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早期对持续红细胞生成素受体激动剂的反应可预测肾脏预后,并由非透析慢性肾脏病中的新型抗氧化标记物决定:一项前瞻性、观察性、单中心研究。

Early responsiveness to continuous erythropoietin receptor activator predicts renal prognosis and is determined by a novel antioxidative marker in non-dialysis chronic kidney disease: a prospective, observational, single-center study.

机构信息

Department of Nephrology, Toda Central General Hospital, 1-19-3 Hon-cho, Toda city, Saitama, 335-0023, Japan.

Department of Internal Medicine IV, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjyuku-ku, Tokyo, 162-0054, Japan.

出版信息

Clin Exp Nephrol. 2020 Jul;24(7):590-597. doi: 10.1007/s10157-020-01873-0. Epub 2020 Mar 17.

DOI:10.1007/s10157-020-01873-0
PMID:32185544
Abstract

BACKGROUND

Responsiveness to erythropoietin-stimulating agents (ESAs) is important for anemia management in chronic kidney disease (CKD). We assessed the effects of a continuous erythropoietin receptor activator (CERA) on renoprotection beyond anemia management and the correlation between the responsiveness to ESAs and oxidative stress markers in CKD.

METHODS

This single-center, prospective, observational study was conducted over 24 months. We administered CERA to 35 non-dialysis patients with hemoglobin (Hb) < 11 g/dL and examined the results of the serum diacron-reactive oxygen metabolite (dROMs) test for oxidative stress markers and biological antioxidant potential (BAP) test for antioxidant markers. We then examined the renoprotective effects of CERA and the responsiveness to CERA.

RESULTS

Eighteen patients experienced renal events (doubling of serum creatinine levels, decreased estimated glomerular filtration rate to < 6.0 mL/min/1.73 m, or initiation of renal replacement therapy), seventeen of which survived. Kaplan-Meier analysis showed that responsiveness to CERA during the initial 3-month treatment period was a good predictor of renal events. Moreover, a high response to CERA during the 3 months independently suppressed renal events (hazard ratio, 0.344). High BAP levels at baseline were significantly associated with high responsiveness to CERA during the initial 3-month treatment period.

CONCLUSION

Responsiveness to CERA during the first 3 months was an important indicator of CKD progression. Moreover, BAP test results determined responsiveness to CERA. This is the first report to show how antioxidant levels can be a potential marker of CERA's ability to control anemia in CKD patients.

摘要

背景

促红细胞生成素刺激剂(ESAs)的反应性对于慢性肾脏病(CKD)的贫血管理很重要。我们评估了持续型促红细胞生成素受体激动剂(CERA)在贫血管理之外对肾脏保护的作用,以及 CKD 中 ESAs 反应性与氧化应激标志物之间的相关性。

方法

这是一项为期 24 个月的单中心、前瞻性、观察性研究。我们给 35 名血红蛋白(Hb)<11g/dL 的非透析患者使用 CERA,并检查了血清二克伦氧化应激标志物检测(dROMs)试验和生物抗氧化能力(BAP)试验的氧化应激标志物和抗氧化标志物的结果。然后,我们检查了 CERA 的肾脏保护作用和对 CERA 的反应性。

结果

18 名患者发生了肾脏事件(血清肌酐水平翻倍、估算肾小球滤过率下降至<6.0mL/min/1.73m 或开始肾脏替代治疗),其中 17 名存活。Kaplan-Meier 分析表明,初始 3 个月治疗期间对 CERA 的反应性是肾脏事件的良好预测指标。此外,在最初的 3 个月治疗期间对 CERA 的高反应独立地抑制了肾脏事件(危险比,0.344)。基线时的高 BAP 水平与初始 3 个月治疗期间对 CERA 的高反应性显著相关。

结论

在最初的 3 个月内对 CERA 的反应性是 CKD 进展的一个重要指标。此外,BAP 试验结果决定了对 CERA 的反应性。这是第一项报告表明抗氧化剂水平如何成为 CKD 患者控制贫血的 CERA 能力的潜在标志物。

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本文引用的文献

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Association between responsiveness to methoxy polyethylene glycol-epoetin beta and renal survival in patients with non-dialysis-dependent chronic kidney disease: A pooled analysis of individual patient-level data from clinical trials.非透析依赖性慢性肾脏病患者对聚乙二醇化促红细胞生成素β的反应性与肾脏生存之间的关联:来自临床试验个体患者水平数据的汇总分析
Nephrology (Carlton). 2017 Oct;22(10):769-775. doi: 10.1111/nep.12842.
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Influence of green tea catechins on oxidative stress metabolites at rest and during exercise in healthy humans.
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Responsiveness to erythropoiesis-stimulating agents and renal survival in patients with chronic kidney disease.慢性肾脏病患者对促红细胞生成素刺激剂的反应性与肾脏存活情况
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Redox Rep. 2014 Sep;19(5):190-8. doi: 10.1179/1351000214Y.0000000090. Epub 2014 Apr 3.
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