Macrophages contribute to the development of renal fibrosis following ischaemia/reperfusion-induced acute kidney injury

Gang Jee Ko, Chang Su Boo, Sang Kyung Jo, Won Yong Cho, Hyoung Kyu Kim

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

Background. Ischaemia/reperfusion is a major cause of acute kidney injury and can result in poor long-term graft function. Although most of the patients with acute kidney injury recover their renal function, significant portion of patients suffer from progressive deterioration of renal function. A persistent inflammatory response might be associated with long-term changes following acute ischaemia/reperfusion. Macrophages are known to infiltrate into tubulointersitium in animal models of chronic kidney disease. However, the role of macrophages in long-term changes after ischaemia/reperfusion remains unknown. We aimed to investigate the role of macrophages on the development of tubulointerstitial fibrosis and functional impairment following acute ischaemia/reperfusion injury by depleting macrophages with liposome clodronate. Methods. Male Sprague-Dawley rats underwent right nephrectomy and clamping of left renal vascular pedicle or sham operation. Liposome clodronate or phosphate buffered saline was administered for 8 weeks. Biochemical and histological renal damage and gene expression of various cytokines were assessed at 4 and 8 weeks after ischaemia/reperfusion. Results. Ischaemic/reperfusion injury resulted in persistent inflammation and tubulointerstital fibrosis with decreased creatinine clearance and increased urinary albumin excretion at 4 and 8 weeks. Macrophage depletion attenuated those changes. This beneficial effect was accompanied with a decrease in gene expression of inflammatory and profibrotic cytokines. Conclusions. These results suggest that macrophages play an important role in mediating persistent inflammation and fibrosis after ischaemia/reperfusion leading to a development of chronic kidney disease. Strategies targeting macrophage infiltration or activation can be useful in the prevention of development of chronic kidney disease following ischaemic injury.

Original languageEnglish
Pages (from-to)842-852
Number of pages11
JournalNephrology Dialysis Transplantation
Volume23
Issue number3
DOIs
Publication statusPublished - 2008 Mar 1

Fingerprint

Acute Kidney Injury
Reperfusion
Fibrosis
Ischemia
Macrophages
Kidney
Chronic Renal Insufficiency
Clodronic Acid
Reperfusion Injury
Liposomes
Cytokines
Inflammation
Gene Expression
Nephrectomy
Constriction
Blood Vessels
Sprague Dawley Rats
Albumins
Creatinine
Animal Models

Keywords

  • Acute renal failure
  • Fibrosis
  • Inflammation
  • Ischaemia/reperfusion
  • Long-term effect
  • Macrophage

ASJC Scopus subject areas

  • Nephrology
  • Transplantation
  • Medicine(all)

Cite this

Macrophages contribute to the development of renal fibrosis following ischaemia/reperfusion-induced acute kidney injury. / Ko, Gang Jee; Boo, Chang Su; Jo, Sang Kyung; Cho, Won Yong; Kim, Hyoung Kyu.

In: Nephrology Dialysis Transplantation, Vol. 23, No. 3, 01.03.2008, p. 842-852.

Research output: Contribution to journalArticle

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