Low-Stable FGF23 Trajectory Associated With Decreased Risk of Mortality

Although it is well known that single measurements of elevated circulating levels of fibroblast growth factor 23 (FGF23) can predict all-cause mortality in end-stage kidney disease (ESKD), long-term patterns in FGF23 levels are less well understood. A new study suggests that a low-stable trajectory of FGF23 is associated with a decreased risk of mortality and offers insights on factors that may predict decreasing FGF23 levels.

These findings were presented by Anna Jeanette Jovanovich, MD, of the University of Colorado, at the American Society of Nephrology's annual meeting held October 1 to November 5, 2017, in New Orleans, LA. Other investigators involved in the study included Myles S. Wolf, MD, MMSc, of Duke, and Zhiying You, MD, of University of Colorado, Denver.

"Patients with end-stage renal disease have a high mortality rate," Jovanovich said. "Cardiovascular disease is the leading cause of death and accounts for greater than 50% of all deaths." And abnormal FGF23 levels are a hallmark for cardiovascular disease. "FGF23 levels may change over time," she continued. "Those changes may differ among patients with end-stage renal disease and affect outcomes."

Researchers drew their data from the Hemodialysis (HEMO) study, which was a randomized multicenter trial that compared the effects of high-dose and standard-dose hemodialysis and high-flux and low-flux hemodialysis. Stored serum samples were used to measure baseline serum intact FGF23 (iFGF23) and annual levels thereafter.

Using latent mixture modeling, researchers identified 5 distinct FGF23 trajectories over time in 919 HEMO patients with at least 2 measurements of iFGF23:

  •  Low-stable (16.8%; n = 154)
  •  Moderate-increasing (17.3%; n = 159)
  •  Elevated-increasing (27.5%; n = 253)
  •  Elevated-stable (25.4%; n = 233)
  •  Moderate-decreasing (13.1%; n = 120)

Logistic regression models were used to identify demographics, markers of mineral metabolism, cardiovascular risk factors, and other variables associated with trajectory group membership; the only predictors of the moderate-decreasing trajectory versus the low-stable trajectory were lower serum calcium (OR, 0.50; 95% CI, 0.35-0.71; P < .0001), lower serum phosphorus (OR, 0.64; 95% CI, 0.53-0.78; P = .0001), and lower serum interleukin-6 (OR, 0.58; 95% CI, 0.39-0.87; P = .009).

Cox regression models were used to examine associations between trajectory groups and all-cause mortality. In fully adjusted analyses, participants with elevated-stable FGF23 trajectories had a higher risk of death (HR, 1.61; 95% CI, 1.10-2.40; P = .01) than participants with low-stable trajectories.

Based on these findings, the study made several conclusions for patients with ESKD:

  •  FGF23 trajectories vary in those undergoing hemodialysis
  •  Lower levels of serum calcium, serum phosphorus, and interleukin-6 appear to predict
     decreasing FGF23 levels
  •  Higher FGF23 trajectories appear to be associated with an increased risk of death

Source: Jovanovich AJ, You Z, Nowak, KL, et al. FGF23 trajectories among patients undergoing chronic hemodialysis in the HEMO Study. Presented at: American Society of Nephrology annual meeting, Kidney Week 2017; October 31-November 5, 2017; New Orleans, LA. Oral Presentation 077.