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接受腹膜透析患者血清中Wnt-β-连环蛋白信号通路可溶性抑制剂(硬化蛋白和Dickkopf-1)相关因素

Factors associated with serum soluble inhibitors of Wnt-β-catenin signaling (sclerostin and dickkopf-1) in patients undergoing peritoneal dialysis.

作者信息

Yamada Shunsuke, Tsuruya Kazuhiko, Tokumoto Masanori, Yoshida Hisako, Ooboshi Hiroaki, Kitazono Takanari

机构信息

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Department of Internal Medicine, Fukuoka Dental College, Fukuoka, Japan.

出版信息

Nephrology (Carlton). 2015 Sep;20(9):639-45. doi: 10.1111/nep.12509.

DOI:10.1111/nep.12509
PMID:25974190
Abstract

AIM

Sclerostin and dickkopf-1 (Dkk-1) are soluble inhibitors of Wnt-β-catenin signaling and are involved in decreased bone formation and bone volume in patients with various bone diseases. The clinical characteristics of sclerostin and Dkk-1 and their impacts on mineral and bone metabolism remain undetermined in patients undergoing peritoneal dialysis (PD).

METHODS

This cross-sectional study investigated the association between serum sclerostin and Dkk-1 levels and mineral disorders in 74 outpatients under PD treatment. Levels of sclerostin and Dkk-1 in serum, urine, and peritoneal dialysate were determined using enzyme-linked immunosorbent assay kits. The associations between serum sclerostin and Dkk-1 levels and biochemical parameters were evaluated by linear regression analyses.

RESULTS

Median serum sclerostin and Dkk-1 levels were 138 pmol/L (range, 98.3-195.9 pmol/L) and 38.8 pmol/L (range, 28.5-47.1 pmol/L), respectively. Both sclerostin and Dkk-1 were excreted into urine and peritoneal dialysate. Multivariable linear regression analyses showed that serum sclerostin level was significantly associated with age, sex, parathyroid hormone level, and renal Kt/V. In contrast, serum Dkk-1 level was associated with platelet count and serum fibroblast growth factor 23 level but not with any of the bone metabolic markers.

CONCLUSION

Serum sclerostin was associated with serum intact parathyroid hormone, while Dkk-1 was associated with serum fibroblast growth factor 23 in patients undergoing PD. The utility of determining soluble Wnt-β-catenin inhibitors levels in patients undergoing PD requires further investigation.

摘要

目的

硬化蛋白和 Dickkopf-1(Dkk-1)是 Wnt-β-连环蛋白信号通路的可溶性抑制剂,参与多种骨病患者骨形成减少和骨量降低。在接受腹膜透析(PD)的患者中,硬化蛋白和 Dkk-1 的临床特征及其对矿物质和骨代谢的影响仍未明确。

方法

这项横断面研究调查了 74 例接受 PD 治疗的门诊患者血清硬化蛋白和 Dkk-1 水平与矿物质紊乱之间的关联。使用酶联免疫吸附测定试剂盒测定血清、尿液和腹膜透析液中硬化蛋白和 Dkk-1 的水平。通过线性回归分析评估血清硬化蛋白和 Dkk-1 水平与生化参数之间的关联。

结果

血清硬化蛋白和 Dkk-1 的中位数水平分别为 138 pmol/L(范围 98.3 - 195.9 pmol/L)和 38.8 pmol/L(范围 28.5 - 47.1 pmol/L)。硬化蛋白和 Dkk-1 均排泄到尿液和腹膜透析液中。多变量线性回归分析表明,血清硬化蛋白水平与年龄、性别、甲状旁腺激素水平和肾脏 Kt/V 显著相关。相比之下,血清 Dkk-1 水平与血小板计数和血清成纤维细胞生长因子 23 水平相关,但与任何骨代谢标志物均无关。

结论

在接受 PD 的患者中,血清硬化蛋白与血清完整甲状旁腺激素相关,而 Dkk-1 与血清成纤维细胞生长因子 23 相关。测定接受 PD 患者可溶性 Wnt-β-连环蛋白抑制剂水平的实用性需要进一步研究。

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