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肾性贫血:从 EPO 相对不足到红细胞生成和红细胞皱缩失衡。

Renal anemia: from relative insufficiency of EPO to imbalance of erythropoiesis and eryptosis.

机构信息

Department of Nephrology, Affiliated Hospital of Shandong Second Medical University, 2428 Yuhe Road, Weifang, 261031, Shandong, China.

Department of Clinical Laboratory, Affiliated Hospital of Shandong Second Medical University, 2428 Yuhe Road, Weifang, 261031, Shandong, China.

出版信息

Int Urol Nephrol. 2024 Nov;56(11):3559-3568. doi: 10.1007/s11255-024-04146-x. Epub 2024 Jul 9.

DOI:10.1007/s11255-024-04146-x
PMID:38982020
Abstract

Chronic kidney disease has emerged as a major health issue both in China and worldwide. Renal anemia frequently occurs in patients with chronic kidney disease, and its severity and incidence rate increase as the disease progresses. Over the last 30 years, the administration of exogenous EPO and EPO stimulants has been employed to alleviate renal anemia, suggesting that a relative deficiency in EPO may be a primary cause. However, this approach has overshadowed other contributing factors, particularly eryptosis, which results from the reduced lifespan of red blood cells. Numerous studies reveal that there are nephrogenic and extrarenal EPO secretion indicating that an absolute deficiency of EPO is not always present in patients. Therefore, this paper speculates that renal anemia may arise when EPO-driven erythropoiesis fails to adequately compensate for aggravating eryptosis. Other factors including iron metabolism disorder, uremic toxin accumulation, inflammatory state, oxidative stress, and secondary hyperparathyroidism affect EPO reactivity bone marrow hematopoiesis and eryptosis, leading to an imbalance between red blood cell production and destruction, and cause anemia ultimately. More further studies on the pathogenesis and treatment of renal anemia would be expected to provide evidence to support our opinion.

摘要

慢性肾脏病已成为中国乃至全球的主要健康问题。肾性贫血常发生于慢性肾脏病患者,且随着疾病的进展,其严重程度和发生率均会增加。在过去的 30 年中,外源性 EPO 和 EPO 刺激剂的应用被用于缓解肾性贫血,表明相对 EPO 缺乏可能是主要原因。然而,这种方法掩盖了其他促成因素,特别是红细胞寿命缩短导致的红细胞皱缩。大量研究表明存在肾源性和肾外 EPO 分泌,这表明患者并不总是存在绝对的 EPO 缺乏。因此,本文推测,当 EPO 驱动的红细胞生成不能充分代偿加重的红细胞皱缩时,可能会发生肾性贫血。其他因素包括铁代谢紊乱、尿毒症毒素蓄积、炎症状态、氧化应激和继发性甲状旁腺功能亢进,影响 EPO 反应性骨髓造血和红细胞皱缩,导致红细胞生成和破坏之间的失衡,最终导致贫血。对肾性贫血发病机制和治疗的进一步研究有望为我们的观点提供支持证据。

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Int Urol Nephrol. 2024 Nov;56(11):3559-3568. doi: 10.1007/s11255-024-04146-x. Epub 2024 Jul 9.
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本文引用的文献

1
Growing concerns about using hypoxia-inducible factor prolyl hydroxylase inhibitors for the treatment of renal anemia.对使用缺氧诱导因子脯氨酰羟化酶抑制剂治疗肾性贫血的担忧日益增加。
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Efficacy and safety of hypoxia-inducible factor prolyl hydroxylase inhibitors in patients with chronic kidney disease: meta-analysis of phase 3 randomized controlled trials.缺氧诱导因子脯氨酰羟化酶抑制剂在慢性肾脏病患者中的疗效与安全性:3期随机对照试验的荟萃分析
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Safety and Efficacy of Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitors vs. Erythropoietin-Stimulating Agents in Treating Anemia in Renal Patients (With or Without Dialysis): A Meta-Analysis and Systematic Review.
缺氧诱导因子脯氨酰羟化酶抑制剂与促红细胞生成素刺激剂治疗肾病患者(无论是否接受透析)贫血的安全性和有效性:一项荟萃分析和系统评价
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4
Eryptosis: a driver of anemia in chronic kidney disease.红细胞凋亡:慢性肾脏病贫血的一个驱动因素。
Curr Opin Nephrol Hypertens. 2024 Mar 1;33(2):220-225. doi: 10.1097/MNH.0000000000000957. Epub 2023 Nov 17.
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Metformin-associated Lactic Acidosis Induced by Excessive Alcohol Consumption.因过度饮酒导致的二甲双胍相关性乳酸性酸中毒。
Intern Med. 2024 Jun 15;63(12):1745-1749. doi: 10.2169/internalmedicine.2707-23. Epub 2023 Nov 13.
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Molecular Mechanisms and Pathophysiological Significance of Eryptosis.促红细胞生成性细胞凋亡的分子机制及病理生理学意义。
Int J Mol Sci. 2023 Mar 7;24(6):5079. doi: 10.3390/ijms24065079.
7
The novel GATA1-interacting protein HES6 is an essential transcriptional cofactor for human erythropoiesis.新型 GATA1 相互作用蛋白 HES6 是人红细胞生成的必需转录共激活因子。
Nucleic Acids Res. 2023 Jun 9;51(10):4774-4790. doi: 10.1093/nar/gkad167.
8
Indoxyl sulfate impairs erythropoiesis at BFU-E stage in chronic kidney disease.硫酸吲哚酚在慢性肾脏病的BFU-E阶段损害红细胞生成。
Cell Signal. 2023 Apr;104:110583. doi: 10.1016/j.cellsig.2022.110583. Epub 2022 Dec 31.
9
Association of Red Blood Cell Life Span with Abnormal Changes in Cardiac Structure and Function in Non-Dialysis Patients with Chronic Kidney Disease Stages 3-5.非透析慢性肾脏病3-5期患者红细胞寿命与心脏结构和功能异常变化的关联
J Clin Med. 2022 Dec 12;11(24):7373. doi: 10.3390/jcm11247373.
10
Eryptosis in Patients with Chronic Kidney Disease: A Possible Relationship with Oxidative Stress and Inflammatory Markers.慢性肾脏病患者的红细胞凋亡:与氧化应激和炎症标志物的可能关系。
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