Hemodiafiltration Attenuates NETosis Compared With High-Flux Hemodialysis in End-Stage Kidney Disease Patients

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports Pub Date : 2025-09-01 DOI:10.1016/j.ekir.2025.06.002

Lital Remez-Gabay , Olga Vdovich , Faten Y. Andrawes Barbara , George Jiries , Etty Kruzel-Davila

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Abstract

Introduction

Patients with chronic kidney disease (CKD) and diabetes mellitus face a heightened risk of cardiovascular complications and infections, potentially exacerbated by dysregulated NETosis. Given the superior survival rates observed with hemodiafiltration (HDF) over high-flux hemodialysis (HD; HFHD) and the documented NETosis dysregulation in HD and in patients with diabetes mellitus, this study aimed to investigate the impact of dialysis modality on NETosis activity in patients on HD, stratified by diabetes status.

Methods

A total of 20 patients on HD (10 with diabetes, 10 without diabetes) undergoing HDF treatment were recruited. Blood samples were collected before and after HDF. After transition to HFHD treatment, blood samples were taken again after 1 and 3 weeks of HDFD treatment. Neutrophils were isolated, stimulated with phorbol-12-myristate-13-acetate, and stained for the following NETosis markers: peptidyl arginine deiminase 4 (PAD4), neutrophil elastase (NE), myeloperoxidase (MPO), histone H3, and double-stranded DNA (dsDNA). Data were acquired using a flow cytometer. In addition, serum levels of citrullinated histone H3 (citH3), MPO, and NE were measured using enzyme-linked immunosorbent assay.

Results

Our results demonstrate a significant increase in NETosis activation and markers after HFHD treatment compared with HDF treatment. NETosis markers significantly increased in serum after 3 weeks of HFHD treatment. In addition, significantly lower NETosis markers were observed in patients with diabetes than in patients without diabetes.

Conclusion

The increase in NETosis markers after 3 weeks of HFHD compared with HDF highlights the role of HDF in mitigating dysregulated NETosis. Further research is needed to explore differences in NETosis profiles across patient populations and assess their clinical implications based on dialysis modality.

Abstract Image

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与高通量血液透析相比，血液滤过可减轻终末期肾病患者的NETosis

慢性肾脏疾病（CKD）和糖尿病患者面临心血管并发症和感染的高风险，NETosis失调可能加剧这种风险。鉴于血液滤过（HDF）比高通量血液透析（HD； HFHD）观察到更高的生存率，以及HD和糖尿病患者中已记录的NETosis失调，本研究旨在研究透析方式对HD患者NETosis活性的影响，并按糖尿病状态分层。方法共招募20例接受HDF治疗的HD患者（合并糖尿病10例，非糖尿病10例）。分别在HDF前后采集血样。过渡到HFHD治疗后，在HDFD治疗1周和3周后再次采集血样。分离中性粒细胞，用phorpol -12-肉豆酸酯-13-醋酸酯刺激，并染色以下NETosis标记物：肽基精氨酸脱亚胺酶4 （PAD4）、中性粒细胞弹性酶（NE）、髓过氧化物酶（MPO）、组蛋白H3和双链DNA （dsDNA）。使用流式细胞仪获取数据。此外，采用酶联免疫吸附法测定血清瓜氨酸组蛋白H3 （citH3）、MPO和NE水平。结果与HDF治疗相比，HFHD治疗后NETosis激活和标志物显著增加。HFHD治疗3周后血清NETosis标志物显著升高。此外，糖尿病患者的NETosis标志物明显低于非糖尿病患者。结论与HDF相比，HFHD治疗3周后NETosis标记物升高，表明HDF在缓解NETosis失调中的作用。需要进一步的研究来探索NETosis在不同患者群体中的差异，并根据透析方式评估其临床意义。

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.