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PHILADELPHIA — A high level of a hormone that regulates phosphate is associated with an increased risk of kidney failure and death among chronic kidney disease (CKD) patients, according to a recent study led by researchers at the University of Miami and the Perelman School of Medicine at the University of Pennsylvania and funded by the National Institute of Diabetes and Digestive Diseases and Kidney Diseases (NIDDK). Results were published in the June 15 issue of the Journal of the American Medical Association.

CKD affects over 20 million Americans and costs the nation nearly $58 billion per year. The findings come from the Chronic Renal Insufficiency Cohort (CRIC) Study, led by principal investigator Harold I. Feldman, MD, MSCE, professor of Medicine, Renal Electrolyte and Hypertension Division, and professor of Epidemiology, and co-principal investigator J. Richard Landis, PhD, professor of Biostatistics.

The CRIC Study follows nearly 4,000 individuals with CKD for the purpose of identifying risk factors for the progression of kidney disease and the development of cardiovascular disease. The current investigation was led by Myles Wolf, MD, MMSc at the University of Miami and was based on a median follow-up period of 3.5 years, during which 266 study participants died and 410 developed kidney failure requiring renal replacement therapy. The study's Scientific and Data Coordinating Center is located at the Perelman School of Medicine.

Researchers report that among patients with earlier stage kidney disease, elevations in fibroblast growth factor 23 (FGF23), a novel hormone regulating phosphate metabolism, were linked to a 1.7-fold higher risk of kidney failure if their baseline estimated glomerular filtration rate (eGFR) was 45 ml/min/1.73m² or higher. Among all CKD patients regardless of their eGFR, the highest FGF23 levels were associated with a 3-fold higher risk of death compared to lower levels of the hormone. The eGFR is a measure of kidney function.

Phosphorus is needed to build and repair bones and teeth, help cells function and maintain DNA. The kidneys, supported by regulatory hormones like FGF23, help control the amount of phosphate in the blood by eliminating the excess. Kidney damage is associated with elevated phosphate levels, which, in turn, may also worsen kidney disease.

"FGF23 is one of the strongest predictors of poor outcomes among CRIC Study participants all of whom have CKD," said Feldman. "FGF23 represents an exciting new possible target for therapies that could reduce the enormous burden of disease in this population."

This research was also supported by NIH's National Center for Research Resources. For more information, please read the NIDDK release.


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