Significance of podocyte DNA damage and glomerular DNA methylation in CKD patients with proteinuria

Norifumi Yoshimoto, Kaori Hayashi, Akihito Hishikawa, Akinori Hashiguchi, Ran Nakamichi, Erina Sugita-Nishimura, Eriko Yoshida-Hama, Tatsuhiko Azegami, Takashin Nakayama, Hiroshi Itoh

研究成果: Article査読

6 被引用数 (Scopus)

抄録

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. [Figure not available: see fulltext.].

本文言語English
ページ(範囲)1000-1008
ページ数9
ジャーナルHypertension Research
46
4
DOI
出版ステータスPublished - 2023 4月

ASJC Scopus subject areas

  • 内科学
  • 生理学
  • 循環器および心血管医学

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