Moderate aging does not exacerbate cisplatin-induced kidney injury or fibrosis despite altered inflammatory cytokine expression and immune cell infiltration

Am J Physiol Renal Physiol. 2019 Jan 1;316(1):F162-F172. doi: 10.1152/ajprenal.00463.2018. Epub 2018 Nov 28.

Abstract

Aging is a risk factor for certain forms of kidney injury due to normal physiological changes, but the role of aging in cisplatin-induced kidney injury is not well defined in humans or animal models of the disease. To improve on current knowledge in this field, we treated 8- and 40-wk-old FVB/n mice with one high dose of cisplatin as a model of acute kidney injury or with repeated low doses of cisplatin (7 mg/kg cisplatin once a week for 4 wk) as a clinically relevant model of chronic kidney disease to determine if aging exacerbates cisplatin-induced kidney injury. Levels of acute kidney injury were comparable in 8- and 40-wk-old mice. In 40-wk-old mice, fibrotic markers were elevated basally, but treatment with cisplatin did not exacerbate fibrosis. We concluded that this may be the result of a decreased inflammatory response in 40-wk-old cisplatin-treated mice compared with 8-wk-old mice. Despite a decreased inflammatory response, the level of immune cell infiltration was greater in 40-wk-old cisplatin-treated mice than 8-wk-old mice. Our data highlight the importance of examining age as a risk factor for cisplatin-induced kidney injury.

Keywords: AKI; CKD; cisplatin; fibrosis; nephrotoxicity.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / immunology*
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Age Factors
  • Aging / immunology*
  • Aging / metabolism
  • Animals
  • Cisplatin*
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Fibrosis
  • Inflammation Mediators / immunology*
  • Inflammation Mediators / metabolism
  • Kidney / immunology*
  • Kidney / metabolism
  • Kidney / pathology
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice
  • Risk Factors
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology

Substances

  • Cytokines
  • Inflammation Mediators
  • Cisplatin