Significance of podocyte DNA damage and glomerular DNA methylation in CKD patients with proteinuria
Significance of podocyte DNA damage and glomerular DNA methylation in CKD patients with proteinuria
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CKD蛋白尿患者足细胞DNA损伤及肾小球DNA甲基化的意义
DOI：
10.1038/s41440-023-01169-2
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发表时间：
2023
影响因子：
5.4
通讯作者：
Itoh Hiroshi
中科院分区：
文献类型：
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作者：
Yoshimoto Norifumi;Hayashi Kaori;Hishikawa Akihito;Hashiguchi Akinori;Nakamichi Ran;Sugita-Nishimura Erina;Yoshida-Hama Eriko;Azegami Tatsuhiko;Nakayama Takashin;Itoh Hiroshi
世界范围内慢性肾脏病（CKD）患者的数量正在增加，有必要对CKD患者进行早期诊断以改善其预后。以前，在一项使用人体样本的研究中，我们报道了足细胞中的DNA甲基化和DNA损伤是伊加肾病肾功能下降的潜在标志物;然而，这些候选标志物在其他肾小球疾病中尚未得到充分研究。在这里，我们报告足细胞DNA损伤和DNA甲基化与eGFR下降和蛋白尿的相关性取决于肾小球疾病的类型。纳入了2015年至2017年在庆应义塾大学医院肾活检后诊断为轻微肾小球异常（MGA，n= 33）、膜性肾病（MN，n= 9）或糖尿病肾病（DN，n= 10）的患者。在MGA患者中，足细胞DNA损伤和肾小球DNA甲基化均与蛋白尿的严重程度相关。在DN患者中，足细胞DNA双链断裂（DSB）和肾小球DNA甲基化与eGFR下降相关。当检测尿蛋白水平超过1 g/gCr的患者时，MN患者中检测到的足细胞DNA DSB少于MGA患者，MN患者中肾小球DNA甲基化水平低于MGA或DN患者。这些结果表明，研究足细胞DNA DSB和DNA甲基化变化可能有助于了解人类CKD伴蛋白尿的发病机制。本研究表明，足细胞DNA损伤和随后的DNA甲基化分别与肾小球轻微异常（MGA）患者和糖尿病肾病（DN）患者eGFR下降的蛋白尿相关。
The number of chronic kidney disease (CKD) patients is increasing worldwide, and it is necessary to diagnose CKD patients in earlier stages to improve their prognosis. Previously, in a study using human samples, we reported that DNA methylation and DNA damage in podocytes are potential markers for kidney function decline in IgA nephropathy; however, these candidate markers have not been adequately investigated in other glomerular diseases. Here, we report that the association of podocyte DNA damage and DNA methylation with eGFR decline and proteinuria differs depending on the type of glomerular disease. Patients diagnosed with minor glomerular abnormality (MGA,n= 33), membranous nephropathy (MN,n= 9) or diabetic nephropathy (DN,n= 10) following kidney biopsy at Keio University Hospital from 2015 to 2017 were included. In MGA patients, both podocyte DNA damage and glomerular DNA methylation were associated with the severity of proteinuria. In DN patients, podocyte DNA double-strand breaks (DSBs) and glomerular DNA methylation were associated with an eGFR decline. When patients with urinary protein levels of more than 1 g/gCr were examined, fewer podocyte DNA DSBs were detected in MN patients than in MGA patients, and the level of glomerular DNA methylation was lower in MN patients than in MGA or DN patients. These results indicate that investigating podocyte DNA DSBs and DNA methylation changes may be useful for understanding the pathogenesis of CKD with proteinuria in humans.This study suggested the association of podocyte DNA damage and subsequent DNA methylation with proteinuria in minor glomerular abnormalities (MGA) patients and those with eGFR declines in diabetic nephropathy (DN) patients, respectively.