The Impact of Preexisting Chronic Kidney Disease on the Severity and Recovery of Acute Kidney Injury

Sung Yoon Lim, Yoon Sook Ko, Hee Young Lee, Ji Hyun Yang, Myung-Gyu Kim, Sang Kyung Jo, Won Yong Cho

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Recent observational studies have shown that in chronic kidney disease (CKD) patients, a significantly smaller percentage of patients with an episode of acute kidney injury (AKI) have full recovery of renal function compared to those without CKD. However, precise mechanisms involved in the incomplete repair after AKI with preexisting CKD have not been completely ascertained. Here, we assessed the impact of preexisting CKD on the severity and recovery of AKI in a mouse model of 5/6 nephrectomy. Methods: Male CD-1 mice underwent 5/6 nephrectomy (Nx). Six weeks post surgery, ischemia reperfusion injury (IRI) or a sham operation was performed and functional, histological, and various molecular parameters were compared between them. Results: Serum creatinine level on day 1 after IRI was comparable between control and Nx mice. However, serum creatinine remained significantly higher throughout the recovery phase in Nx mice compared to control mice. mRNA and protein expression of the cell cycle regulatory proteins were persistently elevated in Nx mice and this was associated with significantly increased levels of the G1 cell cycle arrest markers. Treatment with a p53 inhibitor following IRI resulted in not only decreased expression of G1 arrest markers but also decreased fibrosis, suggesting that prolonged epithelial G1 cell cycle arrest might be partially responsible for impaired recovery from superimposed AKI on CKD. Conclusion: Taken together, reduced nephron mass have a negative effect on the repair process that is partially mediated by the disruption of the cell cycle regulation.

Original languageEnglish
JournalNephron
DOIs
Publication statusAccepted/In press - 2018 Apr 12

Fingerprint

Chronic Renal Insufficiency
Acute Kidney Injury
Reperfusion Injury
G1 Phase Cell Cycle Checkpoints
Nephrectomy
Creatinine
Cell Cycle Proteins
Nephrons
Recovery of Function
Serum
Observational Studies
Cell Cycle
Fibrosis
Epithelial Cells
Kidney
Messenger RNA
Proteins

Keywords

  • Acute kidney injury
  • Cell cycle arrest
  • Chronic kidney disease
  • Insulin-like growth factor-binding protein 7
  • Tissue inhibitor of metalloproteinase-2

ASJC Scopus subject areas

  • Physiology
  • Nephrology
  • Urology
  • Physiology (medical)

Cite this

The Impact of Preexisting Chronic Kidney Disease on the Severity and Recovery of Acute Kidney Injury. / Lim, Sung Yoon; Ko, Yoon Sook; Lee, Hee Young; Yang, Ji Hyun; Kim, Myung-Gyu; Jo, Sang Kyung; Cho, Won Yong.

In: Nephron, 12.04.2018.

Research output: Contribution to journalArticle

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