Changes in Fibroblast Growth Factor 23 and Soluble Klotho Levels After Hemodialysis Initiation

Chiaki Kawabata; Hirotaka Komaba; Hiroaki Ishida; Yosuke Nakagawa; Naoto Hamano; Masahiro Koizumi; Genta Kanai; Takehiko Wada; Michio Nakamura; Masafumi Fukagawa

doi:10.1016/j.xkme.2019.09.007

Changes in Fibroblast Growth Factor 23 and Soluble Klotho Levels After Hemodialysis Initiation

Kidney Med. 2019 Dec 4;2(1):59-67. doi: 10.1016/j.xkme.2019.09.007. eCollection 2020 Jan-Feb.

Authors

Affiliations

¹ Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan.
² The Institute of Medical Sciences, Tokai University, Isehara, Japan.
³ Department of Transplant Surgery, Tokai University School of Medicine, Isehara, Japan.

Abstract

Rationale & objective: Patients with chronic kidney failure have markedly elevated fibroblast growth factor 23 (FGF-23) levels and decreased soluble Klotho levels. However, no studies have examined the effects of hemodialysis initiation on the levels of these hormones and other parameters of mineral metabolism.

Study design: Prospective single-arm study.

Setting & participants: 20 individuals with incident kidney failure initiating hemodialysis.

Exposure: Initiation of hemodialysis. Dose adjustments of phosphate binders and vitamin D receptor activators and use of calcimimetics, erythropoiesis-stimulating agents, and intravenous iron were prohibited.

Outcomes: Changes in serum levels of FGF-23, soluble Klotho, and other biochemical parameters of mineral metabolism, measured before and after each hemodialysis session, for a total of 4 sessions over 5 days.

Analytical approach: Repeated-measures analysis of variance.

Results: At baseline, participants had 18-fold higher median FGF-23 levels and 1.6-fold lower mean soluble Klotho levels compared with age- and sex-matched healthy individuals. Initiation of hemodialysis led to progressive reductions in serum phosphorus, intact parathyroid hormone, and FGF-23 levels, with dialysis-related fluctuations. No reductions were observed in levels of α₁-microglobulin, which has molecular weight comparable to FGF-23. The magnitude of the FGF-23 level reductions was strongly associated with concomitant changes in serum phosphorus levels but not with the changes in intact parathyroid hormone levels. Soluble Klotho levels did not change after the initiation of hemodialysis.

Limitations: Single-arm design, small sample size, short follow-up period.

Conclusions: Initiation of hemodialysis in patients with chronic kidney failure led to progressive reductions in FGF-23 levels in association with reductions in serum phosphorus levels. These results suggest that phosphorus is a strong inducer of FGF-23 production and that regulation of FGF-23 production is a rapid process.

Keywords: Chronic kidney failure; FGF23; Klotho; hemodialysis; hyperphosphatemia.