Association of circulating fibroblast growth factor-23 with renal phosphate excretion among hemodialysis patients with residual renal function

Abstract

Background and objectives: High serum levels of fibroblast growth factor-23 (FGF-23) are associated with mortality in patients with ESRD, but whether it still acts as a phosphaturic factor is unknown. This study aimed to explore the role of circulating FGF-23 on urinary phosphate excretion and phosphate balance in maintenance hemodialysis (MHD) patients with residual renal function (RRF).

Design, setting, participants, & measurements: There were 134 MHD patients enrolled in this cross-sectional study from June to July 2010. Demographics, laboratory data, and excretion capacity of phosphate were recorded. Multivariable linear regression was used to analyze the relationship of serum phosphate and the tubular reabsorption rate of phosphate with other factors.

Results: The median age of the patients was 61.0 years and 47.8% were male. Thirty percent of the patients had high urinary output (>200 ml/d) accompanied by lower serum levels of phosphate, calcium, intact parathyroid hormone, and FGF-23 compared with those with low urine output (≤200 ml/d). The independent predictors of serum phosphate were normalized protein nitrogen appearance, intact parathyroid hormone, and FGF-23 in the low urine output group and female sex and GFR in the high urine output group. The tubular reabsorption rate of phosphate decreased to 50% of the normal level in patients with RRF. Elevated circulating FGF-23 was significantly associated with lower tubular phosphate reabsorption after adjusting for GFR.

Conclusions: RRF is associated with significant capacity to excrete phosphate in MHD patients and high levels of serum FGF-23 may promote phosphate excretion by remnant nephrons.

Figure 1.

Removal of phosphate in MHD patients from groups I (anuric), II (urine output ≤200 ml/d), and III (urine output >200 ml/d). (A) Changes of dialysate phosphate concentration during a 4-hour hemodialysis treatment. (B) Total amount of phosphate removal by a 4-hour hemodialysis. *P<0.05 group I versus group II. ^†P<0.01 group I versus group III. (C) Daily urinary phosphate excretion (group II versus group III). ^‡P<0.001. Values show means ± SDs.

Figure 2.

Tubular reabsorption of electrolytes in MHD patients with high urinary output. (A) Renal tubular reabsorption rates of sodium, calcium, chlorine, and phosphate in MHD patients and healthy controls. Boxes represent the interquartile range, with the upper and lower edges representing the 75th and 25th percentiles, respectively. The central horizontal lines represent the median levels. The vertical whiskers above and below the boxes represent the range of 5%–95% percentiles. Circles beyond the whiskers represent severe outliers. ^§P<0.001 versus control. (B) Percentage decrease in the rate of electrolytes in MHD patients. ^∥P<0.001 comparison of phosphate with sodium, calcium, or chlorine.

Figure 3.

Correlation of tubular reabsorption rate of phosphate and GFR, Log₁₀ FGF-23, Log₁₀ iPTH, 1,25(OH)₂D₃, Log₁₀ α-Klotho, and serum phosphate in 40 patients whose urinary output was >200 ml/d.