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IgA 肾病患者外周血线粒体 DNA 拷贝数:一项横断面研究。

Mitochondrial DNA copy number in peripheral blood of IgA nephropathy: a cross-sectional study.

机构信息

Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

NHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China.

出版信息

Ren Fail. 2023 Dec;45(1):2182133. doi: 10.1080/0886022X.2023.2182133.

Abstract

Mitochondrial DNA (mtDNA) copy number (CN) is a biomarker of mitochondrial function and has been reported associated with kidney disease. However, its association with IgA nephropathy (IgAN), the most common cause of glomerulonephritis (GN), has not been evaluated. We included 664 patients with biopsy-proven IgAN and measured mtDNA-CN in peripheral blood by multiplexed real-time quantitative polymerase chain reaction (RT-qPCR). We examined the associations between mtDNA-CN and clinical variables and found that patients with higher mtDNA-CN had higher estimated glomerular filtration rate (eGFR) ( = 0.1009,  = .0092) and lower serum creatinine (SCr), blood urea nitrogen (BUN), and uric acid (UA) (=-0.1101, -0.1023, -0.07806, respectively, all values <.05). In terms of pathological injury, mtDNA-CN was higher in patients with less mesangial hypercellularity ( = .0385, 0 vs. 1 score by Oxford classification). Multivariable logistic regression analyses also showed that mtDNA-CN was lower for patients with moderate to severe renal impairment (defined as eGFR < 60 mL/min/1.73 m) vs. mild renal impairment, with the odds ratio of 0.757 (95% confidence interval: 0.579-0.990,  = .042). In conclusion, mtDNA-CN was correlated with better renal function and less pathological injury in patients with IgAN, proposing that systemic mitochondrial dysfunction may be involved in or reflect the development of IgAN.

摘要

线粒体 DNA(mtDNA)拷贝数(CN)是线粒体功能的生物标志物,已有报道称其与肾脏疾病相关。然而,其与 IgA 肾病(IgAN)的相关性尚未得到评估,IgAN 是最常见的肾小球肾炎(GN)病因。我们纳入了 664 例经活检证实的 IgAN 患者,并通过多重实时定量聚合酶链反应(RT-qPCR)测量外周血中的 mtDNA-CN。我们检验了 mtDNA-CN 与临床变量之间的关联,发现 mtDNA-CN 较高的患者估算肾小球滤过率(eGFR)较高(=0.1009,=0.0092),血清肌酐(SCr)、血尿素氮(BUN)和尿酸(UA)较低(=-0.1101,-0.1023,-0.07806,均<0.05)。在病理损伤方面,Oxford 分类中系膜细胞增生程度较轻的患者 mtDNA-CN 更高(=0.0385,0 分与 1 分)。多变量逻辑回归分析还显示,与轻度肾功能损害患者相比,中重度肾功能损害(定义为 eGFR<60 mL/min/1.73 m)患者的 mtDNA-CN 较低,比值比为 0.757(95%置信区间:0.579-0.990,=0.042)。总之,mtDNA-CN 与 IgAN 患者的肾功能更好和病理损伤更轻相关,提示系统性线粒体功能障碍可能参与或反映了 IgAN 的发生发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/258d/10013479/44b11fda40b9/IRNF_A_2182133_F0001_B.jpg

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