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临床试验:自体树突状细胞给药对糖尿病肾病患者肾血流动力学及炎症生物标志物的影响

Clinical Trial: Effects of Autologous Dendritic Cell Administration on Renal Hemodynamics and Inflammatory Biomarkers in Diabetic Kidney Disease.

作者信息

Drajat Endang, Icksan Aziza Ghanie, Jonny Jonny, Lokeswara Aditya Pratama, Hernowo Bhimo Aji, Daulay Elvita Rahmi, Putranto Terawan Agus

机构信息

Faculty of Medicine, Dentistry, and Health Sciences, Universitas Prima Indonesia, Medan 20118, Indonesia.

Department of Radiology, Gatot Soebroto Army Hospital, Jakarta 10410, Indonesia.

出版信息

Diseases. 2025 Apr 21;13(4):122. doi: 10.3390/diseases13040122.

Abstract

BACKGROUND

Diabetic kidney disease (DKD) is a significant risk factor for End-Stage Renal Disease, with a high global incidence and mortality rate. Hyperglycemia in DKD induces inflammation, contributing to glomerular hyperfiltration, fibrosis, and impaired renal function. Current therapies, including SGLT2 inhibitors, ACE inhibitors, and ARBs, show limited efficacy. Autologous dendritic cells (DCs) offer potential anti-inflammatory effects by reducing cytokine activity and fibrosis biomarkers.

METHODS

A quasi-experimental pretest-post-test design was conducted involving 29 DKD patients. Baseline blood and urine samples were collected for MMP-9, TGF-β, and Doppler ultrasound (PSV, EDV) measurements. The subjects received subcutaneous injections of autologous DCs, and follow-up measurements were conducted four weeks after treatment. The statistical analyses included paired t-tests, Wilcoxon signed-rank tests, and linear regression.

RESULTS

After treatment, there were a significant decrease in PSV (from 47.1 ± 23.87 cm/s to 27.85 ± 20.53 cm/s, = 0.044) and a significant increase in EDV (from 13 ± 5.32 cm/s to 15.7 ± 12.55 cm/s, = 0.039). A strong correlation was observed between the TGF-β and MMP-9 levels ( = 0.001). Linear regression analysis showed reduced MMP-9 influence on the TGF-β after treatment, suggesting potential fibrosis reduction. Gender and UACR subgroup analyses revealed significant PSV and EDV improvements in females and the microalbuminuria group.

CONCLUSION

Autologous dendritic cell therapy significantly improved renal hemodynamics and showed potential to reduce fibrosis by modulating TGF-β and MMP-9 levels in DKD patients, warranting further investigation.

摘要

背景

糖尿病肾病(DKD)是终末期肾病的一个重要危险因素,在全球范围内发病率和死亡率都很高。DKD中的高血糖会引发炎症,导致肾小球高滤过、纤维化以及肾功能受损。目前的治疗方法,包括钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂、血管紧张素转换酶(ACE)抑制剂和血管紧张素Ⅱ受体阻滞剂(ARBs),疗效有限。自体树突状细胞(DCs)通过降低细胞因子活性和纤维化生物标志物发挥潜在的抗炎作用。

方法

采用类实验性的前测-后测设计,纳入29例DKD患者。采集基线血液和尿液样本,用于测量基质金属蛋白酶-9(MMP-9)、转化生长因子-β(TGF-β)以及进行多普勒超声检查(测量峰值流速[PSV]、舒张末期流速[EDV])。受试者接受自体DCs皮下注射,并在治疗四周后进行随访测量。统计分析包括配对t检验、Wilcoxon符号秩检验和线性回归。

结果

治疗后,PSV显著降低(从47.1±23.87厘米/秒降至27.85±20.53厘米/秒,P = 0.044),EDV显著升高(从13±5.32厘米/秒升至15.7±12.55厘米/秒,P = 0.039)。观察到TGF-β和MMP-9水平之间存在强相关性(P = 0.001)。线性回归分析显示治疗后MMP-9对TGF-β的影响降低,提示潜在纤维化减轻。性别和尿白蛋白与肌酐比值(UACR)亚组分析显示,女性和微量白蛋白尿组的PSV和EDV有显著改善。

结论

自体树突状细胞疗法显著改善了肾脏血流动力学,并显示出通过调节DKD患者的TGF-β和MMP-9水平来减轻纤维化的潜力,值得进一步研究。

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