Abstract: TH-PO150
Fibroblast Growth Factor 23 (FGF-23) and Endothelial Cell Dysfunction (ECD) in the Dallas Heart Study Cohort
Session Information
- CKD-MBD: Clinical
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 502 Bone and Mineral Metabolism: Clinical
Authors
- Van Buren, Peter N., The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Gattineni, Jyothsna, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
Background
Mineral bone disease (MBD) and ECD are mortality risk factors that associate with each other in advanced chronic kidney disease (CKD). Phosphate (Ph) and parathyroid hormone (PTH) are late CKD MBD markers, but FGF23 is an early marker. Using data from Dallas Heart Study (DHS), a multi-ethnic cohort with largely preserved renal function, we assessed if FGF23 predicted ECD markers.
Methods
We measured FGF23 in stored DHS plasma. We compared demographic and lab measurements across FGF23 quartiles and used linear regression to identify associations with FGF23 and the following markers: asymmetric dimethylarginine (ADMA), vascular cell adhesion molecule (VCAM1), intracellular adhesion molecule (ICAM1), CD40 ligand, monocyte chemotactant protein 1 (MCP1), syndecan-1, and endoglin.
Results
In 1186 participants (37% male, 40% Black, 16% CKD), mean FGF23 was 44.0 (86) pg/mL. Across increasing FGF23 quartiles, coronary artery calcification, PTH, ADMA, MCP1, cholesterol, and CD40 ligand significantly increased while endoglin decreased (Table 1). ICAM1, VCAM1 and syndecan did not differ. Controlling for age, sex, race, diabetes, GFR, Ph, and PTH, log FGF23 independently predicted ADMA (β=0.03, p=.003), log syndecan-1 (β=0.1, p=.03), and log MCP1 (β=0.1, p=.04).
Conclusion
Multiple ECD markers associate with high FGF23. FGF23 independently predicts ADMA, syndecan-1, and MCP1 warranting prospective studies to determine if early MBD exacerbates ECD when renal function is normal or mildly reduced.
Characteristics Across FGF23 Quartiles
| Quartile 1 (6.2-28.3 pg/mL) | Quartile 2 (28.3-36.4 pg/mL) | Quartile 3 (36.4-45.2 pg/mL) | Quartile 4 (45.3-2034 pg/mL) | p-value for trend | |
| Age (years) | 43 (35, 52) | 42 (36, 50) | 44 (37, 52) | 45 (37, 52) | .1 |
| Diabetes (%) | 17 (6%) | 27 (9%) | 19 (6%) | 35 (12%) | .03 |
| BMI (kg/m2) | 27.3 (24-32) | 27.8 (24-32) | 28.8 (25-34) | 29.1 (25-34) | .003 |
| Estimated MDRD Glomerular Filtration Rate (mL/min) | 101 (90-118) | 99.5 (87-114) | 94.1 (81-111) | 91.1 (78-104) | <.0001 |
| Serum Phosphate (mg/dL) | 3.1 (2.8-3.5) | 3.2 (2.8-3.5) | 3.1 (2.8-3.5) | 3.3 (2.9-3.7) | .001 |
| Serum Calcium (mg/dL) | 9.2 (9-9.5) | 9.2 (9-9.5) | 9.3 (9.1-9.5) | 9.3 (9-9.6) | .02 |
| Intact Parathyroid Hormone (pg/mL) | 35.6 (27-51) | 37 (27-50) | 35.3 (28-46) | 40.3 (29-57) | .03 |
| Total cholesterol (mg/dL) | 167 (147-196) | 175 (151-201) | 179 (154-203) | 191 (160-208) | .0001 |
| Electron Beam Computed Tomography Coronary Artery Calcification (Agatston) | 0 (0-2.6) | 0.5 (0-3.8) | 0.5 (0-8.8) | 1 (0-11.5) | .001 |
| Asymmetric Dimethylarginine (μmol/L) | 0.47 (0.4-0.53) | 0.47 (0.42-0.54) | 0.48 (0.41-0.56) | 0.51 (0.44-0.57) | .0001 |
| CD40 Ligand (ng/mL) | 1.35 (0.8-2.2) | 1.36 (0.8-2.3) | 1.42 (0.8-2.3) | 1.85 (1.1-3.2) | <.0001 |
| Monocyte Chemotactant Protein-1 (pg/mL) | 160 (113-211) | 163 (111-214) | 170 (127-242) | 187 (137-248) | <.0001 |
| Soluble endoglin (ng/mL) | 1.71 (1.3-2.1) | 1.64 (1.3-2.0) | 1.58 (1.3-2.0) | 1.56 (1.2-2.0) | .008 |
| Syndecan-1 (ng/mL) | 3.05 (2.3-4.3) | 3.16 (2.3-4.3) | 3.11 (2.3-4.2) | 3.01 (2.4-4.4) | .6 |
| Intracellular Adhesion Molecule-1 (ng/mL) | 594 (462-819) | 605 (435-801) | 584 (417-787) | 641 (468-886) | .3 |
| Vascular Cell Adhesion Molecule 1 (ng/mL) | 968 (706-1372) | 982 (659-1342) | 975 (700-1313) | 994 (752-1404) | .4 |
Funding
- NIDDK Support