, ESA resistance, and endogenous EPO inhemodialysis patients.Methods:We analyzed cross-sectionaldata from a cohort of 654 maintenance hemodialysis patients.We examined the associations of intact or C-terminal FGF23with ESA treatment, ESA resistance index (ERI), hemoglobin,C-reactive protein, and endogenous EPO levels using linearregression models. EPO was measured only in patients notreceiving ESAs.Results:A total of 458 patients (70%) weretreated with ESAs. The median EPO concentration in non-ESAusers was 7.8 (interquartile range, 5.3-14.4) mIU/mL. Themedian levels of intact and C-terminal FGF23 were 1,598(interquartile range, 548-4,586) pg/mL and 38.7 (interquartilerange, 14.0-127.6) pmol/L, respectively, in non-ESA users and1,955 (interquartile range, 573-5,264) pg/mL and 41.4(interquartile range, 13.9-116.8) pmol/L, respectively, in ESAusers. After adjustment for potential confounders, higher ESAdose was associated with higher FGF23 levels measured byboth intact and C-terminal assays. Higher C-terminal FGF23was also associated with higher ERI, lower hemoglobin, andhigher endogenous EPO, but no such associations wereobserved for intact FGF23 levels.Conclusions:Both intact andC-terminal FGF23 showed similar associations with ESA dose,but they showed different patterns of association with otherparameters related to anemia. Further research is needed toelucidate the mechanisms underlying these differentassociations.(c) 2025 S. Karger AG, Basel