血液透析开始后成纤维细胞生长因子23和可溶性klotho水平的变化
Changes in Fibroblast Growth Factor 23 and Soluble Klotho Levels After Hemodialysis Initiation.
作者信息
Kawabata Chiaki, Komaba Hirotaka, Ishida Hiroaki, Nakagawa Yosuke, Hamano Naoto, Koizumi Masahiro, Kanai Genta, Wada Takehiko, Nakamura Michio, Fukagawa Masafumi
机构信息
Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan.
The Institute of Medical Sciences, Tokai University, Isehara, Japan.
出版信息
Kidney Med. 2019 Dec 4;2(1):59-67. doi: 10.1016/j.xkme.2019.09.007. eCollection 2020 Jan-Feb.
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 α-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.
原理与目的
慢性肾衰竭患者的成纤维细胞生长因子23(FGF - 23)水平显著升高,可溶性Klotho水平降低。然而,尚无研究探讨开始血液透析对这些激素水平及其他矿物质代谢参数的影响。
研究设计
前瞻性单臂研究。
研究地点与参与者
20例初发肾衰竭并开始血液透析的个体。
暴露因素
开始血液透析。禁止调整磷结合剂和维生素D受体激活剂的剂量,禁止使用拟钙剂、促红细胞生成剂和静脉铁剂。
观察指标
在每次血液透析治疗前后测定血清FGF - 23、可溶性Klotho水平及其他矿物质代谢生化参数的变化,共进行5天4次治疗。
分析方法
重复测量方差分析。
结果
与年龄和性别匹配的健康个体相比,基线时参与者的FGF - 23中位数水平高18倍,可溶性Klotho平均水平低1.6倍。开始血液透析导致血清磷、全段甲状旁腺激素和FGF - 23水平逐渐降低,并伴有与透析相关的波动。分子量与FGF - 23相当的α - 微球蛋白水平未见降低。FGF - 23水平降低的幅度与血清磷水平的伴随变化密切相关,但与全段甲状旁腺激素水平的变化无关。开始血液透析后可溶性Klotho水平未发生变化。
局限性
单臂设计、样本量小、随访期短。
结论
慢性肾衰竭患者开始血液透析导致FGF - 23水平随血清磷水平降低而逐渐降低。这些结果表明磷是FGF - 23产生的强诱导剂,且FGF - 23产生的调节是一个快速过程。
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