Anti-FGF23 monoclonal antibody

Introduction/objectives Fibroblast growth factor (FGF23) is an endocrine hormone that can be induced by inflammation and plays a role in the pathogenesis of cardiac abnormalities. Few studies have reported plasma FGF23 levels in patients with Takayasu arteritis (TAK). We hypothesized that the production of FGF23 in TAK is associated with abnormal cardiac mass. Method Forty-seven patients diagnosed with TAK and 52 age- and gender-matched healthy controls were included in this observational study. Plasma FGF23 was detected by human enzyme-linked immunosorbent assay. Multivariable linear regression analyses were performed to examine the association between FGF23 and left ventricular mass index (LVMI). Results Patients with TAK had higher plasma FGF23 than healthy controls [121.8 (84.5-168.8) vs. 86.7 (70.5-101.1) RU/ml, P < 0.001]. Patients with higher FGF23 concentrations were more likely to be females (100.0% vs. 75.0%, P = 0.01), angiographic type V (69.6% vs. 33.3%, P = 0.013), heart failure (43.5% vs. 12.5%, P = 0.018), and have higher LVMI [126.3 (81.1-177.7) vs. 85.9 (69.7-114.3) g/m(2), P = 0.041]. Plasma FGF23 was significantly associated with LVMI in TAK patients [beta = 0.402, 95% confidence interval (CI) 0.032-0.301, P = 0.016], after adjusting for age, gender, disease duration, angiographic type (angiographic type V vs. non-angiographic type V), the presence of cardiovascular events and hypertension, and serum N-terminal pro-B-type natriuretic peptide in the multivariate linear regression. Age (beta = - 0.399, P = 0.016) and the presence of angiographic type V (beta = 0.376, P = 0.018) were identified to be significant determinants of plasma FGF23 in patients with TAK. Conclusions Plasma FGF23 was elevated in patients with TAK and was associated with LVMI. FGF23 may participate in the development of abnormal cardiac mass in patients with TAK.

Background. Erythropoietin (EPO) has been reported as a novel determinant of fibroblast growth factor 23 (FGF23) production; however, it is unknown whether FGF23 is stimulated by chronic exposure to EPO or by EPO administration in nonpolycystic chronic kidney disease (CKD) models. Methods. We analyzed the effects of chronic EPO on FGF23 in murine models with chronically high EPO levels and normal kidney function. We studied the effects of exogenous EPO on FGF23 in wild-type mice, with and without CKD, injected with EPO. Also, in four independent human CKD cohorts, we evaluated associations between FGF23 and serum EPO levels or exogenous EPO dose. Results. Mice with high endogenous EPO have elevated circulating total FGF23, increased disproportionately to intact FGF23, suggesting coupling of increased FGF23 production with increased proteolytic cleavage. Similarly, in wild-type mice with and without CKD, a single exogenous EPO dose acutely increases circulating total FGF23 out of proportion to intact FGF23. In these murine models, the bone marrow is shown to be a novel source of EPO-stimulated FGF23 production. In humans, serum EPO levels and recombinant human EPO dose are positively and independently associated with total FGF23 levels across the spectrum of CKD and after kidney transplantation. In our largest cohort of 680 renal transplant recipients, serum EPO levels are associated with total FGF23, but not intact FGF23, consistent with the effects of EPO on FGF23 production andmetabolismobserved in our murine models. Conclusion. EPO affects FGF23 production and metabolism, whichmay have important implications for CKD patients.