FGF23 protein expression in coronary arteries is associated with impaired kidney function

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2014-08, Vol.29 (8), p.1525-1532
• Main Authors: van Venrooij, Natalie A, Pereira, Renata C, Tintut, Yin, Fishbein, Michael C, Tumber, Navdeep, Demer, Linda L, Salusky, Isidro B, Wesseling-Perry, Katherine
• Format: Article
• Language: English
• Subjects: Calcinosis - etiology; Calcinosis - genetics; Calcinosis - metabolism; CLINICAL SCIENCE; Coronary Artery Disease - etiology; Coronary Artery Disease - genetics; Coronary Artery Disease - metabolism; Coronary Vessels - metabolism; Coronary Vessels - pathology; Female; Fibroblast Growth Factors - biosynthesis; Fibroblast Growth Factors - genetics; Follow-Up Studies; Gene Expression Regulation; Humans; Immunohistochemistry; Male; Middle Aged; Real-Time Polymerase Chain Reaction; Renal Insufficiency, Chronic - complications; Renal Insufficiency, Chronic - genetics; Renal Insufficiency, Chronic - metabolism; Retrospective Studies; RNA - genetics
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gft523

Fibroblast growth factor 23 (FGF23) levels are elevated in chronic kidney disease (CKD) and elevated values have been associated with both heart disease and mortality. Recent studies show that FGF23, a protein synthesized by osteocytes, is also present in calcified atherosclerotic plaques and may be induced by heart disease. Whether vascular expression of FGF23 is associated with progressive CKD, however, remains unknown. Therefore, the relationship between kidney function, vascular calcification and FGF23 expression was evaluated in patients with heart disease. Immunohistochemistry for FGF23 was performed in coronary arteries of all patients undergoing heart transplantation at UCLA between February 2008 and 2010. Immunohistochemical staining for Klotho, DMP1, FGFR1, and FGFR3; calcium deposition; and RNA expression of Klotho and DMP1 were assessed in a subset of eight samples. FGF23 was detected by immunohistochemistry in 56% of the coronary artery specimens. Vascular FGF23 expression correlated with declining kidney function, as evidenced by reduced creatinine clearance. FGFR1 and FGFR3 were detected throughout the vascular tissue and in calcified plaques. Calcium deposition, Klotho expression and DMP1 expression correlated with FGF23 immunoreactivity. The findings suggest that the Klotho-FGF23-FGFR system is active in coronary arteries and its upregulation correlates with impaired renal function and matrix calcium deposition.