GFR is a Key Determinant of Red Blood Cell Survival in Anemia Associated With Progressive CKD

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports Pub Date : 2025-03-01 DOI:10.1016/j.ekir.2024.12.023

Rosi Bissinger , Lina Schaefer , Bernhard N. Bohnert , Anja Schork , Sebastian Hoerber , Andreas Peter , Syed M. Qadri , Andreas L. Birkenfeld , Nils Heyne , Tamam Bakchoul , Thomas Wieder , Ferruh Artunc

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Abstract

Introduction

Anemia is a common and clinically significant complication observed in patients with chronic kidney disease (CKD), resulting from complex interactions between renal dysfunction, erythropoietin (EPO) deficiency, and altered iron metabolism. In murine CKD models, red blood cell (RBC) death or eryptosis, characterized by exposure of phosphatidylserine (PS) on the outer membrane of RBCs, was observed to drive anemia. However, there is limited research that has investigated this phenomenon in patients with non–dialysis-dependent CKD (NDD-CKD).

Methods

In this cross-sectional cohort study, we describe the relationship between RBC death and anemia in all stages of NDD-CKD (n = 122). Blood samples from 133 healthy blood donors were additionally analyzed as controls.

Results

Patients with CKD had a significantly lower hemoglobin (Hb) concentration (12.4 [interquartile range: 11.1–13.7] g/dl) when compared with the healthy group (13.8 [13.0–14.8] g/dl, P < 0.001). Hb concentrations exhibited a significant positive correlation with the estimated glomerular filtration rate (eGFR) across the entire cohort (r = 0.5, P < 0.001). RBC death rates, quantified by the binding of freshly isolated RBCs to the ligand annexin V using flow cytometry (FACS), were significantly increased by approximately 1.4-fold in patients with CKD compared with the RBC death rates in healthy blood donors. RBC death correlated with the glomerular filtration rate (GFR) stage but not with the albuminuria stage of CKD, the degree of anemia, and serum iron concentration. Using multiple linear regression, eGFR was identified as the sole independent predictor of RBC death with an inverse relationship.

Conclusion

RBC death is stimulated in progressive NDD-CKD, possibly contributing to the development of renal anemia.

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导言：贫血是慢性肾脏病（CKD）患者常见的、具有临床意义的并发症，它是由肾功能障碍、促红细胞生成素（EPO）缺乏和铁代谢改变之间复杂的相互作用引起的。在小鼠 CKD 模型中，观察到红细胞（RBC）死亡或红细胞沉着病（以红细胞外膜上的磷脂酰丝氨酸（PS）暴露为特征）可导致贫血。方法在这项横断面队列研究中，我们描述了 RBC 死亡与 NDD-CKD 各阶段贫血之间的关系（n = 122）。结果与健康组（13.8 [13.0-14.8] g/dl，P < 0.001）相比，CKD 患者的血红蛋白 (Hb) 浓度明显较低（12.4 [四分位间范围：11.1-13.7] g/dl）。在整个组群中，血红蛋白浓度与肾小球滤过率（eGFR）呈显著正相关（r = 0.5，P < 0.001）。与健康献血者的红细胞死亡率相比，CKD 患者的红细胞死亡率显著增加了约 1.4 倍。红细胞死亡率与肾小球滤过率（GFR）分期相关，但与白蛋白尿分期、贫血程度和血清铁浓度无关。通过多元线性回归，发现 eGFR 是唯一能独立预测 RBC 死亡的因素，两者呈反比关系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Kidney International Reports Medicine-Nephrology

CiteScore

7.70

自引率

3.30%

发文量

1578

审稿时长

8 weeks

期刊介绍： Kidney International Reports, an official journal of the International Society of Nephrology, is a peer-reviewed, open access journal devoted to the publication of leading research and developments related to kidney disease. With the primary aim of contributing to improved care of patients with kidney disease, the journal will publish original clinical and select translational articles and educational content related to the pathogenesis, evaluation and management of acute and chronic kidney disease, end stage renal disease (including transplantation), acid-base, fluid and electrolyte disturbances and hypertension. Of particular interest are submissions related to clinical trials, epidemiology, systematic reviews (including meta-analyses) and outcomes research. The journal will also provide a platform for wider dissemination of national and regional guidelines as well as consensus meeting reports.