ABSTRACT
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Subject(s)
Coronary Artery Disease/metabolism , Coronary Vessels/metabolism , Fibroblast Growth Factors/genetics , Gene Expression Regulation , RNA/genetics , Renal Insufficiency, Chronic/complications , Calcinosis/etiology , Calcinosis/genetics , Calcinosis/metabolism , Coronary Artery Disease/etiology , Coronary Artery Disease/genetics , Coronary Vessels/pathology , Female , Fibroblast Growth Factor-23 , Fibroblast Growth Factors/biosynthesis , Follow-Up Studies , Humans , Immunohistochemistry , Male , Middle Aged , Real-Time Polymerase Chain Reaction , Renal Insufficiency, Chronic/genetics , Renal Insufficiency, Chronic/metabolism , Retrospective StudiesABSTRACT
BACKGROUND: Low birth-weight infants are at risk for renal disease when renal insults occur in the neonatal period. Renal growth as measured by sonography over time is utilized by many nephrologists as predictors of future renal disease. OBJECTIVE: To identify infants at risk by defining normal renal growth for the very premature infant. MATERIALS AND METHODS: Renal growth was evaluated in 30 infants whose birth weight was 1,500 g or less and gestational age was <31 weeks. During a 2-month time period, three US measurements were taken (first week of life, age 28 days, and age 56 days or earlier if discharged). Infants were divided according to birth weight: the extremely low birth-weight group (ELBW) was <1,000 g (n = 14), and the very low birth-weight group (VLBW) was 1,000-1,500 g (n = 16). RESULTS: In both groups, the right and left renal lengths were similar. In the ELBW group, the initial mean length was 3.25 cm and grew to 4.16 cm, while the mean volume was 4.85 cm and grew to 10.39 cm. In the VLBW group the initial mean length was 3.69 cm and grew to 4.35 cm while the mean volume was 7.25 cm and grew to 11.83 cm. CONCLUSION: These data establish normal expected growth for future studies.
