Dialysis – Transplantation
Kidney International (2005) 67, 1171–1178; doi:10.1111/j.1523-1755.2005.00184.x
Serum fibroblast growth factor-23 levels predict the future refractory hyperparathyroidism in dialysis patients
SHOHEI NAKANISHI, JUNICHIRO JAMES KAZAMA, TOMOKO NII-KONO, KENTARO OMORI, TAKEYOSHI YAMASHITA, SEIJI FUKUMOTO, FUMITAKE GEJYO, TAKASHI SHIGEMATSU and MASAFUMI FUKAGAWA
Division of Nephrology and Dialysis Center, Kobe University School of Medicine, Kobe, Japan; Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Pharmaceutical Research Labs, KIRIN Brewery Co., Ltd., Takasaki, Japan; Division of Laboratory Medicine, University of Tokyo Faculty of Medicine, Bunkyo, Japan; and Division of Nephrology, Tokyo-Jikeikai Medical School Aoto Hospital, Katsushika, Japan
Correspondence: Masafumi Fukagawa, M.D., Ph.D., FJSIM, Associate Professor and Director, Division of Nephrology and Dialysis Center, Kobe University School of Medicine, 7–5-2 Kusunoki-cho, Chuo-ku, Kobe 650–0017, Japan. E-mail:fukagawa@med.kobe-u.ac.jp
Received 24 December 2003; Revised 19 July 2004; Re-revised 11 September 2004; Accepted 30 September 2004.
Abstract
Serum fibroblast growth factor-23 levels predict the future refractory hyperparathyroidism in dialysis patients.
Background
Secondary hyperparathyroidism is a common complication among long-term dialysis patients. The method of predicting future parathyroid function has not yet been established. Fibroblast growth factor-23 (FGF-23) is a newly found humoral phosphaturic factor.
Methods
One hundred and three nondiabetic dialysis patients whose plasma intact parathyroid hormone (PTH) levels were below 300 pg/mL were included in the study. Blood samples were stored at -80°C for 2 years. Meanwhile, each physician in charge decided upon the strategy of medical therapy for maintaining intact PTH levels between 150 and 300 pg/mL. Patients were judged 2 years after the sample collection with regard to whether the hyperparathyroidism responded to the medical therapy. The definition of refractory secondary hyperparathyroidism was either (1) retaining intact PTH levels greater than 300 pg/mL 2 years after sample collection, or (2) having received the parathyroid intervention therapy during the observation period. Serum FGF-23 levels were determined with a sandwich enzyme-linked immunosorbent assay system that detects biologically active human FGF-23.
Results
Seventeen patients with intact PTH levels greater than 300 pg/mL were judged as having secondary hyperparathyroidism refractory to medical therapy. A stepwise regression analysis revealed that only serum levels of FGF-23 were significantly related to the prognosis of parathyroid function. A receiver-operated characteristic analysis demonstrated that the area under the curves obtained from FGF-23 (7099.9) was significantly greater than that obtained from intact PTH (6306.4, P < .01) and Ca 
Pi (5670.3, P <.0001). Although the plasma intact PTH levels at the beginning of the observation period were comparable to each other, the intact PTH levels at 2 years after the sample collection were significantly higher in the patients with FGF-23 
7500 ng/L than in those with FGF-23 <7500 ng/L (P < .0001).
Conclusion
Serum FGF-23 level was found to be the most useful factor in predicting future development of refractory secondary hyperparathyroidism in long-term dialysis patients with mild secondary hyperparathyroidism. The measurement of serum FGF-23 levels is a promising laboratory examination that can be applied in the clinical practice of uremic secondary hyperparathyroidism.
Keywords:
FGF-23, hyperparathyroidism, PTH, vitamin D, dialysis, phosphate
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