Disordered phosphorus and vitamin D metabolism are novel risk factors for cardiovascular disease (CVD) and mortality in patients with chronic kidney disease (CKD), a public health epidemic estimated to affect 20 million people in the US. Fibroblast growth factor-23 (FGF-23) is a recently discovered hormone that regulates serum phosphate and 1, 25-dihydroxyvitamin D (1,25D) levels. The most common disorder of FGF-23 excess is CKD in which progressive, severe increases help maintain normophosphatemia despite declining nephron mass. Preliminary data from our group suggest that increased FGF-23 levels in normophosphatemic CKD patients are also associated with coronary artery calcification, left ventricular hypertrophy, and mortality. Importantly, FGF-23 levels rise long before hyperphosphatemia first develops and can be lowered with routine clinical interventions such as dietary phosphorus restriction and phosphorus binders. Thus, we hypothesize that FGF-23 excess is a modifiable risk factor for adverse outcomes in CKD and a novel biomarker to help guide phosphate reduction strategies in normophosphatemic CKD patients who are not currently treated. Our experienced investigative team will study FGF-23 excess as a novel risk factor for adverse cardiovascular and renal outcomes in the Chronic Renal Insufficiency Cohort, an NIH-supported prospective study of 3800 predialysis CKD patients, the vast majority of whom have normal serum phosphate levels. The results could suggest a major paradigm shift for clinical practice with public health implications: phosphate reduction strategies for far more people far earlier in their course of CKD.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Special Emphasis Panel (ZDK1-GRB-N (M3))
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Kimmel, Paul
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University of Miami School of Medicine
Internal Medicine/Medicine
Schools of Medicine
Coral Gables
United States
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