June 20, 2011

Hormone Level Predicts Progressive Kidney Failure

Illustration of the body’s internal organs, with the kidneys highlighted

A high level of a hormone is associated with an increased risk of kidney failure and death among patients with chronic kidney disease (CKD). The discovery could lead to earlier diagnosis and treatment of patients at risk.

CKD affects an estimated 23 million American adults. With time, it can turn into kidney failure, at which point dialysis or a kidney transplant is needed. Nearly 400,000 people in the United States and 2 million worldwide now depend on dialysis to treat kidney failure. CKD costs the nation $57.5 billion per year, or roughly 23% of total Medicare expenditures, and end stage renal disease carries a cost of $39.5 billion.

In a previous study of people beginning dialysis to treat kidney failure, patients with elevated blood levels of the hormone fibroblast growth factor 23 (FGF23) were found to be at nearly 6-fold greater risk of death compared to those with lower levels. FGF23 helps regulate phosphate levels in the body. We need phosphate to build and repair bones and teeth, maintain DNA and help cells function. The kidneys, responding to hormones like FGF23, help control the amount of phosphate in the blood by eliminating the excess.

A team led by Dr. Myles Wolf at the University of Miami set out to examine whether FGF23 levels in patients with less advanced CKD could predict outcomes and potentially guide treatment strategies. The scientists examined FGF23 levels in almost 3,900 racially diverse patients with CKD who enrolled in a study at 13 clinical sites between June 2003 and September 2008. The study was funded by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Center for Research Resources (NCRR). The results appeared in the June 15, 2011, issue of the Journal of the American Medical Association.

During a median follow up period of 3.5 years, 266 patients died and 410 developed kidney failure. FGF23 levels were significantly higher in the patients who later died or reached end-stage renal disease than in those who didn’t. Patients with higher FGF23 levels, the researchers found, are at a 3-fold higher risk of death compared to patients with lower levels of the hormone. Patients with higher FGF23 levels are also at nearly 2-fold higher risk of kidney failure if their baseline estimated glomerular filtration rate (a measure of kidney function) is 45 ml or higher.

These findings could lead to earlier diagnosis and treatment of phosphate problems in people with CKD. Treatment typically consists of dietary phosphate restriction and phosphate binders — medications that work like a sponge to soak up phosphate in the gut.

“Since FGF23 rises before phosphate in people with early or intermediate-stage chronic kidney disease, this hormone could be an early marker — like a road sign — pointing to patients who may benefit from early management of phosphate levels, which may help preserve kidney function and reduce deaths,” Wolf says.

Further work will be needed to understand the role of FGF23 in CKD. In addition to serving as a marker for high-risk patients, it might serve as a future target for treatments.

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